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Sample records for entry supports calcium

  1. Local Calcium Entry and the Guidance of Growth

    NASA Technical Reports Server (NTRS)

    Robinson, K. R.

    1983-01-01

    The role of calcium in developing cells is illustrated. The Fucus egg, a brown algae is used to describe this phenomenom. Results of local calcium entry and forced calcium entry into the eggs are given.

  2. Store-operated calcium entry is essential for glial calcium signalling in CNS white matter.

    PubMed

    Papanikolaou, M; Lewis, A; Butt, A M

    2017-02-28

    'Calcium signalling' is the ubiquitous response of glial cells to multiple extracellular stimuli. The primary mechanism of glial calcium signalling is by release of calcium from intracellular stores of the endoplasmic reticulum (ER). Replenishment of ER Ca(2+) stores relies on store-operated calcium entry (SOCE). However, despite the importance of calcium signalling in glial cells, little is known about their mechanisms of SOCE. Here, we investigated SOCE in glia of the mouse optic nerve, a typical CNS white matter tract that comprises bundles of myelinated axons and the oligodendrocytes and astrocytes that support them. Using quantitative RT-PCR, we identified Orai1 channels, both Stim1 and Stim2, and the transient receptor potential M3 channel (TRPM3) as the primary channels for SOCE in the optic nerve, and their expression in both astrocytes and oligodendrocytes was demonstrated by immunolabelling of optic nerve sections and cultures. The functional importance of SOCE was demonstrated by fluo-4 calcium imaging on isolated intact optic nerves and optic nerve cultures. Removal of extracellular calcium ([Ca(2+)]o) resulted in a marked depletion of glial cytosolic calcium ([Ca(2+)]i), which recovered rapidly on restoration of [Ca(2+)]o via SOCE. 2-aminoethoxydiphenylborane (2APB) significantly decreased SOCE and severely attenuated ATP-mediated calcium signalling. The results provide evidence that Orai/Stim and TRPM3 are important components of the 'calcium toolkit' that underpins SOCE and the sustainability of calcium signalling in white matter glia.

  3. Antibody to dihydropyridine calcium entry blockers

    SciTech Connect

    Thayer, S.; Minaskanian, G.; Fairhurst, A.

    1986-03-05

    Antibodies that recognize dihydropyridine calcium entry blockers were elicited from rabbits. A sensitive and specific radioimmunoassay for dihydropyridines was developed and its specificity compared to the DHP binding site in skeletal muscle membranes. The antibody bound (/sup 3/H)nitrendipine with a higher affinity (K/sub D/ = 0.155 nM) than did the DHP receptor of skeletal muscle (K/sub D/ = 1-3 nM). However, in contrast to the DHP receptor, the antibody recognized only those DHP drugs with meta-nitrophenyl substituents at the 4-position on the DHP ring, and thus reflected the meta position of the nitro group on the DHP hapten used as an antigen. Both the antibody and the receptor exhibited stereospecificity, with each site recognizing the (+) isomer of nicardipine as the more potent. This antibody should prove useful in the studies of some potentially irreversible DHP molecules and for use in the production of anti-idotype antibodies.

  4. Sodium entry through endothelial store-operated calcium entry channels: regulation by Orai1.

    PubMed

    Xu, Ningyong; Cioffi, Donna L; Alexeyev, Mikhail; Rich, Thomas C; Stevens, Troy

    2015-02-15

    Orai1 interacts with transient receptor potential protein of the canonical subfamily (TRPC4) and contributes to calcium selectivity of the endothelial cell store-operated calcium entry current (ISOC). Orai1 silencing increases sodium permeability and decreases membrane-associated calcium, although it is not known whether Orai1 is an important determinant of cytosolic sodium transitions. We test the hypothesis that, upon activation of store-operated calcium entry channels, Orai1 is a critical determinant of cytosolic sodium transitions. Activation of store-operated calcium entry channels transiently increased cytosolic calcium and sodium, characteristic of release from an intracellular store. The sodium response occurred more abruptly and returned to baseline more rapidly than did the transient calcium rise. Extracellular choline substitution for sodium did not inhibit the response, although 2-aminoethoxydiphenyl borate and YM-58483 reduced it by ∼50%. After this transient response, cytosolic sodium continued to increase due to influx through activated store-operated calcium entry channels. The magnitude of this sustained increase in cytosolic sodium was greater when experiments were conducted in low extracellular calcium and when Orai1 expression was silenced; these two interventions were not additive, suggesting a common mechanism. 2-Aminoethoxydiphenyl borate and YM-58483 inhibited the sustained increase in cytosolic sodium, only in the presence of Orai1. These studies demonstrate that sodium permeates activated store-operated calcium entry channels, resulting in an increase in cytosolic sodium; the magnitude of this response is determined by Orai1.

  5. Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles.

    PubMed

    Mosca, Barbara; Eckhardt, Jan; Bergamelli, Leda; Treves, Susan; Bongianino, Rossana; De Negri, Marco; Priori, Silvia G; Protasi, Feliciano; Zorzato, Francesco

    2016-07-08

    We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La(3+)- and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45-CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca(2+) concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca(2+) concentrations similar to those present in the SR lumen after depolarization-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs.

  6. Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles*

    PubMed Central

    Mosca, Barbara; Eckhardt, Jan; Bergamelli, Leda; Treves, Susan; Bongianino, Rossana; De Negri, Marco; Priori, Silvia G.; Protasi, Feliciano; Zorzato, Francesco

    2016-01-01

    We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La3+- and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45-CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca2+ concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca2+ concentrations similar to those present in the SR lumen after depolarization-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs. PMID:27189940

  7. Remodeling of Calcium Entry Pathways in Cancer.

    PubMed

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2016-01-01

    Ca(2+) entry pathways play important roles in control of many cellular functions, including long-term proliferation, migration and cell death. In recent years, it is becoming increasingly clear that, in some types of tumors, remodeling of Ca(2+) entry pathways could contribute to cancer hallmarks such as excessive proliferation, cell migration and invasion as well as resistance to cell death or survival. In this chapter we briefly review findings related to remodeling of Ca(2+) entry pathways in cancer with emphasis on the mechanisms that contribute to increased store-operated Ca(2+) entry (SOCE) and store-operated currents (SOCs) in colorectal cancer cells. Finally, since SOCE appears critically involved in colon tumorogenesis, the inhibition of SOCE by aspirin and other NSAIDs and its possible contribution to colon cancer chemoprevention is reviewed.

  8. T-Type Calcium Channel: A Privileged Gate for Calcium Entry and Control of Adrenal Steroidogenesis

    PubMed Central

    Rossier, Michel F.

    2016-01-01

    Intracellular calcium plays a crucial role in modulating a variety of functions such as muscle contraction, hormone secretion, gene expression, or cell growth. Calcium signaling has been however shown to be more complex than initially thought. Indeed, it is confined within cell microdomains, and different calcium channels are associated with different functions, as shown by various channelopathies. Sporadic mutations on voltage-operated L-type calcium channels in adrenal glomerulosa cells have been shown recently to be the second most prevalent genetic abnormalities present in human aldosterone-producing adenoma. The observed modification of the threshold of activation of the mutated channels not only provides an explanation for this gain of function but also reminds us on the importance of maintaining adequate electrophysiological characteristics to make channels able to exert specific cellular functions. Indeed, the contribution to steroid production of the various calcium channels expressed in adrenocortical cells is not equal, and the reason has been investigated for a long time. Given the very negative resting potential of these cells, and the small membrane depolarization induced by their physiological agonists, low threshold T-type calcium channels are particularly well suited for responding under these conditions and conveying calcium into the cell, at the right place for controlling steroidogenesis. In contrast, high threshold L-type channels are normally activated by much stronger cell depolarizations. The fact that dihydropyridine calcium antagonists, specific for L-type channels, are poorly efficient for reducing aldosterone secretion either in vivo or in vitro, strongly supports the view that these two types of channels differently affect steroid biosynthesis. Whether a similar analysis is transposable to fasciculata cells and cortisol secretion is one of the questions addressed in the present review. No similar mutations on L-type or T-type channels

  9. Calcium influx factor (CIF) as a diffusible messenger for the activation of capacitative calcium entry in Xenopus oocytes.

    PubMed

    Kim, H Y; Hanley, M R

    1999-06-30

    Acid extracts of thapsigargin-treated Xenopus oocytes revealed Ca2(+)-dependent Cl- currents by microinjection into Xenopus oocytes. These currents were detected in highly purified fractions by carrying out a sequence of purification steps including gel filtration chromatography and high performance thin layer chromatography. The nature of the membrane currents evoked by the highly purified fractions were carried by chloride ions as blockade by the selective chloride channel blocker 1 mM niflumic acid. Injection of the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) eradicated the current activities, indicating that the current responses are completely Ca2(+)-dependent. Moreover, the currents were sensitive to the removal of extracellular calcium, indicating the dependence on calcium entry through plasma membrane calcium entry channels. These results elucidate that the highly purified fractions aquired by thapsigargin-stimulated oocytes is an authentic calcium influx factor (CIF). Thus, the detection of increased CIF production from thapsigargin treatment in Xenopus oocytes would give strong support for the existence of CIF as a diffusible messenger for the activation of capacitative calcium entry pathways in Xenopus oocytes.

  10. Effects of calcium entry blockers on tension development and calcium influx in rat uterus.

    PubMed Central

    Granger, S. E.; Hollingsworth, M.; Weston, A. H.

    1986-01-01

    Spontaneous and potassium chloride (KCl)-induced tension development of strips of whole uterus from the day-22 pregnant rat was reduced when the tissues were incubated in a calcium ion (Ca2+)-free medium. Strips of whole uterus, in an initially Ca2+-free medium, responded to the cumulative addition of Ca2+ with graded phasic tension development and associated rapid electrical discharges. The spasms were inhibited by gallopamil (100 nM) and diltiazem (1 microM). Strips of whole uterus in a depolarizing (40 mM K+) medium, which was initially Ca2+-free, responded to the cumulative addition of Ca2+ with graded tonic tension development without associated electrical discharges. These spasms were inhibited by calcium entry blockers with a rank order of potency of nifedipine = gallopamil greater than diltiazem greater than cinnarizine. KCl-induced tension development in endometrium-free uterine strips was antagonized by calcium entry blockers with a rank order of potency of nifedipine greater than gallopamil greater than diltiazem greater than cinnarizine. Ca2+ influx into endometrium-free uterine strips was assessed by means of the 'lanthanum method'. KCl induced a concentration-dependent increase in 45Ca2+ influx which was suppressed or abolished by nifedipine (2.5 nM), gallopamil (100 nM), diltiazem (500 nM) or cinnarizine (5 microM). It is concluded that spontaneous and KCl-induced tension development of rat uterus involves Ca2+ influx from the extracellular medium into the myometrial cell. These results support the hypothesis that nifedipine, gallopamil, diltiazem and cinnarizine inhibit Ca2+- and KCl-induced tension development of rat uterus by reduction of Ca2+ influx. PMID:3955298

  11. Modulation of Calcium Entry by Mitochondria.

    PubMed

    Fonteriz, Rosalba; Matesanz-Isabel, Jessica; Arias-Del-Val, Jessica; Alvarez-Illera, Pilar; Montero, Mayte; Alvarez, Javier

    2016-01-01

    The role of mitochondria in intracellular Ca(2+) signaling relies mainly in its capacity to take up Ca(2+) from the cytosol and thus modulate the cytosolic [Ca(2+)]. Because of the low Ca(2+)-affinity of the mitochondrial Ca(2+)-uptake system, this organelle appears specially adapted to take up Ca(2+) from local high-Ca(2+) microdomains and not from the bulk cytosol. Mitochondria would then act as local Ca(2+) buffers in cellular regions where high-Ca(2+) microdomains form, that is, mainly close to the cytosolic mouth of Ca(2+) channels, both in the plasma membrane and in the endoplasmic reticulum (ER). One of the first targets proposed already in the 1990s to be regulated in this way by mitochondria were the store-operated Ca(2+) channels (SOCE). Mitochondria, by taking up Ca(2+) from the region around the cytosolic mouth of the SOCE channels, would prevent its slow Ca(2+)-dependent inactivation, thus keeping them active for longer. Since then, evidence for this mechanism has accumulated mainly in immunitary cells, where mitochondria actually move towards the immune synapse during T cell activation. However, in many other cell types the available data indicate that the close apposition between plasma and ER membranes occurring during SOCE activation precludes mitochondria from getting close to the Ca(2+)-entry sites. Alternative pathways for mitochondrial modulation of SOCE, both Ca(2+)-dependent and Ca(2+)-independent, have also been proposed, but further work will be required to elucidate the actual mechanisms at work. Hopefully, the recent knowledge of the molecular nature of the mitochondrial Ca(2+) uniporter will allow soon more precise studies on this matter.

  12. Release of calcium from endolysosomes increases calcium influx through N-type calcium channels: Evidence for acidic store-operated calcium entry in neurons.

    PubMed

    Hui, Liang; Geiger, Nicholas H; Bloor-Young, Duncan; Churchill, Grant C; Geiger, Jonathan D; Chen, Xuesong

    2015-12-01

    Neurons possess an elaborate system of endolysosomes. Recently, endolysosomes were found to have readily releasable stores of intracellular calcium; however, relatively little is known about how such 'acidic calcium stores' affect calcium signaling in neurons. Here we demonstrated in primary cultured neurons that calcium released from acidic calcium stores triggered calcium influx across the plasma membrane, a phenomenon we have termed "acidic store-operated calcium entry (aSOCE)". aSOCE was functionally distinct from store-operated calcium release and calcium entry involving endoplasmic reticulum. aSOCE appeared to be governed by N-type calcium channels (NTCCs) because aSOCE was attenuated significantly by selectively blocking NTCCs or by siRNA knockdown of NTCCs. Furthermore, we demonstrated that NTCCs co-immunoprecipitated with the lysosome associated membrane protein 1 (LAMP1), and that aSOCE is accompanied by increased cell-surface expression levels of NTCC and LAMP1 proteins. Moreover, we demonstrated that siRNA knockdown of LAMP1 or Rab27a, both of which are key proteins involved in lysosome exocytosis, attenuated significantly aSOCE. Taken together our data suggest that aSOCE occurs in neurons, that aSOCE plays an important role in regulating the levels and actions of intraneuronal calcium, and that aSOCE is regulated at least in part by exocytotic insertion of N-type calcium channels into plasma membranes through LAMP1-dependent lysosome exocytosis.

  13. Role of TRPC Channels in Store-Operated Calcium Entry.

    PubMed

    Ong, Hwei Ling; de Souza, Lorena Brito; Ambudkar, Indu S

    2016-01-01

    Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of Ca(2+) stores within the endoplasmic reticulum (ER) and contributes to the control of various physiological functions in a wide variety of cell types. The transient receptor potential canonical (TRPC) channels (TRPCs 1-7), that are activated by stimuli leading to PIP2 hydrolysis, were first identified as molecular components of SOCE channels. TRPC channels show a miscellany of tissue expression, physiological functions and channel properties. However, none of the TRPC members display currents that resemble I CRAC. Intensive search for the CRAC channel component led to identification of Orai1 and STIM1, now established as being the primary constituents of the CRAC channel. There is now considerable evidence that STIM1 activates both Orai1 and TRPC1 via distinct domains in its C-terminus. Intriguingly, TRPC1 function is not only dependent on STIM1 but also requires Orai1. The critical functional interaction between TRPC1 and Orai1, which determines the activation of TRPC1, has also been identified. In this review, we will discuss current concepts regarding the role of TRPC channels in SOCE, the physiological functions regulated by TRPC-mediated SOCE, and the complex mechanisms underlying the regulation of TRPCs, including the functional interactions with Orai1 and STIM1.

  14. A mammalian capacitative calcium entry channel homologous to Drosophila TRP and TRPL.

    PubMed Central

    Philipp, S; Cavalié, A; Freichel, M; Wissenbach, U; Zimmer, S; Trost, C; Marquart, A; Murakami, M; Flockerzi, V

    1996-01-01

    Intracellular Ca2+ signalling evoked by Ca2+ mobilizing agonists, like angiotensin II in the adrenal gland, involves the activation of inositol(1,4,5)trisphosphate(InsP3)-mediated Ca2+ release from internal stores followed by activation of a Ca2+ influx termed capacitative calcium entry. Here we report the amino acid sequence of a functional capacitative Ca2+ entry (CCE) channel that supports inward Ca2+ currents in the range of the cell resting potential. The expressed CCE channel opens upon depletion of Ca2+ stores by InsP3 or thapsigargin, suggesting that the newly identified channel supports the CCE coupled to InsP3 signalling. Images PMID:8947038

  15. The coupling of plasma membrane calcium entry to calcium uptake by endoplasmic reticulum and mitochondria

    PubMed Central

    García-Sancho, Javier

    2014-01-01

    Abstract Cross-talk between organelles and plasma membrane Ca2+ channels is essential for modulation of the cytosolic Ca2+ ([Ca2+]C) signals, but such modulation may differ among cells. In chromaffin cells Ca2+ entry through voltage-operated channels induces calcium release from the endoplasmic reticulum (ER) that amplifies the signal. [Ca2+]C microdomains as high as 20–50 μm are sensed by subplasmalemmal mitochondria, which accumulate large amounts of Ca2+ through the mitochondrial Ca2+ uniporter (MCU). Mitochondria confine the high-Ca2+ microdomains (HCMDs) to beneath the plasma membrane, where exocytosis of secretory vesicles happens. Cell core [Ca2+]C is much smaller (1–2 μm). By acting as a Ca2+ sink, mitochondria stabilise the HCMD in space and time. In non-excitable HEK293 cells, activation of store-operated Ca2+ entry, triggered by ER Ca2+ emptying, also generated subplasmalemmal HCMDs, but, in this case, most of the Ca2+ was taken up by the ER rather than by mitochondria. The smaller size of the [Ca2+]C peak in this case (about 2 μm) may contribute to this outcome, as the sarco-endoplasmic reticulum Ca2+ ATPase has much higher Ca2+ affinity than MCU. It is also possible that the relative positioning of organelles, channels and effectors, as well as cytoskeleton and accessory proteins plays an important role. Key points Cross-talk between organelles and plasma membrane Ca2+ channels modulates cytosolic Ca2+ signals in different ways. In chromaffin cells Ca2+ entry through voltage-operated channels is amplified by Ca2+ release from the endoplasmic reticulum (ER) and generates subplasmalemmal high Ca2+ microdomains (HCMDs) as high as 20–50 μm, which trigger exocytosis. Subplasmalemmal mitochondria take up Ca2+ from HCMDs and avoid progression of the Ca2+ wave towards the cell core. In non-excitable HEK293 cells activation of store-operated Ca2+ entry triggered by ER Ca2+ emptying also generates subplasmalemmal HCMDs of about 2 μm. In this case

  16. The actin cytoskeleton in store-mediated calcium entry

    PubMed Central

    Rosado, Juan A; Sage, Stewart O

    2000-01-01

    Store-mediated Ca2+ entry is the main pathway for Ca2+ influx in platelets and many other cells. Several hypotheses have considered both direct and indirect coupling mechanisms between the endoplasmic reticulum and the plasma membrane. Here we pay particular attention to new insights into the regulation of store-mediated Ca2+ entry: the role of the cytoskeleton in a secretion-like coupling model. In this model, Ca2+ entry may be mediated by a reversible trafficking and coupling of the endoplasmic reticulum with the plasma membrane, that shows close parallels to the events mediating secretion. As with secretion, the actin cytoskeleton plays an inhibitory role in the activation of Ca2+ entry by preventing the approach and coupling of the endoplasmic reticulum with the plasma membrane, making cytoskeletal remodelling a key event in the activation of Ca2+ entry. We also review recent advances investigating the regulation of store-mediated Ca2+ entry by small GTPases and phosphoinositides, which might be involved in the store-mediated Ca2+ entry pathway through roles in the remodelling of the cytoskeleton. PMID:10896713

  17. In vivo effects of calcium entry blockers on human parathyroid adenoma cells with special reference to calcium sensing ability and the hormone secretion.

    PubMed

    Horikawa, Y; Nakajima, H; Iizuka, K; Imagawa, A; Tomita, K; Shiba, E; Takai, S; Miyagawa, J; Kuwajima, M; Namba, M; Hanafusa, T; Matsuzawa, Y

    1999-01-01

    We evaluated the effects of calcium-entry blockers on parathyroid hormone (PTH) secretion by human parathyroid adenoma cells in vitro. Nifedipine and bamidipine inhibited PTH secretion, while diltiazem had no significant effect. Cytosolic calcium concentrations were measured by use of the calcium-sensitive fluorescent dye fluo-3 with confocal laser scanning microscopy. Nifedipine increased the cytosolic concentration of calcium, whereas diltiazem decreased it. Results suggest that, in parathyroid adenoma cells, regulation of PTH secretion with respect to intracellular calcium concentration would be maintained despite differing response of intracellular calcium concentration following exposure to calcium-entry blockers.

  18. Dystrophin/α1-syntrophin scaffold regulated PLC/PKC-dependent store-operated calcium entry in myotubes.

    PubMed

    Sabourin, Jessica; Harisseh, Rania; Harnois, Thomas; Magaud, Christophe; Bourmeyster, Nicolas; Déliot, Nadine; Constantin, Bruno

    2012-12-01

    In skeletal muscles from patient suffering of Duchenne Muscular Dystrophy and from mdx mice, the absence of the cytoskeleton protein dystrophin has been shown to be essential for maintaining a normal calcium influx. We showed that a TRPC store-dependent cation influx is increased by loss of dystrophin or a scaffolding protein α1-syntrophin, however the mechanisms of this calcium mishandling are incompletely understood. First of all, we confirmed that TRPC1 but also STIM1 and Orai1 are supporting the store-operated cation entry which is enhanced in dystrophin-deficient myotubes. Next, we demonstrated that inhibition of PLC or PKC in dystrophin-deficient myotubes restores elevated cation entry to normal levels similarly to enforced minidystrophin expression. In addition, silencing α1-syntrophin also increased cation influx in a PLC/PKC dependent pathway. We also showed that α1-syntrophin and PLCβ are part of a same protein complex reinforcing the idea of their inter-relation in calcium influx regulation. This elevated cation entry was decreased to normal levels by chelating intracellular free calcium with BAPTA-AM. Double treatments with BAPTA-AM and PLC or PKC inhibitors suggested that the elevation of cation influx by PLC/PKC pathway is dependent on cytosolic calcium. All these results demonstrate an involvement in dystrophin-deficient myotubes of a specific calcium/PKC/PLC pathway in elevation of store-operated cation influx supported by the STIM1/Orai1/TRPC1 proteins, which is normally regulated by the α1-syntrophin/dystrophin scaffold.

  19. Isradipine, a calcium-entry blocker, decreases vascular (125-I)low-density lipoprotein entry in hypercholesterolemic rabbits

    SciTech Connect

    Sinzinger, H.; Lupattelli, G.; Virgolini, I.; Gerakakis, A.; Fitscha, P.; Molinari, E.; Angelberger, P. Vienna, Austria)

    1991-04-01

    In 72 male rabbits aged 6 months, the endothelium of the abdominal aorta was abraded by a Fogarthy catheter. The animals were then fed a 1% cholesterol-supplemented diet for 4 weeks. In addition, half of the animals were treated for the entire period with isradipine (0.3 mg/kg daily), a dihydropyridine calcium antagonist; the other 36 animals served as controls. One hour and 3, 6, 12, 24, and 48 hours before the animals were killed, (125-I)low-density lipoprotein (LDL 10 microCi) was administered intravenously (i.v.) to six animals in each group. The (125-I)LDL entry was quantified in the abdominal aorta according to the type and presence of endothelial lining. Isradipine significantly reduced the (125-I)LDL entry at most time intervals. In parallel, an increase in vascular prostaglandin (PGI2) synthesis was noted, which might be the underlying mechanism for the decreased LDL entry.

  20. Stardust Hypervelocity Entry Observing Campaign Support

    NASA Technical Reports Server (NTRS)

    Kontinos, Dean A.; Jordan, David E.; Jenniskens, Peter

    2009-01-01

    In the early morning of January 15, 2006, the Stardust Sample Return Capsule (SRC) successfully delivered its precious cargo of cometary particles to the awaiting recovery team at the Utah Test and Training Range (UTTR). As the SRC entered at 12.8 km/s, the fastest manmade object to traverse the atmosphere, a team of researchers imaged the event aboard the NASA DC-8 airborne observatory. At SRC entry, the airplane was at an altitude of 11.9 km positioned within 6.4 km of the prescribed, preferred target view location. The incoming SRC was first acquired approximately 18 seconds (s) after atmospheric interface and tracked for approximately 60 s, an observation period that is roughly centered in time around predicted peak heating.

  1. NEUROD2 Regulates Stim1 Expression and Store-Operated Calcium Entry in Cortical Neurons

    PubMed Central

    Akkaya, Cansu; Bayam, Efil

    2017-01-01

    Abstract Calcium signaling controls many key processes in neurons, including gene expression, axon guidance, and synaptic plasticity. In contrast to calcium influx through voltage- or neurotransmitter-gated channels, regulatory pathways that control store-operated calcium entry (SOCE) in neurons are poorly understood. Here, we report a transcriptional control of Stim1 (stromal interaction molecule 1) gene, which is a major sensor of endoplasmic reticulum (ER) calcium levels and a regulator of SOCE. By using a genome-wide chromatin immunoprecipitation and sequencing approach in mice, we find that NEUROD2, a neurogenic transcription factor, binds to an intronic element within the Stim1 gene. We show that NEUROD2 limits Stim1 expression in cortical neurons and consequently fine-tunes the SOCE response upon depletion of ER calcium. Our findings reveal a novel mechanism that regulates neuronal calcium homeostasis during cortical development. PMID:28303257

  2. Adaptation of mammalian auditory hair cell mechanotransduction is independent of calcium entry.

    PubMed

    Peng, Anthony W; Effertz, Thomas; Ricci, Anthony J

    2013-11-20

    Adaptation is a hallmark of hair cell mechanotransduction, extending the sensory hair bundle dynamic range while providing mechanical filtering of incoming sound. In hair cells responsive to low frequencies, two distinct adaptation mechanisms exist, a fast component of debatable origin and a slow myosin-based component. It is generally believed that Ca(2+) entry through mechano-electric transducer channels is required for both forms of adaptation. This study investigates the calcium dependence of adaptation in the mammalian auditory system. Recordings from rat cochlear hair cells demonstrate that altering Ca(2+) entry or internal Ca(2+) buffering has little effect on either adaptation kinetics or steady-state adaptation responses. Two additional findings include a voltage-dependent process and an extracellular Ca(2+) binding site, both modulating the resting open probability independent of adaptation. These data suggest that slow motor adaptation is negligible in mammalian auditory cells and that the remaining adaptation process is independent of calcium entry.

  3. JIMO Delivery and Support of a Jupiter Deep Entry Probe

    NASA Technical Reports Server (NTRS)

    Spilker, T. R.; Young, R. E.

    2003-01-01

    The 2003 Solar System Exploration Decadal Survey ('SSEDS') emphasizes the significant science available from Jupiter deep entry probes. Studies performed at JPL this year identified a mission design that would allow JIMO to deliver and support one or more entry probes that reach the 100-bar level in Jupiter's atmosphere, with relatively minor modifications to JIMO s preliminary mission design. Notably, the icy moon tour mission design, beginning with Callisto approach, is unaffected. This proposed mission design would offer the option of adding a rich new set of high-priority SSEDS science objectives to the planned JIMO mission for a relatively small investment.

  4. T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels.

    PubMed

    Matza, Didi; Badou, Abdallah; Klemic, Kathryn G; Stein, Judith; Govindarajulu, Usha; Nadler, Monica J; Kinet, Jean-Pierre; Peled, Amnon; Shapira, Oz M; Kaczmarek, Leonard K; Flavell, Richard A

    2016-01-01

    The process of calcium entry in T cells is a multichannel and multi-step process. We have studied the requirement for L-type calcium channels (Cav1.1) α1S subunits during calcium entry after TCR stimulation. High expression levels of Cav1.1 channels were detected in activated T cells. Sequencing and cloning of Cav1.1 channel cDNA from T cells revealed that a single splice variant is expressed. This variant lacks exon 29, which encodes the linker region adjacent to the voltage sensor, but contains five new N-terminal exons that substitute for exons 1 and 2, which are found in the Cav1.1 muscle counterpart. Overexpression studies using cloned T cell Cav1.1 in 293HEK cells (that lack TCR) suggest that the gating of these channels was altered. Knockdown of Cav1.1 channels in T cells abrogated calcium entry after TCR stimulation, suggesting that Cav1.1 channels are controlled by TCR signaling.

  5. T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels

    PubMed Central

    Matza, Didi; Badou, Abdallah; Klemic, Kathryn G.; Stein, Judith; Govindarajulu, Usha; Nadler, Monica J.; Kinet, Jean-Pierre; Peled, Amnon; Shapira, Oz M.; Kaczmarek, Leonard K.; Flavell, Richard A.

    2016-01-01

    The process of calcium entry in T cells is a multichannel and multi-step process. We have studied the requirement for L-type calcium channels (Cav1.1) α1S subunits during calcium entry after TCR stimulation. High expression levels of Cav1.1 channels were detected in activated T cells. Sequencing and cloning of Cav1.1 channel cDNA from T cells revealed that a single splice variant is expressed. This variant lacks exon 29, which encodes the linker region adjacent to the voltage sensor, but contains five new N-terminal exons that substitute for exons 1 and 2, which are found in the Cav1.1 muscle counterpart. Overexpression studies using cloned T cell Cav1.1 in 293HEK cells (that lack TCR) suggest that the gating of these channels was altered. Knockdown of Cav1.1 channels in T cells abrogated calcium entry after TCR stimulation, suggesting that Cav1.1 channels are controlled by TCR signaling. PMID:26815481

  6. Copper-induced activation of TRP channels promotes extracellular calcium entry, activation of CaMs and CDPKs, copper entry and membrane depolarization in Ulva compressa

    PubMed Central

    Gómez, Melissa; González, Alberto; Sáez, Claudio A.; Morales, Bernardo; Moenne, Alejandra

    2015-01-01

    In order to identify channels involved in membrane depolarization, Ulva compressa was incubated with agonists of TRP channels C5, A1 and V1, and the level of intracellular calcium was detected. Agonists of TRPC5, A1 and V1 induced increases in intracellular calcium at 4, 9, and 11 min of exposure, respectively, and antagonists of TRPC5, A1, and V1 corresponding to SKF-96365 (SKF), HC-030031 (HC), and capsazepin (CPZ), respectively, inhibited calcium increases indicating that functional TRPs exist in U. compressa. In addition, copper excess induced increases in intracellular calcium at 4, 9, and 12 min which were inhibited by SKF, HC, and CPZ, respectively, indicating that copper activate TRPC5, A1, and V1 channels. Moreover, copper-induced calcium increases were inhibited by EGTA, a non-permeable calcium chelating agent, but not by thapsigargin, an inhibitor of endoplasmic reticulum (ER) calcium ATPase, indicating that activation of TRPs leads to extracellular calcium entry. Furthermore, copper-induced calcium increases were not inhibited by W-7, an inhibitor of CaMs, and staurosporine, an inhibitor of CDPKs, indicating that extracellular calcium entry did not require activation of CaMs and CDPKs. In addition, copper induced membrane depolarization events at 4, 8, and 11 min and these events were inhibited by SKF, HC, CPZ, and bathocuproine, a specific copper chelating agent, indicating that copper entry through TRP channels leads to membrane depolarization. Moreover, membrane depolarization events were inhibited by W-7 and staurosporine, indicating that activation of CaMs and CDPKs is required to allow copper entry through TRPs. Interestingly, copper-induced calcium increases and depolarization events were light-dependent and were inhibited by DCMU, an inhibitor of photosystem II, and ATP-γ-S, a non-hydrolizable analog of ATP, suggesting that ATP derived from photosynthesis is required to activate TRPs. Thus, light-dependent copper-induced activation TRPC5, A1

  7. Copper-induced activation of TRP channels promotes extracellular calcium entry, activation of CaMs and CDPKs, copper entry and membrane depolarization in Ulva compressa.

    PubMed

    Gómez, Melissa; González, Alberto; Sáez, Claudio A; Morales, Bernardo; Moenne, Alejandra

    2015-01-01

    In order to identify channels involved in membrane depolarization, Ulva compressa was incubated with agonists of TRP channels C5, A1 and V1, and the level of intracellular calcium was detected. Agonists of TRPC5, A1 and V1 induced increases in intracellular calcium at 4, 9, and 11 min of exposure, respectively, and antagonists of TRPC5, A1, and V1 corresponding to SKF-96365 (SKF), HC-030031 (HC), and capsazepin (CPZ), respectively, inhibited calcium increases indicating that functional TRPs exist in U. compressa. In addition, copper excess induced increases in intracellular calcium at 4, 9, and 12 min which were inhibited by SKF, HC, and CPZ, respectively, indicating that copper activate TRPC5, A1, and V1 channels. Moreover, copper-induced calcium increases were inhibited by EGTA, a non-permeable calcium chelating agent, but not by thapsigargin, an inhibitor of endoplasmic reticulum (ER) calcium ATPase, indicating that activation of TRPs leads to extracellular calcium entry. Furthermore, copper-induced calcium increases were not inhibited by W-7, an inhibitor of CaMs, and staurosporine, an inhibitor of CDPKs, indicating that extracellular calcium entry did not require activation of CaMs and CDPKs. In addition, copper induced membrane depolarization events at 4, 8, and 11 min and these events were inhibited by SKF, HC, CPZ, and bathocuproine, a specific copper chelating agent, indicating that copper entry through TRP channels leads to membrane depolarization. Moreover, membrane depolarization events were inhibited by W-7 and staurosporine, indicating that activation of CaMs and CDPKs is required to allow copper entry through TRPs. Interestingly, copper-induced calcium increases and depolarization events were light-dependent and were inhibited by DCMU, an inhibitor of photosystem II, and ATP-γ-S, a non-hydrolizable analog of ATP, suggesting that ATP derived from photosynthesis is required to activate TRPs. Thus, light-dependent copper-induced activation TRPC5, A1

  8. Clinical decision support for physician order-entry: design challenges.

    PubMed

    Broverman, C A; Clyman, J I; Schlesinger, J M; Want, E

    1996-01-01

    We report on a joint development effort between ALLTEL Information Services Health Care Division and IBM Worldwide Healthcare Industry to demonstrate concurrent clinical decision support using Arden Syntax at order-entry time. The goal of the partnership is to build a high performance CDS toolkit that may be easily customized for multiple health care enterprises. Our work uses and promotes open technologies and health care standards while building a generalizable interface to a legacy patient-care system and clinical database. This paper identifies four areas of design challenges and solutions unique to a concurrent order-entry environment: the clinical information model, the currency of the patient virtual chart, the granularity of event triggers and rule evaluation context, and performance.

  9. Hepatitis B virus modulates store-operated calcium entry to enhance viral replication in primary hepatocytes

    PubMed Central

    Casciano, Jessica C.; Duchemin, Nicholas J.; Lamontagne, R. Jason; Steel, Laura F.; Bouchard, Michael J.

    2017-01-01

    Many viruses modulate calcium (Ca2+) signaling to create a cellular environment that is more permissive to viral replication, but for most viruses that regulate Ca2+ signaling, the mechanism underlying this regulation is not well understood. The hepatitis B virus (HBV) HBx protein modulates cytosolic Ca2+ levels to stimulate HBV replication in some liver cell lines. A chronic HBV infection is associated with life-threatening liver diseases, including hepatocellular carcinoma (HCC), and HBx modulation of cytosolic Ca2+ levels could have an important role in HBV pathogenesis. Whether HBx affects cytosolic Ca2+ in a normal hepatocyte, the natural site of an HBV infection, has not been addressed. Here, we report that HBx alters cytosolic Ca2+ signaling in cultured primary hepatocytes. We used single cell Ca2+ imaging of cultured primary rat hepatocytes to demonstrate that HBx elevates the cytosolic Ca2+ level in hepatocytes following an IP3-linked Ca2+ response; HBx effects were similar when expressed alone or in the context of replicating HBV. HBx elevation of the cytosolic Ca2+ level required extracellular Ca2+ influx and store-operated Ca2+ (SOC) entry and stimulated HBV replication in hepatocytes. We used both targeted RT-qPCR and transcriptome-wide RNAseq analyses to compare levels of SOC channel components and other Ca2+ signaling regulators in HBV-expressing and control hepatocytes and show that the transcript levels of these various proteins are not affected by HBV. We also show that HBx regulation of SOC-regulated Ca2+ accumulation is likely the consequence of HBV modulation of a SOC channel regulatory mechanism. In support of this, we link HBx enhancement of SOC-regulated Ca2+ accumulation to Ca2+ uptake by mitochondria and demonstrate that HBx stimulates mitochondrial Ca2+ uptake in primary hepatocytes. The results of our study may provide insights into viral mechanisms that affect Ca2+ signaling to regulate viral replication and virus-associated diseases

  10. Hepatitis B virus modulates store-operated calcium entry to enhance viral replication in primary hepatocytes.

    PubMed

    Casciano, Jessica C; Duchemin, Nicholas J; Lamontagne, R Jason; Steel, Laura F; Bouchard, Michael J

    2017-01-01

    Many viruses modulate calcium (Ca2+) signaling to create a cellular environment that is more permissive to viral replication, but for most viruses that regulate Ca2+ signaling, the mechanism underlying this regulation is not well understood. The hepatitis B virus (HBV) HBx protein modulates cytosolic Ca2+ levels to stimulate HBV replication in some liver cell lines. A chronic HBV infection is associated with life-threatening liver diseases, including hepatocellular carcinoma (HCC), and HBx modulation of cytosolic Ca2+ levels could have an important role in HBV pathogenesis. Whether HBx affects cytosolic Ca2+ in a normal hepatocyte, the natural site of an HBV infection, has not been addressed. Here, we report that HBx alters cytosolic Ca2+ signaling in cultured primary hepatocytes. We used single cell Ca2+ imaging of cultured primary rat hepatocytes to demonstrate that HBx elevates the cytosolic Ca2+ level in hepatocytes following an IP3-linked Ca2+ response; HBx effects were similar when expressed alone or in the context of replicating HBV. HBx elevation of the cytosolic Ca2+ level required extracellular Ca2+ influx and store-operated Ca2+ (SOC) entry and stimulated HBV replication in hepatocytes. We used both targeted RT-qPCR and transcriptome-wide RNAseq analyses to compare levels of SOC channel components and other Ca2+ signaling regulators in HBV-expressing and control hepatocytes and show that the transcript levels of these various proteins are not affected by HBV. We also show that HBx regulation of SOC-regulated Ca2+ accumulation is likely the consequence of HBV modulation of a SOC channel regulatory mechanism. In support of this, we link HBx enhancement of SOC-regulated Ca2+ accumulation to Ca2+ uptake by mitochondria and demonstrate that HBx stimulates mitochondrial Ca2+ uptake in primary hepatocytes. The results of our study may provide insights into viral mechanisms that affect Ca2+ signaling to regulate viral replication and virus-associated diseases.

  11. 2-Ethynylbenzenealkanamines: a new class of calcium entry blockers with potential antihypertensive and antianginal properties

    SciTech Connect

    Brannan, M.D.; Carson, J.R.; Gill, A.; Keely, S.L.; Flaim, S.F.; Sit, S.P.; Damiano, B.P.; Carmosin, R.R.J.; Gleason, M.M.; Ludovici, D.W.; Pitis, P.M.

    1986-03-05

    2-Ethynylbenzenealkanamines represent a newly discovered class of calcium channel blockers in that they inhibited KCl-stimulated /sup 45/Ca influx and isometric tension development in isolated vascular smooth muscle and prolonged AV-nodal conduction time in canine hearts. Testing revealed optimal activity in the following structure where R1 is aryl, R2 and R4 are methyl, R3 is aralkyl and X is methoxy: compounds in this group lowered arterial pressures in conscious spontaneously hypertensive rats and renal hypertensive dogs following either oral or parenteral administration, and thus are potential antihypertensive agents. These compounds also caused coronary vasodilation at concentrations which did not affect rate or force of contraction in the isolated, perfused guinea pig heart preparation, they increased coronary blood flow and decreased coronary vascular resistance in the anesthetized canine, and thus are potential antianginal agents. In summary, 2-ethynylbenzenealkanamines represent a new class of calcium entry blockers which have potential antihypertensive and antianginal properties.

  12. Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium

    PubMed Central

    Fan, Hanlu; Du, Xiaohong; Zhang, Jingyuan; Zheng, Han; Lu, Xiaohui; Wu, Qihui; Li, Haifeng; Wang, Han; Shi, Yi; Gao, George; Zhou, Zhuan; Tan, Dun-Xian; Li, Xiangdong

    2017-01-01

    The Ebola crisis occurred in West-Africa highlights the urgency for its clinical treatments. Currently, no Food and Drug Administration (FDA)-approved therapeutics are available. Several FDA-approved drugs, including selective estrogen receptor modulators (SERMs), possess selective anti-Ebola activities. However, the inhibitory mechanisms of these drugs remain elusive. By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection. Herein, we demonstrated that the same dosages of SERMs which induced cholesterol accumulation also inhibited Ebola infection. SERMs reduced the cellular sphingosine and subsequently caused endolysosomal calcium accumulation, which in turn led to blocking the Ebola entry. Our study clarified the specific anti-Ebola mechanism of SERMs, even the cationic amphiphilic drugs (CADs), this mechanism led to the endolysosomal calcium as a critical target for development of anti-Ebola drugs. PMID:28117364

  13. Calcium-induced calcium release supports recruitment of synaptic vesicles in auditory hair cells

    PubMed Central

    Schnee, Michael E.; Ricci, Anthony J.

    2015-01-01

    Hair cells from auditory and vestibular systems transmit continuous sound and balance information to the central nervous system through the release of synaptic vesicles at ribbon synapses. The high activity experienced by hair cells requires a unique mechanism to sustain recruitment and replenishment of synaptic vesicles for continuous release. Using pre- and postsynaptic electrophysiological recordings, we explored the potential contribution of calcium-induced calcium release (CICR) in modulating the recruitment of vesicles to auditory hair cell ribbon synapses. Pharmacological manipulation of CICR with agents targeting endoplasmic reticulum calcium stores reduced both spontaneous postsynaptic multiunit activity and the frequency of excitatory postsynaptic currents (EPSCs). Pharmacological treatments had no effect on hair cell resting potential or activation curves for calcium and potassium channels. However, these drugs exerted a reduction in vesicle release measured by dual-sine capacitance methods. In addition, calcium substitution by barium reduced release efficacy by delaying release onset and diminishing vesicle recruitment. Together these results demonstrate a role for calcium stores in hair cell ribbon synaptic transmission and suggest a novel contribution of CICR in hair cell vesicle recruitment. We hypothesize that calcium entry via calcium channels is tightly regulated to control timing of vesicle fusion at the synapse, whereas CICR is used to maintain a tonic calcium signal to modulate vesicle trafficking. PMID:26510758

  14. Shear stress-induced NO production is dependent on ATP autocrine signaling and capacitative calcium entry

    PubMed Central

    Andrews, Allison M.; Jaron, Dov; Buerk, Donald G.; Barbee, Kenneth A.

    2014-01-01

    Flow-induced production of nitric oxide (NO) by endothelial cells plays a fundamental role in vascular homeostasis. However, the mechanisms by which shear stress activates NO production remain unclear due in part to limitations in measuring NO, especially under flow conditions. Shear stress elicits the release of ATP, but the relative contribution of autocrine stimulation by ATP to flow-induced NO production has not been established. Furthermore, the importance of calcium in shear stress-induced NO production remains controversial, and in particular the role of capacitive calcium entry (CCE) has yet to be determined. We have utilized our unique NO measurement device to investigate the role of ATP autocrine signaling and CCE in shear stress-induced NO production. We found that endogenously released ATP and downstream activation of purinergic receptors and CCE plays a significant role in shear stress-induced NO production. ATP-induced eNOS phophorylation under static conditions is also dependent on CCE. Inhibition of protein kinase C significantly inhibited eNOS phosphorylation and the calcium response. To our knowledge, we are the first to report on the role of CCE in the mechanism of acute shear stress-induced NO response. In addition, our work highlights the importance of ATP autocrine signaling in shear stress-induced NO production. PMID:25386222

  15. Electroporation-induced formation of individual calcium entry sites in the cell body and processes of adherent cells.

    PubMed Central

    Teruel, M N; Meyer, T

    1997-01-01

    Electroporation is a widely used method for introducing macromolecules into cells. We developed an electroporation device that requires only 1 microl of sample to load adherent cells in a 10-mm2 surface area while retaining greater than 90% cell survivability. To better understand this device, field-induced permeabilization of adherent rat basophilic leukemia and neocortical neuroblastoma cells was investigated by using fluorescent calcium and voltage indicators. Rectangular field pulses led to the formation of only a few calcium entry sites, preferentially in the hyperpolarized parts of the cell body and processes. Individual entry sites were formed at the same locations when field pulses were repeated. Before calcium entry, a partial breakdown of the membrane potential was observed in both polar regions. Based on our results, a model is proposed for the formation and closure of macromolecule entry sites in adherent cells. First, the rapid formation of a large number of small pores leads to a partial membrane potential breakdown in both polar regions of the cell. Second, over tens of milliseconds, a few entry sites for macromolecules are formed, preferentially in the hyperpolarized part of cell body and processes, at locations defined by the local membrane structure. These entry sites reseal on a time scale of 50 ms to several seconds, with residual small pores remaining open for several minutes. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 8 FIGURE 9 PMID:9336174

  16. Progesterone suppressed vasoconstriction in human umbilical vein via reducing calcium entry.

    PubMed

    He, Yun; Gao, Qinqin; Han, Bing; Zhu, Xiaolin; Zhu, Di; Tao, Jianying; Chen, Jie; Xu, Zhice

    2016-04-01

    The aim of this study was to evaluate the actions of progesterone on human umbilical vein (HUV) from normal pregnancies and the possible underlying mechanisms involved. HUV rings were suspended in organ baths and exposed to progesterone followed by phenylephrine (PE) or serotonin (5-HT). Progesterone suppressed PE- or 5-HT-induced vasoconstriction in HUV rings. The inhibitory effect induced by progesterone was not influenced by nitric oxide syntheses inhibitor, prostaglandins syntheses blocker, the integrity of endothelium, selective progesterone receptor or potassium channel antagonists. Further testing showed that progesterone and nifedipine (a blocker for L-type calcium channels) produced similar inhibitory effects on PE-, 5-HT-, Bay-k8644-, KCl-induced vasoconstriction in Krebs solution as well as CaCl2-induced vasoconstriction in Ca(2+)-free Krebs solution. But the inhibitory effect of mibefradil (mibe, a blocker for L-type (CaV1.2) and T-type calcium channels (CaV3.2)) on PE-, 5-HT-induced vasoconstriction was significantly greater than progesterone or nifedipine in Krebs solution. Furthermore, progesterone did not affect the vasoconstriction caused by PE, 5-HT, or caffeine in Ca(2+)-free Krebs solution. In addition, incubation HUV with progesterone did not change CaV1.2 and progesterone receptor (PR) expressions. The results gained demonstrated that progesterone could suppress multiple agonist-induced vasoconstrictions in HUV, mainly due to a reduction of calcium entry through L-type calcium channels, not endothelium-dependent vascular relaxation pathways, potassium channels, or Ca(2+) release from intracellular stores, providing new information important to further understanding the contribution of progesterone in the regulation of the placental-fetal circulation.

  17. SLO3 K+ channels control calcium entry through CATSPER channels in sperm.

    PubMed

    Chávez, Julio César; Ferreira, Juan José; Butler, Alice; De La Vega Beltrán, José Luis; Treviño, Claudia L; Darszon, Alberto; Salkoff, Lawrence; Santi, Celia M

    2014-11-14

    Here we show how a sperm-specific potassium channel (SLO3) controls Ca(2+) entry into sperm through a sperm-specific Ca(2+) channel, CATSPER, in a totally unanticipated manner. The genetic deletion of either of those channels confers male infertility in mice. During sperm capacitation SLO3 hyperpolarizes the sperm, whereas CATSPER allows Ca(2+) entry. These two channels may be functionally connected, but it had not been demonstrated that SLO3-dependent hyperpolarization is required for Ca(2+) entry through CATSPER channels, nor has a functional mechanism linking the two channels been shown. In this study we show that Ca(2+) entry through CATSPER channels is deficient in Slo3 mutant sperm lacking hyperpolarization; we also present evidence supporting the hypothesis that SLO3 channels activate CATSPER channels indirectly by promoting a rise in intracellular pH through a voltage-dependent mechanism. This mechanism may work through a Na(+)/H(+) exchanger (sNHE) and/or a bicarbonate transporter, which utilizes the inward driving force of the Na(+) gradient, rendering it intrinsically voltage-dependent. In addition, the sperm-specific Na(+)/H(+) exchanger (sNHE) possess a putative voltage sensor that might be activated by membrane hyperpolarization, thus increasing the voltage sensitivity of internal alkalization.

  18. Atlastin regulates store-operated calcium entry for nerve growth factor-induced neurite outgrowth

    PubMed Central

    Li, Jing; Yan, Bing; Si, Hongjiang; Peng, Xu; Zhang, Shenyuan L.; Hu, Junjie

    2017-01-01

    Homotypic membrane fusion of the endoplasmic reticulum (ER) is mediated by a class of dynamin-like GTPases known as atlastin (ATL). Depletion of or mutations in ATL cause an unbranched ER morphology and hereditary spastic paraplegia (HSP), a neurodegenerative disease characterized by axon shortening in corticospinal motor neurons and progressive spasticity of the lower limbs. How ER shaping is linked to neuronal defects is poorly understood. Here, we show that dominant-negative mutants of ATL1 in PC-12 cells inhibit nerve growth factor (NGF)-induced neurite outgrowth. Overexpression of wild-type or mutant ATL1 or depletion of ATLs alters ER morphology and affects store-operated calcium entry (SOCE) by decreasing STIM1 puncta formation near the plasma membrane upon calcium depletion of the ER. In addition, blockage of the STIM1-Orai pathway effectively abolishes neurite outgrowth of PC-12 cells stimulated by NGF. These results suggest that SOCE plays an important role in neuronal regeneration, and mutations in ATL1 may cause HSP, partly by undermining SOCE. PMID:28240257

  19. TFEB-mediated increase in peripheral lysosomes regulates store-operated calcium entry

    PubMed Central

    Sbano, Luigi; Bonora, Massimo; Marchi, Saverio; Baldassari, Federica; Medina, Diego L.; Ballabio, Andrea; Giorgi, Carlotta; Pinton, Paolo

    2017-01-01

    Lysosomes are membrane-bound organelles mainly involved in catabolic processes. In addition, lysosomes can expel their contents outside of the cell via lysosomal exocytosis. Some of the key steps involved in these important cellular processes, such as vesicular fusion and trafficking, require calcium (Ca2+) signaling. Recent data show that lysosomal functions are transcriptionally regulated by transcription factor EB (TFEB) through the induction of genes involved in lysosomal biogenesis and exocytosis. Given these observations, we investigated the roles of TFEB and lysosomes in intracellular Ca2+ homeostasis. We studied the effect of transient modulation of TFEB expression in HeLa cells by measuring the cytosolic Ca2+ response after capacitative Ca2+ entry activation and Ca2+ dynamics in the endoplasmic reticulum (ER) and directly in lysosomes. Our observations show that transient TFEB overexpression significantly reduces cytosolic Ca2+ levels under a capacitative influx model and ER re-uptake of calcium, increasing the lysosomal Ca2+ buffering capacity. Moreover, lysosomal destruction or damage abolishes these TFEB-dependent effects in both the cytosol and ER. These results suggest a possible Ca2+ buffering role for lysosomes and shed new light on lysosomal functions during intracellular Ca2+ homeostasis. PMID:28084445

  20. Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.

    PubMed

    Mamenko, Mykola; Dhande, Isha; Tomilin, Viktor; Zaika, Oleg; Boukelmoune, Nabila; Zhu, Yaming; Gonzalez-Garay, Manuel L; Pochynyuk, Oleh; Doris, Peter A

    2016-07-01

    Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca(2+)) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca(2+) levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca(2+) mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca(2+) levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling.

  1. Store-operated calcium entry contributes to abnormal Ca²⁺ signalling in dystrophic mdx mouse myoblasts.

    PubMed

    Onopiuk, Marta; Brutkowski, Wojciech; Young, Christopher; Krasowska, Elżbieta; Róg, Justyna; Ritso, Morten; Wojciechowska, Sylwia; Arkle, Stephen; Zabłocki, Krzysztof; Górecki, Dariusz C

    2015-03-01

    Sarcolemma damage and activation of various calcium channels are implicated in altered Ca(2+) homeostasis in muscle fibres of both Duchenne muscular dystrophy (DMD) sufferers and in the mdx mouse model of DMD. Previously we have demonstrated that also in mdx myoblasts extracellular nucleotides trigger elevated cytoplasmic Ca(2+) concentrations due to alterations of both ionotropic and metabotropic purinergic receptors. Here we extend these findings to show that the mdx mutation is associated with enhanced store-operated calcium entry (SOCE). Substantially increased rate of SOCE in mdx myoblasts in comparison to that in control cells correlated with significantly elevated STIM1 protein levels. These results reveal that mutation in the dystrophin-encoding Dmd gene may significantly impact cellular calcium response to metabotropic stimulation involving depletion of the intracellular calcium stores followed by activation of the store-operated calcium entry, as early as in undifferentiated myoblasts. These data are in agreement with the increasing number of reports showing that the dystrophic pathology resulting from dystrophin mutations may be developmentally regulated. Moreover, our results showing that aberrant responses to extracellular stimuli may contribute to DMD pathogenesis suggest that treatments inhibiting such responses might alter progression of this lethal disease.

  2. Sustained calcium entry through P2X nucleotide receptor channels in human airway epithelial cells.

    PubMed

    Zsembery, Akos; Boyce, Amanda T; Liang, Lihua; Peti-Peterdi, János; Bell, P Darwin; Schwiebert, Erik M

    2003-04-11

    Purinergic receptor stimulation has potential therapeutic effects for cystic fibrosis (CF). Thus, we explored roles for P2Y and P2X receptors in stably increasing [Ca(2+)](i) in human CF (IB3-1) and non-CF (16HBE14o(-)) airway epithelial cells. Cytosolic Ca(2+) was measured by fluorospectrometry using the fluorescent dye Fura-2/AM. Expression of P2X receptor (P2XR) subtypes was assessed by immunoblotting and biotinylation. In IB3-1 cells, ATP and other P2Y agonists caused only a transient increase in [Ca(2+)](i) derived from intracellular stores in a Na(+)-rich environment. In contrast, ATP induced an increase in [Ca(2+)](i) that had transient and sustained components in a Na(+)-free medium; the sustained plateau was potentiated by zinc or increasing extracellular pH. Benzoyl-benzoyl-ATP, a P2XR-selective agonist, increased [Ca(2+)](i) only in Na(+)-free medium, suggesting competition between Na(+) and Ca(2+) through P2XRs. Biochemical evidence showed that the P2X(4) receptor is the major subtype shared by these airway epithelial cells. A role for store-operated Ca(2+) channels, voltage-dependent Ca(2+) channels, or Na(+)/Ca(2+) exchanger in the ATP-induced sustained Ca(2+) signal was ruled out. In conclusion, these data show that epithelial P2X(4) receptors serve as ATP-gated calcium entry channels that induce a sustained increase in [Ca(2+)](i). In airway epithelia, a P2XR-mediated Ca(2+) signal may have therapeutic benefit for CF.

  3. Nonlinear Waves on Stochastic Support: Calcium Waves in Astrocyte Syncytia

    NASA Astrophysics Data System (ADS)

    Jung, P.; Cornell-Bell, A. H.

    Astrocyte-signaling has been observed in cell cultures and brain slices in the form of Calcium waves. Their functional relevance for neuronal communication, brain functions and diseases is, however, not understood. In this paper, the propagation of intercellular calcium waves is modeled in terms of waves in excitable media on a stochastic support. We utilize a novel method to decompose the spatiotemporal patterns into space-time clusters (wave fragments). Based on this cluster decomposition, a statistical description of wave patterns is developed.

  4. Chemotherapy Order Entry by a Clinical Support Pharmacy Technician in an Outpatient Medical Day Unit

    PubMed Central

    Neville, Heather; Broadfield, Larry; Harding, Claudia; Heukshorst, Shelley; Sweetapple, Jennifer; Rolle, Megan

    2016-01-01

    Background: Pharmacy technicians are expanding their scope of practice, often in partnership with pharmacists. In oncology, such a shift in responsibilities may lead to workflow efficiencies, but may also cause concerns about patient risk and medication errors. Objectives: The primary objective was to compare the time spent on order entry and order-entry checking before and after training of a clinical support pharmacy technician (CSPT) to perform chemotherapy order entry. The secondary objectives were to document workflow interruptions and to assess medication errors. Methods: This before-and-after observational study investigated chemotherapy order entry for ambulatory oncology patients. Order entry was performed by pharmacists before the process change (phase 1) and by 1 CSPT after the change (phase 2); order-entry checking was performed by a pharmacist during both phases. The tasks were timed by an independent observer using a personal digital assistant. A convenience sample of 125 orders was targeted for each phase. Data were exported to Microsoft Excel software, and timing differences for each task were tested with an unpaired t test. Results: Totals of 143 and 128 individual orders were timed for order entry during phase 1 (pharmacist) and phase 2 (CSPT), respectively. The mean total time to perform order entry was greater during phase 1 (1:37 min versus 1:20 min; p = 0.044). Totals of 144 and 122 individual orders were timed for order-entry checking (by a pharmacist) in phases 1 and 2, respectively, and there was no difference in mean total time for order-entry checking (1:21 min versus 1:20 min; p = 0.69). There were 33 interruptions not related to order entry (totalling 39:38 min) during phase 1 and 25 interruptions (totalling 30:08 min) during phase 2. Three errors were observed during order entry in phase 1 and one error during order-entry checking in phase 2; the errors were rated as having no effect on patient care. Conclusions: Chemotherapy order

  5. Don/Doff support stand for use with rear entry space suits

    NASA Technical Reports Server (NTRS)

    Kosmo, Joseph J. (Inventor); Tri, Terry O. (Inventor); Spenny, William E. (Inventor); West, Philip R. (Inventor)

    1989-01-01

    A don/doff support stand for use with rear entry space suits is disclosed. The support stand is designed for use in one-g environments; however, certain features of the stand can be used on future space-craft, lunar or planetary bases. The present invention has a retainer which receives a protruding lug fixed on the torso section of the space suit. When the lug is locked in the retainer, the space suit is held in a generally upright position. In a one-g environment a portable ladder is positioned adjacent to the rear entry of the space suit supported by the stand. The astronaut climbs up the ladder and grasps a hand bar assembly positioned above the rear entry. The astronaut then slips his legs through the open rear entry and down into the abdominal portion of the suit. The astronaut then lowers himself fully into the suit. The portable ladder is then removed and the astronaut can close the rear entry door. The lug is then disengaged from the retainer and the astronaut is free to engage in training exercises in the suit. When suit use is over, the astronaut returns to the stand and inserts the lug into the retainer. A technician repositions the ladder. The astronaut opens the rear entry door, grasps the hand bar assembly and does a chin-up to extricate himself from the suit. The astronaut climbs down the movable ladder while the suit is supported by the stand.

  6. Pathophysiological Significance of Store-Operated Calcium Entry in Megakaryocyte Function: Opening New Paths for Understanding the Role of Calcium in Thrombopoiesis

    PubMed Central

    Di Buduo, Christian A.; Balduini, Alessandra; Moccia, Francesco

    2016-01-01

    Store-Operated Calcium Entry (SOCE) is a universal calcium (Ca2+) influx mechanism expressed by several different cell types. It is now known that Stromal Interaction Molecule (STIM), the Ca2+ sensor of the intracellular compartments, together with Orai and Transient Receptor Potential Canonical (TRPC), the subunits of Ca2+ permeable channels on the plasma membrane, cooperate in regulating multiple cellular functions as diverse as proliferation, differentiation, migration, gene expression, and many others, depending on the cell type. In particular, a growing body of evidences suggests that a tight control of SOCE expression and function is achieved by megakaryocytes along their route from hematopoietic stem cells to platelet production. This review attempts to provide an overview about the SOCE dynamics in megakaryocyte development, with a focus on most recent findings related to its involvement in physiological and pathological thrombopoiesis. PMID:27941645

  7. Altered membrane lipid domains limit pulmonary endothelial calcium entry following chronic hypoxia.

    PubMed

    Paffett, Michael L; Naik, Jay S; Riddle, Melissa A; Menicucci, Steven D; Gonzales, Antonio J; Resta, Thomas C; Walker, Benjimen R

    2011-10-01

    Agonist-induced Ca(2+) entry into the pulmonary endothelium depends on activation of both store-operated Ca(2+) (SOC) entry and receptor-operated Ca(2+) (ROC) entry. We previously reported that pulmonary endothelial cell SOC entry and ROC entry are reduced in chronic hypoxia (CH)-induced pulmonary hypertension. We hypothesized that diminished endothelial Ca(2+) entry following CH is due to derangement of caveolin-1 (cav-1) containing cholesterol-enriched membrane domains important in agonist-induced Ca(2+) entry. To test this hypothesis, we measured Ca(2+) influx by fura-2 fluorescence following application of ATP (20 μM) in freshly isolated endothelial cells pretreated with the caveolar-disrupting agent methyl-β-cyclodextrin (mβCD; 10 mM). Cholesterol depletion with mβCD attenuated agonist-induced Ca(2+) entry in control endothelial cells to the level of that from CH rats. Interestingly, endothelial membrane cholesterol was lower in cells isolated from CH rats compared with controls although the density of caveolae did not differ between groups. Cholesterol repletion with a cholesterol:mβCD mixture or the introduction of the cav-1 scaffolding peptide (AP-cav; 10 μM) rescued ATP-induced Ca(2+) entry in endothelia from CH arteries. Agonist-induced Ca(2+) entry assessed by Mn(2+) quenching of fura-2 fluorescence was also significantly elevated by luminal AP-cav in pressurized intrapulmonary arteries from CH rats to levels of controls. Similarly, patch-clamp experiments revealed diminished inward current in response to ATP in cells from CH rats compared with controls that was restored by AP-cav. These data suggest that CH-induced pulmonary hypertension leads to reduced membrane cholesterol that limits the activity of ion channels necessary for agonist-activated Ca(2+) entry.

  8. Automated support requirement system user's guide for nondata entry personnel

    NASA Technical Reports Server (NTRS)

    Maryland, J. E., Jr.

    1985-01-01

    ASRS provides the capability to process intercenter/agency support requirements and commitments necessary for support of the Space Shuttle Launch and Landing, Flight, and Cargo operations. The instructions and commands that users will be allowed to utilize are presented. ASRS utilizes a data base stored on Honeywell DPS8 computer. ASRS programs are written in COBOL 74 utilizing the Honeywell DMIV-TP Processing System and the GCOS8 Operating System; they can also be accessed through Telenet or Datanet.

  9. A pupal transcriptomic screen identifies Ral as a target of store-operated calcium entry in Drosophila neurons

    PubMed Central

    Richhariya, Shlesha; Jayakumar, Siddharth; Abruzzi, Katharine; Rosbash, Michael; Hasan, Gaiti

    2017-01-01

    Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement for SOCE in neurons that regulate Drosophila flight bouts. We refine this requirement temporally to the early pupal stage and use RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. Down regulation of dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system, altered the expression of 131 genes including Ral, a small GTPase. Disruption of Ral function in neurons impaired flight, whereas ectopic expression of Ral in SOCE-compromised neurons restored flight. Through live imaging of calcium transients from cultured pupal neurons, we confirmed that Ral does not participate in SOCE, but acts downstream of it. These results identify neuronal SOCE as a mechanism that regulates expression of specific genes during development of the pupal nervous system and emphasizes the relevance of SOCE-regulated gene expression to flight circuit maturation. PMID:28195208

  10. Calcium sensing receptor modulates extracellular calcium entry and proliferation via TRPC3/6 channels in cultured human mesangial cells.

    PubMed

    Meng, Kexin; Xu, Jia; Zhang, Chengwei; Zhang, Rui; Yang, He; Liao, Chang; Jiao, Jundong

    2014-01-01

    Calcium-sensing receptor (CaSR) has been demonstrated to be present in several tissues and cells unrelated to systemic calcium homeostasis, where it regulates a series of diverse cellular functions. A previous study indicated that CaSR is expressed in mouse glomerular mesangial cells (MCs), and stimulation of CaSR induces cell proliferation. However, the signaling cascades initiated by CaSR activation in MCs are currently unknown. In this study, our data demonstrate that CaSR mRNA and protein are expressed in a human mesangial cell line. Activating CaSR with high extracellular Ca2+ concentration ([Ca2+]o) or spermine induces a phospholipase C (PLC)-dependent increase in intracellular Ca2+ concentration ([Ca2+]i). Interestingly, the CaSR activation-induced increase in [Ca2+]i results not only from intracellular Ca2+ release from internal stores but also from canonical transient receptor potential (TRPC)-dependent Ca2+ influx. This increase in Ca2+ was attenuated by treatment with a nonselective TRPC channel blocker but not by treatment with a voltage-gated calcium blocker or Na+/Ca2+ exchanger inhibitor. Furthermore, stimulation of CaSR by high [Ca2+]o enhanced the expression of TRPC3 and TRPC6 but not TRPC1 and TRPC4, and siRNA targeting TRPC3 and TRPC6 attenuated the CaSR activation-induced [Ca2+]i increase. Further experiments indicate that 1-oleoyl-2-acetyl-sn-glycerol (OAG), a known activator of receptor-operated calcium channels, significantly enhances the CaSR activation-induced [Ca2+]i increase. Moreover, under conditions in which intracellular stores were already depleted with thapsigargin (TG), CaSR agonists also induced an increase in [Ca2+]i, suggesting that calcium influx stimulated by CaSR agonists does not require the release of calcium stores. Finally, our data indicate that pharmacological inhibition and knock down of TRPC3 and TRPC6 attenuates the CaSR activation-induced cell proliferation in human MCs. With these data, we conclude that Ca

  11. Stimulated calcium entry and constitutive RhoA kinase activity cause stretch-induced detrusor contraction.

    PubMed

    Poley, Rainer N; Dosier, Christopher R; Speich, John E; Miner, Amy S; Ratz, Paul H

    2008-12-03

    Urinary bladder wall muscle (i.e., detrusor smooth muscle; DSM) contracts in response to a quick-stretch, but this response is neither fully characterized, nor completely understood at the subcellular level. Strips of rabbit DSM were quick-stretched (5 ms) and held isometric for 10 s to measure the resulting peak quick-stretch contractile response (PQSR). The ability of selective Ca(2+) channel blockers and kinase inhibitors to alter the PQSR was measured, and the phosphorylation levels of myosin light chain (MLC) and myosin phosphatase targeting regulatory subunit (MYPT1) were recorded. DSM responded to a quick-stretch with a biphasic response consisting of an initial contraction peaking at 0.24+/-0.02-fold the maximum KCl-induced contraction (F(o)) by 1.48+/-0.17 s (PQSR) before falling to a weaker tonic (10 s) level (0.12+/-0.03-fold F(o)). The PQSR was dependent on the rate and degree of muscle stretch, displayed a refractory period, and was converted to a sustained response in the presence of muscarinic receptor stimulation. The PQSR was inhibited by nifedipine, 2-aminoethoxydiphenyl borate (2-APB), 100 microM gadolinium and Y-27632, but not by atropine, 10 microM gadolinium, LOE-908, cyclopiazonic acid, or GF-109203X. Y-27632 and nifedipine abolished the increase in MLC phosphorylation induced by a quick-stretch. Y-27632, but not nifedipine, inhibited basal MYPT1 phosphorylation, and a quick-stretch failed to increase phosphorylation of this rhoA kinase (ROCK) substrate above the basal level. These data support the hypothesis that constitutive ROCK activity is required for a quick-stretch to activate Ca(2+) entry and cause a myogenic contraction of DSM.

  12. Woodchuck sodium taurocholate cotransporting polypeptide supports low-level hepatitis B and D virus entry.

    PubMed

    Fu, Liran; Hu, Hongjie; Liu, Yang; Jing, Zhiyi; Li, Wenhui

    2017-05-01

    Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for human hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). Species barriers to HBV/HDV infection are mainly determined at entry level by variations in the sequences of particular NTCP orthologs. In this study, we sought to determine whether the NTCP ortholog in woodchuck (Marmota monax), woodchuck NTCP (wNTCP) supports viral infection. We found that wNTCP is capable of supporting HBV/HDV infection in HepG2 cells, but to much lower extent than human NTCP (hNTCP), which is about 90% reduction of hNTCP. Comprehensive site-directed mutagenesis mapping of hNTCP and wNTCP revealed that the residue at position 263 is a novel site crucial for viral entry. The important role of site 263 in infection is conserved among NTCP orthologs and may therefore be a potential target for blocking the viral entry.

  13. Exploring Efficacy in Negotiating Support: Women Re-Entry Students in Higher Education

    ERIC Educational Resources Information Center

    Filipponi-Berardinelli, Josephine Oriana

    2013-01-01

    The existing literature on women re-entry students reveals that women students concurrently struggle with family, work, and sometimes health issues. Women students often do not receive adequate support from their partners or from other sources in helping manage the multiple roles that compete for their time, and often face constraints that affect…

  14. Entry-Level Information Services and Support Personnel: Needed Workplace and Technology Skills.

    ERIC Educational Resources Information Center

    Awang, Faridah; Anderson, Marcia A.; Baker, Clora Mae

    2003-01-01

    Responses to an Illinois survey by 19 human resource managers and 26 university and 71 community college information systems instructors rated the importance of workplace and technology skills for entry-level information services and support personnel. Both groups ranked nontechnical/soft skills and information technology certification as…

  15. Store-Operated Calcium Entry in Müller Glia Is Controlled by Synergistic Activation of TRPC and Orai Channels

    PubMed Central

    Molnár, Tünde; Yarishkin, Oleg; Iuso, Anthony; Barabas, Peter; Jones, Bryan; Marc, Robert E.; Phuong, Tam T.T.

    2016-01-01

    The endoplasmic reticulum (ER) is at the epicenter of astrocyte Ca2+ signaling. We sought to identify the molecular mechanism underlying store-operated calcium entry that replenishes ER stores in mouse Müller cells. Store depletion, induced through blockade of sequestration transporters in Ca2+-free saline, induced synergistic activation of canonical transient receptor potential 1 (TRPC1) and Orai channels. Store-operated TRPC1 channels were identified by their electrophysiological properties, pharmacological blockers, and ablation of the Trpc1 gene. Ca2+ release-activated currents (ICRAC) were identified by ion permeability, voltage dependence, and sensitivity to selective Orai antagonists Synta66 and GSK7975A. Depletion-evoked calcium influx was initiated at the Müller end-foot and apical process, triggering centrifugal propagation of Ca2+ waves into the cell body. EM analysis of the end-foot compartment showed high-density ER cisternae that shadow retinal ganglion cell (RGC) somata and axons, protoplasmic astrocytes, vascular endothelial cells, and ER–mitochondrial contacts at the vitreal surface of the end-foot. The mouse retina expresses transcripts encoding both Stim and all known Orai genes; Müller glia predominantly express stromal interacting molecule 1 (STIM1), whereas STIM2 is mainly confined to the outer plexiform and RGC layers. Elimination of TRPC1 facilitated Müller gliosis induced by the elevation of intraocular pressure, suggesting that TRPC channels might play a neuroprotective role during mechanical stress. By characterizing the properties of store-operated signaling pathways in Müller cells, these studies expand the current knowledge about the functional roles these cells play in retinal physiology and pathology while also providing further evidence for the complexity of calcium signaling mechanisms in CNS astroglia. SIGNIFICANCE STATEMENT Store-operated Ca2+ signaling represents a major signaling pathway and source of cytosolic Ca2+ in

  16. Reticulon 4 Is Necessary for Endoplasmic Reticulum Tubulation, STIM1-Orai1 Coupling, and Store-operated Calcium Entry

    PubMed Central

    Jozsef, Levente; Tashiro, Keitaro; Kuo, Andrew; Park, Eon Joo; Skoura, Athanasia; Albinsson, Sebastian; Rivera-Molina, Felix; Harrison, Kenneth D.; Iwakiri, Yasuko; Toomre, Derek; Sessa, William C.

    2014-01-01

    Despite recent advances in understanding store-operated calcium entry (SOCE) regulation, the fundamental question of how ER morphology affects this process remains unanswered. Here we show that the loss of RTN4, is sufficient to alter ER morphology and severely compromise SOCE. Mechanistically, we show this to be the result of defective STIM1-Orai1 coupling because of loss of ER tubulation and redistribution of STIM1 to ER sheets. As a functional consequence, RTN4-depleted cells fail to sustain elevated cytoplasmic Ca2+ levels via SOCE and therefor are less susceptible to Ca2+ overload induced apoptosis. Thus, for the first time, our results show a direct correlation between ER morphology and SOCE and highlight the importance of RTN4 in cellular Ca2+ homeostasis. PMID:24558039

  17. Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells

    PubMed Central

    Guéguinou, Maxime; Chourpa, Igor; Fromont, Gaëlle; Bouchet, Ana Maria; Burlaud-Gaillard, Julien; Potier-Cartereau, Marie; Roger, Sébastien; Aucagne, Vincent; Chevalier, Stéphan; Vandier, Christophe

    2016-01-01

    Expression of the antimicrobial peptide hCAP18/LL-37 is associated to malignancy in various cancer forms, stimulating cell migration and metastasis. We report that LL-37 induces migration of three cancer cell lines by activating the TRPV2 calcium-permeable channel and recruiting it to pseudopodia through activation of the PI3K/AKT pathway. Ca2+ entry through TRPV2 cooperated with a K+ efflux through the BKCa channel. In a panel of human breast tumors, the expression of TRPV2 and LL-37 was found to be positively correlated. The D-enantiomer of LL-37 showed identical effects as the L-peptide, suggesting that no binding to a specific receptor was involved. LL-37 attached to caveolae and pseudopodia membranes and decreased membrane fluidity, suggesting that a modification of the physical properties of the lipid membrane bilayer was the underlying mechanism of its effects. PMID:26993604

  18. Mechanosensitive store-operated calcium entry regulates the formation of cell polarity.

    PubMed

    Huang, Yi-Wei; Chang, Shu-Jing; I-Chen Harn, Hans; Huang, Hui-Ting; Lin, Hsi-Hui; Shen, Meng-Ru; Tang, Ming-Jer; Chiu, Wen-Tai

    2015-09-01

    Ca(2+) -mediated formation of cell polarity is essential for directional migration which plays an important role in physiological and pathological processes in organisms. To examine the critical role of store-operated Ca(2+) entry, which is the major form of extracellular Ca(2+) influx in non-excitable cells, in the formation of cell polarity, we employed human bone osteosarcoma U2OS cells, which exhibit distinct morphological polarity during directional migration. Our analyses showed that Ca(2+) was concentrated at the rear end of cells and that extracellular Ca(2+) influx was important for cell polarization. Inhibition of store-operated Ca(2+) entry using specific inhibitors disrupted the formation of cell polarity in a dose-dependent manner. Moreover, the channelosomal components caveolin-1, TRPC1, and Orai1 were concentrated at the rear end of polarized cells. Knockdown of TRPC1 or a TRPC inhibitor, but not knockdown of Orai1, reduced cell polarization. Furthermore, disruption of lipid rafts or overexpression of caveolin-1 contributed to the downregulation of cell polarity. On the other hand, we also found that cell polarity, store-operated Ca(2+) entry activity, and cell stiffness were markedly decreased by low substrate rigidity, which may be caused by the disorganization of actin filaments and microtubules that occurs while regulating the activity of the mechanosensitive TRPC1 channel.

  19. AMPA Receptors Are Involved in Store-Operated Calcium Entry and Interact with STIM Proteins in Rat Primary Cortical Neurons

    PubMed Central

    Gruszczynska-Biegala, Joanna; Sladowska, Maria; Kuznicki, Jacek

    2016-01-01

    The process of store-operated calcium entry (SOCE) leads to refilling the endoplasmic reticulum (ER) with calcium ions (Ca2+) after their release into the cytoplasm. Interactions between (ER)-located Ca2+ sensors (stromal interaction molecule 1 [STIM1] and STIM2) and plasma membrane-located Ca2+ channel-forming protein (Orai1) underlie SOCE and are well described in non-excitable cells. In neurons, however, SOCE appears to be more complex because of the importance of Ca2+ influx via voltage-gated or ionotropic receptor-operated Ca2+ channels. We found that the SOCE inhibitors ML-9 and SKF96365 reduced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced [Ca2+]i amplitude by 80% and 53%, respectively. To assess the possible involvement of AMPA receptors (AMPARs) in SOCE, we used their specific inhibitors. As estimated by Fura-2 acetoxymethyl (AM) single-cell Ca2+ measurements in the presence of CNQX or NBQX, thapsigargin (TG)-induced Ca2+ influx decreased 2.2 or 3.7 times, respectively. These results suggest that under experimental conditions of SOCE when Ca2+ stores are depleted, Ca2+ can enter neurons also through AMPARs. Using specific antibodies against STIM proteins or GluA1/GluA2 AMPAR subunits, co-immunoprecipitation assays indicated that when Ca2+ levels are low in the neuronal ER, a physical association occurs between endogenous STIM proteins and endogenous AMPAR receptors. Altogether, our data suggest that STIM proteins in neurons can control AMPA-induced Ca2+ entry as a part of the mechanism of SOCE. PMID:27826230

  20. Support for calcium channel gene defects in autism spectrum disorders

    PubMed Central

    2012-01-01

    Background Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD). Calcium channel genes (CCG) contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS) data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis. Methods A total of 2,176 single-nucleotide polymorphisms (SNP) (703 genotyped and 1,473 imputed) covering the genes that encode the α1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE) and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP). SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel. Results Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations. Conclusions These associations support a role for common CCG SNPs in ASD. PMID:23241247

  1. FGF4 induces epithelial-mesenchymal transition by inducing store-operated calcium entry in lung adenocarcinoma

    PubMed Central

    Qi, Lisha; Song, Wangzhao; Li, Lingmei; Cao, Lu; Yu, Yue; Song, Chunmin; Wang, Yalei; Zhang, Fei; Li, Yang; Zhang, Bin; Cao, Wenfeng

    2016-01-01

    Several fibroblast growth factor (FGF) isoforms act to stimulate epithelial-mesenchymal transition (EMT) during cancer progression. FGF4 and FGF7 are two ligands of FGF receptor 2 (FGFR2). Using two lung adenocarcinoma (ADC) cell lines, A549 and H1299, we showed that FGF4, but not FGF7, altered cell morphology, promoted EMT-associated protein expression, and enhanced cell proliferation, migration/invasion and colony initiation. In addition, FGF4 increased store-operated calcium entry (SOCE) and expression of the calcium signal-associated protein Orai1. The SOCE inhibitor 2,5-di-tert-butylhydroquinone (BHQ) or Orai1 knockdown reversed all of the EMT-promoting effects of FGF4. BHQ also inhibited FGF4-induced EMT in a mouse xenograft model. Finally, 60 human lung ADC samples and 21 sets of matched specimens (primary and metastatic foci in lymph nodes from one patient) were used to confirm the clinicopathologic significance of FGF4 and its correlation with E-cadherin, Vimentin and Orai1 expression. Our study thus shows that FGF4 induces EMT by elevating SOCE in lung ADC. PMID:27677589

  2. The cell surface expressed nucleolin is a glycoprotein that triggers calcium entry into mammalian cells

    SciTech Connect

    Losfeld, Marie-Estelle; Khoury, Diala El; Mariot, Pascal; Carpentier, Mathieu; Krust, Bernard; Briand, Jean-Paul; Mazurier, Joel; Hovanessian, Ara G.; Legrand, Dominique

    2009-01-15

    Nucleolin is an ubiquitous nucleolar phosphoprotein involved in fundamental aspects of transcription regulation, cell proliferation and growth. It has also been described as a shuttling molecule between nucleus, cytosol and the cell surface. Several studies have demonstrated that surface nucleolin serves as a receptor for various extracellular ligands implicated in cell proliferation, differentiation, adhesion, mitogenesis and angiogenesis. Previously, we reported that nucleolin in the extranuclear cell compartment is a glycoprotein containing N- and O-glycans. In the present study, we show that glycosylation is an essential requirement for surface nucleolin expression, since it is prevented when cells are cultured in the presence of tunicamycin, an inhibitor of N-glycosylation. Accordingly, surface but not nuclear nucleolin is radioactively labeled upon metabolic labeling of cells with [{sup 3}H]glucosamine. Besides its well-demonstrated role in the internalization of specific ligands, here we show that ligand binding to surface nucleolin could also induce Ca{sup 2+} entry into cells. Indeed, by flow cytometry, microscopy and patch-clamp experiments, we show that the HB-19 pseudopeptide, which binds specifically surface nucleolin, triggers rapid and intense membrane Ca{sup 2+} fluxes in various types of cells. The use of several drugs then indicated that Store-Operated Ca{sup 2+} Entry (SOCE)-like channels are involved in the generation of these fluxes. Taken together, our findings suggest that binding of an extracellular ligand to surface nucleolin could be involved in the activation of signaling pathways by promoting Ca{sup 2+} entry into cells.

  3. Comparative capacitative calcium entry mechanisms in canine pulmonary and renal arterial smooth muscle cells

    PubMed Central

    Wilson, Sean M; Mason, Helen S; Smith, Gregory D; Nicholson, Neil; Johnston, Louise; Janiak, Robert; Hume, Joseph R

    2002-01-01

    Experiments were performed to determine whether capacitative Ca2+ entry (CCE) can be activated in canine pulmonary and renal arterial smooth muscle cells (ASMCs) and whether activation of CCE parallels the different functional structure of the sarcoplasmic reticulum (SR) in these two cell types. The cytosolic [Ca2+] was measured by imaging fura-2-loaded individual cells. Increases in the cytosolic [Ca2+] due to store depletion in pulmonary ASMCs required simultaneous depletion of both the inositol 1,4,5-trisphosphate (InsP3)- and ryanodine (RY)-sensitive SR Ca2+ stores. In contrast, the cytosolic [Ca2+] rises in renal ASMCs occurred when the SR stores were depleted through either the InsP3 or RY pathways. The increase in the cytosolic [Ca2+] due to store depletion in both pulmonary and renal ASMCs was present in cells that were voltage clamped and was abolished when cells were perfused with a Ca2+-free bathing solution. Rapid quenching of the fura-2 signal by 100 μM Mn2+ following SR store depletion indicated that extracellular Ca2+ entry increased in both cell types and also verified that activation of CCE in pulmonary ASMCs required the simultaneous depletion of the InsP3- and RY-sensitive SR Ca2+ stores, while CCE could be activated in renal ASMCs by the depletion of either of the InsP3- or RY-sensitive SR stores. Store depletion Ca2+ entry in both pulmonary and renal ASMCs was strongly inhibited by Ni2+ (0.1–10 mM), slightly inhibited by Cd2+ (200–500 μM), but was not significantly affected by the voltage-gated Ca2+ channel (VGCC) blocker nisoldipine (10 μM). The non-selective cation channel blocker Gd3+ (100 μM) inhibited a portion of the Ca2+ entry in 6 of 18 renal but not pulmonary ASMCs. These results provide evidence that SR Ca2+ store depletion activates CCE in parallel with the organization of intracellular Ca2+ stores in canine pulmonary and renal ASMCs. PMID:12231648

  4. STIM and Orai1 Variants in Store-Operated Calcium Entry

    PubMed Central

    Rosado, Juan A.; Diez, Raquel; Smani, Tarik; Jardín, Isaac

    2016-01-01

    Store-operated Ca2+ entry (SOCE) is an ubiquitous mechanism for Ca2+ entry in eukaryotic cells. This route for Ca2+ influx is regulated by the filling state of the intracellular Ca2+ stores communicated to the plasma membrane channels by the proteins of the Stromal Interaction Molecule (STIM) family, STIM1, and STIM2. Store-dependent, STIM1-modulated, channels include the Ca2+ release-activated Ca2+ channels, comprised of subunits of Orai proteins, as well as the store-operated Ca2+ (SOC) channels, involving Orai1, and members of the canonical transient receptor potential family of proteins. Recent studies have revealed the expression of splice variants of STIM1, STIM2, and Orai1 in different cell types. While certain variants are ubiquitously expressed, others, such as STIM1L, show a more restricted expression. The splice variants for STIM and Orai1 proteins exhibit significant functional differences and reveal that alternative splicing enhance the functional diversity of STIM1, STIM2, and Orai1 genes to modulate the dynamics of Ca2+ signals. PMID:26793113

  5. Carbon nanotubes activate store-operated calcium entry in human blood platelets.

    PubMed

    Lacerda, Silvia H De Paoli; Semberova, Jana; Holada, Karel; Simakova, Olga; Hudson, Steven D; Simak, Jan

    2011-07-26

    Carbon nanotubes (CNTs) are known to potentiate arterial thrombosis in animal models, which raises serious safety issues concerning environmental or occupational exposure to CNTs and their use in various biomedical applications. We have shown previously that different CNTs, but not fullerene (nC60), induce the aggregation of human blood platelets. To date, however, a mechanism of potentially thrombogenic CNT-induced platelet activation has not been elucidated. Here we show that pristine multiwalled CNTs (MWCNTs) penetrate platelet plasma membrane without any discernible damage but interact with the dense tubular system (DTS) causing depletion of platelet intracellular Ca(2+) stores. This process is accompanied by the clustering of stromal interaction molecule 1 (STIM1) colocalized with Orai1, indicating the activation of store-operated Ca(2+) entry (SOCE). Our findings reveal the molecular mechanism of CNT-induced platelet activation which is critical in the evaluation of the biocompatibility of carbon nanomaterials with blood.

  6. Mars Reconnaissance Orbiter Navigation Strategy for Mars Science Laboratory Entry, Descent and Landing Telecommunication Relay Support

    NASA Technical Reports Server (NTRS)

    Williams, Jessica L.; Menon, Premkumar R.; Demcak, Stuart W.

    2012-01-01

    The Mars Reconnaissance Orbiter (MRO) is an orbiting asset that performs remote sensing observations in order to characterize the surface, subsurface and atmosphere of Mars. To support upcoming NASA Mars Exploration Program Office objectives, MRO will be used as a relay communication link for the Mars Science Laboratory (MSL) mission during the MSL Entry, Descent and Landing sequence. To do so, MRO Navigation must synchronize the MRO Primary Science Orbit (PSO) with a set of target conditions requested by the MSL Navigation Team; this may be accomplished via propulsive maneuvers. This paper describes the MRO Navigation strategy for and operational performance of MSL EDL relay telecommunication support.

  7. The relationship of social support to treatment entry and engagement: The Community Assessment Inventory

    PubMed Central

    Kelly, Sharon M.; O'Grady, Kevin E.; Schwartz, Robert P.; Peterson, James A.; Wilson, Monique E.; Brown, Barry S.

    2010-01-01

    This study was conducted to determine the psychometric properties of a measure of social support, the Community Assessment Inventory (CAI), and to examine the role of social support in recovery. The CAI and the Addiction Severity Index (ASI) were administered to 196 opioid-dependent adults in (n = 135) or out of methadone treatment (n = 61) in Baltimore, Maryland between 2004 and 2006. Baseline CAI scale scores indicated a generally high level of internal consistency (α scores). Pearson correlations showed that the scales were stable and had good discriminant validity with the ASI composite scores. One-way analysis of variance indicated that in-treatment participants reported significantly more support at baseline than out-of-treatment participants. This study's findings indicate the CAI may be a useful measure of social support and that such support is an important factor in treatment entry. PMID:20391269

  8. New tacrine-dihydropyridine hybrids that inhibit acetylcholinesterase, calcium entry, and exhibit neuroprotection properties.

    PubMed

    León, Rafael; de los Ríos, Cristóbal; Marco-Contelles, José; Huertas, Oscar; Barril, Xavier; Luque, F Javier; López, Manuela G; García, Antonio G; Villarroya, Mercedes

    2008-08-15

    In this communication, we describe the synthesis and biological evaluation of tacripyrimedones 1-5, a series of new tacrine-1,4-dihydropyridine hybrids bearing the general structure of 11-amino-12-aryl-3,3-dimethyl-3,4,5,7,8,9,10,12-octahydrodibenzo[b,g][1,8]naphthyridine-1(2H)-one. These multifunctional compounds are moderately potent and selective AChEIs, with no activity toward BuChE. Kinetic analysis and molecular modeling studies point out that the new compounds preferentially bind the peripheral anionic site of AChE. In addition, compounds 1-5 show an excellent neuroprotective profile, and a moderate blocking effect of L-type voltage-dependent calcium channels due to the mitigation of [Ca(2+)] elevation elicited by K(+) depolarization. Therefore, they represent a new family of molecules with potential therapeutic application for the treatment of Alzheimer's disease.

  9. Calcium entry via TRPC1 channels activates chloride currents in human glioma cells

    PubMed Central

    Cuddapah, Vishnu Anand; Turner, Kathryn L.; Sontheimer, Harald

    2012-01-01

    Malignant gliomas are highly-invasive brain cancers that carry a dismal prognosis. Recent studies indicate that Cl− channels facilitate glioma cell invasion by promoting hydrodynamic cell shape and volume changes. Here we asked how Cl− channels are regulated in the context of migration. Using patch-clamp recordings we show Cl− currents are activated by physiological increases of [Ca2+]i to 65 and 180 nM. Cl− currents appear to be mediated by ClC-3, a voltage-gated, CaMKII-regulated Cl− channel highly expressed by glioma cells. ClC-3 channels colocalized with TRPC1 on caveolar lipid rafts on glioma cell processes. Using perforated-patch electrophysiological recordings, we demonstrate that inducible knockdown of TRPC1 expression with shRNA significantly inhibited glioma Cl− currents in a Ca2+-dependent fashion, placing Cl− channels under the regulation of Ca2+ entry via TRPC1. In chemotaxis assays epidermal growth factor (EGF)-induced invasion was inhibition by TRPC1 knockdown to the same extent as pharmacological block of Cl− channels. Thus endogenous glioma Cl− channels are regulated by TRPC1. Cl− channels could be an important downstream target of TRPC1 in many other cells types, coupling elevations in [Ca2+]i to the shape and volume changes associated with migrating cells. PMID:23261316

  10. STIM AND ORAI, THE LONG AWAITED CONSTITUENTS OF STORE-OPERATED CALCIUM ENTRY

    PubMed Central

    Várnai, Péter; Hunyady, László; Balla, Tamas

    2011-01-01

    Rapid changes in cytosolic Ca2+ concentrations [Ca2+]i are the most commonly used signals in biology to regulate a whole host of cellular functions including contraction, secretion and gene activation. A widely utilized form of Ca2+ influx is termed store-operated Ca2+ entry (SOCE) due to its control by the Ca2+ content of the endoplasmic reticulum (ER). The underlying molecular mechanism of SOCE has eluded identification until recently when two groups of proteins, the ER Ca2+ sensors, STIM1 and -2, and the plasma membrane channels, Orai1, -2 and -3 have been identified. These landmark discoveries have allowed impressive progress in clarifying how these proteins work in concert and what developmental and cellular processes require their participation most. As we begin to better understand the biology of the STIM and Orai proteins, the attention to the pharmacological tools to influence their functions quickly follow suit. This review will briefly summarize recent developments in this exciting area of Ca2+ signaling. PMID:19187978

  11. Allergens stimulate store-operated calcium entry and cytokine production in airway epithelial cells

    PubMed Central

    Jairaman, Amit; Maguire, Chelsea H.; Schleimer, Robert P.; Prakriya, Murali

    2016-01-01

    Aberrant immune responses to environmental allergens including insect allergens from house dust mites and cockroaches contribute to allergic inflammatory diseases such as asthma in susceptible individuals. Airway epithelial cells (AECs) play a critical role in this process by sensing the proteolytic activity of allergens via protease-activated receptors (PAR2) to initiate inflammatory and immune responses in the airway. Elevation of cytosolic Ca2+ is an important signaling event in this process, yet the fundamental mechanism by which allergens induce Ca2+ elevations in AECs remains poorly understood. Here we find that extracts from dust mite and cockroach induce sustained Ca2+ elevations in AECs through the activation of Ca2+ release-activated Ca2+ (CRAC) channels encoded by Orai1 and STIM1. CRAC channel activation occurs, at least in part, through allergen mediated stimulation of PAR2 receptors. The ensuing Ca2+ entry then activates NFAT/calcineurin signaling to induce transcriptional production of the proinflammatory cytokines IL-6 and IL-8. These findings highlight a key role for CRAC channels as regulators of allergen induced inflammatory responses in the airway. PMID:27604412

  12. Calcium entry into stereocilia drives adaptation of the mechanoelectrical transducer current of mammalian cochlear hair cells.

    PubMed

    Corns, Laura F; Johnson, Stuart L; Kros, Corné J; Marcotti, Walter

    2014-10-14

    Mechanotransduction in the auditory and vestibular systems depends on mechanosensitive ion channels in the stereociliary bundles that project from the apical surface of the sensory hair cells. In lower vertebrates, when the mechanoelectrical transducer (MET) channels are opened by movement of the bundle in the excitatory direction, Ca(2+) entry through the open MET channels causes adaptation, rapidly reducing their open probability and resetting their operating range. It remains uncertain whether such Ca(2+)-dependent adaptation is also present in mammalian hair cells. Hair bundles of both outer and inner hair cells from mice were deflected by using sinewave or step mechanical stimuli applied using a piezo-driven fluid jet. We found that when cochlear hair cells were depolarized near the Ca(2+) reversal potential or their hair bundles were exposed to the in vivo endolymphatic Ca(2+) concentration (40 µM), all manifestations of adaptation, including the rapid decline of the MET current and the reduction of the available resting MET current, were abolished. MET channel adaptation was also reduced or removed when the intracellular Ca(2+) buffer 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) was increased from a concentration of 0.1 to 10 mM. The findings show that MET current adaptation in mouse auditory hair cells is modulated similarly by extracellular Ca(2+), intracellular Ca(2+) buffering, and membrane potential, by their common effect on intracellular free Ca(2+).

  13. Calcium

    MedlinePlus

    ... You'll also find calcium in broccoli and dark green, leafy vegetables (especially collard and turnip greens, ... can enjoy good sources of calcium such as dark green, leafy vegetables, broccoli, chickpeas, and calcium-fortified ...

  14. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    SciTech Connect

    Cui, Ruibing; Yan, Lihui; Luo, Zheng; Guo, Xiaolan; Yan, Ming

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  15. Enhanced excitation-coupled calcium entry in myotubes expressing malignant hyperthermia mutation R163C is attenuated by dantrolene.

    PubMed

    Cherednichenko, Gennady; Ward, Chris W; Feng, Wei; Cabrales, Elaine; Michaelson, Luke; Samso, Montserrat; López, José R; Allen, Paul D; Pessah, Isaac N

    2008-04-01

    Dantrolene is the drug of choice for the treatment of malignant hyperthermia (MH) and is also useful for treatment of spasticity or muscle spasms associated with several clinical conditions. The current study examines the mechanisms of dantrolene's action on skeletal muscle and shows that one of dantrolene's mechanisms of action is to block excitation-coupled calcium entry (ECCE) in both adult mouse flexor digitorum brevis fibers and primary myotubes. A second important new finding is that myotubes isolated from mice heterozygous and homozygous for the ryanodine receptor type 1 R163C MH susceptibility mutation show significantly enhanced ECCE rates that could be restored to those measured in wild-type cells after exposure to clinical concentrations of dantrolene. We propose that this gain of ECCE function is an important etiological component of MH susceptibility and possibly contributes to the fulminant MH episode. The inhibitory potency of dantrolene on ECCE found in wild-type and MH-susceptible muscle is consistent with the drug's clinical potency for reversing the MH syndrome and is incomplete as predicted by its efficacy as a muscle relaxant.

  16. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    SciTech Connect

    Shi, Zi-xuan; Rao, Wei; Wang, Huan; Wang, Nan-ding; Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang; Wang, Zong-ren

    2015-02-13

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion.

  17. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry.

    PubMed

    Shi, Zi-xuan; Rao, Wei; Wang, Huan; Wang, Nan-ding; Si, Jing-wen; Zhao, Jiao; Li, Jun-chang; Wang, Zong-ren

    2015-02-13

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future.

  18. Noggin inhibits hypoxia-induced proliferation by targeting store-operated calcium entry and transient receptor potential cation channels.

    PubMed

    Yang, Kai; Lu, Wenju; Jia, Jing; Zhang, Jie; Zhao, Mingming; Wang, Sabrina; Jiang, Haiyang; Xu, Lei; Wang, Jian

    2015-06-01

    Abnormally elevated bone morphogenetic protein 4 (BMP4) expression and mediated signaling play a critical role in the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH). In this study, we investigated the expression level and functional significance of four reported naturally occurring BMP4 antagonists, noggin, follistatin, gremlin1, and matrix gla protein (MGP), in the lung and distal pulmonary arterial smooth muscle cell (PASMC). A 21-day chronic hypoxic (10% O2) exposure rat model was utilized, which has been previously shown to successfully establish experimental CHPH. Among the four antagonists, noggin, but not the other three, was selectively downregulated by hypoxic exposure in both the lung tissue and PASMC, in correlation with markedly elevated BMP4 expression, suggesting that the loss of noggin might account for the hypoxia-triggered BMP4 signaling transduction. Then, by using treatment of extrogenous recombinant noggin protein, we further found that noggin significantly normalized 1) BMP4-induced phosphorylation of cellular p38 and ERK1/2; 2) BMP4-induced phosphorylation of cellular JAK2 and STAT3; 3) hypoxia-induced PASMC proliferation; 4) hypoxia-induced store-operated calcium entry (SOCE), and 5) hypoxia-increased expression of transient receptor potential cation channels (TRPC1 and TRPC6) in PASMC. In combination, these data strongly indicated that the hypoxia-suppressed noggin accounts, at least partially, for hypoxia-induced excessive PASMC proliferation, while restoration of noggin may be an effective way to inhibit cell proliferation by suppressing SOCE and TRPC expression.

  19. Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade.

    PubMed

    Fernández-Martínez, Eduardo; Ponce-Monter, Héctor; Soria-Jasso, Luis E; Ortiz, Mario I; Arias-Montaño, José-Antonio; Barragán-Ramírez, Guillermo; Mayén-García, Cynthia

    2016-10-07

    Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe) and were compared to rolipram in functional studies of spontaneous phasic, K⁺-induced tonic, and Ca(2+)-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC), in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs). Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca(2+)-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC50 = 125 ± 13.72 and 98.45 ± 8.86 µM, respectively). Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05) and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers.

  20. Noggin inhibits hypoxia-induced proliferation by targeting store-operated calcium entry and transient receptor potential cation channels

    PubMed Central

    Yang, Kai; Lu, Wenju; Jia, Jing; Zhang, Jie; Zhao, Mingming; Wang, Sabrina; Jiang, Haiyang; Xu, Lei

    2015-01-01

    Abnormally elevated bone morphogenetic protein 4 (BMP4) expression and mediated signaling play a critical role in the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH). In this study, we investigated the expression level and functional significance of four reported naturally occurring BMP4 antagonists, noggin, follistatin, gremlin1, and matrix gla protein (MGP), in the lung and distal pulmonary arterial smooth muscle cell (PASMC). A 21-day chronic hypoxic (10% O2) exposure rat model was utilized, which has been previously shown to successfully establish experimental CHPH. Among the four antagonists, noggin, but not the other three, was selectively downregulated by hypoxic exposure in both the lung tissue and PASMC, in correlation with markedly elevated BMP4 expression, suggesting that the loss of noggin might account for the hypoxia-triggered BMP4 signaling transduction. Then, by using treatment of extrogenous recombinant noggin protein, we further found that noggin significantly normalized 1) BMP4-induced phosphorylation of cellular p38 and ERK1/2; 2) BMP4-induced phosphorylation of cellular JAK2 and STAT3; 3) hypoxia-induced PASMC proliferation; 4) hypoxia-induced store-operated calcium entry (SOCE), and 5) hypoxia-increased expression of transient receptor potential cation channels (TRPC1 and TRPC6) in PASMC. In combination, these data strongly indicated that the hypoxia-suppressed noggin accounts, at least partially, for hypoxia-induced excessive PASMC proliferation, while restoration of noggin may be an effective way to inhibit cell proliferation by suppressing SOCE and TRPC expression. PMID:25740156

  1. Stim1 and Orai1 Mediate CRAC Currents and Store-Operated Calcium Entry Important for Endothelial Cell Proliferation

    PubMed Central

    Abdullaev, Iskandar F.; Bisaillon, Jonathan M.; Potier, Marie; Gonzalez, Jose C.; Motiani, Rajender K.; Trebak, Mohamed

    2009-01-01

    Recent breakthroughs in the store-operated Calcium (Ca2+) entry (SOCE) pathway have identified Stim1 as the endoplasmic reticulum (ER) Ca2+ sensor and Orai1 as the pore forming subunit of the highly Ca2+ selective CRAC channel expressed in hematopoietic cells. Previous studies however, have suggested that endothelial cell (EC) SOCE is mediated by the non-selective Canonical Transient Receptor Potential (TRPC) channel family, TRPC1 or TRPC4. Here we show that passive store depletion by thapsigargin or receptor activation by either thrombin or the vascular endothelial growth factor (VEGF) activates the same pathway in primary EC with classical SOCE pharmacological features. EC possess the archetypical Ca2+ release-activated Ca2+ current (ICRAC), albeit of a very small amplitude. Using a maneuver that amplifies currents in divalent free bath solutions, we show that EC CRAC has similar characteristics to that recorded from RBL cells, namely a similar time course of activation, sensitivity to 2-Aminoethoxydiphenyl borate (2-APB) and low concentrations of lanthanides, and large Na+ currents displaying the typical depotentiation. RNA silencing of either Stim1 or Orai1 essentially abolished SOCE and ICRAC in EC which were rescued by ectopic expression of either Stim1 or Orai1, respectively. Surprisingly, knockdown of either TRPC1 or TRPC4 proteins had no effect on SOCE and ICRAC. Ectopic expression of Stim1 in EC increased their ICRAC to a size comparable to that in RBL cells. Knockdown of Stim1, Stim2 or Orai1 inhibited EC proliferation and caused cell cycle arrest at S and G2/M phase, although Orai1 knockdown was more efficient than that of Stim proteins. These results are first to establish the requirement of Stim1/Orai1 in the endothelial SOCE pathway. PMID:18845811

  2. Fyn kinase controls Fc{epsilon}RI receptor-operated calcium entry necessary for full degranulation in mast cells

    SciTech Connect

    Sanchez-Miranda, Elizabeth; Ibarra-Sanchez, Alfredo; Gonzalez-Espinosa, Claudia

    2010-01-22

    IgE-antigen-dependent crosslinking of the high affinity IgE receptor (Fc{epsilon}RI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca{sup 2+}) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls Fc{epsilon}RI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed Fc{epsilon}RI-dependent Ca{sup 2+} mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca{sup 2+} influx after Fc{epsilon}RI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd{sup 3+}) partially blocked Fc{epsilon}RI-induced Ca{sup 2+} influx in WT cells but, in contrast, completely inhibited Ca{sup 2+} mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca{sup 2+} channels (2-aminoethoxyphenyl-borane, 2-APB) blocked Fc{epsilon}RI-induced maximal Ca{sup 2+} rise in WT but not in Fyn -/- cells. Ca{sup 2+} entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in Fc{epsilon}RI-stimulated mast cells.

  3. NASA JSC trajectory operational support for entry of Space Station MIR

    NASA Astrophysics Data System (ADS)

    Paul, Scott D.

    2002-11-01

    In December 2000, Russian Prime Minister Mikhail Kasyanov signed a degree that announced the Russian plans to safely de-orbit the MIR Space Station. While the Russian government maintained sole responsibility for MIR Space Station de-orbit operations, International assistance was requested to obtain access to additional orbital tracking resources. The United States government, while maintaining its position as an observer of the MIR de-orbit, agreed to provide orbital tracking data from its Space Surveillance network (SSN) to the degree possible. The National Aeronautics and Space Administration (NASA) was requested and agreed to coordinate this support due to the strong working relationship and communications channels developed between NASA and Russian Trajectory organizations for the International Space Station (ISS) Program. Additionally, NASA trajectory specialists at Johnson Space Center performed independent orbit decay assessments and re-entry analyses for the MIR de-orbit scenarios.

  4. Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry

    PubMed Central

    Rao, Wei; Peng, Cheng; Zhang, Lei; Su, Ning; Wang, Kai; Hui, Hao; Dai, Shu-hui; Yang, Yue-fan; Luo, Peng; Fei, Zhou

    2016-01-01

    Calcium disequilibrium is extensively involved in oxidative stress-induced neuronal injury. Although Homer1a is known to regulate several neuronal calcium pathways, its effects on, or its exact relationship with, oxidative stress-induced neuronal injury has not yet been fully elucidated. We found that Homer1a protected HT-22 cells from glutamate-induced oxidative stress injury by inhibiting final-phase intracellular calcium overload and mitochondrial oxidative stress. In these cells, stromal interactive molecule 1 (STIM1) puncta, but not the protein level, was significantly increased after glutamate treatment. Store-operated calcium entry (SOCE) inhibitors and cells in which a key component of SOCE (STIM1) was knocked out were used as glutamate-induced oxidative stress injury models. Both models demonstrated significant improvement of HT-22 cell survival after glutamate treatment. Additionally, increased Homer1a protein levels significantly inhibited SOCE and decreased the association of STIM1-Orai1 triggered by glutamate. These results suggest that up-regulation of Homer1a can protect HT-22 cells from glutamate-induced oxidative injury by disrupting the STIM1-Oria1 association, and then by inhibiting the SOCE-mediated final-phrase calcium overload. Thus, regulation of Homer1a, either alone or in conjunction with SOCE inhibition, may serve as key therapeutic interventional targets for neurological diseases in which oxidative stress is involved in the etiology or progression of the disease. PMID:27681296

  5. Entry to nursing practice preceptor education and support: could we do it better?

    PubMed

    Haggerty, Carmel; Holloway, Kathryn; Wilson, Debra

    2012-03-01

    High quality preceptorship during their first year of practice is seen as critical for new graduate nurses' development of competence and confidence. Quality preceptorship is dependent upon skilled and knowledgeable preceptors who are committed to this role. A recent longitudinal evaluation of 21 Nursing Entry to Practice (NETP) programmes in New Zealand identified that preceptorship selection, education and support do not always receive the attention they warrant. Failure to plan preceptor selection leads to ad hoc selection and consequent allocations of many preceptors who may not have attended appropriate education, or have a desire to undertake this role. Such a situation is detrimental to the job satisfaction of both preceptors and new graduate nurses. High workloads, rostering difficulties and increased acuity in many clinical areas often prevent preceptors from attending appropriate education and that, in turn, impacts negatively on the preceptor's expectations and clarity with respect to the role. To offset this effect the authors recommend development of a clearly defined preceptor selection process, along with flexible preceptor education programmes that provide a good foundation for support of new graduates in their first year of practice; but do not increase preceptor workloads.

  6. Herpes Simplex Virus Type 2 Glycoprotein H Interacts with Integrin αvβ3 To Facilitate Viral Entry and Calcium Signaling in Human Genital Tract Epithelial Cells

    PubMed Central

    Cheshenko, Natalia; Trepanier, Janie B.; González, Pablo A.; Eugenin, Eliseo A.; Jacobs, William R.

    2014-01-01

    ABSTRACT Herpes simplex virus (HSV) entry requires multiple interactions at the cell surface and activation of a complex calcium signaling cascade. Previous studies demonstrated that integrins participate in this process, but their precise role has not been determined. These studies were designed to test the hypothesis that integrin αvβ3 signaling promotes the release of intracellular calcium (Ca2+) stores and contributes to viral entry and cell-to-cell spread. Transfection of cells with small interfering RNA (siRNA) targeting integrin αvβ3, but not other integrin subunits, or treatment with cilengitide, an Arg-Gly-Asp (RGD) mimetic, impaired HSV-induced Ca2+ release, viral entry, plaque formation, and cell-to-cell spread of HSV-1 and HSV-2 in human cervical and primary genital tract epithelial cells. Coimmunoprecipitation studies and proximity ligation assays indicated that integrin αvβ3 interacts with glycoprotein H (gH). An HSV-2 gH-null virus was engineered to further assess the role of gH in the virus-induced signaling cascade. The gH-2-null virus bound to cells and activated Akt to induce a small Ca2+ response at the plasma membrane, but it failed to trigger the release of cytoplasmic Ca2+ stores and was impaired for entry and cell-to-cell spread. Silencing of integrin αvβ3 and deletion of gH prevented phosphorylation of focal adhesion kinase (FAK) and the transport of viral capsids to the nuclear pore. Together, these findings demonstrate that integrin signaling is activated downstream of virus-induced Akt signaling and facilitates viral entry through interactions with gH by activating the release of intracellular Ca2+ and FAK phosphorylation. These findings suggest a new target for HSV treatment and suppression. IMPORTANCE Herpes simplex viruses are the leading cause of genital disease worldwide, the most common infection associated with neonatal encephalitis, and a major cofactor for HIV acquisition and transmission. There is no effective vaccine

  7. Decision Support Alerts for Medication Ordering in a Computerized Provider Order Entry (CPOE) System

    PubMed Central

    Beccaro, M. A. Del; Villanueva, R.; Knudson, K. M.; Harvey, E. M.; Langle, J. M.; Paul, W.

    2010-01-01

    Objective We sought to determine the frequency and type of decision support alerts by location and ordering provider role during Computerized Provider Order Entry (CPOE) medication ordering. Using these data we adjusted the decision support tools to reduce the number of alerts. Design Retrospective analyses were performed of dose range checks (DRC), drug-drug interaction and drug-allergy alerts from our electronic medical record. During seven sampling periods (each two weeks long) between April 2006 and October 2008 all alerts in these categories were analyzed. Another audit was performed of all DRC alerts by ordering provider role from November 2008 through January 2009. Medication ordering error counts were obtained from a voluntary error reporting system. Measurement/Results Between April 2006 and October 2008 the percent of medication orders that triggered a dose range alert decreased from 23.9% to 7.4%. The relative risk (RR) for getting an alert was higher at the start of the interventions versus later (RR= 2.40, 95% CI 2.28-2.52; p< 0.0001). The percentage of medication orders that triggered alerts for drug-drug interactions also decreased from 13.5% to 4.8%. The RR for getting a drug interaction alert at the start was 1.63, 95% CI 1.60-1.66; p< 0.0001. Alerts decreased in all clinical areas without an increase in reported medication errors. Conclusion We reduced the quantity of decision support alerts in CPOE using a systematic approach without an increase in reported medication errors PMID:23616845

  8. SAM: speech-aware applications in medicine to support structured data entry.

    PubMed

    Wormek, A K; Ingenerf, J; Orthner, H F

    1997-01-01

    In the last two years, improvement in speech recognition technology has directed the medical community's interest to porting and using such innovations in clinical systems. The acceptance of speech recognition systems in clinical domains increases with recognition speed, large medical vocabulary, high accuracy, continuous speech recognition, and speaker independence. Although some commercial speech engines approach these requirements, the greatest benefit can be achieved in adapting a speech recognizer to a specific medical application. The goals of our work are first, to develop a speech-aware core component which is able to establish connections to speech recognition engines of different vendors. This is realized in SAM. Second, with applications based on SAM we want to support the physician in his/her routine clinical care activities. Within the STAMP project (STAndardized Multimedia report generator in Pathology), we extend SAM by combining a structured data entry approach with speech recognition technology. Another speech-aware application in the field of Diabetes care is connected to a terminology server. The server delivers a controlled vocabulary which can be used for speech recognition.

  9. SAM: speech-aware applications in medicine to support structured data entry.

    PubMed Central

    Wormek, A. K.; Ingenerf, J.; Orthner, H. F.

    1997-01-01

    In the last two years, improvement in speech recognition technology has directed the medical community's interest to porting and using such innovations in clinical systems. The acceptance of speech recognition systems in clinical domains increases with recognition speed, large medical vocabulary, high accuracy, continuous speech recognition, and speaker independence. Although some commercial speech engines approach these requirements, the greatest benefit can be achieved in adapting a speech recognizer to a specific medical application. The goals of our work are first, to develop a speech-aware core component which is able to establish connections to speech recognition engines of different vendors. This is realized in SAM. Second, with applications based on SAM we want to support the physician in his/her routine clinical care activities. Within the STAMP project (STAndardized Multimedia report generator in Pathology), we extend SAM by combining a structured data entry approach with speech recognition technology. Another speech-aware application in the field of Diabetes care is connected to a terminology server. The server delivers a controlled vocabulary which can be used for speech recognition. PMID:9357730

  10. Calcium

    MedlinePlus

    ... milligrams) of calcium each day. Get it from: Dairy products. Low-fat milk, yogurt, cheese, and cottage ... lactase that helps digest the sugar (lactose) in dairy products, and may have gas, bloating, cramps, or ...

  11. The Supporting a Teen's Effective Entry to the Roadway (STEER) Program: Feasibility and Preliminary Support for a Psychosocial Intervention for Teenage Drivers with ADHD

    ERIC Educational Resources Information Center

    Fabiano, Gregory A.; Hulme, Kevin; Linke, Stuart; Nelson-Tuttle, Chris; Pariseau, Meaghan; Gangloff, Brian; Lewis, Kemper; Pelham, William E.; Waschbusch, Daniel A.; Waxmonsky, James G.; Gormley, Matthew; Gera, Shradha; Buck, Melina

    2011-01-01

    Teenage drivers with attention-deficit/hyperactivity disorder (ADHD) are at considerable risk for negative driving outcomes, including traffic citations, accidents, and injuries. Presently, no efficacious psychosocial interventions exist for teenage drivers with ADHD. The Supporting a Teen's Effective Entry to the Roadway (STEER) program is a…

  12. Inhibition of store-operated calcium entry by sub-lethal levels of proteasome inhibition is associated with STIM1/STIM2 degradation.

    PubMed

    Kuang, Xiu-Li; Liu, Yimei; Chang, Yuhua; Zhou, Jing; Zhang, He; Li, Yiping; Qu, Jia; Wu, Shengzhou

    2016-04-01

    Dysfunction of the ubiquitin-proteasome system (UPS) and calcium homeostasis has been implicated in the neurodegeneration of Alzheimer's and Parkinson's diseases. The cytosolic calcium concentration is maintained by store-operated calcium entry (SOCE), which is repressed by Alzheimer's disease-associated mutants, such as mutant presenilins. We hypothesized that inhibition of UPS impacts SOCE. This study showed that pretreatment with sub-lethal levels of proteasome inhibitors, including MG-132 and clasto-lactacystin-β-lactone (LA), reduced SOCE after depletion of endoplasmic reticulum calcium in rat neurons. With the same treatment, MG-132 and LA reduced the protein levels of stromal interaction molecule 1and 2 (STIM1/2), but not the levels of Orai1 and canonical transient receptor potential channel 1 (TRPC1). STIM1 or STIM2 protein was mobilized to lysosome by MG-132/LA treatment as observed under an immunofluorescence confocal laser microscope. In the neurons, MG-132 and LA degraded p62/SQSTM1, promoted autophagy, converted LC3I to LC3II, and promoted co-localization of LC3 and lysosomes. Rapamycin, which enhances autophagy, reduced STIM1/2 protein levels, whereas bafilomycin, which inhibits autophagy, increased their protein levels. The protein levels of STIM1/2 and the amplitude of SOCE were decreased in SH-SY5Y with decreased protein level of proteasome subunit beta type-5 induced by shRNA. We conclude that sub-lethal levels of proteasome inhibition reduce SOCE and promote autophagy-mediated degradation of STIM1/2. UPS inhibition, a common finding in neurodegenerative diseases, interferes with calcium homeostasis via repression of SOCE.

  13. Protein kinase C acts downstream of calcium at entry into the first mitotic interphase of Xenopus laevis.

    PubMed Central

    Bement, W M; Capco, D G

    1990-01-01

    Transit into interphase of the first mitotic cell cycle in amphibian eggs is a process referred to as activation and is accompanied by an increase in intracellular free calcium [( Ca2+]i), which may be transduced into cytoplasmic events characteristic of interphase by protein kinase C (PKC). To investigate the respective roles of [Ca2+]i and PKC in Xenopus laevis egg activation, the calcium signal was blocked by microinjection of the calcium chelator BAPTA, or the activity of PKC was blocked by PKC inhibitors sphingosine or H7. Eggs were then challenged for activation by treatment with either calcium ionophore A23187 or the PKC activator PMA. BAPTA prevented cortical contraction, cortical granule exocytosis, and cleavage furrow formation in eggs challenged with A23187 but not with PMA. In contrast, sphingosine and H7 inhibited cortical granule exocytosis, cortical contraction, and cleavage furrow formation in eggs challenged with either A23187 or PMA. Measurement of egg [Ca2+]i with calcium-sensitive electrodes demonstrated that PMA treatment does not increase egg [Ca2+]i in BAPTA-injected eggs. Further, PMA does not increase [Ca2+]i in eggs that have not been injected with BAPTA. These results show that PKC acts downstream of the [Ca2+]i increase to induce cytoplasmic events of the first Xenopus mitotic cell cycle. Images PMID:2100203

  14. Agomelatine and duloxetine synergistically modulates apoptotic pathway by inhibiting oxidative stress triggered intracellular calcium entry in neuronal PC12 cells: role of TRPM2 and voltage-gated calcium channels.

    PubMed

    Akpinar, Abdullah; Uğuz, Abdülhadi Cihangir; Nazıroğlu, Mustafa

    2014-05-01

    Calcium ion (Ca(2+)) is one of the universal second messengers, which acts in a wide range of cellular processes. Results of recent studies indicated that ROS generated by depression leads to loss of endoplasmic reticulum-Ca(2+) homeostasis, oxidative stress, and apoptosis. Agomelatine and duloxetine are novel antidepressant and antioxidant drugs and may reduce oxidative stress, apoptosis, and Ca(2+) entry through TRPM2 and voltage-gated calcium channels. We tested the effects of agomelatine, duloxetine, and their combination on oxidative stress, Ca(2+) influx, mitochondrial depolarization, apoptosis, and caspase values in the PC-12 neuronal cells. PC-12 neuronal cells were exposed in cell culture and exposed to appropriate non-toxic concentrations and incubation times for agomelatine were determined in the neurons by assessing cell viability. Then PC-12 cells were incubated with agomelatine and duloxetine for 24 h. Treatment of cultured PC-12 cells with agomelatine, duloxetine, and their combination results in a protection on apoptosis, caspase-3, caspase-9, mitochondrial membrane depolarization, cytosolic ROS production, glutathione peroxidase, reduced glutathione, and lipid peroxidation, values. Ca(2+) entry through non-specific TRPM2 channel blocker (2-APB) and voltage-gated Ca(2+) channel blockers (verapamil and diltiazem) was modulated by agomelatine and duloxetine. However, effects of duloxetine on the Ca(2+) entry through TRPM2 channels were higher than in agomelatine. Results of current study suggest that the agomelatine and duloxetine are useful against apoptotic cell death and oxidative stress in PC-12 cells, which seem to be dependent on mitochondrial damage and increased levels of intracellular Ca(2+) through activation of TRPM2 and voltage-gated Ca(2+) channels.

  15. Estrogen controls embryonic stem cell proliferation via store-operated calcium entry and the nuclear factor of activated T-cells (NFAT).

    PubMed

    Wong, Chun-Kit; So, Wing-Yan; Law, Sau-Kwan; Leung, Fung-Ping; Yau, Ka-Long; Yao, Xiaoqiang; Huang, Yu; Li, Xiangdong; Tsang, Suk-Ying

    2012-06-01

    Embryonic stem cells (ESCs) can self-renew indefinitely and differentiate into all cell lineages. Calcium is a universal second messenger which regulates a number of cellular pathways. Previous studies showed that store-operated calcium channels (SOCCs) but not voltage-operated calcium channels are present in mouse ESCs (mESCs). In this study, store-operated calcium entry (SOCE) was found to exist in mESCs using confocal microscopy. SOCC blockers lanthanum, 2-aminoethoxydiphenyl borate (2-APB) and SKF-96365 reduced mESC proliferation in a concentration-dependent manner, suggesting that SOCE is important for ESC proliferation. Pluripotent markers, Sox-2, Klf-4, and Nanog, were down-regulated by 2-APB, suggesting that self-renewal property of mESCs relies on SOCE. 17β-estradiol (E2) enhanced mESC proliferation. This enhanced proliferation was associated with an increment of SOCE. Both stimulated proliferation and increased SOCE could be reversed by SOCC blockers suggesting that E2 mediates its stimulatory effect on proliferation via enhancing SOCE. Also, cyclosporin A and INCA-6, inhibitors of calcineurin [phosphatase that de-phosphorylates and activates nuclear factor of activated T-cells (NFAT)], reversed the proliferative effect of E2, indicating that NFAT is involved in E2-stimulated proliferation. Interestingly, E2 caused the nuclear translocation of NFATc4, and this could be reversed by 2-APB. These results suggested that NFATc4 is the downstream target of E2-induced SOCE. The present investigation provides the first line of evidence that SOCE and NFAT are crucial for ESCs to maintain their unique characteristics. In addition, the present investigation also provides novel information on the mechanisms of how E2, an important female sex hormone, affects ESC proliferation.

  16. Potassium-induced contraction in the lamb proximal urethra: Involvement of norepinephrine and different calcium entry pathways

    SciTech Connect

    Garcia-Pascual, A.; Costa, G.; Isla, M.; Jimenez, E.; Garcia-Sacristan, A. )

    1991-01-01

    The purpose of this work was to investigate the mechanisms involved in the peculiar biphasic response of the lamb urethral smooth muscle to high K+ solutions. The relative amplitude of the phasic and tonic components of the contraction and its reproducibility were dependent on the concentration of K+ used. Only concentrations higher than 80 mM (i.e., 120 mM) showed a tonic component greater in amplitude than the phasic one and manifested a tachyphylactic effect. Phentolamine (10(-6) M), prazosin (10(-6) M) and chemical denervation with 6-hydroxydopamine significantly inhibited the tonic component of the K+ (120 mM)-induced contraction, modifying its morphology. Reproducible contractions to K+ (120 mM) could be obtained in the presence of prazosin (10(-6) M) or cocaine (10(-6) M). The preparations were also shown to accumulate (3H)noradrenaline and release it upon depolarization with K+ (60 and 120 mM). Calcium removal inhibited the K+ (120 mM)-induced contraction. After addition of calcium (0.5-5 mM) the contractile activity was restored. Nifedipine (10(-6) M) and verapamil (10(-6) M) but not sodium nitroprusside (10(-6) M) significantly blocked the contractile response for calcium as well as the phasic component of the K+ contraction in calcium-containing medium. In preparations treated with prazosin (10(-6) M) the tonic component of the K+ (120 mM) contraction was more sensitive to nifedipine and removal of extracellular calcium than the phasic one.

  17. siRNA screen for genes that affect Junín virus entry uncovers voltage-gated calcium channels as a therapeutic target

    PubMed Central

    Lavanya, Madakasira; Cuevas, Christian D.; Thomas, Monica; Cherry, Sara; Ross, Susan R.

    2014-01-01

    New world hemorrhagic fever arenaviruses infection of humans results in 15–30% mortality. We performed a high throughput siRNA screen with Junín virus glycoprotein-pseudotyped viruses to find potential host therapeutic targets. Voltage-gated calcium channels (VGCC) subunits, for which there are FDA-approved drugs, were identified in the screen. Knockdown of VGCC subunits or treatment with channel blockers diminished Junín virus-cell fusion and entry into cells and thereby decreased infection. Gabapentin, an FDA-approved drug used to treat neuropathic pain that targets the α2δ2 subunit, inhibited infection of mice by the Candid 1 vaccine strain of the virus. These findings demonstrate that VGCCs play a role in virus infection and have the potential to lead to therapeutic intervention of new world arenavirus infection. PMID:24068738

  18. Role of the store-operated calcium entry protein, STIM1, in neutrophil chemotaxis and infiltration into a murine model of psoriasis-inflamed skin

    PubMed Central

    Steinckwich, Natacha; Myers, Page; Janardhan, Kyathanahalli S.; Flagler, Norris D.; King, Debra; Petranka, John G.; Putney, James W.

    2015-01-01

    Stromal interaction molecule 1 (STIM1) is a Ca2+ sensor protein that initiates store-operated calcium entry (SOCE). STIM1 is known to be involved in the chemoattractant signaling pathway for FPR1 in cell lines, but its role in in vivo functioning of neutrophils is unclear. Plaque-type psoriasis is a chronic inflammatory skin disorder associated with chemoattractants driving neutrophils into the epidermis. We investigated the involvement of STIM1 in neutrophil chemotaxis in vitro, as well as during chronic psoriatic inflammation. To this end, we used conditional knockout (KO) mice lacking STIM1 in cells of myeloid lineage (STIM1fl/fl LysM-cre). We demonstrate that STIM1 is required for chemotaxis because of multiple chemoattractants in mouse neutrophils in vitro. Using an imiquimod-induced psoriasis-like skin model, we show that KO mice had less neutrophil infiltration in the epidermis than controls, whereas neither chemoattractant production in the epidermis nor macrophage migration was decreased. KO mice displayed a more rapid reversal of the outward signs of psoriasis (plaques). Thus, KO of STIM1 impairs neutrophil contribution to psoriatic inflammation. Our data provide new insights to our understanding of how STIM1 orchestrates the cellular behavior underlying chemotaxis and illustrate the important role of SOCE in a disease-related pathologic model.—Steinckwich, N., Myers, P., Janardhan, K. S., Flagler, N. D., King, D., Petranka, J. G., Putney, J. W. Role of the store-operated calcium entry protein, STIM1, in neutrophil chemotaxis and infiltration into a murine model of psoriasis-inflamed skin. PMID:25837581

  19. Anoctamins support calcium-dependent chloride secretion by facilitating calcium signaling in adult mouse intestine.

    PubMed

    Schreiber, Rainer; Faria, Diana; Skryabin, Boris V; Wanitchakool, Podchanart; Rock, Jason R; Kunzelmann, Karl

    2015-06-01

    Intestinal epithelial electrolyte secretion is activated by increase in intracellular cAMP or Ca(2+) and opening of apical Cl(-) channels. In infants and young animals, but not in adults, Ca(2+)-activated chloride channels may cause secretory diarrhea during rotavirus infection. While detailed knowledge exists concerning the contribution of cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) channels, analysis of the role of Ca(2+)-dependent Cl(-) channels became possible through identification of the anoctamin (TMEM16) family of proteins. We demonstrate expression of several anoctamin paralogues in mouse small and large intestines. Using intestinal-specific mouse knockout models for anoctamin 1 (Ano1) and anoctamin 10 (Ano10) and a conventional knockout model for anoctamin 6 (Ano6), we demonstrate the role of anoctamins for Ca(2+)-dependent Cl(-) secretion induced by the muscarinic agonist carbachol (CCH). Ano1 is preferentially expressed in the ileum and large intestine, where it supports Ca(2+)-activated Cl(-) secretion. In contrast, Ano10 is essential for Ca(2+)-dependent Cl(-) secretion in jejunum, where expression of Ano1 was not detected. Although broadly expressed, Ano6 has no role in intestinal cholinergic Cl(-) secretion. Ano1 is located in a basolateral compartment/membrane rather than in the apical membrane, where it supports CCH-induced Ca(2+) increase, while the essential and possibly only apical Cl(-) channel is CFTR. These results define a new role of Ano1 for intestinal Ca(2+)-dependent Cl(-) secretion and demonstrate for the first time a contribution of Ano10 to intestinal transport.

  20. Calcium bioavailability of vegetarian diets in rats: potential application in a bioregenerative life-support system

    NASA Technical Reports Server (NTRS)

    Nickel, K. P.; Nielsen, S. S.; Smart, D. J.; Mitchell, C. A.; Belury, M. A.

    1997-01-01

    Calcium bioavailability of vegetarian diets containing various proportions of candidate crops for a controlled ecological life-support system (CELSS) was determined by femur 45Ca uptake. Three vegetarian diets and a control diet were labeled extrinsically with 45Ca and fed to 5-wk old male rats. A fifth group of rats fed an unlabeled control diet received an intraperitoneal (IP) injection of 45Ca. There was no significant difference in mean calcium absorption of vegetarian diets (90.80 +/- 5.23%) and control diet (87.85 +/- 5.25%) when calculated as the percent of an IP dose. The amounts of phytate, oxalate, and dietary fiber in the diets did not affect calcium absorption.

  1. Characterization of T cell mutants with defects in capacitative calcium entry: genetic evidence for the physiological roles of CRAC channels

    PubMed Central

    1995-01-01

    Prolonged Ca2+ influx is an essential signal for the activation of T lymphocytes by antigen. This influx is thought to occur through highly selective Ca2+ release-activated Ca2+ (CRAC) channels that are activated by the depletion of intracellular Ca2+ stores. We have isolated mutants of the Jurkat human T cell line NZdipA to explore the molecular mechanisms that underlie capacitative Ca2+ entry and to allow a genetic test of the functions of CRAC channels in T cells. Five mutant cell lines (CJ-1 through CJ-5) were selected based on their failure to express a lethal diphtheria toxin A chain gene and a lacZ reporter gene driven by NF-AT, a Ca(2+)- and protein kinase C-dependent transcription factor. The rate of Ca2+ influx evoked by thapsigargin was reduced to varying degrees in the mutant cells whereas the dependence of NF-AT/lacZ gene transcription on [Ca2+]i was unaltered, suggesting that the transcriptional defect in these cells is caused by a reduced level of capacitative Ca2+ entry. We examined several factors that determine the rate of Ca2+ entry, including CRAC channel activity, K(+)-channel activity, and Ca2+ clearance mechanisms. The only parameter found to be dramatically altered in most of the mutant lines was the amplitude of the Ca2+ current (ICRAC), which ranged from 1 to 41% of that seen in parental control cells. In each case, the severity of the ICRAC defect was closely correlated with deficits in Ca2+ influx rate and Ca(2-)-dependent gene transcription. Behavior of the mutant cells provides genetic evidence for several roles of ICRAC in T cells. First, mitogenic doses of ionomycin appear to elevate [Ca2+]i primarily by activating CRAC channels. Second, ICRAC promotes the refilling of empty Ca2+ stores. Finally, CRAC channels are solely responsible for the Ca2+ influx that underlies antigen-mediated T cell activation. These mutant cell lines may provide a useful system for isolating, expressing, and exploring the functions of genes involved in

  2. Modulation of the Kinetics of Inositol 1,4,5-Trisphosphate-Induced [Ca2+]i Oscillations by Calcium Entry in Pituitary Gonadotrophs

    PubMed Central

    Kukuljan, Manuel; Vergara, Leoncio; Stojilkovic, Stanko S.

    1997-01-01

    Inositol 1,4,5-trisphosphate (InsP3) binds to its receptor channels and causes liberation of Ca2+ from intracellular stores, frequently in an oscillatory manner. In addition to InsP3, the activation and inactivation properties of these intracellular channels are controlled by Ca2+. We studied the influence of Ca2+ entry on the kinetics of InsP3-triggered oscillations in cytosolic calcium ([Ca2+]i) in gonadotrophs stimulated with gonadotropin-releasing hormone, an agonist that activates InsP3 production. The natural expression of voltage-gated Ca2+ channels (VGCC) in these cells was employed to manipulate Ca2+ entry by voltage clamping the cells at different membrane potentials (Vm). Under physiological conditions, the frequency of the GnRH-induced oscillations increased with time, while the amplitude decreased, until both reached stable values. However, in cells with Vm held at -50 mV or lower, both parameters progressively decreased until the signal was abolished. These effects were reverted by a depolarization of the membrane positive to -45 mV in both agonist- and InsP3-stimulated gonadotrophs. Depolarization also led to an increase in the fraction of time during which the [Ca2+]i remained elevated; this effect originated from both an increase in the mean duration of spikes and a decrease in the interval between spikes. The frequency and amplitude of spiking depended on the activity of VGCC, but displayed different temporal courses and voltage relationships. The depolarization-driven recovery of the frequency was instantaneous, whereas the recovery of the amplitude of spiking was more gradual. The midpoints of the Vm sensitivity curve for amplitude and duration of spiking (-15 mV) were close to the value observed for L-type Ca2+ current and for depolarization-induced increase in [Ca2+]i, whereas this parameter was much lower (-35 mV) for interval between spikes and frequency of oscillations. These observations are compatible with at least two distinct effects of

  3. Caffeine inhibits InsP3 responses and capacitative calcium entry in canine pulmonary arterial smooth muscle cells.

    PubMed

    Hume, Joseph R; McAllister, Claire E; Wilson, Sean M

    2009-01-01

    Caffeine is a well described and characterized ryanodine receptor (RyR) activator. Previous evidence from independent research studies also indicate caffeine inhibits InsP3 receptor functionality, which is important to activation of capacitative Ca2+ entry (CCE) in some cell types. In addition, RyR activation elicits excitatory-coupled Ca2+ entry (ECCE) in skeletal muscle myotubes. Recent studies by our group show that canine pulmonary arterial smooth muscle cells (PASMCs) have functional InsP3 receptors as well as RyRs, and that CCE is dependent on InsP3 receptor activity. The potential for caffeine to activate ECCE as well as inhibit InsP3 receptor function and CCE was examined using fura-2 fluorescent imaging in canine PASMCs. The data show caffeine causes transient as well as sustained cytosolic Ca2+ increases, though this is not due to CCE or ECCE activity as evidenced by a lack of an increase in Mn2+ quench of fura-2. The experiments also show caffeine reversibly inhibits 5-HT elicited-InsP3 mediated Ca2+ responses with an IC50 of 6.87x10(-4) M and 10 mM caffeine fully inhibits CCE. These studies provide the first evidence that caffeine is an inhibitor of InsP3 generated Ca2+ signals and CCE in PASMCs.

  4. Plasma membrane associated membranes (PAM) from Jurkat cells contain STIM1 protein is PAM involved in the capacitative calcium entry?

    PubMed

    Kozieł, Katarzyna; Lebiedzinska, Magdalena; Szabadkai, Gyorgy; Onopiuk, Marta; Brutkowski, Wojciech; Wierzbicka, Katarzyna; Wilczyński, Grzegorz; Pinton, Paolo; Duszyński, Jerzy; Zabłocki, Krzysztof; Wieckowski, Mariusz R

    2009-12-01

    A proper cooperation between the plasma membrane, the endoplasmic reticulum and the mitochondria seems to be essential for numerous cellular processes involved in Ca(2+) signalling and maintenance of Ca(2+) homeostasis. A presence of microsomal and mitochondrial proteins together with those characteristic for the plasma membrane in the fraction of the plasma membrane associated membranes (PAM) indicates a formation of stabile interactions between these three structures. We isolated the plasma membrane associated membranes from Jurkat cells and found its significant enrichment in the plasma membrane markers including plasma membrane Ca(2+)-ATPase, Na(+), K(+)-ATPase and CD3 as well as sarco/endoplasmic reticulum Ca(2+) ATPase as a marker of the endoplasmic reticulum membranes. In addition, two proteins involved in the store-operated Ca(2+) entry, Orai1 located in the plasma membrane and an endoplasmic reticulum protein STIM1 were found in this fraction. Furthermore, we observed a rearrangement of STIM1-containing protein complexes isolated from Jurkat cells undergoing stimulation by thapsigargin. We suggest that the inter-membrane compartment composed of the plasma membrane and the endoplasmic reticulum, and isolated as a stabile plasma membrane associated membranes fraction, might be involved in the store-operated Ca(2+) entry, and their formation and rebuilding have an important regulatory role in cellular Ca(2+) homeostasis.

  5. Activation of Store-Operated Calcium Entry in Airway Smooth Muscle Cells: Insight from a Mathematical Model

    PubMed Central

    Croisier, Huguette; Tan, Xiahui; Perez-Zoghbi, Jose F.; Sanderson, Michael J.; Sneyd, James; Brook, Bindi S.

    2013-01-01

    Intracellular dynamics of airway smooth muscle cells (ASMC) mediate ASMC contraction and proliferation, and thus play a key role in airway hyper-responsiveness (AHR) and remodelling in asthma. We evaluate the importance of store-operated entry (SOCE) in these dynamics by constructing a mathematical model of ASMC signaling based on experimental data from lung slices. The model confirms that SOCE is elicited upon sufficient depletion of the sarcoplasmic reticulum (SR), while receptor-operated entry (ROCE) is inhibited in such conditions. It also shows that SOCE can sustain agonist-induced oscillations in the absence of other influx. SOCE up-regulation may thus contribute to AHR by increasing the oscillation frequency that in turn regulates ASMC contraction. The model also provides an explanation for the failure of the SERCA pump blocker CPA to clamp the cytosolic of ASMC in lung slices, by showing that CPA is unable to maintain the SR empty of . This prediction is confirmed by experimental data from mouse lung slices, and strongly suggests that CPA only partially inhibits SERCA in ASMC. PMID:23936056

  6. TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization

    SciTech Connect

    Hu Fen; Sun Wenwu; Zhao Xiao Ting; Cui Zongjie Yang Wenxiu

    2008-05-16

    Synoviocyte hyperplasia is critical for rheumatoid arthritis, therefore, potentially an important target for therapeutics. It was found in this work that a TRPV1 agonist capsaicin, and acidic solution (pH 5.5) induced increases in cytosolic calcium concentration ([Ca{sup 2+}]{sub c}) and reactive oxygen species (ROS) production in synoviocytes isolated from a rat model of collagen-induced arthritis. The increases in both [Ca{sup 2+}]{sub c} and ROS production were completely abolished in calcium-free buffer or by a TRPV1 antagonist capsazepine. Further experiments revealed that capsaicin and pH 5.5 solution caused mitochondrial membrane depolarization and reduction in cell viability; such effects were inhibited by capsazepine, or the NAD(P)H oxidase inhibitor diphenylene iodonium. Both capsaicin and pH 5.5 buffer induced apoptosis as shown by nuclear condensation and fragmentation. Furthermore, RT-PCR readily detected TRPV1 mRNA expression in the isolated synoviocytes. Taken together, these data indicated that TRPV1 activation triggered synoviocyte death by [Ca{sup 2+}]{sub c} elevation, ROS production, and mitochondrial membrane depolarization.

  7. The effects of pre-entry career maturity and support networks in workplace on newcomers' mental health.

    PubMed

    Kawai, Kaoru; Yamazaki, Yoshihiko

    2006-11-01

    The present study examined the effects of pre-entry experiences (i.e. career maturity), as well as support networks (i.e. informational and friendship), on newcomers' mental health (i.e. depression, self-esteem, psychosomatic symptoms, and work motivation). We performed a longitudinal study of 890 men and women who first entered the workplace in 2003. Surveys were distributed at two time points: just prior to entering the workplace, and two months after entering. Results indicated that career maturity related positively to newcomers' mental health, and newcomers with high career maturity were more successful in establishing positive relationships with superiors and co-workers. Although, informational support networks positively related to work motivation, friendship networks did not show any direct effects on mental health. These results underscore the crucial roles of career maturity and informational networks in facilitating the transition to the workplace. The results also provide empirical support for an expanded view of the importance of pre-entry experiences to workplace newcomers' mental health.

  8. Orai1 and Orai2 mediate store-operated calcium entry that regulates HL60 cell migration and FAK phosphorylation.

    PubMed

    Diez-Bello, R; Jardin, I; Salido, G M; Rosado, J A

    2016-11-16

    Store-operated Ca(2+) entry (SOCE) is a major mechanism for the regulation of intracellular Ca(2+) homeostasis and cellular function. Emerging evidence has revealed that altered expression and function of the molecular determinants of SOCE play a critical role in the development or maintenance of several cancer hallmarks, including enhanced proliferation and migration. Here we show that, in the acute myeloid leukemia cell line HL60, Orai2 is highly expressed at the transcript level, followed by the expression of Orai1. Using fluorescence Ca(2+) imaging we found that Orai2 silencing significantly attenuated thapsigargin-induced SOCE, as well as knockdown of Orai1, while silencing the expression of both channels almost completely reduced SOCE, thus suggesting that SOCE in these cells is strongly dependent on Orai1 and Orai2. On the other hand, the expression of TRPC1, TRPC3 and TRPC6 is almost absent at the transcript and protein level. Bromodeoxyuridine cell proliferation assay revealed that Orai1 and Orai2 expression silencing significantly reduced HL60 cell proliferation. Furthermore, knockdown of Orai1 and Orai2 significantly attenuated the ability of HL60 to migrate in vitro as determined by transwell migration assay, probably due to the impairment of FAK tyrosine phosphorylation. These findings provide evidence for a role for Orai1 and Orai2, in SOCE and migration in the human HL60 promyeloblastic cell line. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.

  9. Activation of phospholipase C in SH-SY5Y neuroblastoma cells by potassium-induced calcium entry.

    PubMed Central

    Smart, D.; Wandless, A.; Lambert, D. G.

    1995-01-01

    1. We used SH-SY5Y human neuroblastoma cells to investigate whether depolarization with high K+ could stimulate inositol (1,4,5)trisphosphate (Ins(1,4,5)P3) formation and, if so, the mechanism involved. 2. Ins(1,4,5)P3 was measured by a specific radioreceptor mass assay, whilst [Ca2+]i was measured fluorimetrically with the Ca2+ indicator dye, Fura-2. 3. Depolarization with K+ caused a time- and dose-dependent increase in [Ca2+]i (peak at 27 s, EC50 of 50.0 +/- 9.0 mM) and Ins(1,4,5)P3 formation (peak at 30 s, EC50 of 47.4 +/- 1.1 mM). 4. Both the K(+)-induced Ins(1,4,5)P3 formation and increase in [Ca2+]i were inhibited dose-dependently by the L-type voltage-sensitive Ca2+ channel closer, (R+)-BayK8644, with IC50 values of 53.4 nM and 87.9 nM respectively. 5. These data show a close temporal and dose-response relationship between Ca2+ entry via L-type voltage-sensitive Ca2+ channels and Ins(1,4,5)P3 formation following depolarization with K+, indicating that Ca2+ influx can activate phospholipase C in SH-SY5Y cells. PMID:8528562

  10. Social Support Reciprocity and Occupational Self-Efficacy Beliefs during Mothers' Organizational Re-Entry

    ERIC Educational Resources Information Center

    Jaeckel, Dalit; Seiger, Christine P.; Orth, Ulrich; Wiese, Bettina S.

    2012-01-01

    The present study assesses the effects of a lack of social support reciprocity at work on employees' occupational self-efficacy beliefs. We assume that the self-efficacy effects of received support and support reciprocity depend on the specific work context (e.g., phase in the process of organizational socialization). 297 women who returned to…

  11. Control of type I interferon-induced cell death by Orai1-mediated calcium entry in T cells.

    PubMed

    Yue, Chanyu; Soboloff, Jonathan; Gamero, Ana M

    2012-01-27

    Store-operated Ca(2+) entry (SOCE) is an essential process in T cell activation. SOCE is controlled by the Ca(2+) release-activated Ca(2+) (CRAC) channel encoded by the gene Orai1 that is expressed on the plasma membrane and activated by STIM1 when ER Ca(2+) stores are depleted. Our earlier work showed that a somatic T-cell line Jurkat mutant H123 bearing a defect in Ca(2+) signaling was susceptible to the apoptotic effects of type I interferons (IFN-α/β). The nature of the mutation and whether this mutation was linked to IFN-α/β apoptotic susceptibility was unknown. Here we show that H123 cells lacked Orai1 and exhibit reduced STIM1 protein. Reconstitution of both Orai1 and STIM1 in H123 cells rescued SOCE in response to thapsigargin and ionomycin and abrogated IFN-α/β-induced apoptosis. Reciprocally, overexpression of the dominant negative Orai1-E106A in either parental Jurkat cells or an unrelated human T cell line (CEM391) inhibited SOCE and led to sensitization to IFN-α/β-induced apoptosis. Furthermore, we showed that the Ca(2+) response pathway antagonized the IFN-α/β -induced transcriptional responses; in the absence of SOCE, this negative regulatory effect was lost. However, the inhibitory effect of Ca(2+) on type I IFN-induced gene transcription was diminished by pharmacological inhibition of NF-κB in cells with intact SOCE. Our findings reveal an unexpected and novel regulatory crosstalk mechanism between type I IFNs and store-operated Ca(2+) signaling pathways mediated at least in part by NF-κB activity with significant clinical implications to both viral and tumor immunology.

  12. Modification of STIM1 by O-linked N-Acetylglucosamine (O-GlcNAc) Attenuates Store-operated Calcium Entry in Neonatal Cardiomyocytes*

    PubMed Central

    Zhu-Mauldin, Xiaoyuan; Marsh, Susan A.; Zou, Luyun; Marchase, Richard B.; Chatham, John C.

    2012-01-01

    Store-operated calcium entry (SOCE) is a major Ca2+ signaling pathway responsible for regulating numerous transcriptional events. In cardiomyocytes SOCE has been shown to play an important role in regulating hypertrophic signaling pathways, including nuclear translocation of NFAT. Acute activation of pathways leading to O-GlcNAc synthesis have been shown to impair SOCE-mediated transcription and in diabetes, where O-GlcNAc levels are chronically elevated, cardiac hypertrophic signaling is also impaired. Therefore the goal of this study was to determine whether changes in cardiomyocyte O-GlcNAc levels impaired the function of STIM1, a widely recognized mediator of SOCE. We demonstrated that acute activation of SOCE in neonatal cardiomyocytes resulted in STIM1 puncta formation, which was inhibited in a dose-dependent manner by increasing O-GlcNAc synthesis with glucosamine or inhibiting O-GlcNAcase with thiamet-G. Glucosamine and thiamet-G also inhibited SOCE and were associated with increased O-GlcNAc modification of STIM1. These results suggest that activation of cardiomyocyte O-GlcNAcylation attenuates SOCE via STIM1 O-GlcNAcylation and that this may represent a new mechanism by which increased O-GlcNAc levels regulate Ca2+-mediated events in cardiomyocytes. Further, since SOCE is a fundamental mechanism underlying Ca2+ signaling in most cells and tissues, it is possible that STIM1 represents a nexus linking protein O-GlcNAcylation with Ca2+-mediated transcription. PMID:22992728

  13. A Computer Support System for the Entry and Analysis of Questionnaire Data.

    ERIC Educational Resources Information Center

    Shale, Douglas G.; Milinusic, Tomislav O.

    This paper describes a computer support system that eliminated many of the problems associated with the usual methods of transcribing and analyzing questionnaire data. The system was created to support the course evaluation system at Athabasca University, a distance education university in Canada. The courses evaluated were all home study courses,…

  14. Changing Patterns in Vocational Entry Qualifications, Student Support and Outcomes in Undergraduate Degree Programmes

    ERIC Educational Resources Information Center

    Shields, Robin; Masardo, Alex

    2015-01-01

    This study investigates the differences in degree attainment between students entering higher education through vocational qualification pathways and students entering through traditional A-level routes. The report also analyses how well students with vocational qualifications are prepared for and supported in their studies at higher education.…

  15. The Effect of Child Support on Welfare Exits and Re-Entries

    ERIC Educational Resources Information Center

    Huang, Chien-Chung; Kunz, James; Garfinkel, Irwin

    2002-01-01

    Much of the literature on welfare dynamics has focused on the effects of recipient characteristics and state-level characteristics such as welfare benefits and economic conditions; there has been very little analysis on the effects of child support. This paper, using the 1979-1996 National Longitudinal Survey of Youth, examines whether child…

  16. Clinical data entry.

    PubMed Central

    van Mulligen, E. M.; Stam, H.; van Ginneken, A. M.

    1998-01-01

    Routine capture of patient data for a computer-based patient record system remains a subject of study. Time constraints that require fast data entry and maximal expression power are in favor of free text data entry. However, using patient data directly for decision support systems, for quality assessment, etc. requires structured data entry, which appears to be more tedious and time consuming. In this paper, a prototype clinical data entry application is described that combines free text and structured data entry in one single application and allows clinicians to smoothly switch between these two different input styles. A knowledge base involving a semantic network of clinical data entry terms and their properties and relationships is used by this application to support structured data entry. From structured data, sentences are generated and shown in a text processor together with the free text. This presentation metaphor allows for easy integrated presentation of structured data and free text. Images Figure 1 Figure 2 PMID:9929186

  17. Orai1 and Orai3 in Combination with Stim1 Mediate the Majority of Store-operated Calcium Entry in Astrocytes

    PubMed Central

    Kwon, Jea; An, Heeyoung; Sa, Moonsun; Won, Joungha; Shin, Jeong Im

    2017-01-01

    Astrocytes are non-excitable cells in the brain and their activity largely depends on the intracellular calcium (Ca2+) level. Therefore, maintaining the intracellular Ca2+ homeostasis is critical for proper functioning of astrocytes. One of the key regulatory mechanisms of Ca2+ homeostasis in astrocytes is the store-operated Ca2+ entry (SOCE). This process is mediated by a combination of the Ca2+-store-depletion-sensor, Stim, and the store-operated Ca2+-channels, Orai and TrpC families. Despite the existence of all those families in astrocytes, previous studies have provided conflicting results on the molecular identification of astrocytic SOCE. Here, using the shRNA-based gene-silencing approach and Ca2+-imaging from cultured mouse astrocytes, we report that Stim1 in combination with Orai1 and Orai3 contribute to the major portion of astrocytic SOCE. Gene-silencing of Stim1 showed a 79.2% reduction of SOCE, indicating that Stim1 is the major Ca2+-store-depletion-sensor. Further gene-silencing showed that Orai1, Orai2, Orai3, and TrpC1 contribute to SOCE by 35.7%, 20.3%, 26.8% and 12.2%, respectively. Simultaneous gene-silencing of all three Orai subtypes exhibited a 67.6% reduction of SOCE. Based on the detailed population analysis, we predict that Orai1 and Orai3 are expressed in astrocytes with a large SOCE, whereas TrpC1 is exclusively expressed in astrocytes with a small SOCE. This analytical approach allows us to identify the store operated channel (SOC) subtype in each cell by the degree of SOCE. Our results propose that Stim1 in combination with Orai1 and Orai3 are the major molecular components of astrocytic SOCE under various physiological and pathological conditions. PMID:28243166

  18. Phemindole, a Synthetic Di-indole Derivative Maneuvers the Store Operated Calcium Entry (SOCE) to Induce Potent Anti-Carcinogenic Activity in Human Triple Negative Breast Cancer Cells

    PubMed Central

    Chakraborty, Supriya; Ghosh, Swatilekha; Banerjee, Bhaswati; Santra, Abhishek; Adhikary, Arghya; Misra, Anup K.; Sen, Parimal C.

    2016-01-01

    Triple-negative breast cancer (TNBC), is a specific subtype of epithelial breast tumors that are immuno-histochemically negative for the protein expression of the estrogen receptor (ER), the progesterone receptor (PR) and lack over expression/gene amplification of HER2. This subtype of breast cancers is highly metastatic, shows poor prognosis and hence represents an important clinical challenge to researchers worldwide. Thus alternative approaches of drug development for TNBC have gained utmost importance in the present times. Dietary indole and its derivatives have gained prominence as anti-cancer agents and new therapeutic approaches are being developed to target them against TNBC. But a major drawback with 3, 3′di Indolyl methane (DIM) is their poor bioavailability and high effective concentration against TNBC. However, the Aryl methyl ring substituted analogs of DIM display interesting anti-cancer activity in breast cancer cells. In the current study we report the synthesis of a novel synthetic aryl methyl ring substituted analog of DIM, named as Phemindole as an effective anti-tumor agent against TNBC cells. Furthermore, we enumerated that Phemindole caused reactive oxygen species mediated mitochondrial-dependent apoptosis in MDAMB-231 cells. Furthermore, Phemindole mediated Store Operated Calcium Entry (SOCE) retardation favored inactivation of STIM1 and henceforth activated ER stress to induce apoptosis in TNBC cells. Simultaneously, Phemindole was also found to restrict the in vitro cell migration through its anti mitotic property and pFAK regulation. Studies extended to ex ovo and in vivo mice models further validated the efficacy of Phemindole. Thus our results cumulatively propose Phemindole as a new chemotherapeutic regime which might be effective to target the deadly aspects of the TNBC. PMID:27199756

  19. Peroxisome Proliferator–Activated Receptor γ–Mediated Inhibition on Hypoxia-Triggered Store-Operated Calcium Entry. A Caveolin-1–Dependent Mechanism

    PubMed Central

    Yang, Kai; Lu, Wenju; Jiang, Qian; Yun, Xin; Zhao, Mingming; Jiang, Haiyang

    2015-01-01

    Our previous publication demonstrated that peroxisome proliferator–activated receptor γ (PPARγ) inhibits the pathogenesis of chronic hypoxia (CH)–induced pulmonary hypertension by targeting store-operated calcium entry (SOCE) in rat distal pulmonary arterial smooth muscle cells (PASMCs). In this study, we aim to determine the role of a membrane scaffolding protein, caveolin-1, during the suppressive process of PPARγ on SOCE. Adult (6–8 weeks) male Wistar rats (200–250 g) were exposed to CH (10% O2) for 21 days to establish CH-induced pulmonary hypertension. Primary cultured rat distal PASMCs were applied for the molecular biological experiments. First, hypoxic exposure led to 2.5-fold and 1-fold increases of caveolin-1 protein expression in the distal pulmonary arteries and PASMCs, respectively. Second, effective knockdown of caveolin-1 significantly reduced hypoxia-induced SOCE for 58.2% and 41.5%, measured by Mn2+ quenching and extracellular Ca2+ restoration experiments, respectively. These results suggested that caveolin-1 acts as a crucial regulator of SOCE, and hypoxia–up-regulated caveolin-1 largely accounts for hypoxia-elevated SOCE in PASMCs. Then, by using a high-potency PPARγ agonist, GW1929, we detected that PPARγ activation inhibited SOCE and caveolin-1 protein for 62.5% and 59.8% under hypoxia, respectively, suggesting that caveolin-1 also acts as a key target during the suppressive process of PPARγ on SOCE in PASMCs. Moreover, by using effective small interfering RNAs against PPARγ and caveolin-1, and PPARγ antagonist, T0070907, we observed that PPARγ plays an inhibitory role on caveolin-1 protein by promoting its lysosomal degradation, without affecting the messenger RNA level. PPARγ inhibits SOCE, at least partially, by suppressing cellular caveolin-1 protein in PASMCs. PMID:26020612

  20. Downregulation of ACE2/Ang-(1-7)/Mas axis promotes breast cancer metastasis by enhancing store-operated calcium entry.

    PubMed

    Yu, Changhui; Tang, Wei; Wang, Yuhao; Shen, Qiang; Wang, Bin; Cai, Chunqing; Meng, Xiaojing; Zou, Fei

    2016-07-01

    The renin-angiotensin system (RAS) is an important component of the tumor microenvironment and plays a key role in promoting cancer cell proliferation, angiogenesis, metabolism, migration and invasion. Meanwhile, the arm of angiotensin-converting enzyme (ACE)2/angiotensin-(1-7) [Ang-(1-7)]/Mas axis in connection with RAS is associated with anti-proliferative, vasodilatory and anti-metastatic properties. Previous studies have shown that Ang-(1-7) reduces the proliferation of orthotopic human breast tumor growth by inhibiting cancer-associated fibroblasts. However, the role of ACE/Ang-(1-7)/Mas axis in the metastasis of breast cancer cells is still unknown. In the present study, we found that ACE2 protein level is negatively correlated with the metastatic ability of breast cancer cells and breast tumor grade. Upregulation of ACE2/Ang-(1-7)/Mas axis inhibits breast cancer cell migration and invasion in vivo and in vitro. Mechanistically, ACE2/Ang-(1-7)/Mas axis activation inhibits store-operated calcium entry (SOCE) and PAK1/NF-κB/Snail1 pathways, and induces E-cadherin expression. In summary, our results demonstrate that downregulation of ACE2/Ang-(1-7)/Mas axis stimulates breast cancer metastasis through the activation of SOCE and PAK1/NF-κB/Snail1 pathways. These results provide new mechanisms by which breast cancer develop metastasis and shed light on developing novel anti-metastasis therapeutics for metastatic breast cancer by modulating ACE2/Ang-(1-7)/Mas axis.

  1. Peroxisome Proliferator-Activated Receptor γ-Mediated Inhibition on Hypoxia-Triggered Store-Operated Calcium Entry. A Caveolin-1-Dependent Mechanism.

    PubMed

    Yang, Kai; Lu, Wenju; Jiang, Qian; Yun, Xin; Zhao, Mingming; Jiang, Haiyang; Wang, Jian

    2015-12-01

    Our previous publication demonstrated that peroxisome proliferator-activated receptor γ (PPARγ) inhibits the pathogenesis of chronic hypoxia (CH)-induced pulmonary hypertension by targeting store-operated calcium entry (SOCE) in rat distal pulmonary arterial smooth muscle cells (PASMCs). In this study, we aim to determine the role of a membrane scaffolding protein, caveolin-1, during the suppressive process of PPARγ on SOCE. Adult (6-8 weeks) male Wistar rats (200-250 g) were exposed to CH (10% O2) for 21 days to establish CH-induced pulmonary hypertension. Primary cultured rat distal PASMCs were applied for the molecular biological experiments. First, hypoxic exposure led to 2.5-fold and 1-fold increases of caveolin-1 protein expression in the distal pulmonary arteries and PASMCs, respectively. Second, effective knockdown of caveolin-1 significantly reduced hypoxia-induced SOCE for 58.2% and 41.5%, measured by Mn(2+) quenching and extracellular Ca(2+) restoration experiments, respectively. These results suggested that caveolin-1 acts as a crucial regulator of SOCE, and hypoxia-up-regulated caveolin-1 largely accounts for hypoxia-elevated SOCE in PASMCs. Then, by using a high-potency PPARγ agonist, GW1929, we detected that PPARγ activation inhibited SOCE and caveolin-1 protein for 62.5% and 59.8% under hypoxia, respectively, suggesting that caveolin-1 also acts as a key target during the suppressive process of PPARγ on SOCE in PASMCs. Moreover, by using effective small interfering RNAs against PPARγ and caveolin-1, and PPARγ antagonist, T0070907, we observed that PPARγ plays an inhibitory role on caveolin-1 protein by promoting its lysosomal degradation, without affecting the messenger RNA level. PPARγ inhibits SOCE, at least partially, by suppressing cellular caveolin-1 protein in PASMCs.

  2. Outer planet entry probe system study. Volume 2: Supporting technical studies

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The environment, science investigations, and general mission analysis considerations are given first. These data are followed by discussions of the studies pertaining to the planets Jupiter, Saturn, Uranus, and Neptune. Except for Neptune, each planet discussion is divided into two parts: (1) parametric activities and (2) probe definition for that planet, or the application of a given probe for that planet. The Neptune discussion is limited to parametrics in the area of science and mission analysis. Each of the probe system definitions consists of system and subsystem details including telecommunications, data handling, power pyrotechnics, attitude control, structures, propulsion, thermal control, and probe to spacecraft integration. The first configuration is discussed in detail and the subsequent configuration discussions are limited to the differences. Finally, the hardware availability to support a probe system and commonality of science, missions, and subsystems for use at the various planets are considered.

  3. Piloting the Post-Entry Language Assessment: Outcomes from a New System for Supporting Research Candidates with English as an Additional Language

    ERIC Educational Resources Information Center

    Tynan, Liz; Johns, Kellie

    2015-01-01

    The Post-Entry Language Assessment (PELA) was introduced by the James Cook University Graduate Research School in February 2013 as a pilot programme to test a new mechanism for initiating post-enrolment support for research degree candidates who have English as an additional language. Language ability does not necessarily, on its own, predict…

  4. Computerized physician order entry with clinical decision support in long-term care facilities: costs and benefits to stakeholders.

    PubMed

    Subramanian, Sujha; Hoover, Sonja; Gilman, Boyd; Field, Terry S; Mutter, Ryan; Gurwitz, Jerry H

    2007-09-01

    Nursing homes are the setting of care for growing numbers of our nation's older people, and adverse drug events are an increasingly recognized safety and quality concern in this population. Health information technology, including computerized physician/provider order entry (CPOE) with clinical decision support (CDS), has been proposed as an important systems-based approach for reducing medication errors and preventable drug-related injuries. This article describes the costs and benefits of CPOE with CDS for the various stakeholders involved in long-term care (LTC), including nurses, physicians, the pharmacy, the laboratory, the payer (e.g., the insurer), nursing home residents, and the LTC facility. Critical barriers to adoption of these systems are discussed, primarily from an economic perspective. The analysis suggests that multiple stakeholders will incur the costs related to implementation of CPOE with CDS in the LTC setting, but the costs incurred by each may not be aligned with the benefits, which may present a major barrier to broad adoption. Physicians and LTC facilities are likely to bear a large burden of the costs, whereas residents and payers will enjoy a large portion of the benefits. Consideration of these costs and benefits suggests that financial incentives to physicians and facilities may be necessary to encourage and accelerate widespread use of these systems in the LTC setting.

  5. Pancreatic β-cell-specific ablation of TASK-1 channels augments glucose-stimulated calcium entry and insulin secretion, improving glucose tolerance.

    PubMed

    Dadi, Prasanna K; Vierra, Nicholas C; Jacobson, David A

    2014-10-01

    Calcium entry through voltage-dependent Ca(2+) channels (VDCCs) is required for pancreatic β-cell insulin secretion. The 2-pore-domain acid-sensitive potassium channel (TASK-1) regulates neuronal excitability and VDCC activation by hyperpolarizing the plasma membrane potential (Δψp); however, a role for pancreatic β-cell TASK-1 channels is unknown. Here we examined the influence of TASK-1 channel activity on the β-cell Δψp and insulin secretion during secretagogue stimulation. TASK-1 channels were found to be highly expressed in human and rodent islets and localized to the plasma membrane of β-cells. TASK-1-like currents of mouse and human β-cells were blocked by the potent TASK-1 channel inhibitor, A1899 (250nM). Although inhibition of TASK-1 currents did not influence the β-cell Δψp in the presence of low (2mM) glucose, A1899 significantly enhanced glucose-stimulated (14mM) Δψp depolarization of human and mouse β-cells. TASK-1 inhibition also resulted in greater secretagogue-stimulated Ca(2+) influx in both human and mouse islets. Moreover, conditional ablation of mouse β-cell TASK-1 channels reduced K2P currents, increased glucose-stimulated Δψp depolarization, and augmented secretagogue-stimulated Ca(2+) influx. The Δψp depolarization caused by TASK-1 inhibition resulted in a transient increase in glucose-stimulated mouse β-cell action potential (AP) firing frequency. However, secretagogue-stimulated β-cell AP duration eventually increased in the presence of A1899 as well as in β-cells without TASK-1, causing a decrease in AP firing frequency. Ablation or inhibition of mouse β-cell TASK-1 channels also significantly enhanced glucose-stimulated insulin secretion, which improved glucose tolerance. Conversely, TASK-1 ablation did not perturb β-cell Δψp, Ca(2+) influx, or insulin secretion under low-glucose conditions (2mM). These results reveal a glucose-dependent role for β-cell TASK-1 channels of limiting glucose-stimulated

  6. Qualitative analysis of vendor discussions on the procurement of Computerised Physician Order Entry and Clinical Decision Support systems in hospitals

    PubMed Central

    Cresswell, Kathrin M; Lee, Lisa; Slee, Ann; Coleman, Jamie; Bates, David W; Sheikh, Aziz

    2015-01-01

    Objectives We studied vendor perspectives about potentially transferable lessons for implementing organisations and national strategies surrounding the procurement of Computerised Physician Order Entry (CPOE)/Clinical Decision Support (CDS) systems in English hospitals. Setting Data were collected from digitally audio-recorded discussions from a series of CPOE/CDS vendor round-table discussions held in September 2014 in the UK. Participants Nine participants, representing 6 key vendors operating in the UK, attended. The discussions were transcribed verbatim and thematically analysed. Results Vendors reported a range of challenges surrounding the procurement and contracting processes of CPOE/CDS systems, including hospitals’ inability to adequately assess their own needs and then select a suitable product, rushed procurement and implementation processes that resulted in difficulties in meaningfully engaging with vendors, as well as challenges relating to contracting leading to ambiguities in implementation roles. Consequently, relationships between system vendors and hospitals were often strained, the vendors attributing this to a lack of hospital management's appreciation of the complexities associated with implementation efforts. Future anticipated challenges included issues surrounding the standardisation of data to enable their aggregation across systems for effective secondary uses, and implementation of data exchange with providers outside the hospital. Conclusions Our results indicate that there are significant issues surrounding capacity to procure and optimise CPOE/CDS systems among UK hospitals. There is an urgent need to encourage more synergistic and collaborative working between providers and vendors and for a more centralised support for National Health Service hospitals, which draws on a wider body of experience, including a formalised procurement framework with value-based product specifications. PMID:26503385

  7. Simultaneous determination of a novel calcium entry blocker, monatepil maleate, and its metabolites in rat plasma by means of solid-phase extraction and reversed-phase liquid chromatography with electrochemical detection.

    PubMed

    Kurono, M; Suzuki, K; Yoshida, K; Naruto, S

    1997-02-21

    A reversed-phase LC method with electrochemical detection is described for the simultaneous determination of monatepil maleate (AJ-2615, AJ), a novel calcium entry blocker, and its three S-oxidized metabolites in plasma. These compounds were extracted from plasma by solid-phase extraction and injected onto an ODS column. The determination limit in plasma (0.5 ml) was 10 ng/ml for AJ and 5 ng/ml for the three metabolites. The method was applied to the determination of AJ and the metabolites in rat plasma samples.

  8. Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex

    PubMed Central

    McDougal, Robert A.; Bulanova, Anna S.; Zeki, Mustafa; Lakatos, Peter; Terman, David; Hines, Michael L.; Lytton, William W.

    2016-01-01

    Neuronal persistent activity has been primarily assessed in terms of electrical mechanisms, without attention to the complex array of molecular events that also control cell excitability. We developed a multiscale neocortical model proceeding from the molecular to the network level to assess the contributions of calcium regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in providing additional and complementary support of continuing activation in the network. The network contained 776 compartmental neurons arranged in the cortical layers, connected using synapses containing AMPA/NMDA/GABAA/GABAB receptors. Metabotropic glutamate receptors (mGluR) produced inositol triphosphate (IP3) which caused release of Ca2+ from endoplasmic reticulum (ER) stores, with reuptake by sarco/ER Ca2+-ATP-ase pumps (SERCA), and influence on HCN channels. Stimulus-induced depolarization led to Ca2+ influx via NMDA and voltage-gated Ca2+ channels (VGCCs). After a delay, mGluR activation led to ER Ca2+ release via IP3 receptors. These factors increased HCN channel conductance and produced firing lasting for ~1 minute. The model displayed inter-scale synergies among synaptic weights, excitation/inhibition balance, firing rates, membrane depolarization, calcium levels, regulation of HCN channels, and induction of persistent activity. The interaction between inhibition and Ca2+ at the HCN channel nexus determined a limited range of inhibition strengths for which intracellular Ca2+ could prepare population-specific persistent activity. Interactions between metabotropic and ionotropic inputs to the neuron demonstrated how multiple pathways could contribute in a complementary manner to persistent activity. Such redundancy and complementarity via multiple pathways is a critical feature of biological systems. Mediation of activation at different time scales, and through different pathways, would be expected to protect against disruption, in this case providing

  9. Occurrence of cGMP/nitric oxide-sensitive store-operated calcium entry in fibroblasts and its effect on matrix metalloproteinase secretion

    PubMed Central

    Huang, Yong; Lu, Min-Qiang; Li, Hua; Xu, Chi; Yi, Shu-Hong; Chen, Gui-Hua

    2006-01-01

    AIM: To examine the existence of Nitric oxide/cGMP sensitive store-operated Ca2+ entry in mouse fibroblast NIH/3T3 cells and its influence on matrix metalloproteinase (MMP) production and adhesion ability of fibroblasts. METHODS: NIH/3T3 cells were cultured. Confocal laser scanning microscopy was used to examine the existence of thapsigargin-induced store-operated Ca2+ entry in fibroblasts. Gelatin zymography and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were employed to detect the involvement of [Ca2+]i and NO/cGMP in MMP secretion. The involvement of NO/cGMP-sensitive Ca2+ entry in adhesion was determined using matrigel-coated culture plates. RESULTS: 8-bromo-cGMP inhibited the thapsigargin-induced Ca2+ entry in 3T3 cells. The cGMP-induced inhibition was abolished by an inhibitor of protein kinase G, KT5823 (1μmol/L). A similar effect on the Ca2+ entry was observed in 3T3 cells in response to a NO donor, (±)-S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin-induced Ca2+ entry was also observed, indicating NO/cGMP-regulated Ca2+ entry in 3T3 cells. Results of gelatin zymography assay showed that addition of extracellular Ca2+ concentration induced MMP release and activation in a dose-dependent manner. RT-PCR also showed that cGMP and SNAP reduced the production of MMP mRNA in 3T3 cells. Experiments investigating adhesion potentials demonstrated that cGMP and SNAP could upgrade 3T3 cell attachment rate to the matrigel-coated culture plates. CONCLUSION: NO/cGMP sensitive store-operated Ca2+ entry occurs in fibroblasts, and attenuates their adhesion potentials through its influence on MMP secretion. PMID:17006985

  10. Expression and role of TRPC proteins in human platelets: evidence that TRPC6 forms the store-independent calcium entry channel.

    PubMed

    Hassock, Sheila R; Zhu, Michael X; Trost, Claudia; Flockerzi, Veit; Authi, Kalwant S

    2002-10-15

    Store-operated Ca(++) entry (SOCE) is thought to comprise the major pathway for Ca(++) entry in platelets. Recently, a number of transient receptor potential (TRP) proteins, which have been divided into 3 groups (TRPC, TRPM, and TRPV), have been suggested as SOCE channels. We report the expression and function of TRPC proteins in human platelets. TRPC6 is found at high levels and TRPC1 at low levels. Using purified plasma (PM) and intracellular membranes (IM), TRPC6 is found in the PM, but TRPC1 is localized to the IM. Using Fura-2-loaded platelets, we report that, in line with TRPC6 expression, 1-oleoyl-2-acetyl-sn-glycerol (OAG) stimulated the entry of Ca(++) and Ba(2+) independently of protein kinase C. Thrombin also induced the entry of Ca(++) and Ba(2+), but thapsigargin, which depletes the stores, induced the entry of only Ca(++). Thus, thrombin activated TRPC6 via a SOCE-independent mechanism. In phosphorylation studies, we report that neither TRPC6 nor TRPC1 was a substrate for tyrosine kinases. TRPC6 was phosphorylated by cAMP-dependent protein kinase (cAMP-PK) and associated with other cAMP-PK substrates. TRPC1 was not phosphorylated by cAMP-PK but also associated with other substrates. Activation of cAMP-PK inhibited Ca(++) but not Ba(2+) entry induced by thrombin and neither Ca(++) nor Ba(2+) entry stimulated by OAG. These results suggest that TRPC6 is a SOCE-independent, nonselective cation entry channel stimulated by thrombin and OAG. TRPC6 is a substrate for cAMP-PK, although phosphorylation appears to not affect cation permeation. TRPC1 is located in IM, suggesting a role at the level of the stores.

  11. Clinical decision support for atypical orders: detection and warning of atypical medication orders submitted to a computerized provider order entry system.

    PubMed

    Woods, Allie D; Mulherin, David P; Flynn, Allen J; Stevenson, James G; Zimmerman, Christopher R; Chaffee, Bruce W

    2014-01-01

    The specificity of medication-related alerts must be improved to overcome the pernicious effects of alert fatigue. A systematic comparison of new drug orders to historical orders could improve alert specificity and relevance. Using historical order data from a computerized provider order entry system, we alerted physicians to atypical orders during the prescribing of five medications: calcium, clopidogrel, heparin, magnesium, and potassium. The percentage of atypical orders placed for these five medications decreased during the 92 days the alerts were active when compared to the same period in the previous year (from 0.81% to 0.53%; p=0.015). Some atypical orders were appropriate. Fifty of the 68 atypical order alerts were over-ridden (74%). However, the over-ride rate is misleading because 28 of the atypical medication orders (41%) were changed. Atypical order alerts were relatively few, identified problems with frequencies as well as doses, and had a higher specificity than dose check alerts.

  12. Controlled environment life support system: Calcium-related leaf injuries on plants

    NASA Technical Reports Server (NTRS)

    Tibbitts, T. W.

    1985-01-01

    A calcium related injury in lettuce termed tipburn was the focus of this study. It affects the young developing leaves as they become enclosed during head formation. It is a good model system to study because the injury can be induced with good predictability and lettuce is one of the crops chosen by the CELSS program for concentrated study. Investigations were undertaken to study a number of different procedures, that would have the potential for encouraging movement of calcium into the young developing leaves and to study the time course and pattern of calcium accumulation in developing leaves to provide a basis for developing effective control procedures for this injury.

  13. Data supporting the cardiac mitochondria calcium handling in female normotensive and spontaneously hypertensive rats

    PubMed Central

    Ciocci Pardo, Alejandro; Rinaldi, Gustavo J.; Mosca, Susana M.

    2016-01-01

    In association with the published article “Mitochondrial calcium handling in normotensive and spontaneously hypertensive rats: correlation with systolic blood pressure levels” [1], this data article contains information about calcium handling of cardiac mitochondria isolated from female of both rats strains (WKY and SHR). Dataset of mitochondrial permeability transition pore (mPTP) resistance to opening Ca2+-mediated, Ca2+ retention capacity (CRC), time constants and mitochondrial membrane potential (ΔΨm) are showed. PMID:26977446

  14. ATP release due to Thy-1–integrin binding induces P2X7-mediated calcium entry required for focal adhesion formation

    PubMed Central

    Henríquez, Mauricio; Herrera-Molina, Rodrigo; Valdivia, Alejandra; Alvarez, Alvaro; Kong, Milene; Muñoz, Nicolás; Eisner, Verónica; Jaimovich, Enrique; Schneider, Pascal; Quest, Andrew F. G.; Leyton, Lisette

    2011-01-01

    Thy-1, an abundant mammalian glycoprotein, interacts with αvβ3 integrin and syndecan-4 in astrocytes and thus triggers signaling events that involve RhoA and its effector p160ROCK, thereby increasing astrocyte adhesion to the extracellular matrix. The signaling cascade includes calcium-dependent activation of protein kinase Cα upstream of Rho; however, what causes the intracellular calcium transients required to promote adhesion remains unclear. Purinergic P2X7 receptors are important for astrocyte function and form large non-selective cation pores upon binding to their ligand, ATP. Thus, we evaluated whether the intracellular calcium required for Thy-1-induced cell adhesion stems from influx mediated by ATP-activated P2X7 receptors. Results show that adhesion induced by the fusion protein Thy-1-Fc was preceded by both ATP release and sustained intracellular calcium elevation. Elimination of extracellular ATP with Apyrase, chelation of extracellular calcium with EGTA, or inhibition of P2X7 with oxidized ATP, all individually blocked intracellular calcium increase and Thy-1-stimulated adhesion. Moreover, Thy-1 mutated in the integrin-binding site did not trigger ATP release, and silencing of P2X7 with specific siRNA blocked Thy-1-induced adhesion. This study is the first to demonstrate a functional link between αvβ3 integrin and P2X7 receptors, and to reveal an important, hitherto unanticipated, role for P2X7 in calcium-dependent signaling required for Thy-1-stimulated astrocyte adhesion. PMID:21502139

  15. Controlled environment life support system: Calcium-related leaf injuries on plants

    NASA Technical Reports Server (NTRS)

    Tibbitts, T. W.

    1986-01-01

    Calcium related injuries to plants grown in controlled environments under conditions which maximize plant growth rates are described. Procedures to encourage movement of calcium into developing leaves of lettuce plants were investigated. The time course and pattern of calcium accumulation was determined to develop effective control procedures for this injury, termed tipburn. Procedures investigated were: (1) increasing the relative humidity to saturation during the dark period and altering root temperatures, (2) maximizing water stress during light and minimizing water stress during dark periods, (3) shortening the light-dark cycle lengths in combination with elevated moisture levels during the dark cycles, (4) reducing nutrient concentrations and (5) vibrating the plants. Saturated humidities at night increased the rate of growth and the large fluctuation in plant water potential encouraged calcium movement to the young leaves and delayed tipburn. Root temperature regulation between 15 and 26 C was not effective in preventing tipburn. Attempts to modulate water stress produced little variation, but no difference in tipburn development. Variations in light-dark cycle lengths also had no effect on calcium concentrations within developing leaves and no variation in tipburn development. Low concentrations of nutrient solution delayed tipburn, presumably because of greater calcium transport in the low concentration plants. Shaking of the plants did not prevent tipburn, but did delay it slightly.

  16. Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex.

    PubMed

    Neymotin, S A; McDougal, R A; Bulanova, A S; Zeki, M; Lakatos, P; Terman, D; Hines, M L; Lytton, W W

    2016-03-01

    Neuronal persistent activity has been primarily assessed in terms of electrical mechanisms, without attention to the complex array of molecular events that also control cell excitability. We developed a multiscale neocortical model proceeding from the molecular to the network level to assess the contributions of calcium (Ca(2+)) regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in providing additional and complementary support of continuing activation in the network. The network contained 776 compartmental neurons arranged in the cortical layers, connected using synapses containing AMPA/NMDA/GABAA/GABAB receptors. Metabotropic glutamate receptors (mGluR) produced inositol triphosphate (IP3) which caused the release of Ca(2+) from endoplasmic reticulum (ER) stores, with reuptake by sarco/ER Ca(2+)-ATP-ase pumps (SERCA), and influence on HCN channels. Stimulus-induced depolarization led to Ca(2+) influx via NMDA and voltage-gated Ca(2+) channels (VGCCs). After a delay, mGluR activation led to ER Ca(2+) release via IP3 receptors. These factors increased HCN channel conductance and produced firing lasting for ∼1min. The model displayed inter-scale synergies among synaptic weights, excitation/inhibition balance, firing rates, membrane depolarization, Ca(2+) levels, regulation of HCN channels, and induction of persistent activity. The interaction between inhibition and Ca(2+) at the HCN channel nexus determined a limited range of inhibition strengths for which intracellular Ca(2+) could prepare population-specific persistent activity. Interactions between metabotropic and ionotropic inputs to the neuron demonstrated how multiple pathways could contribute in a complementary manner to persistent activity. Such redundancy and complementarity via multiple pathways is a critical feature of biological systems. Mediation of activation at different time scales, and through different pathways, would be expected to protect against disruption, in

  17. Reduction in traumatic brain injury-induced oxidative stress, apoptosis, and calcium entry in rat hippocampus by melatonin: Possible involvement of TRPM2 channels.

    PubMed

    Yürüker, Vehbi; Nazıroğlu, Mustafa; Şenol, Nilgün

    2015-02-01

    Melatonin, which is a very effective reactive oxygen species (ROS) scavenger, acts through a direct reaction with free radicals. Ca(2+) entry induced by traumatic brain injury (TBI) has deleterious effects on human hippocampal function. TRPM2 is a Ca(2+) permeable non-selective channel in hippocampal neurons, and its activation of during oxidative stress has been linked to cell death. Despite the importance of oxidative stress in TBI, its role in apoptosis and Ca(2+) entry in TBI is poorly understood. Therefore, we tested the effects of melatonin on apoptosis, oxidative stress, and Ca(2+) entry through the TRPM2 channel in the hippocampal neurons of TBI-induced rats. Thirty-two rats were divided into the following four groups: control, melatonin, TBI, and TBI + melatonin groups. Melatonin (5 mg/kg body weight) was intraperitoneally given to animals in the melatonin group and the TBI + melatonin group after 1 h of brain trauma. Hippocampal neurons were freshly isolated from the four groups, incubated with a nonspecific TRPM2 blocker (2-aminoethyl diphenylborinate, 2-APB), and then stimulated with cumene hydroperoxide. Apoptosis, caspase-3, caspase-9, intracellular ROS production, mitochondrial membrane depolarization and intracellular free Ca(2+) ([Ca(2+)]i) values were high in the TBI group, and low in the TBI + melatonin group. The [Ca(2+)]i concentration was decreased in the four groups by 2-APB. In our TBI experimental model, TRPM2 channels were involved in Ca(2+) entry-induced neuronal death, and the negative modulation of the activity of this channel by melatonin pretreatment may account for the neuroprotective activity of TRPM2 channels against oxidative stress, apoptosis, and Ca(2+) entry.

  18. Stardust Entry Reconstruction

    NASA Technical Reports Server (NTRS)

    Desai, Prasun N.; Qualls, Garry D.

    2008-01-01

    An overview of the reconstruction analyses performed for the Stardust capsule entry is described. The results indicate that the actual entry was very close to the pre-entry predictions. The capsule landed 8.1 km north-northwest of the desired target at Utah Test and Training Range. Analyses of infrared video footage and radar range data (obtained from tracking stations) during the descent show that drogue parachute deployment was 4.8 s later than the pre-entry prediction, while main parachute deployment was 19.3 s earlier than the pre-set timer indicating that main deployment was actually triggered by the backup baroswitch. Reconstruction of a best estimated trajectory revealed that the aerodynamic drag experienced by the capsule during hypersonic flight was within 1% of pre-entry predications. Observations of the heatshield support the pre-entry estimates of small hypersonic angles of attack, since there was very little, if any, charring of the shoulder region or the aftbody. Through this investigation, an overall assertion can be made that all the data gathered from the Stardust capsule entry were consistent with flight performance close to nominal pre-entry predictions. Consequently, the design principles and methodologies utilized for the flight dynamics, aerodynamics, and aerothermodynamics analyses have been corroborated.

  19. Cloning and expression of a novel mammalian homolog of Drosophila transient receptor potential (Trp) involved in calcium entry secondary to activation of receptors coupled by the Gq class of G protein.

    PubMed

    Boulay, G; Zhu, X; Peyton, M; Jiang, M; Hurst, R; Stefani, E; Birnbaumer, L

    1997-11-21

    Hormonal stimulation of Gq-protein coupled receptors triggers Ca2+ mobilization from internal stores. This is followed by a Ca2+ entry through the plasma membrane. Drosophila Trp and Trpl proteins have been implicated in Ca2+ entry and three mammalian homologues of Drosophila Trp/Trpl, hTrp1, hTrp3 and bTrp4 (also bCCE) have been cloned and expressed. Using mouse brain RNA as template, we report here the polymerase chain reaction-based cloning and functional expression of a novel Trp, mTrp6. The cDNA encodes a protein of 930 amino acids, the sequence of which is 36.8, 36.3, 43.1, 38.6, and 74. 1% identical to Drosophila Trp and Trpl, bovine Trp4, and human Trp1 and Trp3, respectively. Transient expression of mTrp6 in COS.M6 cells by transfection of the full-length mTrp6 cDNA increases Ca2+ entry induced by stimulation of co-transfected M5 muscarinic acetylcholine receptor with carbachol (CCh), as seen by dual wavelength fura 2 fluorescence ratio measurements. The mTrp6-mediated increase in Ca2+ entry activity was blocked by SKF-96365 and La3+. Ca2+ entry activity induced by thapsigargin was similar in COS cells transfected with or without the mTrp6 cDNA. The thapsigargin-stimulated Ca2+ entry could not be further stimulated by CCh in control cells but was markedly increased in mTrp6-transfected cells. Records of whole cell transmembrane currents developed in response to voltage ramps from -80 to +40 mV in control HEK cells and HEK cells stably expressing mTrp6 revealed the presence of a muscarinic receptor responsive non-selective cation conductance in Trp6 cells that was absent in control cells. Our data support the hypothesis that mTrp6 encodes an ion channel subunit that mediates Ca2+ entry stimulated by a G-protein coupled receptor, but not Ca2+ entry stimulated by intracellular Ca2+ store depletion.

  20. Fluorescence-based measurement of store-operated calcium entry in live cells: from cultured cancer cell to skeletal muscle fiber.

    PubMed

    Pan, Zui; Zhao, Xiaoli; Brotto, Marco

    2012-02-13

    Store operated Ca(2+) entry (SOCE), earlier termed capacitative Ca(2+) entry, is a tightly regulated mechanism for influx of extracellular Ca(2+) into cells to replenish depleted endoplasmic reticulum (ER) or sarcoplasmic reticulum (SR) Ca(2+) stores. Since Ca(2+) is a ubiquitous second messenger, it is not surprising to see that SOCE plays important roles in a variety of cellular processes, including proliferation, apoptosis, gene transcription and motility. Due to its wide occurrence in nearly all cell types, including epithelial cells and skeletal muscles, this pathway has received great interest. However, the heterogeneity of SOCE characteristics in different cell types and the physiological function are still not clear. The functional channel properties of SOCE can be revealed by patch-clamp studies, whereas a large body of knowledge about this pathway has been gained by fluorescence-based intracellular Ca(2+) measurements because of its convenience and feasibility for high-throughput screening. The objective of this report is to summarize a few fluorescence-based methods to measure the activation of SOCE in monolayer cells, suspended cells and muscle fibers. The most commonly used of these fluorescence methods is to directly monitor the dynamics of intracellular Ca(2+) using the ratio of F(340nm;) and F(380nm;) (510 nm for emission wavelength) of the ratiometric Ca(2+) indicator Fura-2. To isolate the activity of unidirectional SOCE from intracellular Ca(2+) release and Ca(2+) extrusion, a Mn(2+) quenching assay is frequently used. Mn(2+) is known to be able to permeate into cells via SOCE while it is impervious to the surface membrane extrusion processes or to ER uptake by Ca(2+) pumps due to its very high affinity with Fura-2. As a result, the quenching of Fura-2 fluorescence induced by the entry of extracellular Mn(2+) into the cells represents a measurement of activity of SOCE. Ratiometric measurement and the Mn(+2) quenching assays can be performed on a

  1. Magnesium/Calcium Competition at Excitable Membranes.

    ERIC Educational Resources Information Center

    Belzer, Bill; Fry, Panni

    1998-01-01

    Considers some consequences of altering intracellular calcium supply by magnesium concentration changes. Focuses on using this procedure as an exercise with allied health students as they witness therapeutic uses of magnesium and other calcium entry inhibitors. (DDR)

  2. Calcium-activated K(+) channel (K(Ca)3.1) activity during Ca(2+) store depletion and store-operated Ca(2+) entry in human macrophages.

    PubMed

    Gao, Ya-dong; Hanley, Peter J; Rinné, Susanne; Zuzarte, Marylou; Daut, Jurgen

    2010-07-01

    STIM1 'senses' decreases in endoplasmic reticular (ER) luminal Ca(2+) and induces store-operated Ca(2+) (SOC) entry through plasma membrane Orai channels. The Ca(2+)/calmodulin-activated K(+) channel K(Ca)3.1 (previously known as SK4) has been implicated as an 'amplifier' of the Ca(2+)-release activated Ca(2+) (CRAC) current, especially in T lymphocytes. We have previously shown that human macrophages express K(Ca)3.1, and here we used the whole-cell patch-clamp technique to investigate the activity of these channels during Ca(2+) store depletion and store-operated Ca(2+) influx. Using RT-PCR, we found that macrophages express the elementary CRAC channel components Orai1 and STIM1, as well as Orai2, Orai3 and STIM2, but not the putatively STIM1-activated channels TRPC1, TRPC3-7 or TRPV6. In whole-cell configuration, a robust Ca(2+)-induced outwardly rectifying K(+) current inhibited by clotrimazole and augmented by DC-EBIO could be detected, consistent with K(Ca)3.1 channel current (also known as intermediate-conductance IK1). Introduction of extracellular Ca(2+) following Ca(2+) store depletion via P2Y(2) receptors induced a robust charybdotoxin (CTX)- and 2-APB-sensitive outward K(+) current and hyperpolarization. We also found that SOC entry induced by thapsigargin treatment induced CTX-sensitive K(+) current in HEK293 cells transiently expressing K(Ca)3.1. Our data suggest that SOC and K(Ca)3.1 channels are tightly coupled, such that a small Ca(2+) influx current induces a much large K(Ca)3.1 channel current and hyperpolarization, providing the necessary electrochemical driving force for prolonged Ca(2+) signaling and store repletion.

  3. Calcium carbonate formation on mica supported extracellular polymeric substance produced by Rhodococcus opacus

    NASA Astrophysics Data System (ADS)

    Szcześ, Aleksandra; Czemierska, Magdalena; Jarosz-Wilkołazka, Anna

    2016-10-01

    Extracellular polymeric substance (EPS) extracted from Rhodococcus opacus bacterial strain was used as a matrix for calcium carbonate precipitation using the vapour diffusion method. The total exopolymer and water-soluble exopolymer fraction of different concentrations were spread on the mica surface by the spin-coating method. The obtained layers were characterized using the atomic force microscopy measurement and XPS analysis. The effects of polymer concentration, initial pH of calcium chloride solution and precipitation time on the obtained crystals properties were investigated. Raman spectroscopy and scanning electron microscopy were used to characterize the precipitated minerals. It was found that the type of precipitated CaCO3 polymorph and the crystal size depend on the kind of EPS fraction. The obtained results indicates that the water soluble fraction favours vaterite dissolution and calcite growth, whereas the total EPS stabilizes vaterite and this effect is stronger at basic pH. It seems to be due to different contents of the functional group of EPS fractions.

  4. Monolithic calcium phosphate/poly(lactic acid) composite versus calcium phosphate-coated poly(lactic acid) for support of osteogenic differentiation of human mesenchymal stromal cells.

    PubMed

    Tahmasebi Birgani, Zeinab; van Blitterswijk, Clemens A; Habibovic, Pamela

    2016-03-01

    Calcium phosphates (CaPs), extensively used synthetic bone graft substitutes, are often combined with other materials with the aim to overcome issues related to poor mechanical properties of most CaP ceramics. Thin ceramic coatings on metallic implants and polymer-ceramic composites are examples of such hybrid materials. Both the properties of the CaP used and the method of incorporation into a hybrid structure are determinant for the bioactivity of the final construct. In the present study, a monolithic composite comprising nano-sized CaP and poly(lactic acid) (PLA) and a CaP-coated PLA were comparatively investigated for their ability to support proliferation and osteogenic differentiation of bone marrow-derived human mesenchymal stromal cells (hMSCs). Both, the PLA/CaP composite, produced using physical mixing and extrusion and CaP-coated PLA, resulting from a biomimetic coating process at near-physiological conditions, supported proliferation of hMSCs with highest rates at PLA/CaP composite. Enzymatic alkaline phosphatase activity as well as the mRNA expression of bone morphogenetic protein-2, osteopontin and osteocalcin were higher on the composite and coated polymer as compared to the PLA control, while no significant differences were observed between the two methods of combining CaP and PLA. The results of this study confirmed the importance of CaP in osteogenic differentiation while the exact properties and the method of incorporation into the hybrid material played a less prominent role.

  5. Modulated Entry

    NASA Technical Reports Server (NTRS)

    Grant, Frederick C.

    1960-01-01

    The technique of modulation, or variable coefficients, is discussed and the analytical formulation is reviewed. Representative numerical results of the use of modulation are shown for the lifting and nonlifting cases. These results include the effects of modulation on peak acceleration, entry corridor, and heat absorption. Results are given for entry at satellite speed and escape speed. The indications are that coefficient modulation on a vehicle with good lifting capability offers the possibility of sizable loading reductions or, alternatively, wider corridors; thus, steep entries become practical from the loading standpoint. The amount of steepness depends on the acceptable heating penalty. The price of sizable fractions of the possible gains does not appear to be excessive.

  6. The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels

    PubMed Central

    Akpınar, Hatice; Nazıroğlu, Mustafa; Övey, İshak Suat; Çiğ, Bilal; Akpınar, Orhan

    2016-01-01

    Dexmedetomidine (DEX) may act as an antioxidant through regulation of TRPM2 and TRPV1 channel activations in the neurons by reducing cerebral ischemia-induced oxidative stress and apoptosis. The neuroprotective roles of DEX were tested on cerebral ischemia (ISC) in the cultures of rat primary hippocampal and DRG neurons. Fifty-six rats were divided into five groups. A placebo was given to control, sham control, and ISC groups, respectively. In the third group, ISC was induced. The DEX and ISC+DEX groups received intraperitoneal DEX (40 μg/kg) 3, 24, and 48 hours after ISC induction. DEX effectively reversed capsaicin and cumene hydroperoxide/ADP-ribose-induced TRPV1 and TRPM2 densities and cytosolic calcium ion accumulation in the neurons, respectively. In addition, DEX completely reduced ISC-induced oxidative toxicity and apoptosis through intracellular reactive oxygen species production and depolarization of mitochondrial membrane. The DEX and ISC+DEX treatments also decreased the expression levels of caspase 3, caspase 9, and poly (ADP-ribose) polymerase in the hippocampus and DRG. In conclusion, the current results are the first to demonstrate the molecular level effects of DEX on TRPM2 and TRPV1 activation. Therefore, DEX can have remarkable neuroprotective impairment effects in the hippocampus and DRG of ISC-induced rats. PMID:27872485

  7. An Automated System for Generating Situation-Specific Decision Support in Clinical Order Entry from Local Empirical Data

    ERIC Educational Resources Information Center

    Klann, Jeffrey G.

    2011-01-01

    Clinical Decision Support is one of the only aspects of health information technology that has demonstrated decreased costs and increased quality in healthcare delivery, yet it is extremely expensive and time-consuming to create, maintain, and localize. Consequently, a majority of health care systems do not utilize it, and even when it is…

  8. Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats.

    PubMed

    Ghazizadeh, Vahid; Nazıroğlu, Mustafa

    2014-09-01

    Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.

  9. QSAR and classification study of 1,4-dihydropyridine calcium channel antagonists based on least squares support vector machines.

    PubMed

    Yao, Xiaojun; Liu, Huanxiang; Zhang, Ruisheng; Liu, Mancang; Hu, Zhide; Panaye, A; Doucet, J P; Fan, Botao

    2005-01-01

    The least squares support vector machine (LSSVM), as a novel machine learning algorithm, was used to develop quantitative and classification models as a potential screening mechanism for a novel series of 1,4-dihydropyridine calcium channel antagonists for the first time. Each compound was represented by calculated structural descriptors that encode constitutional, topological, geometrical, electrostatic, quantum-chemical features. The heuristic method was then used to search the descriptor space and select the descriptors responsible for activity. Quantitative modeling results in a nonlinear, seven-descriptor model based on LSSVM with mean-square errors 0.2593, a predicted correlation coefficient (R(2)) 0.8696, and a cross-validated correlation coefficient (R(cv)(2)) 0.8167. The best classification results are found using LSSVM: the percentage (%) of correct prediction based on leave one out cross-validation was 91.1%. This paper provides a new and effective method for drug design and screening.

  10. Neurotransmitter Release Can Be Stabilized by a Mechanism That Prevents Voltage Changes Near the End of Action Potentials from Affecting Calcium Currents.

    PubMed

    Clarke, Stephen G; Scarnati, Matthew S; Paradiso, Kenneth G

    2016-11-09

    At chemical synapses, presynaptic action potentials (APs) activate voltage-gated calcium channels, allowing calcium to enter and trigger neurotransmitter release. The duration, peak amplitude, and shape of the AP falling phase alter calcium entry, which can affect neurotransmitter release significantly. In many neurons, APs do not immediately return to the resting potential, but instead exhibit a period of depolarization or hyperpolarization referred to as an afterpotential. We hypothesized that presynaptic afterpotentials should alter neurotransmitter release by affecting the electrical driving force for calcium entry and calcium channel gating. In support of this, presynaptic calcium entry is affected by afterpotentials after standard instant voltage jumps. Here, we used the mouse calyx of Held synapse, which allows simultaneous presynaptic and postsynaptic patch-clamp recording, to show that the postsynaptic response is affected significantly by presynaptic afterpotentials after voltage jumps. We therefore tested the effects of presynaptic afterpotentials using simultaneous presynaptic and postsynaptic recordings and AP waveforms or real APs. Surprisingly, presynaptic afterpotentials after AP stimuli did not alter calcium channel responses or neurotransmitter release appreciably. We show that the AP repolarization time course causes afterpotential-induced changes in calcium driving force and changes in calcium channel gating to effectively cancel each other out. This mechanism, in which electrical driving force is balanced by channel gating, prevents changes in calcium influx from occurring at the end of the AP and therefore acts to stabilize synaptic transmission. In addition, this mechanism can act to stabilize neurotransmitter release when the presynaptic resting potential changes.

  11. What are the Right Fire Support Requirements for Army Airborne Forced Entry Operations with the Changing Contemporary Operational Environment?

    DTIC Science & Technology

    2007-11-02

    bundles that could be air dropped out of the door or attached to the bottom of the C-47. Once over the drop zone, the artillerymen would release the... Dinosaur ,” examines the current artillery force structure, how will it be seen in the information age, and the support of full-spectrum operations. He...options and posed an additional threat for the Iraqi regime. This airdrop of fifteen C-17s allowed a rapid buildup of over 1,000 forces and opened

  12. Dried calcium alginate/magnetite spheres: a new support for chromatographic separations and enzyme immobilization

    SciTech Connect

    Burns, M.A.; Kvesitadze, G.I.; Graves, D.J.

    1985-02-01

    Dried spheres made from an alginate solution containing magnetite particles have excellent potential as a support for enzyme immobilization and chromatographic applications. The beads were found to be much stronger than gels such as polyacrylamide and dextran, indicating that high flow rates and pressures could be used in column separations. The support withstood not only temperatures of up to 120/sup 0/C, but also most pH values and common solvents. While some solutions, such as phosphate buffers, dissolved the spheres, stabilization with Tyzor TE eliminated this problem. The physical properties of the beads include a glasslike density of 2.2 g/mL, excellent sphericity, low porosity, and a narrow size distribution. The magnetite present in the support allows the beads to be used for magnetic separations such as high gradient magnetic filtration. Their high degree of microroughness provides a large exposed surface area for enzyme and ligand binding. Mixed Actinomyces fradiae proteases and Aspergillus niger ..cap alpha..-amylase, two enzymes representative of classes which attack large substrates, were immobilized on the bead's surface with high activity and stability. A cyanuric dye which can be used in chromatographic applications (Cibacron Blue F3GA) was also readily coupled to the surface of this support with good yield.

  13. The addition of decision support into computerized physician order entry reduces red blood cell transfusion resource utilization in the intensive care unit.

    PubMed

    Fernández Pérez, Evans R; Winters, Jeffrey L; Gajic, Ognjen

    2007-07-01

    Computerized physician order entry (CPOE) has the potential for cost containment in critically ill patients through practice standardization and elimination of unnecessary interventions. Previous study demonstrated the beneficial short-term effect of adding a decision support for red blood cell (RBC) transfusion into the hospital CPOE. We evaluated the effect of such intervention on RBC resource utilization during the two-year study period. From the institutional APACHE III database we identified 2,200 patients with anemia, but no active bleeding on admission: 1,100 during a year before and 1,100 during a year after the intervention. The mean number of RBC transfusions per patient decreased from 1.5 +/- 1.9 units to 1.3 +/- 1.8 units after the intervention (P = 0.045). RBC transfusion cost decreased from $616,442 to $556,226 after the intervention. Hospital length of stay and adjusted hospital mortality did not differ before and after protocol implementation. In conclusion, the implementation of an evidenced-based decision support system through a CPOE can decrease RBC transfusion resource utilization in critically ill patients.

  14. Immobilization and kinetics of catalase on calcium carbonate nanoparticles attached epoxy support.

    PubMed

    Preety; Hooda, Vinita

    2014-01-01

    A novel hybrid epoxy/nano CaCO3 composite matrix for catalase immobilization was prepared by polymerizing epoxy resin in the presence of CaCO3 nanoparticles. The hybrid support was characterized using scanning electron microscopy and Fourier transform infrared spectroscopy. Catalase was successfully immobilized onto epoxy/nano CaCO3 support with a conjugation yield of 0.67 ± 0.01 mg/cm(2) and 92.63 ± 0.80 % retention of activity. Optimum pH and optimum temperature of free and immobilized catalases were found to be 7.0 and 35 °C. The value of Km for H2O2 was higher for immobilized enzyme (31.42 mM) than native enzyme (27.73 mM). A decrease in Vmax value from 1,500 to 421.10 μmol (min mg protein)(-1) was observed after immobilization. Thermal and storage stabilities of catalase improved immensely after immobilization. Immobilized enzyme retained three times than the activity of free enzyme when kept at 75 °C for 1 h and the half-life of enzyme increased five times when stored in phosphate buffer (0.01 M, pH 7.0) at 5 °C. The enzyme could be reused 30 times without any significant loss of its initial activity. Desorption of catalase from the hybrid support was minimum at pH 7.0.

  15. Privileged crosstalk between TRPV1 channels and mitochondrial calcium shuttling machinery controls nociception.

    PubMed

    Nita, Iulia I; Caspi, Yaki; Gudes, Sagi; Fishman, Dimitri; Lev, Shaya; Hersfinkel, Michal; Sekler, Israel; Binshtok, Alexander M

    2016-12-01

    The nociceptive noxious heat-activated receptor - TRPV1, conducts calcium and sodium, thus producing a depolarizing receptor potential, leading to activation of nociceptive neurons. TRPV1-mediated calcium and sodium influx is negatively modulated by calcium, via calcium-dependent desensitization of TRPV1 channels. A mitochondrial Ca(2+) uniporter - MCU, controls mitochondrial Ca(2+) entry while a sodium/calcium transporter - NCLX shapes calcium and sodium transients by mediating sodium entry into and removing calcium from the mitochondria. The functional interplay between TRPV1, MCU and NCLX, in controlling the cytosolic and mitochondrial calcium and sodium transients and subsequently the nociceptive excitability, is poorly understood. Here, we used cytosolic and mitochondrial fluorescent calcium and sodium imaging together with electrophysiological recordings of TRPV1-induced currents in HEK293T cells and nociceptor-like dissociated rat dorsal root ganglion neurons, while modulating NCLX or MCU expression using specific small interfering RNA (siNCLX). We show that the propagation of the TRPV1-induced cytosolic calcium and sodium fluxes into mitochondria is dependent on coordinated activity of NCLX and MCU. Thus, knocking-down of NCLX triggers down regulation of MCU dependent mitochondrial Ca(2+) uptake. This in turn decreases rate and amplitude of TRPV1-mediated cytosolic calcium, which inhibits capsaicin-induced inward current and neuronal firing. TRPV1-mediated currents were fully rescued by intracellular inclusion of the fast calcium chelator BAPTA. Finally, NCLX controls capsaicin-induced cell death, by supporting massive mitochondrial Ca(2+) shuttling. Altogether, our results suggest that NCLX, by regulating cytosolic and mitochondrial ionic transients, modulates calcium-dependent desensitization of TRPV1 channels, thereby, controlling nociceptive signaling.

  16. Calcium supplements

    MedlinePlus

    ... TYPES OF CALCIUM SUPPLEMENTS Forms of calcium include: Calcium carbonate: Over-the-counter (OTC) antacid products, such as Tums and Rolaids, contain calcium carbonate. These sources of calcium do not cost much. ...

  17. Effects of a computerized provider order entry and a clinical decision support system to improve cefazolin use in surgical prophylaxis: a cost saving analysis

    PubMed Central

    Veroneze, Izelandia; Burgardt, Celia I.; Fragoso, Marta F.

    2016-01-01

    Background: Computerized Provider Order Entry (CPOE) and Clinical Decision Support System (CDSS) help practitioners to choose evidence-based decisions, regarding patients’ needs. Despite its use in developed countries, in Brazil, the impact of a CPOE/CDSS to improve cefazolin use in surgical prophylaxis was not assessed yet. Objective: We aimed to evaluate the impact of a CDSS to improve the use of prophylactic cefazolin and to assess the cost savings associated to inappropriate prescribing. Methods: This is a cross-sectional study that compared two different scenarios: one prior CPOE/CDSS versus after software implementation. We conducted twelve years of data analysis (3 years prior and 9 years after CDSS implementation), where main outcomes from this study included: cefazolin Defined Daily Doses/100 bed-days (DDD), crude costs and product of costs-DDD (cost-DDD/100 bed-days). We applied a Spearman rho non-parametric test to assess the reduction of cefazolin consumption through the years. Results: In twelve years, 84,383 vials of cefazolin were dispensed and represented 38.89 DDD/100 bed-days or USD 44,722.99. Surgical wards were the largest drug prescribers and comprised >95% of our studied sample. While in 2002, there were 6.31 DDD/100 bed-days, 9 years later there was a reduction to 2.15 (p<0.05). In a scenario without CDSS, the hospital would have consumed 75.72 DDD/100 bed-days, which is equivalent to USD 116 998.07. It is estimated that CDSS provided USD 50,433.39 of cost savings. Conclusion: The implementation of a CPOE/CDSS helped to improve prophylactic cefazolin use by reducing its consumption and estimated direct costs. PMID:27785159

  18. Fixed Full Arches Supported by Tapered Implants with Knife-Edge Thread Design and Nanostructured, Calcium-Incorporated Surface: A Short-Term Prospective Clinical Study.

    PubMed

    Bechara, Soheil; Lukosiunas, Algirdas; Dolcini, Giorgio Andrea; Kubilius, Ricardas

    2017-01-01

    Purpose. To evaluate implant survival, peri-implant bone loss, and complications affecting fixed full-arch (FFA) restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface. Methods. Between January 2013 and December 2015, all patients referred for implant-supported FFA restorations were considered for enrollment in this study. All patients received implants with a knife-edge thread design and nanostructured calcium-incorporated surface (Anyridge®, Megagen, South Korea) were restored with FFA restorations and enrolled in a recall program. The final outcomes were implant survival, peri-implant bone loss, biologic/prosthetic complications, and "complication-free" survival of restorations. Results. Twenty-four patients were selected. Overall, 215 implants were inserted (130 maxilla, 85 mandible), 144 in extraction sockets and 71 in healed ridges. Thirty-six FFAs were delivered (21 maxilla, 15 mandible): 27 were immediately loaded and 9 were conventionally loaded. The follow-up ranged from 1 to 3 years. Two fixtures failed, yielding an implant survival rate of 95.9% (patient-based). A few complications were registered, for a "complication-free" survival of restorations of 88.9%. Conclusions. FFA restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface are successful in the short term, with high survival and low complication rates; long-term studies are needed to confirm these outcomes.

  19. Fixed Full Arches Supported by Tapered Implants with Knife-Edge Thread Design and Nanostructured, Calcium-Incorporated Surface: A Short-Term Prospective Clinical Study

    PubMed Central

    Bechara, Soheil; Lukosiunas, Algirdas; Kubilius, Ricardas

    2017-01-01

    Purpose. To evaluate implant survival, peri-implant bone loss, and complications affecting fixed full-arch (FFA) restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface. Methods. Between January 2013 and December 2015, all patients referred for implant-supported FFA restorations were considered for enrollment in this study. All patients received implants with a knife-edge thread design and nanostructured calcium-incorporated surface (Anyridge®, Megagen, South Korea) were restored with FFA restorations and enrolled in a recall program. The final outcomes were implant survival, peri-implant bone loss, biologic/prosthetic complications, and “complication-free” survival of restorations. Results. Twenty-four patients were selected. Overall, 215 implants were inserted (130 maxilla, 85 mandible), 144 in extraction sockets and 71 in healed ridges. Thirty-six FFAs were delivered (21 maxilla, 15 mandible): 27 were immediately loaded and 9 were conventionally loaded. The follow-up ranged from 1 to 3 years. Two fixtures failed, yielding an implant survival rate of 95.9% (patient-based). A few complications were registered, for a “complication-free” survival of restorations of 88.9%. Conclusions. FFA restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface are successful in the short term, with high survival and low complication rates; long-term studies are needed to confirm these outcomes. PMID:28246595

  20. Development, Implementation, and Validation of Supported Employment Model(s) for Traumatically Brain Injured Persons. Head Injury Re-entry Project (Project HIRe). Final Report.

    ERIC Educational Resources Information Center

    Thomas, Dale F.; Menz, Fredrick E.

    The final report of the Head Injury Re-entry Project (Project HIRe) describes activities of this 3-year (1987 to 1990) project, which used a "best practices" model approach and a community-based employment strategy with persons having traumatic brain injury (TBI) in nonurban areas. Among 15 project accomplishments are the following: (1)…

  1. Calcium signalling and calcium channels: evolution and general principles.

    PubMed

    Verkhratsky, Alexei; Parpura, Vladimir

    2014-09-15

    Calcium as a divalent cation was selected early in evolution as a signaling molecule to be used by both prokaryotes and eukaryotes. Its low cytosolic concentration likely reflects the initial concentration of this ion in the primordial soup/ocean as unicellular organisms were formed. As the concentration of calcium in the ocean subsequently increased, so did the diversity of homeostatic molecules handling calcium. This includes the plasma membrane channels that allowed the calcium entry, as well as extrusion mechanisms, i.e., exchangers and pumps. Further diversification occurred with the evolution of intracellular organelles, in particular the endoplasmic reticulum and mitochondria, which also contain channels, exchanger(s) and pumps to handle the homeostasis of calcium ions. Calcium signalling system, based around coordinated interactions of the above molecular entities, can be activated by the opening of voltage-gated channels, neurotransmitters, second messengers and/or mechanical stimulation, and as such is all-pervading pathway in physiology and pathophysiology of organisms.

  2. Kidney and calcium homeostasis.

    PubMed

    Jeon, Un Sil

    2008-12-01

    Plasma calcium concentration is maintained within a narrow range (8.5-10.5 mg/dL) by the coordinated action of parathyroid hormone (PTH), 1,25(OH)2D3, calcitonin, and ionized calcium (iCa(2+)) itself. The kidney plays a key role in this process by the fine regulation of calcium excretion. More than 95% of filtered calcium is reabsorbed along the renal tubules. In the proximal tubules, 60% of filtered calcium is reabsorbed by passive mechanisms. In the thick ascending limb, 15% of calcium is reabsorbed by paracellular diffusion through paracellin-1 (claudin-16). The calcium sensing receptor (CaSR) in the basolateral membrane of the thick ascending limb senses the change in iCa(2+) and inhibits calcium reabsorption independent to PTH and 1,25(OH)2D3. The fine regulation of calcium excretion occurs in the distal convoluted tubules and connecting tubules despite the fact that only 10-15% of filtered calcium is reabsorbed there. Transient receptor potential vanilloid 5 (TRPV5) and 6 (TRPV6) in the apical membrane act as the main portal of entry, calbindin-D28K delivers Ca(2+) in the cytoplasm, and then Na(2+)/Ca(2+) exchanger (NCX1) and plasma membrane Ca(2+)-ATPase in the basolateral membrane serve as an exit. In the cortical collecting duct, TRPV6 is expressed, but the role might be negligible. In addition to PTH and 1,25(OH)2D3, acid-base disturbance, diuretics, and estrogen affect on these calcium channels. Recently, klotho and fibroblast growth factor 23 (FGF23) are suggested as new players in the calcium metabolism. Klotho is exclusively expressed in the kidney and co-localized with TRPV5, NCX1, and calbindin-D28K. Klotho increases calcium reabsorption through trafficking of TRPV5 to the plasma membrane, and also converts FGF receptor to the specific FGF23 receptor. FGF23:klotho complex bound to FGF receptor inhibits 1α-hydroxylase of vitamin D, and contributes to calcium reabsorption and phosphate excretion in the kidney.

  3. N-cadherin modulates voltage activated calcium influx via RhoA, p120-catenin, and myosinactin interaction

    PubMed Central

    Marrs, Glen S.; Theisen, Christopher S.; Brusés, Juan L.

    2010-01-01

    N-cadherin is a transmembrane adhesion receptor that contributes to neuronal development and synapse formation through homophilic interactions that provide structural-adhesive support to contacts between cell membranes. In addition, N-cadherin homotypic binding may initiate cell signaling that regulates neuronal physiology. In this study, we investigated signaling capabilities of N-cadherin that control voltage activated calcium influx. Using whole-cell voltage clamp recording of isolated inward calcium currents in freshly isolated chick ciliary ganglion neurons we show that the juxtamembrane region of N-cadherin cytoplasmic domain regulates high-threshold voltage activated calcium currents by interacting with p120-catenin and activating RhoA. This regulatory mechanism requires myosin interaction with actin. Furthermore, N-cadherin homophilic binding enhanced voltage activated calcium current amplitude in dissociated neurons that have already developed mature synaptic contacts in vivo. The increase in calcium current amplitude was not affected by brefeldin A suggesting that the effect is caused via direct channel modulation and not by increasing channel expression. In contrast, homotypic N-cadherin interaction failed to regulate calcium influx in freshly isolated immature neurons. However, RhoA inhibitors enhanced calcium current amplitude in these immature neurons, suggesting that the inhibitory effect of RhoA on calcium entry is regulated during neuronal development and synapse maturation. These results indicate that N-cadherin modulates voltage activated calcium entry by a mechanism that involves RhoA activity and its downstream effects on the cytoskeleton, and suggest that N-cadherin provides support for synaptic maturation and sustained synaptic activity by facilitating voltage activated calcium influx. PMID:19162191

  4. Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells

    PubMed Central

    Drews, Anna; Flint, Jennie; Shivji, Nadia; Jönsson, Peter; Wirthensohn, David; De Genst, Erwin; Vincke, Cécile; Muyldermans, Serge; Dobson, Chris; Klenerman, David

    2016-01-01

    Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations. PMID:27553885

  5. Synaptic Calcium Regulation in Hair Cells of the Chicken Basilar Papilla

    PubMed Central

    Im, Gi Jung; Moskowitz, Howard S.; Lehar, Mohammed; Hiel, Hakim

    2014-01-01

    Cholinergic inhibition of hair cells occurs by activation of calcium-dependent potassium channels. A near-membrane postsynaptic cistern has been proposed to serve as a store from which calcium is released to supplement influx through the ionotropic ACh receptor. However, the time and voltage dependence of acetylcholine (ACh)-evoked potassium currents reveal a more complex relationship between calcium entry and release from stores. The present work uses voltage steps to regulate calcium influx during the application of ACh to hair cells in the chicken basilar papilla. When calcium influx was terminated at positive membrane potential, the ACh-evoked potassium current decayed exponentially over ∼100 ms. However, at negative membrane potentials, this current exhibited a secondary rise in amplitude that could be eliminated by dihydropyridine block of the voltage-gated calcium channels of the hair cell. Calcium entering through voltage-gated channels may transit through the postsynaptic cistern, since ryanodine and sarcoendoplasmic reticulum calcium-ATPase blockers altered the time course and magnitude of this secondary, voltage-dependent contribution to ACh-evoked potassium current. Serial section electron microscopy showed that efferent and afferent synaptic structures are juxtaposed, supporting the possibility that voltage-gated influx at afferent ribbon synapses influences calcium homeostasis during long-lasting cholinergic inhibition. In contrast, spontaneous postsynaptic currents (“minis”) resulting from stochastic efferent release of ACh were made briefer by ryanodine, supporting the hypothesis that the synaptic cistern serves primarily as a calcium barrier and sink during low-level synaptic activity. Hypolemmal cisterns such as that at the efferent synapse of the hair cell can play a dynamic role in segregating near-membrane calcium for short-term and long-term signaling. PMID:25505321

  6. Technology for Entry Probes

    NASA Technical Reports Server (NTRS)

    Cutts, James A.; Arnold, James; Venkatapathy, Ethiraj; Kolawa, Elizabeth; Munk, Michelle; Wercinski, Paul; Laub, Bernard

    2005-01-01

    A viewgraph describing technologies for entry probes is presented. The topics include: 1) Entry Phase; 2) Descent Phase; 3) Long duration atmospheric observations; 4) Survivability at high temperatures; and 5) Summary.

  7. The ins and outs of mitochondrial calcium.

    PubMed

    Finkel, Toren; Menazza, Sara; Holmström, Kira M; Parks, Randi J; Liu, Julia; Sun, Junhui; Liu, Jie; Pan, Xin; Murphy, Elizabeth

    2015-05-22

    Calcium is thought to play an important role in regulating mitochondrial function. Evidence suggests that an increase in mitochondrial calcium can augment ATP production by altering the activity of calcium-sensitive mitochondrial matrix enzymes. In contrast, the entry of large amounts of mitochondrial calcium in the setting of ischemia-reperfusion injury is thought to be a critical event in triggering cellular necrosis. For many decades, the details of how calcium entered the mitochondria remained a biological mystery. In the past few years, significant progress has been made in identifying the molecular components of the mitochondrial calcium uniporter complex. Here, we review how calcium enters and leaves the mitochondria, the growing insight into the topology, stoichiometry and function of the uniporter complex, and the early lessons learned from some initial mouse models that genetically perturb mitochondrial calcium homeostasis.

  8. Role of a T-type calcium current in supporting a depolarizing potential, damped oscillations, and phasic firing in vasopressinergic guinea pig supraoptic neurons.

    PubMed

    Erickson, K R; Ronnekleiv, O K; Kelly, M J

    1993-05-01

    Guinea pig magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) were studied using the in vitro slice preparation. Intracellular recordings were made with biocytin-filled electrodes, permitting immunocytochemical identification of the recorded cells as arginine vasopressin- (AVP) versus oxytocin- (OT) containing. Only AVP cells displaying a depolarizing potential (DP) fired phasically. The DP was associated with a transient inward current measured in voltage clamp, which exhibited a number of properties of the T-type calcium current: activation threshold of -64 mV, time course of up to 250 ms, blockade by nickel and augmentation by barium chloride. This current has not been reported previously in SON neurons. The T-type current (IT) was always associated with a damped oscillation of the membrane following the offset from hyperpolarizing steps. In all cells tested, an apamin-sensitive afterhyperpolarization (AHP) was observed, similar to the calcium-dependent potassium current (IK, Ca) described in rat SON and other CNS regions. Therefore, as with other CNS regions displaying damped oscillations, guinea pig SON cells possess both an IT and an IK, Ca. We have previously described an Ih activating at hyperpolarized potentials in these cells, which depolarizes the membrane to a range in which the IT and IK, Ca can interactively support oscillations. In summary, the IT and associated depolarizing potential appears to be a requisite feature for phasic firing in AVP cells of guinea pig SON.

  9. Plasma membrane calcium channels in cancer: Alterations and consequences for cell proliferation and migration.

    PubMed

    Déliot, Nadine; Constantin, Bruno

    2015-10-01

    The study of calcium channels in molecular mechanisms of cancer transformation is still a novel area of research. Several studies, mostly conducted on cancer cell lines, however support the idea that a diversity of plasma membrane channels participates in the remodeling of Ca2+ homeostasis, which regulates various cancer hallmarks such as uncontrolled multiplication and increase in migration and invasion abilities. However few is still understood concerning the intracellular signaling cascades mobilized by calcium influx participating to cancer cell behavior. This review intends to gather some of these pathways dependent on plasma membrane calcium channels and described in prostate, breast and lung cancer cell lines. In these cancer cell types, the calcium channels involved in calcium signaling pathways promoting cancer behaviors are mostly non-voltage activated calcium channels and belong to the TRP superfamily (TRPC, TPRPV and TRPM families) and the Orai family. TRP and Orai channels are part of many signaling cascades involving the activation of transmembrane receptors by extracellular ligand from the tumor environment. TRPV can sense changes in the physical and chemical environment of cancer cells and TRPM7 are stretch activated and sensitive to cholesterol. Changes in activation and or expression of plasma-membrane calcium channels affect calcium-dependent signaling processes relevant to tumorigenesis. The studies cited in this review suggest that an increase in plasma membrane calcium channel expression and/or activity sustain an elevated calcium entry (constitutive or under the control of extracellular signals) promoting higher cell proliferation and migration in most cases. A variety of non-voltage-operated calcium channels display change expression and/or activity in a same cancer type and cooperate to the same process relevant to cancer cell behavior, or can be involved in a different sequence of events during the tumorigenesis. This article is part of a

  10. Equilibrium radiative heating tables for Earth entry

    NASA Technical Reports Server (NTRS)

    Sutton, Kenneth; Hartung, Lin C.

    1990-01-01

    The recent resurgence of interest in blunt-body atmospheric entry for applications such as aeroassisted orbital transfer and planetary return has engendered a corresponding revival of interest in radiative heating. Radiative heating may be of importance in these blunt-body flows because of the highly energetic shock layer around the blunt nose. Sutton developed an inviscid, stagnation point, radiation coupled flow field code for investigating blunt-body atmospheric entry. The method has been compared with ground-based and flight data, and reasonable agreement has been found. To provide information for entry body studies in support of lunar and Mars return scenarios of interest in the 1970's, the code was exercised over a matrix of Earth entry conditions. Recently, this matrix was extended slightly to reflect entry vehicle designs of current interest. Complete results are presented.

  11. Entry at Venus

    NASA Technical Reports Server (NTRS)

    Venkatapathy, Ethiraj; Smith, Brandon

    2016-01-01

    This is lecture to be given at the IPPW 2016, as part of the 2 day course on Short Course on Destination Venus: Science, Technology and Mission Architectures. The attached presentation material is intended to be introduction to entry aspects of Venus in-situ robotic missions. The presentation introduces the audience to the aerodynamic and aerothermodynamic aspects as well as the loads, both aero and thermal, generated during entry. The course touches upon the system design aspects such as TPS design and both high and low ballistic coefficient entry system concepts that allow the science payload to be protected from the extreme entry environment and yet meet the mission objectives.

  12. NGSI student activities in open source information analysis in support of the training program of the U.S. DOE laboratories for the entry into force of the additional protocol

    SciTech Connect

    Sandoval, M Analisa; Uribe, Eva C; Sandoval, Marisa N; Boyer, Brian D; Stevens, Rebecca S

    2009-01-01

    In 2008 a joint team from Los Alamos National Laboratory (LANL) and Brookhaven National Laboratory (BNL) consisting of specialists in training of IAEA inspectors in the use of complementary access activities formulated a training program to prepare the U.S. Doe laboratories for the entry into force of the Additional Protocol. As a major part of the support of the activity, LANL summer interns provided open source information analysis to the LANL-BNL mock inspection team. They were a part of the Next Generation Safeguards Initiative's (NGSI) summer intern program aimed at producing the next generation of safeguards specialists. This paper describes how they used open source information to 'backstop' the LANL-BNL team's effort to construct meaningful Additional Protocol Complementary Access training scenarios for each of the three DOE laboratories, Lawrence Livermore National Laboratory, Idaho National Laboratory, and Oak Ridge National Laboratory.

  13. Calcium - urine

    MedlinePlus

    ... into the urine, which causes calcium kidney stones Sarcoidosis Taking too much calcium Too much production of ... Milk-alkali syndrome Proximal renal tubular acidosis Rickets Sarcoidosis Vitamin D Review Date 5/3/2015 Updated ...

  14. Superoxide enhances Ca2+ entry through L-type channels in the renal afferent arteriole.

    PubMed

    Vogel, Paul A; Yang, Xi; Moss, Nicholas G; Arendshorst, William J

    2015-08-01

    Reactive oxygen species regulate cardiovascular and renal function in health and disease. Superoxide participates in acute calcium signaling in afferent arterioles and renal vasoconstriction produced by angiotensin II, endothelin, thromboxane, and pressure-induced myogenic tone. Known mechanisms by which superoxide acts include quenching of nitric oxide and increased ADP ribosyl cyclase/ryanodine-mediated calcium mobilization. The effect(s) of superoxide on other calcium signaling pathways in the renal microcirculation is poorly understood. The present experiments examined the acute effect of superoxide generated by paraquat on calcium entry pathways in isolated rat afferent arterioles. The peak increase in cytosolic calcium concentration caused by KCl (40 mmol/L) was 99±14 nmol/L. The response to this membrane depolarization was mediated exclusively by L-type channels because it was abolished by nifedipine but was unaffected by the T-type channel blocker mibefradil. Paraquat increased superoxide production (dihydroethidium fluorescence), tripled the peak response to KCl to 314±68 nmol/L (P<0.001) and doubled the plateau response. These effects were abolished by tempol and nitroblue tetrazolium, but not by catalase, confirming actions of superoxide and not of hydrogen peroxide. Unaffected by paraquat and superoxide was calcium entry through store-operated calcium channels activated by thapsigargin-induced calcium depletion of sarcoplasmic reticular stores. Also unresponsive to paraquat was ryanodine receptor-mediated calcium-induced calcium release from the sarcoplasmic reticulum. Our results provide new evidence that superoxide enhances calcium entry through L-type channels activated by membrane depolarization in rat cortical afferent arterioles, without affecting calcium entry through store-operated entry or ryanodine receptor-mediated calcium mobilization.

  15. Twenty New Ways To Help Our Colleges: Outstanding Entries From the Annual Awards Program for Innovations in Corporate Support of Higher Education.

    ERIC Educational Resources Information Center

    Wilson, William L.

    Innovative programs in higher education that have been supported by American business during 1978-80 are described. Programs that have been selected for overall excellence, as part of the awards program sponsored by the Council for Financial Aid to Education, are examined, as are programs judged to have merit. The following award-winning programs…

  16. Bioceramic vertebral augmentation with a calcium sulphate/hydroxyapatite composite (Cerament SpineSupport): in vertebral compression fractures due to osteoporosis.

    PubMed

    Rauschmann, Michael; Vogl, Thomas; Verheyden, Akhil; Pflugmacher, Robert; Werba, Thomas; Schmidt, Sven; Hierholzer, Johannes

    2010-06-01

    A prospective, non-randomized multicenter study was initiated to study efficacy and safety of a partly resorbable composite of calcium sulphate and hydroxyapatite (Cerament SpineSupport), a novel, injectable bioceramic, in osteoporotic patients with vertebral compression fractures during 18-month follow-up. Fifteen patients with low-energy trauma and 1-2 vertebral compression fractures verified by magnetic resonance imaging were recruited to undergo percutaneous bioceramic vertebral augmentation under fluoroscopy. The patients were treated with a highly flowable bioceramic containing calcium sulphate, hydroxyapatite and the non-ionic radiocontrast agent iohexol, with final setting time within 1 h. After the procedure, the patients were allowed to mobilize after 2 h. Pain (VAS), occurrence of remote and adjacent fractures, and Quality of Life (QoL; SF-36 and EQ-5D) was recorded during 18 months. The injected volume of the composite material ranged from 2.8 to 9 mL (mean 4.2 mL). Pre-operative VAS score was mean 70.3 (CI95% +/-8.7) with an immediate post-operative pain relief, which was maintained at the 4-week visit (mean 26.4 with CI95% +/-16.1) and 8-week visit (mean 18.0 with CI95% +/-13.5 pain relief). Eighty percent of the patients demonstrated a clinical improvement. The pain relief was maintained over 18 months and no adjacent fractures were observed. There was a statistically significant improvement of physical components in the QoL assessment. No extra-vertebral leakage or neurological deficits were reported in this series. This first prospective multicenter study on a partly resorbable bioceramic material indicate that fracture healing can be achieved with sustained pain relief over a follow-up period of 18 months in an osteoporotic patient population with vertebral compression fractures.

  17. LFA-1-dependent Ca2+ entry following suboptimal T cell receptor triggering proceeds without mobilization of intracellular Ca2+.

    PubMed

    Kim, Kwangmi; Wang, Lin; Hwang, Inkyu

    2009-08-14

    A surge in cytosolic calcium ion concentration by entry of extracellular Ca2+ is a hallmark of T cell activation. According to store-operated Ca2+ entry mechanism, the Ca2+ entry is preceded by activation of phospholipase C-gamma1 (PLC-gamma1) and the consequent mobilization of intracellular Ca2+. Using membrane vesicles expressing the mouse class I major histocompatibility complex, i.e. Ld plus costimulatory ligands, i.e. B7-1 and intercellular adhesion molecule-1 along with 2C T cell receptor transgenic T cells, we investigated the roles of CD28 and LFA-1 (lymphocyte function-associated antigen-1) in the activation of PLC-gamma1 and Ca2+ signaling. Both CD28 and LFA-1 made significant and comparable contributions to the activation of PLC-gamma1 as gauged by the level of its phosphorylation at tyrosine 783. In contrast, their roles in Ca2+ signaling were quite distinct so that LFA-1/intercellular adhesion molecule-1 interaction exerted a determining role, whereas CD28/B7-1 interaction played only a minimal role. In particular, when the T cells were activated by suboptimal T cell receptor stimulation, LFA-1 played an indispensable role in the Ca2+ signaling. Further experiments using Ca2+-free medium demonstrated that the entry of extracellular Ca2+ was not always accompanied by mobilization of intracellular Ca2+. Thus, intracellular Ca2+ mobilization was hardly detected under the condition that LFA-1 played the indispensable role in the entry of extracellular Ca2+, while a distinct level of intracellular Ca2+ mobilization was readily detected under the condition that LFA-1 played only the supporting role. These results ensure the unique role of LFA-1 in T cell Ca2+ signaling and reveal that LFA-1-dependent Ca2+ entry proceeds via a mechanism separate from store-operated Ca2+ entry.

  18. Calcium3D: a visual software package for the simulation of calcium buffered diffusion in neuroendocrine cells.

    PubMed

    Carrera, Germán; Gil, Amparo; Segura, Javier

    2005-11-01

    We present Calcium3D, a user-friendly software package for simulating calcium triggered processes in neuroendocrine cells. We use Monte Carlo methods for the simulation of the basic processes involved: entry of calcium into the cytoplasm, the diffusion of ions and mobile intracellular calcium buffers inside the intracellular medium, and the kinetics of the reaction of calcium with these buffers. The outputs of the simulation are calcium and buffer concentrations as a function of time and for different depths from the cellular membrane.

  19. T-type calcium channels contribute to calcium disturbances in brain during hyponatremia.

    PubMed

    Odackal, John; Sherpa, Ang D; Patel, Nisha; Colbourn, Robert; Hrabetova, Sabina

    2015-11-01

    Disturbance of calcium homeostasis is implicated in the normal process of aging and brain pathology prevalent in the elderly such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Previous studies demonstrated that applying a hyponatremic iso-osmotic (low-NaCl) artificial cerebrospinal fluid (ACSF) to rodent hippocampus causes extracellular calcium to rapidly decrease. Restoring normonatremia after low-NaCl treatment causes a rapid increase in extracellular calcium that overshoots baseline. This study examined the amplitude, timing, and mechanism of these surprising calcium changes. We also tested whether hyponatremia increased calcium entry into brain cells or calcium binding to chondroitin sulfate (CS), a negatively charged constituent of the extracellular matrix (ECM) that may be occupied by sodium during normonatremia. We report three major findings. First we show that CS does not contribute to extracellular calcium changes during low-NaCl treatments. Second, we show that the time to minimum extracellular calcium during low-NaCl treatment is significantly shorter than the time to maximum extracellular calcium in recovery from low-NaCl treatment. Third, we show that the decrease in extracellular calcium observed during hyponatremia is attenuated by ML 218, a highly selective T-type calcium channel blocker. Together these data suggest that calcium rapidly enters cells at the onset of low-NaCl treatment and is extruded from cells when normonatremia is restored. Calcium binding to CS does not significantly contribute to calcium changes in brain during hyponatremia. Differences in timing suggest that extracellular calcium changes during and in recovery from hyponatremia occur by distinct mechanisms or by a multistep process. Finally, partial block of extracellular calcium influx by ML 218 suggests that T-type channels are involved in calcium entering cells during hyponatremia. Given the high prevalence of hyponatremia among elderly patients and the

  20. Teaching Calcium-Induced Calcium Release in Cardiomyocytes Using a Classic Paper by Fabiato

    ERIC Educational Resources Information Center

    Liang, Willmann

    2008-01-01

    This teaching paper utilizes the materials presented by Dr. Fabiato in his review article entitled "Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum." In the review, supporting evidence of calcium-induced calcium release (CICR) is presented. Data concerning potential objections to the CICR theory are discussed as well. In…

  1. Activation of store-mediated calcium entry by secretion-like coupling between the inositol 1,4,5-trisphosphate receptor type II and human transient receptor potential (hTrp1) channels in human platelets.

    PubMed Central

    Rosado, J A; Sage, S O

    2001-01-01

    Physical coupling between inositol 1,4,5-trisphosphate (IP(3)) receptors and transient receptor potential (Trp) channels has been demonstrated in both transfected and normal cells as a candidate mechanism for the activation of store-mediated Ca(2+) entry (SMCE). We have investigated the properties of the coupling between the type II IP(3) receptor and naturally expressed human Trp1 (hTrp1) in human platelets. Treatment with xestospongin C, an inhibitor of IP(3) receptor function, abolished SMCE and coupling between the IP(3) receptor and hTrp1. The coupling was activated by depletion of the intracellular Ca(2+) stores, and was reversed by refilling of the stores. We have also examined the role of actin filaments in the activation and maintenance of the coupling. Stabilization of the cortical actin network with jasplakinolide prevented the coupling, indicating that, as with secretion, the actin filaments at the cell periphery act as a negative clamp which prevents constitutive coupling. In addition, the actin cytoskeleton plays a positive role, since disruption of the actin network inhibited the coupling when the Ca(2+) stores were depleted. These results provide strong evidence for the activation of SMCE by a secretion-like coupling mechanism involving a reversible association between IP(3) receptors and hTrp1 in normal human cells. PMID:11336651

  2. Calcium Signaling and Neurodegeneration

    PubMed Central

    2010-01-01

    Neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and spinocerebellar ataxias (SCA) are very important both for fundamental science and for practical medicine. Despite extensive research into the causes of these diseases, clinical researchers have had very limited progress and, as of now, there is still no cure for any of these diseases. One of the main obstacles in the way of creating treatments for these disorders is the fact that their etiology and pathophysiology still remain unclear. This paper reviews results that support the so–called “calcium hypothesis of neurodegenerative diseases.” The calcium hypothesis states that the atrophic and degenerative processes in the neurons of AD, PD, ALS, HD, and SCA patients are accompanied by alterations in calcium homeostasis. Moreover, the calcium hypothesis states that this deregulation of calcium signaling is one of the early–stage and key processes in the pathogenesis of these diseases. Based on the results we reviewed, we conclude that the calcium channels and other proteins involved in the neuronal calcium signaling system are potential drug targets for AD, PD, ALS, HD, and SCA therapy. PMID:22649630

  3. The role of calcium in the effects of noradrenaline and phenoxybenzamine on adrenergic transmitter release from atria: no support for negative feedback of release

    PubMed Central

    Kalsner, Stanley

    1981-01-01

    1 The relation of calcium ion influx into nerve terminals to presynaptic adrenoceptor function and the possible masking, by desensitization due to intraneuronal calcium accumulation, of the effects of adrenoceptor agonists and antagonists on presynaptic α-adrenoceptors was investigated in guinea-pig atria previously incubated with [3H]-noradrenaline. 2 Atria were stimulated with 100 pulses at various frequencies (1 to 15 Hz) in standard (2.3 mm), low (0.26 mm) and high (6.9 mm) calcium-Krebs solution in the absence and then the presence first of noradrenaline and subsequently phenoxybenzamine. 3 The per pulse overflow of tritium was directly related to the calcium concentration of the Krebs solution, being much reduced and substantially increased in 0.26 and 6.9 mm calcium-Krebs solutions respectively. 4 Noradrenaline inhibited the overflow of tritium in low calcium-Krebs solution, to a relatively constant extent, independently of frequency. In addition, the agonist had a greater maximal inhibitory effect in standard than in reduced calcium-Krebs. The catecholamine was as effective an inhibitor of overflow at the lowest and highest frequencies in high as it was in standard calcium-Krebs solution. Phenoxybenzamine invariably increased the tritium overflow but was generally less effective both in low and in high calcium-Krebs solution. The patterns of inhibition and enhancement of stimulation-induced tritium overflow by these two agents do not indicate an intimate relationship between calcium influx and adrenoceptor activation; nor does desensitization appear to be an adequate explanation of the relationship between frequency of stimulation and the intensity of agonist and antagonist effect in the three different calcium concentrations. 5 It is concluded that the perineuronal levels of adrenergic transmitter do not establish the magnitudes of effect of exogenous adrenoceptor agonists and antagonists on tritium overflow and that a negative feedback regulation of

  4. Calcium channel antagonists in hypertension.

    PubMed

    Ambrosioni, E; Borghi, C

    1989-02-01

    The clinical usefulness of calcium entry-blockers for the treatment of high blood pressure is related to their capacity to act upon the primary hemodynamic derangement in hypertension: the increased peripheral vascular resistance. They can be used alone or in combination with other antihypertensive agents for the treatment of various forms of hypertensive disease. The calcium entry-blockers appear to be the most useful agents for the treatment of hypertension in the elderly and for the treatment of hypertension associated with ischemic heart disease, pulmonary obstructive disease, peripheral vascular disease, and supraventricular arrhythmias. They are effective in reducing blood pressure in pregnancy-associated hypertension and must be considered as first-line therapy for the treatment of hypertensive crisis.

  5. Orion Entry Monitor

    NASA Technical Reports Server (NTRS)

    Smith, Kelly M.

    2016-01-01

    NASA is scheduled to launch the Orion spacecraft atop the Space Launch System on Exploration Mission 1 in late 2018. When Orion returns from its lunar sortie, it will encounter Earth's atmosphere with speeds in excess of 11 kilometers per second, and Orion will attempt its first precision-guided skip entry. A suite of flight software algorithms collectively called the Entry Monitor has been developed in order to enhance crew situational awareness and enable high levels of onboard autonomy. The Entry Monitor determines the vehicle capability footprint in real-time, provides manual piloting cues, evaluates landing target feasibility, predicts the ballistic instantaneous impact point, and provides intelligent recommendations for alternative landing sites if the primary landing site is not achievable. The primary engineering challenges of the Entry Monitor is in the algorithmic implementation in making a highly reliable, efficient set of algorithms suitable for onboard applications.

  6. Calcium-Sensing Receptor: A Key Target for Extracellular Calcium Signaling in Neurons

    PubMed Central

    Jones, Brian L.; Smith, Stephen M.

    2016-01-01

    Though both clinicians and scientists have long recognized the influence of extracellular calcium on the function of muscle and nervous tissue, recent insights reveal that the mechanisms allowing changes in extracellular calcium to alter cellular excitability have been incompletely understood. For many years the effects of calcium on neuronal signaling were explained only in terms of calcium entry through voltage-gated calcium channels and biophysical charge screening. More recently however, it has been recognized that the calcium-sensing receptor is prevalent in the nervous system and regulates synaptic transmission and neuronal activity via multiple signaling pathways. Here we review the multiplicity of mechanisms by which changes in extracellular calcium alter neuronal signaling and propose that multiple mechanisms are required to describe the full range of experimental observations. PMID:27065884

  7. Project Prometheus and Future Entry Probe Missions

    NASA Technical Reports Server (NTRS)

    Spilker, Thomas R.

    2005-01-01

    A viewgraph presentation on project Prometheus and future entry probe missions is shown. The topics include: 1) What Is Project Prometheus?; 2) What Capabilities Can Project Prometheus Offer? What Mission Types Are Being Considered?; 3) Jupiter Icy Moons Orbiter (JIMO); 4) How Are Mission Opportunities Changing?; 5) Missions Of Interest a Year Ago; 6) Missions Now Being Considered For Further Study; 7) Galileo-Style (Conventional) Probe Delivery; 8) Galileo-Style Probe Support; 9) Conventional Delivery and Support of Multiple Probes; 10) How Entry Probe Delivery From an NEP Vehicle Is Different; and 11) Concluding Remarks.

  8. Evaluation of the antihypertensive effect of barnidipine, a dihydropyridine calcium entry blocker, as determined by the ambulatory blood pressure level averaged for 24 h, daytime, and nighttime. Barnidipine Study Group.

    PubMed

    Imai, Y; Abe, K; Nishiyama, A; Sekino, M; Yoshinaga, K

    1997-12-01

    We evaluated the effect of barnidipine, a dihydropyridine calcium antagonist, administered once daily in the morning in a dose of 5, 10, or 15 mg on ambulatory blood pressure (BP) in 34 patients (51.3+/-9.6 years). Hypertension was diagnosed based on the clinic BP. The patients were classified into groups according to the ambulatory BP: group 1, dippers with true hypertension; group 2, nondippers with true hypertension; group 3, dippers with false hypertension; and Group 4, nondippers with false hypertension. Barnidipine reduced the clinic systolic BP (SBP) and diastolic BP (DBP) in all groups and significantly reduced the average 24 h ambulatory BP (133.0+/-16.5/90.7+/-12.3 mm Hg v 119.7+/-13.7/81.8+/-10.3 mm Hg, P < .0001 for both SBP and DBP). Barnidipine significantly reduced the daytime ambulatory SBP in groups 1, 2, and 3, but not in group 4, and significantly reduced daytime ambulatory DBP in group 1 but not in groups 2, 3, and 4. Barnidipine significantly reduced the nighttime ambulatory SBP only in group 2 and the nighttime ambulatory DBP in groups 2 and 4. Once-a-day administration of barnidipine influenced 24 h BP on true hypertensives (the ratio of the trough to peak effect > 50%), but had minimal effect on low BP such as the nocturnal BP in dippers and the ambulatory BP in false hypertensives. These findings suggest that barnidipine can be used safely in patients with isolated clinic ("white coat") hypertension and in those with dipping patterns of circadian BP variation whose nocturnal BP is low before treatment.

  9. Trajectory Reconstruction for the Genesis Entry

    NASA Technical Reports Server (NTRS)

    Desai, Prasun N.; Qualls, Garry D.; Schoenenberger, Mark

    2005-01-01

    An overview of the reconstruction analyses performed for the Genesis capsule entry is described. The results indicate that the actual entry prior to the drogue deployment failure was very close to the pre-entry predictions. The capsule landed 8.3 km south of the desired target at Utah Test and Training Range. Analysis on infrared video footage (obtained from the tracking stations) during the descent estimated the onset of the capsule tumble at Mach 0.9. Frequency analysis on the infrared video data indicates that the aerodynamics generated for the Genesis capsule reasonably predicted the drag and static stability. Observations of the heatshield support the pre-entry simulation estimates of a small hypersonic angles-of-attack, since there is very little, if any, charring of the shoulder region or the afterbody. Through this investigation, an overall assertion can be made that all the data gathered from the Genesis entry is consistent with flight performance close to the nominal pre-entry prediction. Consequently, the design principles and methodologies utilized for the flight dynamics, aerodynamics, and aerothermodynamics analyses have been corroborated.

  10. Shuttle entry guidance

    NASA Technical Reports Server (NTRS)

    Harpold, J. C.; Graves, C. A., Jr.

    1978-01-01

    This paper describes the design of the entry guidance for the Space Shuttle Orbiter. This guidance provides the steering commands for trajectory control from initial penetration of the earth's atmosphere until the terminal area guidance is activated at an earth-relative speed of 2500 fps. At this point, the Orbiter is at a distance of about 50 nmi from the runway threshold, and at an altitude of about 80,000 ft. The entry guidance design is based on an analytic solution of the equations of motion defining the drag acceleration profile that meets the terminal criteria of the entry flight while maintaining the flight within systems and operational constraints. Guidance commands, which are based on a control law that ensures damping of oscillatory type trajectory motion, are computed to steer the Orbiter to this drag acceleration profile.

  11. Orbiter entry aerothermodynamics

    NASA Technical Reports Server (NTRS)

    Ried, R. C.

    1985-01-01

    The challenge in the definition of the entry aerothermodynamic environment arising from the challenge of a reliable and reusable Orbiter is reviewed in light of the existing technology. Select problems pertinent to the orbiter development are discussed with reference to comprehensive treatments. These problems include boundary layer transition, leeward-side heating, shock/shock interaction scaling, tile gap heating, and nonequilibrium effects such as surface catalysis. Sample measurements obtained from test flights of the Orbiter are presented with comparison to preflight expectations. Numerical and wind tunnel simulations gave efficient information for defining the entry environment and an adequate level of preflight confidence. The high quality flight data provide an opportunity to refine the operational capability of the orbiter and serve as a benchmark both for the development of aerothermodynamic technology and for use in meeting future entry heating challenges.

  12. Mobile physician order entry.

    PubMed

    Ying, Alan

    2003-01-01

    Because both computerized physician order entry (CPOE) systems and mobile technologies such as handheld devices have the potential to greatly impact the industry's future, IT vendors, hospitals, and clinicians are simply merging them into a logical convergence--"CPOE on a handheld"--with an expectation of full functionality on all platforms: computer workstations, rolling laptops, tablet PCs, and handheld devices. For these trends to succeed together, however, this expectation must be revised to establish a distinct category--mobile physician order entry (MPOE)--that is different from CPOE in form, function, and implementation.

  13. Calcium in diet

    MedlinePlus

    ... of calcium dietary supplements include calcium citrate and calcium carbonate. Calcium citrate is the more expensive form of ... the body on a full or empty stomach. Calcium carbonate is less expensive. It is absorbed better by ...

  14. Atmospheric Entry Studies for Uranus

    NASA Technical Reports Server (NTRS)

    Agrawal, Parul; Allen, Gary A.; Hwang, Helen; Prabhu, Dinesh; Aliaga, Jose; Marley, Mark; McGuire, Kathy; Huynh, Loc; Garcia, Joseph; Moses, Robert; Winski, Rick; Skylanskiy, Evgeniy

    2013-01-01

    The Objectives of this work are: 1) Establish a range of probe atmospheric entry environments based on the Uranus Flagship mission outlined in the Planetary Science Decadal Survey for two launch windows: Year 2021 and 2034. 2) Define Uranus entry trade space by performing parametric studies, by varying vehicle mass and size and entry Flight Path Angle (FPA). 3) Investigate various trajectory options, including direct ballistic entry and aero-capture entry. 4) Identify entry technologies that could be leveraged to enable a viable mission to Uranus that meets science objectives.

  15. Think Exit at Entry

    ERIC Educational Resources Information Center

    O'Rourke, Tom; Satterfield, Coy E.

    2005-01-01

    This paper describes the "Think Exit at Entry" program that has become the guiding principle for the Georgia Department of Juvenile Justice (DJJ). The Georgia DJJ believes that the transition process begins the day the youth enters the system and continues well after release from the institution. Literature points the need for transition…

  16. Calcium - ionized

    MedlinePlus

    ... 245. Read More Acute kidney failure Albumin - blood (serum) test Bone tumor Calcium blood test Hyperparathyroidism Hypoparathyroidism Malabsorption Milk-alkali syndrome Multiple myeloma Osteomalacia Paget disease of the bone Rickets Sarcoidosis Vitamin D Review ...

  17. 9. FIRST FLOOR, ENTRY HALL, LOOKING SOUTHWEST TOWARDS FRONT ENTRY ...

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

    9. FIRST FLOOR, ENTRY HALL, LOOKING SOUTHWEST TOWARDS FRONT ENTRY WITH OPEN DOORWAY TO WINDER STAIRWAY ON RIGHT - Open Gate Farm, House, Ridge Road, 1 mile East of Elephant Road, Perkasie, Bucks County, PA

  18. Calcium Carbonate.

    PubMed

    Al Omari, M M H; Rashid, I S; Qinna, N A; Jaber, A M; Badwan, A A

    2016-01-01

    Calcium carbonate is a chemical compound with the formula CaCO3 formed by three main elements: carbon, oxygen, and calcium. It is a common substance found in rocks in all parts of the world (most notably as limestone), and is the main component of shells of marine organisms, snails, coal balls, pearls, and eggshells. CaCO3 exists in different polymorphs, each with specific stability that depends on a diversity of variables.

  19. Calcium Hydroxylapatite

    PubMed Central

    Yutskovskaya, Yana Alexandrovna; Philip Werschler, WM.

    2015-01-01

    Background: Calcium hydroxylapatite is one of the most well-studied dermal fillers worldwide and has been extensively used for the correction of moderate-to-severe facial lines and folds and to replenish lost volume. Objectives: To mark the milestone of 10 years of use in the aesthetic field, this review will consider the evolution of calcium hydroxylapatite in aesthetic medicine, provide a detailed injection protocol for a global facial approach, and examine how the unique properties of calcium hydroxylapatite provide it with an important place in today’s market. Methods: This article is an up-to-date review of calcium hydroxylapatite in aesthetic medicine along with procedures for its use, including a detailed injection protocol for a global facial approach by three expert injectors. Conclusion: Calcium hydroxylapatite is a very effective agent for many areas of facial soft tissue augmentation and is associated with a high and well-established safety profile. Calcium hydroxylapatite combines high elasticity and viscosity with an ability to induce long-term collagen formation making it an ideal agent for a global facial approach. PMID:25610523

  20. Calcium orthophosphates

    PubMed Central

    Dorozhkin, Sergey V.

    2011-01-01

    The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates. This type of materials is of special significance for human beings, because they represent the inorganic part of major normal (bones, teeth and antlers) and pathological (i.e., those appearing due to various diseases) calcified tissues of mammals. For example, atherosclerosis results in blood vessel blockage caused by a solid composite of cholesterol with calcium orthophosphates, while dental caries and osteoporosis mean a partial decalcification of teeth and bones, respectively, that results in replacement of a less soluble and harder biological apatite by more soluble and softer calcium hydrogenphosphates. Therefore, the processes of both normal and pathological calcifications are just an in vivo crystallization of calcium orthophosphates. Similarly, dental caries and osteoporosis might be considered an in vivo dissolution of calcium orthophosphates. Thus, calcium orthophosphates hold a great significance for humankind, and in this paper, an overview on the current knowledge on this subject is provided. PMID:23507744

  1. Calcium signalling and calcium channels: Evolution and general principles

    PubMed Central

    Verkhratsky, Alexei; Parpura, Vladimir

    2014-01-01

    Calcium as a divalent ion was selected early in evolution as a signaling molecule to be used by both prokaryotes and eukaryotes. Its low cytosolic concentration likely reflects the initial concentration of this ion in the primordial soup/ocean as unicellular organisms were formed. As the concentration of calcium in the ocean subsequently increased, so did the diversity of homeostatic molecules. This includes the plasma membrane channels that allowed the calcium entry, as well as extrusion mechanisms, i.e., exchangers and pumps. Further diversification occurred with the evolution of intracellular organelles, in particular the endoplasmic reticulum and mitochondria, which also contain channels, exchanger(s) and pumps to handle the homeostasis of calcium ions. Calcium signalling system, based around coordinated interactions of the above molecular entities, can be activated by the opening of voltage-gated channels, by neurotransmitters, by second messengers and/or mechanical stimulation, and as such is all-pervading pathway in physiology and pathophysiology of organisms. PMID:24291103

  2. DLMS Voice Data Entry.

    DTIC Science & Technology

    1980-06-01

    RUN program features a syntactic structure based upon a group of subroutines to perform a group of functions involved in data entry for the DLMS...Code # 120 AGRICULTURAL 430 10 HOSPITAL GABLE 632 121 STOCKYARD 433 151 OBSERVATORY .640 122 WIND I LL 434 152 OBSERVATORY DOME 641 123 CEMETARY BLGS ...associated with each word or group of words. To illustrate the procedure to be followed with the CREATE program, an example is in order. In this example

  3. The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp.

    PubMed

    Lourido, Sebastian; Moreno, Silvia N J

    2015-03-01

    Apicomplexan parasites have complex life cycles, frequently split between different hosts and reliant on rapid responses as the parasites react to changing environmental conditions. Calcium ion (Ca(2+)) signaling is consequently essential for the cellular and developmental changes that support Apicomplexan parasitism. Apicomplexan genomes reveal a rich repertoire of genes involved in calcium signaling, although many of the genes responsible for observed physiological changes remain unknown. There is evidence, for example, for the presence of a nifedipine-sensitive calcium entry mechanism in Toxoplasma, but the molecular components involved in Ca(2+) entry in both Toxoplasma and Plasmodium, have not been identified. The major calcium stores are the endoplasmic reticulum (ER), the acidocalcisomes, and the plant-like vacuole in Toxoplasma, or the food vacuole in Plasmodium spp. Pharmacological evidence suggests that Ca(2+) release from intracellular stores may be mediated by inositol 1,4,5-trisphosphate (IP3) or cyclic ADP ribose (cADPR) although there is no molecular evidence for the presence of receptors for these second messengers in the parasites. Several Ca(2+)-ATPases are present in Apicomplexans and a putative mitochondrial Ca(2+)/H(+) exchanger has been identified. Apicomplexan genomes contain numerous genes encoding Ca(2+)-binding proteins, with the notable expansion of calcium-dependent protein kinases (CDPKs), whose study has revealed roles in gliding motility, microneme secretion, host cell invasion and egress, and parasite differentiation. Microneme secretion has also been shown to depend on the C2 domain containing protein DOC2 in both Plasmodium spp. and Toxoplasma, providing further evidence for the complex transduction of Ca(2+) signals in these organisms. The characterization of these pathways could lead to the discovery of novel drug targets and to a better understanding of the role of Ca(2+) in these parasites.

  4. Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆

    PubMed Central

    Gómez-Sánchez, Rubén; Gegg, Matthew E.; Bravo-San Pedro, José M.; Niso-Santano, Mireia; Alvarez-Erviti, Lydia; Pizarro-Estrella, Elisa; Gutiérrez-Martín, Yolanda; Alvarez-Barrientos, Alberto; Fuentes, José M.; González-Polo, Rosa Ana; Schapira, Anthony H.V.

    2014-01-01

    Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24 h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3 h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection. PMID:24184327

  5. Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression.

    PubMed

    Gómez-Sánchez, Rubén; Gegg, Matthew E; Bravo-San Pedro, José M; Niso-Santano, Mireia; Alvarez-Erviti, Lydia; Pizarro-Estrella, Elisa; Gutiérrez-Martín, Yolanda; Alvarez-Barrientos, Alberto; Fuentes, José M; González-Polo, Rosa Ana; Schapira, Anthony H V

    2014-02-01

    Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection.

  6. Computational study of a calcium release-activated calcium channel

    NASA Astrophysics Data System (ADS)

    Talukdar, Keka; Shantappa, Anil

    2016-05-01

    The naturally occurring proteins that form hole in membrane are commonly known as ion channels. They play multiple roles in many important biological processes. Deletion or alteration of these channels often leads to serious problems in the physiological processes as it controls the flow of ions through it. The proper maintenance of the flow of ions, in turn, is required for normal health. Here we have investigated the behavior of a calcium release-activated calcium ion channel with pdb entry 4HKR in Drosophila Melanogaster. The equilibrium energy as well as molecular dynamics simulation is performed first. The protein is subjected to molecular dynamics simulation to find their energy minimized value. Simulation of the protein in the environment of water and ions has given us important results too. The solvation energy is also found using Charmm potential.

  7. Calcium Test

    MedlinePlus

    ... if a person has symptoms of a parathyroid disorder , malabsorption , or an overactive thyroid. A total calcium level is often measured as part of a routine health screening. It is included in the comprehensive metabolic panel (CMP) and the basic metabolic panel (BMP) , ...

  8. Calcium cyanide

    Integrated Risk Information System (IRIS)

    Jump to main content . Integrated Risk Information System Recent Additions | Contact Us Search : All EPA IRIS • You are here : EPA Home • Research • Environmental Assessment • IRIS • IRIS Summaries Redirect Page As of September 28 , 2010 , the assessment summary for calcium cyanide is included in th

  9. Orion Entry Flight Control Stability and Performance

    NASA Technical Reports Server (NTRS)

    Strahan, Alan L.; Loe, Greg R.; Seiler, Pete

    2007-01-01

    The Orion Spacecraft will be required to perform entry and landing functions for both Low Earth Orbit (LEO) and Lunar return missions, utilizing only the Command Module (CM) with its unique systems and GN&C design. This paper presents the current CM Flight Control System (FCS) design to support entry and landing, with a focus on analyses that have supported its development to date. The CM FCS will have to provide for spacecraft stability and control while following guidance or manual commands during exo-atmospheric flight, after Service Module separation, translational powered flight required of the CM, atmospheric flight supporting both direct entry and skip trajectories down to drogue chute deploy, and during roll attitude reorientation just prior to touchdown. Various studies and analyses have been performed or are on-going supporting an overall FCS design with reasonably sized Reaction Control System (RCS) jets, that minimizes fuel usage, that provides appropriate command following but with reasonable stability and control margin. Results from these efforts to date are included, with particular attention on design issues that have emerged, such as the struggle to accommodate sub-sonic pitch and yaw control without using excessively large jets that could have a detrimental impact on vehicle weight. Apollo, with a similar shape, struggled with this issue as well. Outstanding CM FCS related design and analysis issues, planned for future effort, are also briefly be discussed.

  10. Entry Systems Panel

    NASA Technical Reports Server (NTRS)

    Rasky, Daniel J.; Rummler, Donald R.; Bersch, Charlie; Dixon, Sidney C.

    1993-01-01

    As general findings, lessons learned from shuttle are: (1) bridge established between development center (JSC) Research Centers (ARC, LARC), and industry (RI, LMSC, Corning, Mansville, 3M LTV, Union Carbide, Hexcel) for shuttle TPS; (2) not all test results adequately analyzed or in hindsight, completely encompassing all failure modes; (3) gap heating effects from ground facilities not totally indicative of flight experience; (4) need to design with operations in mind (not just to cost) example: moisture intrusion of GR/EP, many other examples; (5) RSI- developed as point design for maneuvering entry vehicle of high L/D; and (6) RSI - 15 years from invention to use on flight hardware.

  11. Planetary entry experiments

    NASA Technical Reports Server (NTRS)

    Craig, Roger A.

    1994-01-01

    The final report summarizes the results from three research areas: (1) window design for the radiometric measurement of the forebody radiative heating experienced by atmospheric entry spaceraft; (2) survey of the current understanding of chemical species on selected solar system bodies and assess the importance of measurements with regard to vehicle environment and with regard to understanding of planetary atmospheres with emphasis on Venus, Mars, and Titan; and (3) measure and analyze the radiation (VUV to near-IR) from the shock heated gas cap of a blunt body in an Ames arc Jet wind-tunnel facility.

  12. Entry guidance and entry autopilot (STS-1 baseline)

    NASA Astrophysics Data System (ADS)

    Harpold, J. C.; Hill, O.

    1980-08-01

    Preliminary entry guidance and autopilot software formulations, for use in the Mission Control Center (MCC) entry processor, are presented. The MCC requirements are met by a definition of coordinate systems, a list of parameter definitions for the software formulations, a description of the entry guidance detailed formulation requirements, a description of the detailed autopilot formualtion requirements, a description of the targeting routine, and a set of formulation flow charts.

  13. Entry guidance and entry autopilot (STS-1 baseline)

    NASA Technical Reports Server (NTRS)

    Harpold, J. C.; Hill, O.

    1980-01-01

    Preliminary entry guidance and autopilot software formulations, for use in the Mission Control Center (MCC) entry processor, are presented. The MCC requirements are met by a definition of coordinate systems, a list of parameter definitions for the software formulations, a description of the entry guidance detailed formulation requirements, a description of the detailed autopilot formualtion requirements, a description of the targeting routine, and a set of formulation flow charts.

  14. Market entry decisions: effects of absolute and relative confidence.

    PubMed

    Bolger, Fergus; Pulford, Briony D; Colman, Andrew M

    2008-01-01

    In a market entry game, the number of entrants usually approaches game-theoretic equilibrium quickly, but in real-world markets business start-ups typically exceed market capacity, resulting in chronically high failure rates and suboptimal industry profits. Excessive entry has been attributed to overconfidence arising when expected payoffs depend partly on skill. In an experimental test of this hypothesis, 96 participants played 24 rounds of a market entry game, with expected payoffs dependent partly on skill on half the rounds, after their confidence was manipulated and measured. The results provide direct support for the hypothesis that high levels of confidence are largely responsible for excessive entry, and they suggest that absolute confidence, independent of interpersonal comparison, rather than confidence about one's abilities relative to others, drives excessive entry decisions when skill is involved.

  15. Regulation of voltage gated calcium channels by GPCRs and post-translational modification.

    PubMed

    Huang, Junting; Zamponi, Gerald W

    2016-10-18

    Calcium entry via voltage gated calcium channels mediates a wide range of physiological functions, whereas calcium channel dysregulation has been associated with numerous pathophysiological conditions. There are myriad cell signaling pathways that act on voltage gated calcium channels to fine tune their activities and to regulate their cell surface expression. These regulatory mechanisms include the activation of G protein-coupled receptors and downstream phosphorylation events, and their control over calcium channel trafficking through direct physical interactions. Calcium channels also undergo post-translational modifications that alter both function and density of the channels in the plasma membrane. Here we focus on select aspects of these regulatory mechanisms and highlight recent developments.

  16. Shuttle Entry Imaging Using Infrared Thermography

    NASA Technical Reports Server (NTRS)

    Horvath, Thomas; Berry, Scott; Alter, Stephen; Blanchard, Robert; Schwartz, Richard; Ross, Martin; Tack, Steve

    2007-01-01

    During the Columbia Accident Investigation, imaging teams supporting debris shedding analysis were hampered by poor entry image quality and the general lack of information on optical signatures associated with a nominal Shuttle entry. After the accident, recommendations were made to NASA management to develop and maintain a state-of-the-art imagery database for Shuttle engineering performance assessments and to improve entry imaging capability to support anomaly and contingency analysis during a mission. As a result, the Space Shuttle Program sponsored an observation campaign to qualitatively characterize a nominal Shuttle entry over the widest possible Mach number range. The initial objectives focused on an assessment of capability to identify/resolve debris liberated from the Shuttle during entry, characterization of potential anomalous events associated with RCS jet firings and unusual phenomenon associated with the plasma trail. The aeroheating technical community viewed the Space Shuttle Program sponsored activity as an opportunity to influence the observation objectives and incrementally demonstrate key elements of a quantitative spatially resolved temperature measurement capability over a series of flights. One long-term desire of the Shuttle engineering community is to calibrate boundary layer transition prediction methodologies that are presently part of the Shuttle damage assessment process using flight data provided by a controlled Shuttle flight experiment. Quantitative global imaging may offer a complementary method of data collection to more traditional methods such as surface thermocouples. This paper reviews the process used by the engineering community to influence data collection methods and analysis of global infrared images of the Shuttle obtained during hypersonic entry. Emphasis is placed upon airborne imaging assets sponsored by the Shuttle program during Return to Flight. Visual and IR entry imagery were obtained with available airborne

  17. Cannabinoid Receptor Activation Modifies NMDA Receptor Mediated Release of Intracellular Calcium: Implications for Endocannabinoid Control of Hippocampal Neural Plasticity

    PubMed Central

    Hampson, Robert E.; Miller, Frances; Palchik, Guillermo; Deadwyler, Sam A.

    2011-01-01

    Chronic activation or inhibition of cannabinoid receptors (CB1) leads to continuous suppression of neuronal plasticity in hippocampus and other brain regions, suggesting that endocannabinoids may have a functional role in synaptic processes that produce state-dependent transient modulation of hippocampal cell activity. In support of this, it has previously been shown in vitro that cannabinoid CB1 receptors modulate second messenger systems in hippocampal neurons that can modulate intracellular ion channels, including channels which release calcium from intracellular stores. Here we demonstrate in hippocampal slices a similar endocannabinoid action on excitatory glutamatergic synapses via modulation of NMDA-receptor mediated intracellular calcium levels in confocal imaged neurons. Calcium entry through glutamatergic NMDA-mediated ion channels increases intracellular calcium concentrations via modulation of release from ryanodine-sensitive channels in endoplasmic reticulum. The studies reported here show that NMDA-elicited increases in Calcium Green fluorescence are enhanced by CB1 receptor antagonists (i.e. rimonabant), and inhibited by CB1 agonists (i.e. WIN 55,212-2). Suppression of endocannabinoid breakdown by either reuptake inhibition (AM404) or fatty-acid amide hydrolase inhibition (URB597) produced suppression of NMDA elicited calcium increases comparable to WIN 55,212-2, while enhancement of calcium release provoked by endocannabinoid receptor antagonists (Rimonabant) was shown to depend on the blockade of CB1 receptor mediated de-phosphorylation of Ryanodine receptors. Such CB1 receptor modulation of NMDA elicited increases in intracellular calcium may account for the respective disruption and enhancement by CB1 agents of trial-specific hippocampal neuron ensemble firing patterns during performance of a short-term memory task, reported previously from this laboratory. PMID:21288475

  18. Advertising and generic market entry.

    PubMed

    Königbauer, Ingrid

    2007-03-01

    The effect of purely persuasive advertising on generic market entry and social welfare is analysed. An incumbent has the possibility to invest in advertising which affects the prescribing physician's perceived relative qualities of the brand-name and the generic version of the drug. Advertising creates product differentiation and can induce generic market entry which is deterred without differentiation due to strong Bertrand competition. However, over-investment in advertising can deter generic market entry under certain conditions and reduces welfare as compared to accommodated market entry.

  19. Membrane fusion during poxvirus entry.

    PubMed

    Moss, Bernard

    2016-12-01

    Poxviruses comprise a large family of enveloped DNA viruses that infect vertebrates and invertebrates. Poxviruses, unlike most DNA viruses, replicate in the cytoplasm and encode enzymes and other proteins that enable entry, gene expression, genome replication, virion assembly and resistance to host defenses. Entry of vaccinia virus, the prototype member of the family, can occur at the plasma membrane or following endocytosis. Whereas many viruses encode one or two proteins for attachment and membrane fusion, vaccinia virus encodes four proteins for attachment and eleven more for membrane fusion and core entry. The entry-fusion proteins are conserved in all poxviruses and form a complex, known as the Entry Fusion Complex (EFC), which is embedded in the membrane of the mature virion. An additional membrane that encloses the mature virion and is discarded prior to entry is present on an extracellular form of the virus. The EFC is held together by multiple interactions that depend on nine of the eleven proteins. The entry process can be divided into attachment, hemifusion and core entry. All eleven EFC proteins are required for core entry and at least eight for hemifusion. To mediate fusion the virus particle is activated by low pH, which removes one or more fusion repressors that interact with EFC components. Additional EFC-interacting fusion repressors insert into cell membranes and prevent secondary infection. The absence of detailed structural information, except for two attachment proteins and one EFC protein, is delaying efforts to determine the fusion mechanism.

  20. Calcium and bone disease

    PubMed Central

    Blair, Harry C.; Robinson, Lisa J.; Huang, Christopher L.-H.; Sun, Li; Friedman, Peter A.; Schlesinger, Paul H.; Zaidi, Mone

    2013-01-01

    Calcium transport and calcium signaling are of basic importance in bone cells. Bone is the major store of calcium and a key regulatory organ for calcium homeostasis. Bone, in major part, responds to calcium-dependent signals from the parathyroids and via vitamin D metabolites, although bone retains direct response to extracellular calcium if parathyroid regulation is lost. Improved understanding of calcium transporters and calcium-regulated cellular processes has resulted from analysis of genetic defects, including several defects with low or high bone mass. Osteoblasts deposit calcium by mechanisms including phosphate and calcium transport with alkalinization to absorb acid created by mineral deposition; cartilage calcium mineralization occurs by passive diffusion and phosphate production. Calcium mobilization by osteoclasts is mediated by acid secretion. Both bone forming and bone resorbing cells use calcium signals as regulators of differentiation and activity. This has been studied in more detail in osteoclasts, where both osteoclast differentiation and motility are regulated by calcium. PMID:21674636

  1. Presynaptic calcium currents in squid giant synapse.

    PubMed Central

    Llinás, R; Steinberg, I Z; Walton, K

    1981-01-01

    A voltage clamp study has been performed in the presynaptic terminal of the squid stellate ganglion. After blockage of the voltage-dependent sodium and potassium conductances, an inward calcium current is demonstrated. Given a step-depolarization pulse, this voltage- and time-dependent conductance has an S-shaped onset. At the "break" of the voltage step, a rapid tail current is observed. From these results a kinetic model is generated which accounts for the experimental results and predicts for the time course and amplitude a possible calcium entry during presynaptic action potentials. Images FIGURE 1 PMID:7225510

  2. Water Entry of Projectiles

    NASA Astrophysics Data System (ADS)

    Truscott, Tadd T.; Epps, Brenden P.; Belden, Jesse

    2014-01-01

    The free-surface impact of solid objects has been investigated for well over a century. This canonical problem is influenced by many physical parameters, including projectile geometry, material properties, fluid properties, and impact parameters. Through advances in high-speed imaging and visualization techniques, discoveries about the underlying physics have improved our understanding of these phenomena. Improvements to analytical and numerical models have led to critical insights into cavity formation, the depth and time of pinch-off, forces, and trajectories for myriad different impact parameters. This topic spans a wide range of regimes, from low-speed entry phenomena dominated by surface tension to high-speed ballistics, for which cavitation is important. This review surveys experimental, theoretical, and numerical studies over this broad range, utilizing canonical images where possible to enhance intuition and insight into the rich phenomena.

  3. Shuttle entry guidance revisited

    NASA Astrophysics Data System (ADS)

    Mease, Kenneth D.; Kremer, Jean-Paul

    1992-08-01

    The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

  4. Shuttle entry guidance revisited

    NASA Technical Reports Server (NTRS)

    Mease, Kenneth D.; Kremer, Jean-Paul

    1992-01-01

    The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

  5. Proteolytic maturation of α2δ represents a checkpoint for activation and neuronal trafficking of latent calcium channels

    PubMed Central

    Kadurin, Ivan; Ferron, Laurent; Rothwell, Simon W; Meyer, James O; Douglas, Leon R; Bauer, Claudia S; Lana, Beatrice; Margas, Wojciech; Alexopoulos, Orpheas; Nieto-Rostro, Manuela; Pratt, Wendy S; Dolphin, Annette C

    2016-01-01

    The auxiliary α2δ subunits of voltage-gated calcium channels are extracellular membrane-associated proteins, which are post-translationally cleaved into disulfide-linked polypeptides α2 and δ. We now show, using α2δ constructs containing artificial cleavage sites, that this processing is an essential step permitting voltage-dependent activation of plasma membrane N-type (CaV2.2) calcium channels. Indeed, uncleaved α2δ inhibits native calcium currents in mammalian neurons. By inducing acute cell-surface proteolytic cleavage of α2δ, voltage-dependent activation of channels is promoted, independent from the trafficking role of α2δ. Uncleaved α2δ does not support trafficking of CaV2.2 channel complexes into neuronal processes, and inhibits Ca2+ entry into synaptic boutons, and we can reverse this by controlled intracellular proteolytic cleavage. We propose a model whereby uncleaved α2δ subunits maintain immature calcium channels in an inhibited state. Proteolytic processing of α2δ then permits voltage-dependent activation of the channels, acting as a checkpoint allowing trafficking only of mature calcium channel complexes into neuronal processes. DOI: http://dx.doi.org/10.7554/eLife.21143.001 PMID:27782881

  6. L-Type Calcium Channels Are Required for One Form of Hippocampal Mossy Fiber LTP

    PubMed Central

    Kapur, Ajay; Yeckel, Mark F.; Gray, Richard; Johnston, Daniel

    2010-01-01

    The requirement of postsynaptic calcium influx via L-type channels for the induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal neurons was tested for two different patterns of stimulation. Two types of LTP-inducing stimuli were used based on the suggestion that one of them, brief high-frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons is necessary for LTP induced by either pattern of stimulation, nimodipine, a L-type calcium channel antagonist, was added during stimulation. In these experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was given [34 ± 5% (mean ± SE) increase in control versus 7 ± 4% in nimodipine, P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS (107 ± 10% in control vs. 80 ± 9% in nimodipine, P > 0.05). Administration of nimodipine after the induction of LTP had no effect on the expression of LTP. In addition, B- and L-HFS delivered directly to commissural/ associational fibers in stratum radiatum failed to induce a N-methyl-d-aspartate-independent form of LTP, obviating the possibility that the presumed mossy fiber LTP resulted from potentiation of other synapses. Nimodipine had no effect on calcium transients recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm but reduced postsynaptic calcium transients. Our results support the hypothesis that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and requires entry of calcium through L-type channels into CA3 neurons. PMID:9535977

  7. 19 CFR 10.31 - Entry; bond.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... not over $250, the form prescribed for the informal entry of importations by mail, in baggage, or by... consumption entry summary, each temporary importation bond entry summary shall include: (i) The HTSUS... consumption entry on the date of the original arrival. (d) (e) The entry or invoice shall: (1) Describe...

  8. Orion Entry, Descent, and Landing Simulation

    NASA Technical Reports Server (NTRS)

    Hoelscher, Brian R.

    2007-01-01

    The Orion Entry, Descent, and Landing simulation was created over the past two years to serve as the primary Crew Exploration Vehicle guidance, navigation, and control (GN&C) design and analysis tool at the National Aeronautics and Space Administration (NASA). The Advanced NASA Technology Architecture for Exploration Studies (ANTARES) simulation is a six degree-of-freedom tool with a unique design architecture which has a high level of flexibility. This paper describes the decision history and motivations that guided the creation of this simulation tool. The capabilities of the models within ANTARES are presented in detail. Special attention is given to features of the highly flexible GN&C architecture and the details of the implemented GN&C algorithms. ANTARES provides a foundation simulation for the Orion Project that has already been successfully used for requirements analysis, system definition analysis, and preliminary GN&C design analysis. ANTARES will find useful application in engineering analysis, mission operations, crew training, avionics-in-the-loop testing, etc. This paper focuses on the entry simulation aspect of ANTARES, which is part of a bigger simulation package supporting the entire mission profile of the Orion vehicle. The unique aspects of entry GN&C design are covered, including how the simulation is being used for Monte Carlo dispersion analysis and for support of linear stability analysis. Sample simulation output from ANTARES is presented in an appendix.

  9. Calcium and Vitamin D

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calcium is required for the bone formation phase of bone remodeling. Typically about 5 nmol (200 mg) of calcium is removed from the adult skeleton and replaced each day. To supply this amount, one would need to consume about 600 mg of calcium, since calcium is not very efficiently absorbed. Calcium ...

  10. Calcium-dependent inactivation of the dihydropyridine-sensitive calcium channels in GH3 cells

    PubMed Central

    1988-01-01

    The inactivation of calcium channels in mammalian pituitary tumor cells (GH3) was studied with patch electrodes under voltage clamp in cell- free membrane patches and in dialyzed cells. The calcium current elicited by depolarization from a holding potential of -40 mV passed predominantly through one class of channels previously shown to be modulated by dihydropyridines and cAMP-dependent phosphorylation (Armstrong and Eckert, 1987). When exogenous calcium buffers were omitted from the pipette solution, the macroscopic calcium current through those channels inactivated with a half time of approximately 10 ms to a steady state level 40-75% smaller than the peak. Inactivation was also measured as the reduction in peak current during a test pulse that closely followed a prepulse. Inactivation was largely reduced or eliminated by (a) buffering free calcium in the pipette solution to less than 10(-8) M; (b) replacing extracellular calcium with barium; (c) increasing the prepulse voltage from +10 to +60 mV; or (d) increasing the intracellular concentration of cAMP, either 'directly' with dibutyryl-cAMP or indirectly by activating adenylate cyclase with forskolin or vasoactive intestinal peptide. Thus, inactivation of the dihydropyridine-sensitive calcium channels in GH3 cells only occurs when membrane depolarization leads to calcium ion entry and intracellular accumulation. PMID:2849631

  11. Tactile Data Entry for Extravehicular Activity

    NASA Technical Reports Server (NTRS)

    Adams, Richard J.; Olowin, Aaron B.; Hannaford, Blake; Sands, O Scott

    2012-01-01

    In the task-saturated environment of extravehicular activity (EVA), an astronaut's ability to leverage suit-integrated information systems is limited by a lack of options for data entry. In particular, bulky gloves inhibit the ability to interact with standard computing interfaces such as a mouse or keyboard. This paper presents the results of a preliminary investigation into a system that permits the space suit gloves themselves to be used as data entry devices. Hand motion tracking is combined with simple finger gesture recognition to enable use of a virtual keyboard, while tactile feedback provides touch-based context to the graphical user interface (GUI) and positive confirmation of keystroke events. In human subject trials, conducted with twenty participants using a prototype system, participants entered text significantly faster with tactile feedback than without (p = 0.02). The results support incorporation of vibrotactile information in a future system that will enable full touch typing and general mouse interactions using instrumented EVA gloves.

  12. Cell entry of hepatitis C virus

    SciTech Connect

    Bartosch, Birke . E-mail: Birke.Bartosch@ens-lyon.fr; Cosset, Francois-Loic . E-mail: Francois-Loic.Cosset@ens-lyon.fr

    2006-04-25

    Hepatitis C virus (HCV), an important human pathogen, is an enveloped, positive-stranded RNA virus classified in the hepacivirus genus of the Flaviviridae family. Cell attachment of flaviviruses generally leads to endocytosis of bound virions. Systems that support HCV replication and particle formation in vitro are emerging only now, 16 years after the discovery of the virus. Albeit this limitation, the route of HCV cell entry as well as 'capture' molecules involved in low-affinity interactions for the initial contact of HCV with target cells and potential high-affinity receptor candidates that may mediate HCV trafficking and fusion has been described. The objective of this review is to summarize the contribution of different HCV model systems to our current knowledge about structure of the HCV GPs E1 and E2 and their roles in cell entry comprising cell attachment, interactions with cellular receptors, endocytosis, and fusion.

  13. NASA CEV Reference Entry GN&C System and Analysis

    NASA Technical Reports Server (NTRS)

    Munday, S.; Madsen, C.; Broome, J.; Gay, R.; Tigges, M.; Strahan, A.

    2007-01-01

    As part of its overall objectives, the Orion spacecraft will be required to perform entry and Earth landing functions for Low Earth Orbit (LEO) and Lunar missions. Both of these entry scenarios will begin with separation of the Service Module (SM), making them unique from other Orion mission phases in that only the Command Module (CM) portion of the Crew Exploration Vehicle (CEV) will be involved, requiring a CM specific Guidance, Navigation and Control (GN&C) system. Also common to these mission scenarios will be the need for GN&C to safely return crew (or cargo) to earth within the dynamic thermal and structural constraints of entry and within acceptable accelerations on the crew, utilizing the limited aerodynamic performance of the CM capsule. The lunar return mission could additionally require an initial atmospheric entry designed to support a precision skip and second entry, all to maximize downrange performance and ensure landing in the United States. This paper describes the Entry GN&C reference design, developed by the NASA-led team, that supports these entry scenarios and that was used to validate the Orion System requirements. Description of the reference design will include an overview of the GN&C functions, avionics, and effectors and will relate these to the specific design drivers of the entry scenarios, as well as the desire for commonality in vehicle systems to support the different missions. The discussion will also include the requirement for an Emergency Entry capability beyond that of the nominal performance of the multi-string GNC system, intended to return the crew to the earth in a survivable but unguided manner. Finally, various analyses will be discussed, including those completed to support validation efforts of the current CEV requirements, along with those on-going and planned with the intention to further refine the requirements and to support design development work in conjunction with the prime contractor. Some of these ongoing

  14. 19 CFR 142.17 - One entry summary for multiple entries.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false One entry summary for multiple entries. 142.17...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.17 One entry summary for multiple entries. (a) Requirements. Except as provided in paragraph (b) of this section, the...

  15. 19 CFR 142.17 - One entry summary for multiple entries.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false One entry summary for multiple entries. 142.17...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.17 One entry summary for multiple entries. (a) Requirements. Except as provided in paragraph (b) of this section, the...

  16. 19 CFR 142.17 - One entry summary for multiple entries.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false One entry summary for multiple entries. 142.17...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.17 One entry summary for multiple entries. (a) Requirements. Except as provided in paragraph (b) of this section, the...

  17. 19 CFR 142.17 - One entry summary for multiple entries.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false One entry summary for multiple entries. 142.17...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.17 One entry summary for multiple entries. (a) Requirements. Except as provided in paragraph (b) of this section, the...

  18. Calcium and Vitamin D

    MedlinePlus

    ... A calcium-rich diet (including dairy, nuts, leafy greens and fish) helps to build and protect your ... yogurt and cheese are high in calcium. Certain green vegetables and other foods contain calcium in smaller ...

  19. Coronary Calcium Scan

    MedlinePlus

    ... Scan Coronary Calcium Scan Related Topics Angina Atherosclerosis Coronary Heart Disease Electrocardiogram Heart Attack Send a link to NHLBI ... calcium, or calcifications, are a sign of atherosclerosis, coronary heart disease, or coronary microvascular disease. A coronary calcium scan ...

  20. GOCE Re-Entry Campaign

    NASA Astrophysics Data System (ADS)

    Bastida, B.; Flohrer, T.; Lemmens, S.; Krag, H.

    2015-03-01

    Every year ESA, through the Space Debris Office, participates to an Inter-Agency Space Debris Coordination Committee (IADC) Re-entry Test Campaign.. For the campaign of 2013, ESA’s proposal to select GOCE's re-entry was accepted. The campaign opened on the 21st October 2013 after fuel depletion of the drag-compensating ion propulsion. GOCE was expected to enter into a phase of attitude-controlled fine-pointing mode (FPM) until the attitude controllers would be unable to cope with the atmospheric torques and then the satellite would enter in a phase of fully uncontrolled flight. In this paper, we present the evolution of ESA’s daily predictions on the re-entry epoch using different sources of orbital information. The uncertainties on the spacecraft operability (i.e. the physical limits of the attitude controller) led to a non-standard re-entry scenario were different attitudes had to be considered (instead of the commonly assumed random tumbling mode case that is used whenever no information on the physical properties of a re-entering object is available). A daily assessment of the status, in coordination with the flight control team, was required and implied a continuous update on the predicted failure point of the attitude controller. This in turn imposed the need for considering an asymmetric re-entry window. These operation-bound uncertainties were simulated to predict the attitude evolution after failure at different altitudes and their effects evaluated to be taken into account for the re-entry predictions. We present ESA’s re-entry prediction activities for GOCE, internally, and within the IADC, and address specific technical aspects and challenges for re-entry predictions, which are related to the expected and occurred attitude of GOCE during the final re-entry phase.

  1. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease.

    PubMed

    Hill, Kathleen M; Martin, Berdine R; Wastney, Meryl E; McCabe, George P; Moe, Sharon M; Weaver, Connie M; Peacock, Munro

    2013-05-01

    Patients with chronic kidney disease (CKD) are given calcium carbonate to bind dietary phosphorus, reduce phosphorus retention, and prevent negative calcium balance; however, data are limited on calcium and phosphorus balance during CKD to support this. Here, we studied eight patients with stage 3 or 4 CKD (mean estimated glomerular filtration rate 36 ml/min) who received a controlled diet with or without a calcium carbonate supplement (1500 mg/day calcium) during two 3-week balance periods in a randomized placebo-controlled cross-over design. All feces and urine were collected during weeks 2 and 3 of each balance period and fasting blood, and urine was collected at baseline and at the end of each week. Calcium kinetics were determined using oral and intravenous (45)calcium. Patients were found to be in neutral calcium and phosphorus balance while on the placebo. Calcium carbonate supplementation produced positive calcium balance, did not affect phosphorus balance, and produced only a modest reduction in urine phosphorus excretion compared with placebo. Calcium kinetics demonstrated positive net bone balance but less than overall calcium balance, suggesting soft-tissue deposition. Fasting blood and urine biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate. Thus, the positive calcium balance produced by calcium carbonate treatment within 3 weeks cautions against its use as a phosphate binder in patients with stage 3 or 4 CKD, if these findings can be extrapolated to long-term therapy.

  2. ESA Venus Entry Probe Study

    NASA Technical Reports Server (NTRS)

    vandenBerg, M. L.; Falkner, P.; Phipps, A.; Underwood, J. C.; Lingard, J. S.; Moorhouse, J.; Kraft, S.; Peacock, A.

    2005-01-01

    The Venus Entry Probe is one of ESA s Technology Reference Studies (TRS). The purpose of the Technology Reference Studies is to provide a focus for the development of strategically important technologies that are of likely relevance for future scientific missions. The aim of the Venus Entry Probe TRS is to study approaches for low cost in-situ exploration of Venus and other planetary bodies with a significant atmosphere. In this paper, the mission objectives and an outline of the mission concept of the Venus Entry Probe TRS are presented.

  3. 27. View of entry door to vestibule to MWOC entry ...

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

    27. View of entry door to vestibule to MWOC entry door in transmitter building no. 102 (note coded key pad to left and intercom phone on left) and door to the central systems monitor room (CSMR) to right (out of sight). - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

  4. Adaptable Deployable Entry and Placement Technology (ADEPT)

    NASA Video Gallery

    The Adaptable, Deployable Entry Placement Technology (ADEPT) Project will test and demonstrate a deployable aeroshell concept as a viable thermal protection system for entry, descent, and landing o...

  5. Store-Operated Calcium Channels.

    PubMed

    Prakriya, Murali; Lewis, Richard S

    2015-10-01

    Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca(2+) from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca(2+) sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca(2+) from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca(2+) depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease.

  6. Store-Operated Calcium Channels

    PubMed Central

    Lewis, Richard S.

    2015-01-01

    Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca2+ from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca2+ sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca2+ from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca2+ depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease. PMID:26400989

  7. Calcium, channels, intracellular signaling and autoimmunity.

    PubMed

    Izquierdo, Jorge-Hernán; Bonilla-Abadía, Fabio; Cañas, Carlos A; Tobón, Gabriel J

    2014-01-01

    Calcium (Ca²⁺) is an important cation able to function as a second messenger in different cells of the immune system, particularly in B and T lymphocytes, macrophages and mastocytes, among others. Recent discoveries related to the entry of Ca²⁺ through the store-operated calcium entry (SOCE) has opened a new investigation area about the cell destiny regulated by Ca²⁺ especially in B and T lymphocytes. SOCE acts through calcium-release-activated calcium (CRAC) channels. The function of CRAC depends of two recently discovered regulators: the Ca²⁺ sensor in the endoplasmic reticulum or stromal interaction molecule (STIM-1) and one subunit of CRAC channels called Orai1. This review focuses on the role of Ca²⁺ signals in B and T lymphocytes functions, the signalling pathways leading to Ca²⁺ influx, and the relationship between Ca²⁺ signals and autoimmune diseases.

  8. Hydrolytic and oxidative stability of L-(+)-ascorbic acid supported in pectin films: influence of the macromolecular structure and calcium presence.

    PubMed

    Pérez, Carolina D; Fissore, Eliana N; Gerschenson, Lia N; Cameron, Randall G; Rojas, Ana M

    2012-05-30

    The hydrolytic and oxidative stability of L-(+)-ascorbic acid (AA) into plasticized pectin films were separately studied in view of preserving vitamin C activity and/or to achieve localized antioxidant activity at pharmaceutical and food interfaces. Films were made with each one of the enzymatically tailored pectins (50%, 70%, and 80% DM; Cameron et al. Carbohydr. Polym.2008, 71, 287-299) or commercial high methoxyl pectin (HMP; 72% DM). Since AA stability was dependent on water availability in the network, pectin nanostructure affected the AA kinetics. Higher AA retention and lower browning rates were achieved in HMP films, and calcium presence in them stabilized AA because of higher water immobilization. Air storage did not change AA decay and browning rates in HMP films, but they significantly increased in Ca-HMP films. It was concluded that the ability of the polymeric network to immobilize water seems to be the main factor to consider in order to succeed in retaining AA into film materials.

  9. Entry, Descent, Landing Animation (Animation)

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for Entry, Descent, Landing animation

    This animation illustrates the path the Stardust return capsule will follow once it enters Earth's atmosphere.

  10. Atmospheric maneuvering during Martian entry

    NASA Astrophysics Data System (ADS)

    Tauber, Michael E.; Bowles, Jeffrey V.; Yang, Lily

    A comparative-advantages study is made of two different Martian atmospheric entry maneuvers, on the basis of calculation results for the case of a vehicle with a maximum L/D ratio of 2.3. Entries from a highly elliptical Martian orbit at 5 km/sec are more difficult than those from a lower altitude and speed orbit at 3.5 km/sec, due to their more stringent guidance requirements. Efforts to reduce the deceleration for the higher speed entry by lift-modulation achieved a 40-percent reduction, but at the cost of a 50-percent decrease in lateral range. The lower-speed entry's gliding trajectory is noted to encounter a far more benign atmospheric environment.

  11. Re-entry Experiment Launch

    NASA Video Gallery

    On August 10, 2009, NASA successfully launched the Inflatable Re-entry Vehicle Experiment (IRVE) and proved that spacecraft can use inflatable heat shields to reduce speed and provide protection du...

  12. Atmospheric Entry of Carbonate Micrometeoroids

    NASA Astrophysics Data System (ADS)

    Micca Longo, G.; Longo, S.

    2017-02-01

    Micrometeoroids have similarities in chemistry and mineralogy to the CI, CM, and CR chondrites. A first study of carbonate micrometeoroids atmospheric entry is performed. A thermal decomposition model of initially pure magnesium carbonate is proposed.

  13. Orion Entry Handling Qualities Assessments

    NASA Technical Reports Server (NTRS)

    Bihari, B.; Tiggers, M.; Strahan, A.; Gonzalez, R.; Sullivan, K.; Stephens, J. P.; Hart, J.; Law, H., III; Bilimoria, K.; Bailey, R.

    2011-01-01

    The Orion Command Module (CM) is a capsule designed to bring crew back from the International Space Station (ISS), the moon and beyond. The atmospheric entry portion of the flight is deigned to be flown in autopilot mode for nominal situations. However, there exists the possibility for the crew to take over manual control in off-nominal situations. In these instances, the spacecraft must meet specific handling qualities criteria. To address these criteria two separate assessments of the Orion CM s entry Handling Qualities (HQ) were conducted at NASA s Johnson Space Center (JSC) using the Cooper-Harper scale (Cooper & Harper, 1969). These assessments were conducted in the summers of 2008 and 2010 using the Advanced NASA Technology Architecture for Exploration Studies (ANTARES) six degree of freedom, high fidelity Guidance, Navigation, and Control (GN&C) simulation. This paper will address the specifics of the handling qualities criteria, the vehicle configuration, the scenarios flown, the simulation background and setup, crew interfaces and displays, piloting techniques, ratings and crew comments, pre- and post-fight briefings, lessons learned and changes made to improve the overall system performance. The data collection tools, methods, data reduction and output reports will also be discussed. The objective of the 2008 entry HQ assessment was to evaluate the handling qualities of the CM during a lunar skip return. A lunar skip entry case was selected because it was considered the most demanding of all bank control scenarios. Even though skip entry is not planned to be flown manually, it was hypothesized that if a pilot could fly the harder skip entry case, then they could also fly a simpler loads managed or ballistic (constant bank rate command) entry scenario. In addition, with the evaluation set-up of multiple tasks within the entry case, handling qualities ratings collected in the evaluation could be used to assess other scenarios such as the constant bank angle

  14. Predictors of student success in entry-level science courses

    NASA Astrophysics Data System (ADS)

    Singh, Mamta K.

    Although the educational evaluation process is useful and valuable and is supported by the Higher Education Act, a strong research base for program evaluation of college entry-level science courses is still lacking. Studies in science disciplines such as, biology, chemistry, and physics have addressed various affective and demographic factors and their relationships to student achievement. However, the literature contains little information that specifically addresses student biology content knowledge skills (basics and higher order thinking skills) and identifies factors that affect students' success in entry-level college science courses. These gate-keeping courses require detailed evaluation if the goal of an institution is to increase students' performance and success in these courses. These factors are, in fact, a stepping stone for increasing the number of graduates in Science, Technology, Engineering, and Mathematics (STEM) majors. The present study measured students' biology content knowledge and investigated students' performance and success in college biology, chemistry, and physics entry-level courses. Seven variables---gender, ethnicity, high school Grade Point Average (GPA), high school science, college major, school financial aid support, and work hours were used as independent variables and course final performance as a dichotomous dependent variable. The sample comprised voluntary student participants in entry-level science courses. The study attempted to explore eight research questions. Content knowledge assessments, demographic information analysis, multiple regression analysis, and binary logistic regression analysis were used to address research questions. The results suggested that high school GPA was a consistently good predictor of students' performance and success in entry-level science courses. Additionally, high school chemistry was a significant predictor variable for student success in entry-level biology and chemistry courses

  15. Software for simulating calcium-triggered exocytotic processes.

    PubMed

    Carrera, Germán; Gil, Amparo; Segura, Javier; Soria, Bernat

    2007-02-01

    We describe a software package for the simulation of exocytotic events from readily releasable pools of secretory vesicles in neuroendocrine cells and presynaptic terminals. The visual package Ca3D_Exolab simulates the entry of Ca(2+) through the calcium channels, the kinetic reactions of calcium with buffers, the diffusion of calcium and mobile buffers, and the kinetic reactions of calcium with the secretory vesicles. The location of both channels and secretory vesicles can be set by using a graphical interface. Calcium and buffer concentrations at different depths from the cellular membrane and capacitance time courses are obtained as outputs. The software package also provides a descriptive statistical data analysis of the different output data.

  16. 19 CFR 191.143 - Drawback entry.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) DRAWBACK Foreign-Built Jet Aircraft Engines Processed in the United States § 191.143 Drawback entry. (a) Filing of entry. Drawback entries covering these foreign-built jet aircraft engines shall be filed on Customs Form 7551, modified to show that the entry covers jet aircraft engines processed...

  17. 19 CFR 191.143 - Drawback entry.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) DRAWBACK Foreign-Built Jet Aircraft Engines Processed in the United States § 191.143 Drawback entry. (a) Filing of entry. Drawback entries covering these foreign-built jet aircraft engines shall be filed on Customs Form 7551, modified to show that the entry covers jet aircraft engines processed...

  18. 19 CFR 191.143 - Drawback entry.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) DRAWBACK Foreign-Built Jet Aircraft Engines Processed in the United States § 191.143 Drawback entry. (a) Filing of entry. Drawback entries covering these foreign-built jet aircraft engines shall be filed on Customs Form 7551, modified to show that the entry covers jet aircraft engines processed...

  19. 19 CFR 191.143 - Drawback entry.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) DRAWBACK Foreign-Built Jet Aircraft Engines Processed in the United States § 191.143 Drawback entry. (a) Filing of entry. Drawback entries covering these foreign-built jet aircraft engines shall be filed on Customs Form 7551, modified to show that the entry covers jet aircraft engines processed...

  20. 19 CFR 191.143 - Drawback entry.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) DRAWBACK Foreign-Built Jet Aircraft Engines Processed in the United States § 191.143 Drawback entry. (a) Filing of entry. Drawback entries covering these foreign-built jet aircraft engines shall be filed on Customs Form 7551, modified to show that the entry covers jet aircraft engines processed...

  1. Lunar Entry Downmode Options for Orion

    NASA Technical Reports Server (NTRS)

    Smith, Kelly; Rea, Jeremy

    2016-01-01

    Traditional ballistic entry does not scale well to higher energy entry trajectories. Clutch algorithm is a two-stage approach with the capture stage and load relief stage. Clutch may offer expansion of the operational entry corridor. Clutch is a candidate solution for Exploration Mission-2's degraded entry mode.

  2. Interactions of Mitochondria/Metabolism and Calcium Regulation in Alzheimer's Disease: A Calcinist Point of View.

    PubMed

    Gibson, Gary E; Thakkar, Ankita

    2017-02-08

    Decades of research suggest that alterations in calcium are central to the pathophysiology of Alzheimer's Disease (AD). Highly reproducible changes in calcium dynamics occur in cells from patients with both genetic and non-genetic forms of AD relative to controls. The most robust change is an exaggerated release of calcium from internal stores. Detailed analysis of these changes in animal and cell models of the AD-causing presenilin mutations reveal robust changes in ryanodine receptors, inositol tris-phosphate receptors, calcium leak channels and store activated calcium entry. Similar anomalies in calcium result when AD-like changes in mitochondrial enzymes or oxidative stress are induced experimentally. The calcium abnormalities can be directly linked to the altered tau phosphorylation, amyloid precursor protein processing and synaptic dysfunction that are defining features of AD. A better understanding of these changes is required before using calcium abnormalities as therapeutic targets.

  3. Imaging calcium in neurons.

    PubMed

    Grienberger, Christine; Konnerth, Arthur

    2012-03-08

    Calcium ions generate versatile intracellular signals that control key functions in all types of neurons. Imaging calcium in neurons is particularly important because calcium signals exert their highly specific functions in well-defined cellular subcompartments. In this Primer, we briefly review the general mechanisms of neuronal calcium signaling. We then introduce the calcium imaging devices, including confocal and two-photon microscopy as well as miniaturized devices that are used in freely moving animals. We provide an overview of the classical chemical fluorescent calcium indicators and of the protein-based genetically encoded calcium indicators. Using application examples, we introduce new developments in the field, such as calcium imaging in awake, behaving animals and the use of calcium imaging for mapping single spine sensory inputs in cortical neurons in vivo. We conclude by providing an outlook on the prospects of calcium imaging for the analysis of neuronal signaling and plasticity in various animal models.

  4. 19 CFR 142.16 - Entry summary documentation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry summary documentation. 142.16 Section 142.16... TREASURY (CONTINUED) ENTRY PROCESS Entry Summary Documentation § 142.16 Entry summary documentation. (a) Entry summary not filed at time of entry. When the entry documentation is filed before the entry...

  5. Mars Science Laboratory Entry Guidance

    NASA Technical Reports Server (NTRS)

    Mendeck, Gavin F.

    2011-01-01

    The Mars Science Laboratory will be the first Mars mission to attempt a guided entry with the objective of safely delivering the entry vehicle to a survivable parachute deploy state within 12.5 km of the pre-designated parachute deploy coordinates. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control range based on deviations in range, altitude rate, and drag acceleration from a reference trajectory. For application to Mars landers which must make use of the tenuous Martian atmosphere, it is critical to balance the lift of the vehicle to minimize the range while still ensuring a safe deploy altitude. An overview of the process to generate optimized guidance settings is presented, discussing improvements made over the last nine years. Performance tradeoffs between ellipse size and deploy altitude will be presented, along with imposed constraints of entry acceleration and heating. Performance sensitivities to the bank reversal deadbands, heading alignment, attitude initialization error, and entry delivery errors are presented.

  6. 19 CFR 143.36 - Form of immediate delivery, entry and entry summary.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Form of immediate delivery, entry and entry summary. 143.36 Section 143.36 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) SPECIAL ENTRY PROCEDURES Electronic Entry Filing § 143.36 Form of immediate delivery, entry and...

  7. 1α,25-dihydroxyvitamin D(3) mechanism of action: modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats.

    PubMed

    Zanatta, Leila; Goulart, Paola Bez; Gonçalves, Renata; Pierozan, Paula; Winkelmann-Duarte, Elisa C; Woehl, Viviane Mara; Pessoa-Pureur, Regina; Silva, Fátima Regina Mena Barreto; Zamoner, Ariane

    2012-10-01

    The involvement of calcium-mediated signaling pathways in the mechanism of action of 1α,25-dihydroxyvitamin D(3) (1,25D) is currently demonstrated. In this study we found that 1,25D induces nongenomic effects mediated by membrane vitamin D receptor (VDRm) by modulating intermediate filament (IF) phosphorylation and calcium uptake through L-type voltage-dependent calcium channels (L-VDCC) in cerebral cortex of 10 day-old rats. Results showed that the mechanism of action of 1,25D involves intra- and extracellular calcium levels, as well as the modulation of chloride and potassium channels. The effects of L-VDCCs on membrane voltage occur over a broad potential range and could involve depolarizing or hyperpolarizing coupling modes, supporting a cross-talk among Ca(2+) uptake and potassium and chloride channels. Also, the Na(+)/K(+)-ATPase inactivation by ouabain mimicked the 1,25D action on (45)Ca(2+) uptake. The Na(+)/K(+)-ATPase inhibition observed herein might lead to intracellular Na(+) accumulation with subsequent L-VDCC opening and consequently increased (45)Ca(2+) (calcium, isotope of mass 45) uptake. Moreover, the 1,25D effect is dependent on the activation of the following protein kinases: cAMP-dependent protein kinase (PKA), Ca(2+)/calmodulin-dependent protein kinase (PKCaMII), phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase p38 (p38(MAPK)). The modulation of calcium entry into neural cells by the 1,25D we are highlighting, might take a role in the regulation of a plethora of intracellular processes. Considering that vitamin D deficiency can lead to brain illness, 1,25D may be a possible candidate to be used, at least as an adjuvant, in the pharmacological therapy of neuropathological conditions.

  8. Role of intracellular membranes in transcellular calcium transport

    SciTech Connect

    Coleman, J.R.; Young, L.B.; Wade, P.C.

    1981-01-01

    Models can be tested through the use of various agents that affect different portions of the overall mechanism. The calcium ionophore A23187 can be used to increase the rate of calcium entry through the brush border, effectively removing diffusion through the brush border as a rate-limiting step. It would be expected that treatment with A23187 would thus increase the overall rate of calcium transcellular transport. In contrast, chlorpromazine has been shown to inhibit in vitro calcium uptake by Golgi membranes. Consequently if the model is correct, treatment with A23187 and chlorpromazine would tend to raise the cytoplasmic calcium concentration, since the Golgi membrane uptake mechanism would be inhibited, and calcium would accumulate in mitochondria with little or no increase in transcellular transport. Finally, Golgi membranes have been shown to release calcium in response to ATP. Sodium azide inhibits ATP generation and calcium uptake by mitochondria. Thus, treatment with A23187 and soidum azide should cause accumulation of calcium in the Golgi membranes, if the proposed model is correct. The purpose of this investigation was to use coordinated electron probe x-ray microanalysis and transmission electron microscopy to test the response of the intestinal absorptive cells to the agents mentioned.

  9. The water entry of water

    NASA Astrophysics Data System (ADS)

    Speirs, Nathan; Pan, Zhao; Belden, Jesse; Truscott, Tadd

    2016-11-01

    Though water entry has been studied for over a century, there has been a disconnect between solid object water entry and research on liquid impacting on a liquid pool. In addition, few have studied multiple objects impacting a liquid bath sequentially. We show that the impact of multi-droplet streams and liquid jets on a liquid pool display similar behavior to solid body water entry. In particular, the cavities of both droplet streams and jets exhibit three types of cavity seal previously found for hydrophobic spheres at low Bond numbers. Additionally, low-frequency droplet streams create three novel cavity seal types, which can be predicted with a new non-dimensional frequency. The cavity depth for both droplet and jet impact is rationalized by an energy scaling analysis. Finally, we examine the similarities and differences in cavity dynamics for multi-droplet streams and continuous liquid jets.

  10. Calcium Dyshomeostasis in Tubular Aggregate Myopathy

    PubMed Central

    Lee, Jong-Mok; Noguchi, Satoru

    2016-01-01

    Calcium is a crucial mediator of cell signaling in skeletal muscles for basic cellular functions and specific functions, including contraction, fiber-type differentiation and energy production. The sarcoplasmic reticulum (SR) is an organelle that provides a large supply of intracellular Ca2+ in myofibers. Upon excitation, it releases Ca2+ into the cytosol, inducing contraction of myofibrils. During relaxation, it takes up cytosolic Ca2+ to terminate the contraction. During exercise, Ca2+ is cycled between the cytosol and the SR through a system by which the Ca2+ pool in the SR is restored by uptake of extracellular Ca2+ via a specific channel on the plasma membrane. This channel is called the store-operated Ca2+ channel or the Ca2+ release-activated Ca2+ channel. It is activated by depletion of the Ca2+ store in the SR by coordination of two main molecules: stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (ORAI1). Recently, myopathies with a dominant mutation in these genes have been reported and the pathogenic mechanism of such diseases have been proposed. This review overviews the calcium signaling in skeletal muscles and role of store-operated Ca2+ entry in calcium homeostasis. Finally, we discuss the phenotypes and the pathomechanism of myopathies caused by mutations in the STIM1 and ORAI1 genes. PMID:27879676

  11. MSL EDL Entry Guidance using the Entry Terminal Point Controller

    NASA Technical Reports Server (NTRS)

    2006-01-01

    The Mars Science Laboratory will be the first Mars mission to attempt a guided entry with the objective of safely delivering the entry vehicle to a survivable parachute deploy state within 10 km of the pre-designated landing site. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control range based on deviations in range, altitude rate, and drag acceleration from a reference trajectory. For application to Mars landers which must make use of the tenuous Martian atmosphere, it is critical to balance the lift of the vehicle to minimize the range while still ensuring a safe deploy altitude. An overview of the process to generate optimized guidance settings is presented, discussing improvements made over the last four years. Performance tradeoffs between ellipse size and deploy altitude will be presented, along with imposed constraints of entry acceleration and heating. Performance sensitivities to the bank reversal deadbands, heading alignment, attitude initialization error, and atmospheric delivery errors are presented. Guidance settings for contingency operations, such as those appropriate for severe dust storm scenarios, are evaluated.

  12. Orbiter Return-To-Flight Entry Aeroheating

    NASA Technical Reports Server (NTRS)

    Campbell, Charles H.; Anderson, Brian; Bourland, Gary; Bouslog, Stan; Cassady, Amy; Horvath, Tom; Berry, Scott A.; Gnoffo, Peter; Wood, Bill; Reuther, James; Driver, Dave; Chao, Dennis

    2006-01-01

    The Columbia accident on February 1, 2003 began an unprecedented level of effort within the hypersonic aerothermodynamic community to support the Space Shuttle Program. During the approximately six month time frame of the primary Columbia Accident Investigation Board activity, many technical disciplines were involved in a concerted effort to reconstruct the last moments of the Columbia and her crew, and understand the critical events that led to that loss. Significant contributions to the CAIB activity were made by the hypersonic aerothermodynamic community(REF CAIB) in understanding the re-entry environments that led to the propagation of an ascent foam induced wing leading edge damage to a subsequent breech of the wing spar of Columbia, and the subsequent breakup of the vehicle. A core of the NASA hypersonic aerothermodynamics team that was involved in the CAIB investigation has been combined with the United Space Alliance and Boeing Orbiter engineering team in order to position the Space Shuttle Program with a process to perform in-flight Thermal Protection System damage assessments. This damage assessment process is now part of the baselined plan for Shuttle support, and is a direct out-growth of the Columbia accident and NASAs response. Multiple re-entry aeroheating tools are involved in this damage assessment process, many of which have been developed during the Return To Flight activity. In addition, because these aeroheating tools are part of an overall damage assessment process that also involves the thermal and stress analyses community, in addition to a much broader mission support team, an integrated process for performing the damage assessment activities has been developed by the Space Shuttle Program and the Orbiter engineering community. Several subsets of activity in the Orbiter aeroheating communities support to the Return To Flight effort have been described in previous publications (CFD?, Cavity Heating? Any BLT? Grid Generation?). This work will

  13. 19 CFR 141.64 - Review and correction of entry and entry summary documentation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Presentation of Entry Papers § 141.64... be reviewed before acceptance to ensure that all entry and statistical requirements are complied...

  14. Orbiter Entry Aerothermodynamics Practical Engineering and Applied Research

    NASA Technical Reports Server (NTRS)

    Campbell, Charles H.

    2009-01-01

    The contents include: 1) Organization of the Orbiter Entry Aeroheating Working Group; 2) Overview of the Principal RTF Aeroheating Tools Utilized for Tile Damage Assessment; 3) Description of the Integrated Tile Damage Assessment Team Analyses Process; 4) Space Shuttle Flight Support Process; and 5) JSC Applied Aerosciences and CFD Branch Applied Research Interests.

  15. Application of an Aesthetic Evaluation Model to Data Entry Screens.

    ERIC Educational Resources Information Center

    Ngo, D. C. L.; Byrne, J. G.

    2001-01-01

    Describes a new model for quantitatively assessing screen formats. Results of applying the model to data entry screens support the use of the model. Also described is a critiquing mechanism embedded in a user interface design environment as a demonstration of this approach. (Author/AEF)

  16. Predictors of Student Success in Entry-Level Science Courses

    ERIC Educational Resources Information Center

    Singh, Mamta K.

    2009-01-01

    Although the educational evaluation process is useful and valuable and is supported by the Higher Education Act, a strong research base for program evaluation of college entry-level science courses is still lacking. Studies in science disciplines such as, biology, chemistry, and physics have addressed various affective and demographic factors and…

  17. Multiple Deep Jovian Atmospheric Entry Probes: Building on the Galileo Probe

    NASA Technical Reports Server (NTRS)

    Spilker, T.; Hubbard, W.

    1998-01-01

    Following on the very successful Galileo Entry Probe mission, studies underway at the Jet Propulsion Laboratory (JPL) address the feasibility and cost of the Jupiter Deep Multi-probes (JDMP) mission to deliver and support multiple deep (100 bar level or deeper) atmospheric entry probes to Jupiter.

  18. CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING IN CENTER, ...

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

    CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING IN CENTER, CALCIUM CHLORIDE STORAGE BUILDING ON RIGHT WITH SA (SODA ASH) BUILDING IN RIGHT BACKGROUND. - Solvay Process Company, Calcium Chloride Plant, Between Willis & Milton Avenues, Solvay, Onondaga County, NY

  19. Process for the preparation of calcium superoxide

    NASA Technical Reports Server (NTRS)

    Ballou, E. V.; Wood, P. C.; Wydeven, T. J.; Spitze, L. A. (Inventor)

    1978-01-01

    Calcium superoxide is prepared in high yields by spreading a quantity of calcium peroxide diperoxyhydrate on the surface of a container, positioning said container in a vacuum chamber on a support structure through which a coolant fluid can be circulated, partially evacuating said vacuum chamber, allowing the temperature of the diperoxyhydrate to reach the range of about 0 to about 40 C; maintaining the temperature selected for a period of time sufficient to complete the disproproriation of the diperoxyhydrate to calcium superoxide, calcium hydroxide, oxygen, and water; constantly and systematically removing the water as it is formed by sweeping the reacting material with a current of dry inert gas and/or by condensation of said water on a cold surface; backfilling the chamber with a dry inert gas; and finally, recovering the calcium superoxide produced.

  20. [Do cows drink calcium?].

    PubMed

    Geishauser, T; Lechner, S; Plate, I; Heidemann, B

    2008-03-01

    The objective of this study was to investigate how well cows drink the Propeller calcium drink, and it's effect on blood calcium concentration. Drinking was tested in 120 cows right after calving, before cows drank anything else. 60 cows each were offered 20 liters of Propeller calcium drink or 20 liters of water. Cows drank the Propeller as good as water. 72% of all cows drank all 20 liters, 18% drank on average 8.2 liters and 10% drank less than 1 liter. Blood calcium concentration was studied in 16 cows right after calving. Eight cows each were offered 20 liters of Propeller calcium drink or no calcium drink. Blood calcium significantly increased ten minutes after Propeller intake and stayed significantly elevated for 24 hours. Without calcium drink blood calcium levels decreased significantly. Advantages of the new Propeller calcium drink over calcium gels or boli could be that cows now drink calcium themselves and that the Propeller increases blood calcium concentration rapidly and long lasting.

  1. Numerical Skip-Entry Guidance

    NASA Technical Reports Server (NTRS)

    Tigges, Michael; Crull, Timothy; Rea, Jeremy; Johnson, Wyatt

    2006-01-01

    This paper assesses a preliminary guidance and targeting strategy for accomplishing Skip-Entry (SE) flight during a lunar return-capsule entry flight. One of the primary benefits of flying a SE trajectory is to provide the crew with continuous Continental United States (CONUS) landing site access throughout the lunar month. Without a SE capability, the capsule must land either in water or at one of several distributed land sites in the Southern Hemisphere for a significant portion of a lunar month using a landing and recovery scenario similar to that employed during the Apollo program. With a SE trajectory, the capsule can land either in water at a site in proximity to CONUS or at one of several distributed landing sites within CONUS, thereby simplifying the operational requirements for crew retrieval and vehicle recovery, and possibly enabling a high degree of vehicle reusability. Note that a SE capability does not require that the vehicle land on land. A SE capability enables a longer-range flight than a direct-entry flight, which permits the vehicle to land at a much greater distance from the Entry Interface (EI) point. This does not exclude using this approach to push the landing point to a water location in proximity of CONUS and utilizing water or airborne recovery forces.

  2. Planetary Landers and Entry Probes

    NASA Astrophysics Data System (ADS)

    Ball, Andrew J.; Garry, James R. C.; Lorenz, Ralph D.; Kerzhanovich, Viktor V.

    2007-05-01

    Preface; Acknowledgements; Part I. Engineering Issues Specific to Entry Probes, Landers or Penetrators: 1. Mission goals and system engineering; 2. Accommodation, launch, cruise and arrival from orbit or interplanetary trajectory; 3. Entering atmospheres; 4. Descent through an atmosphere; 5. Descent to an airless body; 6. Planetary balloons, aircraft, submarines and cryobots; 7. Arrival at a surface; 8. Thermal control of landers and entry probes; 9. Power systems; 10. Communication and tracking of entry probes; 11. Radiation environment; 12. Surface activities: arms, drills, moles and mobility; 13. Structures; 14. Contamination of spacecraft and planets; Part II. Previous Atmosphere/Surface Vehicles and Their Payloads: 15. Destructive impact probes; 16. Atmospheric entry probes; 17. Pod landers; 18. Legged landers; 19. Payload delivery penetrators; 20. Small body surface missions; Part III. 'Case Studies': 21. Surveyor landers; 22. Galileo probe; 23. Huygens; 24. Mars Pathfinder and Sojourner; 25. Deep Space 2 Mars microprobes; 26. Rosetta lander Philae; 27. Mars exploration rovers: Spirit and Opportunity; Appendix: Some key parameters for bodies in the Solar System; List of acronyms; Bibliography; References; Index.

  3. Planetary Landers and Entry Probes

    NASA Astrophysics Data System (ADS)

    Ball, Andrew; Garry, James; Lorenz, Ralph; Kerzhanovich, Viktor

    2010-02-01

    Preface; Acknowledgements; Part I. Engineering Issues Specific to Entry Probes, Landers or Penetrators: 1. Mission goals and system engineering; 2. Accommodation, launch, cruise and arrival from orbit or interplanetary trajectory; 3. Entering atmospheres; 4. Descent through an atmosphere; 5. Descent to an airless body; 6. Planetary balloons, aircraft, submarines and cryobots; 7. Arrival at a surface; 8. Thermal control of landers and entry probes; 9. Power systems; 10. Communication and tracking of entry probes; 11. Radiation environment; 12. Surface activities: arms, drills, moles and mobility; 13. Structures; 14. Contamination of spacecraft and planets; Part II. Previous Atmosphere/Surface Vehicles and Their Payloads: 15. Destructive impact probes; 16. Atmospheric entry probes; 17. Pod landers; 18. Legged landers; 19. Payload delivery penetrators; 20. Small body surface missions; Part III. 'Case Studies': 21. Surveyor landers; 22. Galileo probe; 23. Huygens; 24. Mars Pathfinder and Sojourner; 25. Deep Space 2 Mars microprobes; 26. Rosetta lander Philae; 27. Mars exploration rovers: Spirit and Opportunity; Appendix: Some key parameters for bodies in the Solar System; List of acronyms; Bibliography; References; Index.

  4. A novel calcium-sensing domain in the BK channel.

    PubMed Central

    Schreiber, M; Salkoff, L

    1997-01-01

    The high-conductance Ca2+-activated K+ channel (mSlo) plays a vital role in regulating calcium entry in many cell types. mSlo channels behave like voltage-dependent channels, but their voltage range of activity is set by intracellular free calcium. The mSlo subunit has two parts: a "core" resembling a subunit from a voltage-dependent K+ channel, and an appended "tail" that plays a role in calcium sensing. Here we present evidence for a site on the tail that interacts with calcium. This site, the "calcium bowl," is a novel calcium-binding motif that includes a string of conserved aspartate residues. Mutations of the calcium bowl fall into two categories: 1) those that shift the position of the G-V relation a similar amount at all [Ca2+], and 2) those that shift the position of the G-V relation only at low [Ca2+]. None of these mutants alters the slope of the G-V curve. These mutant phenotypes are apparent in calcium ion, but not in cadmium ion, where mutant and wild type are indistinguishable. This suggests that the calcium bowl is sensitive to calcium ion, but insensitive to cadmium ion. The presence and independence of a second calcium-binding site is inferred because channels still respond to increasing levels of [Ca2+] or [Cd2+], even when the calcium bowl is mutationally deleted. Thus a low level of activation in the absence of divalent cations is identical in mutant and wild-type channels, possibly because of activation of this second Ca2+-binding site. PMID:9284303

  5. A toxin from the spider Phoneutria nigriventer that blocks calcium channels coupled to exocytosis

    PubMed Central

    Guatimosim, C; Romano-Silva, M A; Cruz, J S; Beirão, P S L; Kalapothakis, E; Moraes-Santos, T; Cordeiro, M N; Diniz, C R; Gomez, M V; Prado, M A M

    1997-01-01

    The aim of the present experiments was to investigate the pharmacological action of a toxin from the spider Phoneutria nigriventer, Tx3-3, on the function of calcium channels that control exocytosis of synaptic vesicles. Tx3-3, in confirmation of previous work, diminished the intracellular calcium increase induced by membrane depolarization with KCl (25 mM) in rat cerebrocortical synaptosomes. The toxin was very potent (IC50 0.9 nM) at inhibiting calcium channels that regulate calcium entry in synaptosomes. In addition, Tx3-3 blocked the exocytosis of synaptic vesicles, as measured with the fluorescent dye FM1-43. Using ω-toxins that interact selectively with distinct neuronal calcium channels, we investigated whether the target of Tx3-3 overlaps with known channels that mediate exocytosis. The results indicate that the main population of voltage-sensitive calcium channels altered by Tx3-3 can also be inhibited by ω-agatoxin IVA, an antagonist of P/Q calcium channels. ω-conotoxin GVIA, which inhibits N type calcium channels did not decrease significantly the entry of calcium or exocytosis of synaptic vesicles in depolarized synaptosomes. It is concluded that Tx3-3 potently inhibits ω-agatoxin IVA-sensitive calcium channels, which are involved in controlling exocytosis in rat brain cortical synaptosomes. PMID:9351520

  6. Nonequilibrium Calcium Dynamics Regulate the Autonomous Firing Pattern of Rat Striatal Cholinergic Interneurons

    PubMed Central

    Goldberg, Joshua A.; Teagarden, Mark A.; Foehring, Robert C.; Wilson, Charles J.

    2009-01-01

    Striatal cholinergic interneurons discharge rhythmically in two patterns associated with different afterhyperpolarization timescales, each dictated by a different calcium-dependent potassium current. Single spiking depends on a medium-duration afterhyperpolarization (mAHP) generated by rapid SK currents that are associated with N-type calcium channels. Periodic bursting is driven by a delayed and slowly decaying afterhyperpolarization (sAHP) current associated with L-type channels. Using calcium imaging we show that the calcium transients underlying these currents exhibit two corresponding timescales throughout the somatodendritic tree. This result is not consistent with spatial compartmentalization of calcium entering through the two calcium channels and acting on the two potassium currents, or with differences in channel gating kinetics of the calcium dependent potassium currents. Instead, we show that nonequilibrium dynamics of calcium redistribution among cytoplasmic binding sites with different calcium binding kinetics can give rise to multiple timescales within the same cytoplasmic volume. The resulting independence of mAHP and sAHP currents allows cytoplasmic calcium to control two different and incompatible firing patterns (single spiking or bursting and pausing), depending on whether calcium influx is pulsatile or sustained. During irregular firing, calcium entry at both timescales can be detected, suggesting that an interaction between the medium and slow calcium-dependent afterhyperpolarizations may underlie this firing pattern. PMID:19571130

  7. Nonequilibrium calcium dynamics regulate the autonomous firing pattern of rat striatal cholinergic interneurons.

    PubMed

    Goldberg, Joshua A; Teagarden, Mark A; Foehring, Robert C; Wilson, Charles J

    2009-07-01

    Striatal cholinergic interneurons discharge rhythmically in two patterns associated with different afterhyperpolarization timescales, each dictated by a different calcium-dependent potassium current. Single spiking depends on a medium-duration afterhyperpolarization (mAHP) generated by rapid SK currents that are associated with N-type calcium channels. Periodic bursting is driven by a delayed and slowly decaying afterhyperpolarization (sAHP) current associated with L-type channels. Using calcium imaging we show that the calcium transients underlying these currents exhibit two corresponding timescales throughout the somatodendritic tree. This result is not consistent with spatial compartmentalization of calcium entering through the two calcium channels and acting on the two potassium currents, or with differences in channel gating kinetics of the calcium dependent potassium currents. Instead, we show that nonequilibrium dynamics of calcium redistribution among cytoplasmic binding sites with different calcium binding kinetics can give rise to multiple timescales within the same cytoplasmic volume. The resulting independence of mAHP and sAHP currents allows cytoplasmic calcium to control two different and incompatible firing patterns (single spiking or bursting and pausing), depending on whether calcium influx is pulsatile or sustained. During irregular firing, calcium entry at both timescales can be detected, suggesting that an interaction between the medium and slow calcium-dependent afterhyperpolarizations may underlie this firing pattern.

  8. 19 CFR 141.91 - Entry without required invoice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... summary (or the entry, if there is no entry summary) documentation, unless the invoice is needed for... the date of the entry summary (or the entry, if there is no entry summary) is required to be filed... required invoice is not available in proper form at the time the entry or entry summary documentation...

  9. Satellite Re-entry Modeling and Uncertainty Quantification

    NASA Astrophysics Data System (ADS)

    Horsley, M.

    2012-09-01

    LEO trajectory modeling is a fundamental aerospace capability and has applications in many areas of aerospace, such as maneuver planning, sensor scheduling, re-entry prediction, collision avoidance, risk analysis, and formation flying. Somewhat surprisingly, modeling the trajectory of an object in low Earth orbit is still a challenging task. This is primarily due to the large uncertainty in the upper atmospheric density, about 15-20% (1-sigma) for most thermosphere models. Other contributions come from our inability to precisely model future solar and geomagnetic activities, the potentially unknown shape, material construction and attitude history of the satellite, and intermittent, noisy tracking data. Current methods to predict a satellite's re-entry trajectory typically involve making a single prediction, with the uncertainty dealt with in an ad-hoc manner, usually based on past experience. However, due to the extreme speed of a LEO satellite, even small uncertainties in the re-entry time translate into a very large uncertainty in the location of the re-entry event. Currently, most methods simply update the re-entry estimate on a regular basis. This results in a wide range of estimates that are literally spread over the entire globe. With no understanding of the underlying distribution of potential impact points, the sequence of impact points predicted by the current methodology are largely useless until just a few hours before re-entry. This paper will discuss the development of a set of the High Performance Computing (HPC)-based capabilities to support near real-time quantification of the uncertainty inherent in uncontrolled satellite re-entries. An appropriate management of the uncertainties is essential for a rigorous treatment of the re-entry/LEO trajectory problem. The development of HPC-based tools for re-entry analysis is important as it will allow a rigorous and robust approach to risk assessment by decision makers in an operational setting. Uncertainty

  10. Modulation of a sustained calcium current by intracellular pH in horizontal cells of fish retina

    PubMed Central

    1993-01-01

    A sustained high voltage-activated (HVA), nifedipine- and cadmium- sensitive calcium current and a sustained calcium action potential (AP) were recorded from horizontal cells isolated from catfish retina. pH indicator dyes showed that superfusion with NH4Cl alkalinized these cells and that washout of NH4Cl or superfusion with Na-acetate acidified them. HVA current was slightly enhanced during superfusion of NH4Cl but was suppressed upon NH4Cl washout or application of Na- acetate. When 25 mM HEPES was added to the patch pipette to increase intracellular pH buffering, the effects of NH4Cl and Na-acetate on HVA current were reduced. These results indicated that intracellular acidification reduces HVA calcium current and alkalinization increases it. Sustained APs, recorded with high resistance, small diameter microelectrodes, were blocked by cobalt and cadmium and their magnitude varied with extracellular calcium concentration. These results provide confirmatory evidence that the HVA current is a major component of the AP and indicate that the AP can be used as a measure of how the HVA current can be modified in intact, undialyzed cells. The duration of APs was increased by superfusion with NH4Cl and reduced by washout of NH4Cl or superfusion with Na-acetate. The Na-acetate and NH4Cl washout- dependent shortening of the APs was observed in the presence of intracellular BAPTA, a calcium chelator, IBMX, a phosphodiesterase inhibitor, and in Na-free or TEA-enriched saline. These findings provide supportive evidence that intracellular acidification may directly suppress the HVA calcium current in intact cells. Intracellular pH changes would thereby be expected to modulate not only the resting membrane potential of these cells in darkness, but calcium- dependent release of neurotransmitter from these cells as well. Furthermore, this acidification-dependent suppression of calcium current could serve a protective role by reducing calcium entry during retinal ischemia, which

  11. Calcium and Mitosis

    NASA Technical Reports Server (NTRS)

    Hepler, P.

    1983-01-01

    Although the mechanism of calcium regulation is not understood, there is evidence that calcium plays a role in mitosis. Experiments conducted show that: (1) the spindle apparatus contains a highly developed membrane system that has many characteristics of sarcoplasmic reticulum of muscle; (2) this membrane system contains calcium; and (3) there are ionic fluxes occurring during mitosis which can be seen by a variety of fluorescence probes. Whether the process of mitosis can be modulated by experimentally modulating calcium is discussed.

  12. Calcium and bones

    MedlinePlus

    ... very bad at absorbing calcium. Most people absorb only 15% to 20% of the calcium they eat in their diet. Vitamin D is the hormone that helps the gut absorb more calcium. Many older adults have common risks that make bone health worse. ...

  13. Get Enough Calcium

    MedlinePlus

    ... a food with 45% DV of calcium. Check food labels. The Daily Value (DV) on a food label tells you the amount of a nutrient (like ... serving, or 60% DV. Learn how to check food labels for calcium information. Use this calcium shopping list ...

  14. 19 CFR 149.6 - Entry and entry summary documentation and Importer Security Filing submitted via a single...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry and entry summary documentation and Importer...) IMPORTER SECURITY FILING § 149.6 Entry and entry summary documentation and Importer Security Filing... of this part via the same electronic transmission as entry or entry/entry summary...

  15. 19 CFR 149.6 - Entry and entry summary documentation and Importer Security Filing submitted via a single...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Entry and entry summary documentation and Importer...) IMPORTER SECURITY FILING § 149.6 Entry and entry summary documentation and Importer Security Filing... of this part via the same electronic transmission as entry or entry/entry summary...

  16. 19 CFR 149.6 - Entry and entry summary documentation and Importer Security Filing submitted via a single...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Entry and entry summary documentation and Importer...) IMPORTER SECURITY FILING § 149.6 Entry and entry summary documentation and Importer Security Filing... of this part via the same electronic transmission as entry or entry/entry summary...

  17. 19 CFR 149.6 - Entry and entry summary documentation and Importer Security Filing submitted via a single...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Entry and entry summary documentation and Importer...) IMPORTER SECURITY FILING § 149.6 Entry and entry summary documentation and Importer Security Filing... of this part via the same electronic transmission as entry or entry/entry summary...

  18. 19 CFR 149.6 - Entry and entry summary documentation and Importer Security Filing submitted via a single...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Entry and entry summary documentation and Importer...) IMPORTER SECURITY FILING § 149.6 Entry and entry summary documentation and Importer Security Filing... of this part via the same electronic transmission as entry or entry/entry summary...

  19. 32 CFR 770.28 - Entry restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Installations in the... State of Hawaii, entry into a naval installation is not permitted without the permission of...

  20. 32 CFR 770.50 - Entry restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Puget Sound Naval Shipyard, Bremerton, Washington § 770.50 Entry restrictions. Except for military personnel and civilian employees...

  1. 32 CFR 770.50 - Entry restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Puget Sound Naval Shipyard, Bremerton, Washington § 770.50 Entry restrictions. Except for military personnel and civilian employees...

  2. 32 CFR 770.50 - Entry restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Puget Sound Naval Shipyard, Bremerton, Washington § 770.50 Entry restrictions. Except for military personnel and civilian employees...

  3. 32 CFR 770.50 - Entry restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Puget Sound Naval Shipyard, Bremerton, Washington § 770.50 Entry restrictions. Except for military personnel and civilian employees...

  4. 32 CFR 770.50 - Entry restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Puget Sound Naval Shipyard, Bremerton, Washington § 770.50 Entry restrictions. Except for military personnel and civilian employees...

  5. Overview of entry risk predictions

    NASA Astrophysics Data System (ADS)

    Mrozinski, R.; Mendeck, G.; Cutri-Kohart, R.

    Risk to people on the ground from uncontrolled entries of spacecraft is a primary concern when analyzing end-of-life disposal options for satellites. Countries must balance this risk with the need to mitigate an exponentially growing space debris population. Currently the United States does this via guidelines that call for a satellite to be disposed of in a controlled manner if an uncontrolled entry would be too risky to people on the ground. This risk is measured by a quantity called "casualty expectation", or E , where casualty expectation is defined as the expectedc number of people suffering death or injury due to a spacecraft entry event. If Ec exceeds 1 in 10,000, U. S. guidelines state that the entry should be controlled rather than uncontrolled. Since this guideline can have serious impacts on the cost, lifetime, and even the mission and functionality of a satellite, it is critical that this quantity be estimated well, and decision makers understand all assumptions and limitations inherent in the resulting value. This paper discusses several issues regarding estimates of casualty expectation, beginning with an overview of relevant United States policies and guidelines. The equation the space industry typically uses to estimate casualty expectation is presented, along with a look at the sensitivity of the results to the typical assumptions, models, and initial condition uncertainties. Differences in these modeling issues with respect to launch failure Ec estimates are included in the discussion. An alternate quantity to assess risks due to spacecraft entries is introduced. "Probability of casualty", or Pc , is defined as the probability of one or more instances of people suffering death or injury due to a spacecraft entry event. The equation to estimate Pc is derived, where the same assumptions, modeling, and initial condition issues for Ec apply. Several examples are then given of both Ec and Pc estimate calculations. Due to the difficult issues in

  6. Calcium in the regulation of gravitropism by light

    NASA Technical Reports Server (NTRS)

    Perdue, D. O.; LaFavre, A. K.; Leopold, A. C.

    1988-01-01

    The red light requirement for positive gravitropism in roots of corn (Zea mays cv "Merit") provides an entry for examining the participation of calcium in gravitropism. Applications of calcium chelators inhibit the light response. Calcium channel blockers (verapamil, lanthanum) can also inhibit the light response, and a calcium ionophore, A23187, can substitute for light. One can substitute for red light by treatments which have elsewhere been shown to trigger Ca2+ influx into the cytosol, e.g. heat or cold shock. Agents which are known to be agonists of the phosphatidylinositol second messenger system (serotonin, 2,4-dichlorophenoxyacetic acid, deoxycholate) can each partially substitute for the red light, and Li+ can inhibit the light effect. These experiments suggest that the induction of positive gravitropism by red light involves a rise in cytoplasmic Ca2+ concentration, and that a contribution to this end may be made by the phosphatidylinositol second messenger system.

  7. 32 CFR 809a.3 - Unauthorized entry.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Unauthorized entry. 809a.3 Section 809a.3 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION INSTALLATION ENTRY POLICY, CIVIL DISTURBANCE INTERVENTION AND DISASTER ASSISTANCE Installation Entry Policy §...

  8. 19 CFR 122.42 - Aircraft entry.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Aircraft entry. 122.42 Section 122.42 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements...

  9. 32 CFR 770.18 - Entry restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.18 Entry restrictions. Except for military personnel and civilian employees of the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  10. 32 CFR 770.18 - Entry restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.18 Entry restrictions. Except for military personnel and civilian employees of the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  11. 32 CFR 770.18 - Entry restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.18 Entry restrictions. Except for military personnel and civilian employees of the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  12. 32 CFR 770.18 - Entry restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.18 Entry restrictions. Except for military personnel and civilian employees of the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  13. 32 CFR 770.18 - Entry restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.18 Entry restrictions. Except for military personnel and civilian employees of the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  14. 32 CFR 770.51 - Entry procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Entry procedures. 770.51 Section 770.51 National... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Puget Sound Naval Shipyard, Bremerton, Washington § 770.51 Entry procedures. (a) Any person or group of persons desiring the advance consent of...

  15. 32 CFR 770.51 - Entry procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 5 2014-07-01 2014-07-01 false Entry procedures. 770.51 Section 770.51 National... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Puget Sound Naval Shipyard, Bremerton, Washington § 770.51 Entry procedures. (a) Any person or group of persons desiring the advance consent of...

  16. 32 CFR 770.51 - Entry procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Entry procedures. 770.51 Section 770.51 National... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Puget Sound Naval Shipyard, Bremerton, Washington § 770.51 Entry procedures. (a) Any person or group of persons desiring the advance consent of...

  17. 32 CFR 770.51 - Entry procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Entry procedures. 770.51 Section 770.51 National... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Puget Sound Naval Shipyard, Bremerton, Washington § 770.51 Entry procedures. (a) Any person or group of persons desiring the advance consent of...

  18. 32 CFR 763.4 - Entry restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Entry restrictions. 763.4 Section 763.4 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY ISLANDS UNDER NAVY JURISDICTION RULES GOVERNING PUBLIC ACCESS Entry Regulations for Kaho'olawe Island, Hawaii § 763.4 Entry restrictions....

  19. 19 CFR 122.42 - Aircraft entry.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Aircraft entry. 122.42 Section 122.42 Customs... AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Arriving In, Continuing...

  20. 19 CFR 122.42 - Aircraft entry.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Aircraft entry. 122.42 Section 122.42 Customs... AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Arriving In, Continuing...

  1. 19 CFR 122.42 - Aircraft entry.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Aircraft entry. 122.42 Section 122.42 Customs... AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Arriving In, Continuing...

  2. 19 CFR 122.42 - Aircraft entry.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Aircraft entry. 122.42 Section 122.42 Customs... AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Arriving In, Continuing...

  3. 10 CFR 1048.3 - Unauthorized entry.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Unauthorized entry. 1048.3 Section 1048.3 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) TRESPASSING ON STRATEGIC PETROLEUM RESERVE FACILITIES AND OTHER PROPERTY § 1048.3 Unauthorized entry. Unauthorized entry into or upon an SPR facility or real...

  4. 10 CFR 1048.3 - Unauthorized entry.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Unauthorized entry. 1048.3 Section 1048.3 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) TRESPASSING ON STRATEGIC PETROLEUM RESERVE FACILITIES AND OTHER PROPERTY § 1048.3 Unauthorized entry. Unauthorized entry into or upon an SPR facility or real...

  5. 19 CFR 143.36 - Form of immediate delivery, entry and entry summary.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Form of immediate delivery, entry and entry summary. (a) Electronic form of data. If Customs determines... 19 Customs Duties 2 2011-04-01 2011-04-01 false Form of immediate delivery, entry and entry summary. 143.36 Section 143.36 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF...

  6. 76 FR 82315 - Agency Information Collection Activities: Entry/Immediate Delivery Application and Simplified Entry

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-30

    ... Delivery Application and Simplified Entry AGENCY: U.S. Customs and Border Protection, Department of... Delivery Application (Forms 3461 and 3461 ALT) and Simplified Entry. This is a proposed revision and... forms of information. Title: Entry/Immediate Delivery Application and Simplified Entry. OMB Number:...

  7. Re-entry residency training

    PubMed Central

    Jamieson, Jean L.; Webber, Eric M.; Sivertz, Kristin S.

    2010-01-01

    ABSTRACT OBJECTIVE To identify and quantify the reasons general practitioners and family physicians consider retraining and their reasons for not pursuing further training. DESIGN Population-based mailed survey. SETTING British Columbia. PARTICIPANTS Family physicians and general practitioners identified by the College of Physicians and Surgeons of British Columbia. MAIN OUTCOME MEASURES Practising physicians’ level of awareness of the University of British Columbia’s re-entry training program, the number and demographic characteristics of those who had considered retraining, their specialties of interest, and the barriers and possible inducements to retraining. RESULTS Only half of the survey respondents were aware of the re-entry training program at the University of British Columbia. A small but substantial number of practising general practitioners and family physicians were interested in taking specialty training from the Royal College of Physicians and Surgeons of Canada. While several training programs were particularly popular (ie, anesthesia and psychiatry—18.5% of respondents for each), almost every specialty training program was mentioned. Physicians identified the length and hours of training, financial issues, family issues, and the need for relocation as obstacles to retraining. The availability of part-time training, regional training, and return-of-service financial assistance were all identified as potential inducements. CONCLUSION To meet the needs of practising physicians, re-entry training programs will need to consider flexibility, where feasible, with regard to choice of specialty, intensity, and location of postgraduate training. PMID:20547505

  8. Fragmentation and ablation during entry

    SciTech Connect

    Canavan, G.H.

    1997-09-01

    This note discusses objects that both fragment and ablate during entry, using the results of previous reports to describe the velocity, pressure, and fragmentation of entering objects. It shows that the mechanisms used there to describe the breakup of non-ablating objects during deceleration remain valid for most ablating objects. It treats coupled fragmentation and ablation during entry, building on earlier models that separately discuss the entry of objects that are hard, whose high heat of ablation permits little erosion, and those who are strong whose strength prevents fragmentation, which are discussed in ``Radiation from Hard Objects,`` ``Deceleration and Radiation of Strong, Hard, Asteroids During Atmospheric Impact,`` and ``Meteor Signature Interpretation.`` This note provides a more detailed treatment of the further breakup and separation of fragments during descent. It replaces the constraint on mass per unit area used earlier to determine the altitude and magnitude of peak power radiation with a detailed analytic solution of deceleration. Model predictions are shown to be in agreement with the key features of numerical calculations of deceleration. The model equations are solved for the altitudes of maximum radiation, which agree with numerical integrations. The model is inverted analytically to infer object size and speed from measurements of peak power and altitude to provide a complete model for the approximate inversion of meteor data.

  9. Calcium extrusion is critical for cardiac morphogenesis and rhythm in embryonic zebrafish hearts

    PubMed Central

    Ebert, A. M.; Hume, G. L.; Warren, K. S.; Cook, N. P.; Burns, C. G.; Mohideen, M. A.; Siegal, G.; Yelon, D.; Fishman, M. C.; Garrity, D. M.

    2005-01-01

    Calcium entry into myocytes drives contraction of the embryonic heart. To prepare for the next contraction, myocytes must extrude calcium from intracellular space via the Na+/Ca2+ exchanger (NCX1) or sequester it into the sarcoplasmic reticulum, via the sarcoplasmic reticulum Ca2+-ATPase2 (SERCA2). In mammals, defective calcium extrusion correlates with increased intracellular calcium levels and may be relevant to heart failure and sarcoplasmic dysfunction in adults. We report here that mutation of the cardiac-specific NCX1 (NCX1h) gene causes embryonic lethal cardiac arrhythmia in zebrafish tremblor (tre) embryos. The tre ventricle is nearly silent, whereas the atrium manifests a variety of arrhythmias including fibrillation. Calcium extrusion defects in tre mutants correlate with severe disruptions in sarcomere assembly, whereas mutations in the L-type calcium channel that abort calcium entry do not produce this phenotype. Knockdown of SERCA2 activity by morpholino-mediated translational inhibition or pharmacological inhibition causes embryonic lethality due to defects in cardiac contractility and morphology but, in contrast to tre mutation, does not produce arrhythmia. Analysis of intracellular calcium levels indicates that homozygous tre embryos develop calcium overload, which may contribute to the degeneration of cardiac function in this mutant. Thus, the inhibition of NCX1h versus SERCA2 activity differentially affects the pathophysiology of rhythm in the developing heart and suggests that relative levels of NCX1 and SERCA2 function are essential for normal development. PMID:16314582

  10. Automated data entry system: performance issues

    NASA Astrophysics Data System (ADS)

    Thoma, George R.; Ford, Glenn

    2001-12-01

    This paper discusses the performance of a system for extracting bibliographic fields from scanned pages in biomedical journals to populate MEDLINE, the flagship database of the national Library of Medicine (NLM), and heavily used worldwide. This system consists of automated processes to extract the article title, author names, affiliations and abstract, and manual workstations for the entry of other required fields such as pagination, grant support information, databank accession numbers and others needed for a completed bibliographic record in MEDLINE. Labor and time data are given for (1) a wholly manual keyboarding process to create the records, (2) an OCR-based system that requires all fields except the abstract to be manually input, and (3) a more automated system that relies on document image analysis and understanding techniques for the extraction of several fields. It is shown that this last, most automated, approach requires less than 25% of the labor effort in the first, manual, process.

  11. Zinc modulation of calcium activity at the photoreceptor terminal: a calcium imaging study.

    PubMed

    Anastassov, Ivan; Shen, Wen; Ripps, Harris; Chappell, Richard L

    2013-07-01

    There is abundant experimental evidence that zinc ions (Zn(2+)) are present in the synaptic vesicles of vertebrate photoreceptors, and that they are co-released with glutamate. Here we show that increasing the concentration of extracellular zinc (2 μM-2 mM) suppresses the entry of calcium into the synaptic terminals of isolated salamander double cones. The resultant dose-dependent curve was fit by an inverse Hill equation having an IC50 of 38 μM, and Hill coefficient of 1.1. Because there is currently no reliable way to measure the concentration of extracellular zinc, it is not known whether the zinc released under normal circumstances is of physiological significance. In an attempt to circumvent this problem we used zinc chelators to reduce the available pool of endogenous zinc. This enabled us to determine how the absence of zinc affected calcium entry. We found that when intra- or extra-cellular zinc was chelated by 250 μM of membrane-permeable TPEN or 500 μM of membrane-impermeable histidine, there was a significant rise in the depolarization-induced intracellular calcium level within photoreceptor terminals. This increase in internal [Ca(2+)] will undoubtedly lead to a concomitant increase in glutamate release. In addition, we found that blocking the L-type calcium channels that are expressed on the synaptic terminals of photoreceptors with 50 μM nicardipine or 100 μM verapamil abolished the effects of zinc chelation. These findings are a good indication that, when released in vivo, the zinc concentration is sufficient to suppress voltage-gated calcium channels, and reduce the rate of glutamate release from photoreceptor terminals.

  12. Treatment of calcium nephrolithiasis in the patient with hyperuricosuria.

    PubMed

    Arowojolu, Omotayo; Goldfarb, David S

    2014-12-01

    Nearly one-third of patients with calcium stones have hyperuricosuria. In vitro studies and clinical trials have investigated the relationship between uric acid and calcium stones, but the association between hyperuricosuria and calcium stone formation in patients is still being debated. Uric acid appears to cause salting out of calcium oxalate in human urine. However, the importance of this in vitro phenomenon to the proposed association is not supported in cross-sectional observational studies. A small placebo-controlled randomized clinical trial showed that allopurinol decreased the rate of recurrent calcium oxalate calculi in patients with hyperuricosuria and normocalciuria. An assessment of the effect of combination therapy of allopurinol with indapamide showed no additive effect. Allopurinol may have antioxidant effects that are responsible for its reducing calcium stone formation, which are independent of xanthine oxidase inhibition. In addition, a newer xanthine oxidoreductase inhibitor, febuxostat, may also be effective in the prevention of calcium stones, as it reduces urinary uric acid excretion.

  13. Stretch-activated calcium channels relay fast calcium waves propagated by calcium-induced calcium influx.

    PubMed

    Jaffe, Lionel F

    2007-03-01

    For nearly 30 years, fast calcium waves have been attributed to a regenerative process propagated by CICR (calcium-induced calcium release) from the endoplasmic reticulum. Here, I propose a model containing a new subclass of fast calcium waves which is propagated by CICI (calcium-induced calcium influx) through the plasma membrane. They are called fast CICI waves. These move at the order of 100 to 1000 microm/s (at 20 degrees C), rather than the order of 3 to 30 microm/s found for CICR. Moreover, in this proposed subclass, the calcium influx which drives calcium waves is relayed by stretch-activated calcium channels. This model is based upon reports from approx. 60 various systems. In seven of these reports, calcium waves were imaged, and, in five of these, evidence was presented that these waves were regenerated by CICI. Much of this model involves waves that move along functioning flagella and cilia. In these systems, waves of local calcium influx are thought to cause waves of local contraction by inducing the sliding of dynein or of kinesin past tubulin microtubules. Other cells which are reported to exhibit waves, which move at speeds in the fast CICI range, include ones from a dozen protozoa, three polychaete worms, three molluscs, a bryozoan, two sea urchins, one arthropod, four insects, Amphioxus, frogs, two fish and a vascular plant (Equisetum), together with numerous healthy, as well as cancerous, mammalian cells, including ones from human. In two of these systems, very gentle local mechanical stimulation is reported to initiate waves. In these non-flagellar systems, the calcium influxes are thought to speed the sliding of actinomyosin filaments past each other. Finally, I propose that this mechanochemical model could be tested by seeing if gentle mechanical stimulation induces waves in more of these systems and, more importantly, by imaging the predicted calcium waves in more of them.

  14. Atmospheric Entry Experiments at IRS

    NASA Astrophysics Data System (ADS)

    Auweter-Kurtz, M.; Endlich, P.; Herdrich, G.; Kurtz, H.; Laux, T.; Löhle, S.; Nazina, N.; Pidan, S.

    2002-01-01

    Entering the atmosphere of celestial bodies, spacecrafts encounter gases at velocities of several km/s, thereby being subjected to great heat loads. The thermal protection systems and the environment (plasma) have to be investigated by means of computational and ground facility based simulations. For more than a decade, plasma wind tunnels at IRS have been used for the investigation of TPS materials. Nevertheless, ground tests and computer simulations cannot re- place space flights completely. Particularly, entry mission phases encounter challenging problems, such as hypersonic aerothermodynamics. Concerning the TPS, radiation-cooled materials used for reuseable spacecrafts and ablator tech- nologies are of importance. Besides the mentioned technologies, there is the goal to manage guidance navigation, con- trol, landing technology and inflatable technologies such as ballutes that aim to keep vehicles in the atmosphere without landing. The requirement to save mass and energy for planned interplanetary missions such as Mars Society Balloon Mission, Mars Sample Return Mission, Mars Express or Venus Sample Return mission led to the need for manoeuvres like aerocapture, aero-breaking and hyperbolic entries. All three are characterized by very high kinetic vehicle energies to be dissipated by the manoeuvre. In this field flight data are rare. The importance of these manoeuvres and the need to increase the knowledge of required TPS designs and behavior during such mission phases point out the need of flight experiments. As result of the experience within the plasma diagnostic tool development and the plasma wind tunnel data base, flight experiments like the PYrometric RE-entry EXperiment PYREX were developed, fully qualified and successfully flown. Flight experiments such as the entry spectrometer RESPECT and PYREX on HOPE-X are in the conceptual phase. To increase knowledge in the scope of atmospheric manoeuvres and entries, data bases have to be created combining both

  15. Effect of ethionine on hepatic mitochondrial and microsomal calcium uptake

    SciTech Connect

    Agarwal, A.K.; Zinermon, W.D.; Latoni, L.

    1988-02-01

    Ethionine, an ethyl analog of methionine, produces a variety of physiological and pathological effects in animals. These range from acute effects in the liver, kidney, pancreas, and other organs to liver carcinogenesis. Female rats when injected with ethionine exhibit a rapid decrease in hepatic adenosine triphosphate levels followed by a marked inhibition of RNA and protein synthesis and accumulation of triglycerides. Since calcium transport in mitochondria and microsomes is ATP dependent, it becomes interesting to find out if ethionine administration has any effect on subcellular calcium transport. Calcium has recently gained an increased controversy regarding its role in chemical induced lethal cell damage. Certain groups believe that influx of extracellular calcium across the damaged plasma membrane might actually mediate the irreversible damage to the cell, whereas according to other, entry of calcium into the cell is secondary to the damage. The present study was carried out to investigate the calcium (/sup 45/Ca) transport in mitochondria and microsomes following ethionine administration. The effect of carbon tetrachloride on calcium uptake in ethionine treated rats was also studied.

  16. The Phys4Entry database

    NASA Astrophysics Data System (ADS)

    Laricchiuta, Annarita

    2012-10-01

    The Phys4Entry DB is a database of state-selected dynamical information for elementary processes relevant to the state-to-state kinetic modeling of planetary-atmosphere entry conditions. The DB is intended to the challenging goal of complementing the information in the existing web-access databases, collecting and validating data of collisional dynamics of elementary processes involving ground and excited chemical species, with resolution on the electronic, vibrational and rotational degrees of freedom. Four relevant classes of elementary processes are considered, i.e. electron-molecule collisions, atom/molecule-molecule collisions, atom/molecule surface interaction and photon-induced processes, constructing a taxonomy for process classification. Data populating the DB are largely originated by the coordinated research activity done in the frame of the Phys4Entry FP7 project, considering different theoretical approaches from quantum to semi-classical or quasi-classical molecular dynamics. Nevertheless the results, obtained in the Bari plasma chemistry labs in years of research devoted to the construction of reliable state-to-state kinetic models for hydrogen and air plasmas, are also transferred to the DB. Two DB interfaces have been created for different roles allowed to different actions: the contributor, uploading new processes, and the inquirer, submitting queries, to access the complete information about the records, through a graphical tool, displaying energy or roto-vibrational dependence of dynamical data, or through the export action to download ascii datafiles. The DB is expected to have a significant impact on the modeling community working also in scientific fields different from the aerothermodynamics (i.e. fusion, environment, ), making practicable the state-to-state approach.

  17. Atlas F entry aerothermic study

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The feasibility of obtaining heat transfer data on an expended Atlas F booster launch vehicle was investigated in the altitude range of 300,000 to 200,000 feet during entry conditions, with a velocity in the range of 20,000 to 25,000 feet per second, and through a range of vehicle attitudes of plus or minus 90 degrees. These data are desired for correlation with turbulent heat transfer and boundary layer transition data obtained from wind tunnel test facilities. The data would also be valuable in assessing rarified gas and surface catalicity effects in a real gas environment.

  18. Checking your SOCCs and feet: the molecular mechanisms of Ca2+ entry in skeletal muscle.

    PubMed

    Dirksen, Robert T

    2009-07-01

    It has long been known that skeletal muscle contraction persists in the absence of extracellular Ca(2+). Nevertheless, recent evidence indicates that multiple distinct Ca(2+) entry pathways exist in skeletal muscle: one active at negative potentials that requires store depletion (store-operated calcium entry or SOCE) and a second that is independent of store depletion and is activated by depolarization (excitation-coupled calcium entry or ECCE). This review highlights recent findings regarding the molecular identity, subcellular localization, and inter-relationship between SOCE and ECCE in skeletal muscle. The respective roles of ryanodine receptors (RyRs), dihydropyridine receptors (DHPRs), inositol-1,4,5-trisphosphate receptors (IP(3)Rs), canonical transient receptor potential channels (TRPCs), STIM1 Ca(2+) sensor proteins, and Orai1 Ca(2+) permeable channels in mediating SOCE and ECCE in skeletal muscle are discussed. Differences between SOCE and ECCE in skeletal muscle with Ca(2+) entry mechanisms in non-excitable cells are also reviewed. Finally, potential physiological roles for SOCE and ECCE in skeletal muscle development and function, as well as other currently unanswered questions and controversies in the field are also considered.

  19. Pertussis toxin nullifies the depolarization of the membrane potential and the stimulation of the rapid phase of Ca entry through L-type calcium channels that are produced by follicle stimulating hormone in 10- to 12-day-old rat Sertoli cells.

    PubMed

    Jacobus, Ana Paula; Loss, Eloísa Silveira; Wassermann, Guillermo Federico

    2010-01-01

    The aim of this study was to evaluate the effect of pertussis toxin (PTX) on the depolarizing component of the action of follicle stimulating hormone (FSH) on the membrane potential (MP) of Sertoli cells, which is linked to the rapid entry of Ca(2+) into cells and to the Ca(2+)-dependent transport of neutral amino acids by the A system. This model allowed us to analyze the involvement of Gi proteins in the action of FSH in these phenomena. In parallel, using an inactive analog of insulin-like growth factor type I (IGF-1), JB1, and an anti-IGF-I antibody we investigated the possible mediating role of IGF-I on these effects of FSH because IGF-I is produced and released by testicular cells in response to stimulation by FSH and shows depolarization effects on MP similar to those from FSH. Our results have the following implications: (a) the rapid membrane actions of FSH, which occur in a time-frame of seconds to minutes and include the depolarization of the MP, and stimulation of (45)Ca(2+) uptake and [(14)C]-methyl aminoisobutyric acid ([(14)C]-MeAIB) transport, are nullified by the action of PTX and, therefore, are probably mediated by GiPCR activation; (b) the effects of FSH were also nullified by verapamil, an L-type voltage-dependent Ca(2+) channel blocker; (c) wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K), prevented FSH stimulation of (45)Ca(2+) entry and [(14)C]-MeAIB transport; and (d) these FSH actions are independent of the IGF-I effects. In conclusion, these results strongly suggest that the rapid action of FSH on L-type Ca(2+) channel activity in Sertoli cells from 10- to 12-day-old rats is mediated by the Gi/βγ/PI3Kγ pathway, independent of the effects of IGF-I.

  20. Pertussis Toxin Nullifies the Depolarization of the Membrane Potential and the Stimulation of the Rapid Phase of 45Ca2+ Entry Through L-type Calcium Channels that are Produced by Follicle Stimulating Hormone in 10- to 12-Day-Old Rat Sertoli Cells

    PubMed Central

    Jacobus, Ana Paula; Loss, Eloísa Silveira; Wassermann, Guillermo Federico

    2010-01-01

    The aim of this study was to evaluate the effect of pertussis toxin (PTX) on the depolarizing component of the action of follicle stimulating hormone (FSH) on the membrane potential (MP) of Sertoli cells, which is linked to the rapid entry of Ca2+ into cells and to the Ca2+-dependent transport of neutral amino acids by the A system. This model allowed us to analyze the involvement of Gi proteins in the action of FSH in these phenomena. In parallel, using an inactive analog of insulin-like growth factor type I (IGF-1), JB1, and an anti-IGF-I antibody we investigated the possible mediating role of IGF-I on these effects of FSH because IGF-I is produced and released by testicular cells in response to stimulation by FSH and shows depolarization effects on MP similar to those from FSH. Our results have the following implications: (a) the rapid membrane actions of FSH, which occur in a time-frame of seconds to minutes and include the depolarization of the MP, and stimulation of 45Ca2+ uptake and [14C]-methyl aminoisobutyric acid ([14C]-MeAIB) transport, are nullified by the action of PTX and, therefore, are probably mediated by GiPCR activation; (b) the effects of FSH were also nullified by verapamil, an L-type voltage-dependent Ca2+ channel blocker; (c) wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K), prevented FSH stimulation of 45Ca2+ entry and [14C]-MeAIB transport; and (d) these FSH actions are independent of the IGF-I effects. In conclusion, these results strongly suggest that the rapid action of FSH on L-type Ca2+ channel activity in Sertoli cells from 10- to 12-day-old rats is mediated by the Gi/βγ/PI3Kγ pathway, independent of the effects of IGF-I. PMID:21423378

  1. Calcium hydroxide poisoning

    MedlinePlus

    These products contain calcium hydroxide: Cement Limewater Many industrial solvents and cleaners (hundreds to thousands of construction products, flooring strippers, brick cleaners, cement thickening products, and many ...

  2. Calcium: total or ionized?

    PubMed

    Schenck, Patricia A; Chew, Dennis J

    2008-05-01

    Measurement of serum total calcium (tCa) has been relied on for assessment of calcium status, despite the fact that it is the ionized calcium (iCa) fraction that has biologic activity. Serum tCa does not accurately predict iCa status in many clinical conditions. For accurate assessment of iCa status, iCa should be directly measured. Anaerobic measurement of serum iCa under controlled conditions provides the most reliable assessment of calcium status; aerobic measurement of iCa with species-specific pH correction is highly correlated with anaerobic measurements.

  3. Mars Science Laboratory (MSL) Entry, Descent, and Landing Instrumentation (MEDLI): Complete Flight Data Set

    NASA Technical Reports Server (NTRS)

    Cheatwood, F. McNeil; Bose, Deepak; Karlgaard, Christopher D.; Kuhl, Christopher A.; Santos, Jose A.; Wright, Michael J.

    2014-01-01

    The Mars Science Laboratory (MSL) entry vehicle (EV) successfully entered the Mars atmosphere and landed the Curiosity rover safely on the surface of the planet in Gale crater on August 6, 2012. MSL carried the MSL Entry, Descent, and Landing (EDL) Instrumentation (MEDLI). MEDLI delivered the first in-depth understanding of the Mars entry environments and the response of the entry vehicle to those environments. MEDLI was comprised of three major subsystems: the Mars Entry Atmospheric Data System (MEADS), the MEDLI Integrated Sensor Plugs (MISP), and the Sensor Support Electronics (SSE). Ultimately, the entire MEDLI sensor suite consisting of both MEADS and MISP provided measurements that were used for trajectory reconstruction and engineering validation of aerodynamic, atmospheric, and thermal protection system (TPS) models in addition to Earth-based systems testing procedures. This report contains in-depth hardware descriptions, performance evaluation, and data information of the three MEDLI subsystems.

  4. First evidence on phloem transport of nanoscale calcium oxide in groundnut using solution culture technique

    NASA Astrophysics Data System (ADS)

    Deepa, Manchala; Sudhakar, Palagiri; Nagamadhuri, Kandula Venkata; Balakrishna Reddy, Kota; Giridhara Krishna, Thimmavajjula; Prasad, Tollamadugu Naga Venkata Krishna Vara

    2015-06-01

    Nanoscale materials, whose size typically falls below 100 nm, exhibit novel chemical, physical and biological properties which are different from their bulk counterparts. In the present investigation, we demonstrated that nanoscale calcium oxide particles (n-CaO) could transport through phloem tissue of groundnut unlike the corresponding bulk materials. n-CaO particles are prepared using sol-gel method. The size of the as prepared n-CaO measured (69.9 nm) using transmission electron microscopic technique (TEM). Results of the hydroponics experiment using solution culture technique revealed that foliar application of n-CaO at different concentrations (10, 50, 100, 500, 1,000 ppm) on groundnut plants confirmed the entry of calcium into leaves and stems through phloem compared to bulk source of calcium sprayed (CaO and CaNO3). After spraying of n-CaO, calcium content in roots, shoots and leaves significantly increased. Based on visual scoring of calcium deficiency correction and calcium content in plant parts, we may establish the fact that nanoscale calcium oxide particles (size 69.9 nm) could move through phloem tissue in groundnut. This is the first report on phloem transport of nanoscale calcium oxide particles in plants and this result points to the use of nanoscale calcium oxide particles as calcium source to the plants through foliar application, agricultural crops in particular, as bulk calcium application through foliar nutrition is restricted due to its non-mobility in phloem.

  5. Overview of entry risk predictions

    NASA Astrophysics Data System (ADS)

    Mrozinski, R. B.; Mendeck, G. F.; Cutri-Kohart, R. M.

    2004-01-01

    This paper discusses many aspects of "casualty expectation", defined as the expected number of people suffering death or injury due to a spacecraft entry event, normally used when planning the end-of-life disposal of satellites. United States guidelines state a disposal via atmospheric entry should be controlled rather than uncontrolled whenever casualty expectation estimates exceed a specified limit. Since this guideline can have serious impacts on the cost, lifetime, and even the mission and functionality of a satellite, it is critical that casualty expectation ( Ec) be estimated well, and decision-makers understand all assumptions and limitations inherent in the result. This paper begins with an overview of relevant United States guidelines. The equation the space industry typically uses to estimate Ec is presented, along with its sensitivity to typical assumptions, models, and initial condition uncertainties. An alternate quantity is introduced, called "probability of casualty", or Pc. Two examples are given of both Ec and Pc estimations. Because Ec and Pc are dependent on variables with significant uncertainty, confidence in the estimates themselves can be challenged. Fortunately, a precise value is rarely needed. Results typically are well above or well below guideline limits to the extent that even if all variable values were certain, the resulting recommended course of action would not change. Ec and Pc are then ideal to use in relative analyses using a standard tool to assess compliance with guidelines.

  6. Calcium channel blockers in cardiovascular pharmacotherapy.

    PubMed

    Godfraind, Theophile

    2014-11-01

    This paper summarizes the pharmacological properties of calcium channel blockers (CCBs), their established therapeutic uses for cardiovascular disorders and the current improvement of their clinical effects through drug combinations. Their identification resulted from study of small molecules including coronary dilators, which were named calcium antagonists. Further experiments showed that they reduced contraction of arteries by inhibiting calcium entry and by interacting with binding sites identified on voltage-dependent calcium channels. This led to the denomination calcium channel blockers. In short-term studies, by decreasing total peripheral resistance, CCBs lower arterial pressure. By unloading the heart and increasing coronary blood flow, CCBs improve myocardial oxygenation. In long-term treatment, the decrease in blood pressure is more pronounced in hypertensive than in normotensive patients. A controversy on the safety of CCBs ended after a large antihypertensive trial (ALLHAT) sponsored by the National Heart, Lung, and Blood Institute. There are two main types of CCBs: dihydopyridine and non-dihydropyridine; the first type is vascular selective. Dihydropyrines are indicated for hypertension, chronic, stable and vasospastic angina. Non-dihydropyridines have the same indications plus antiarrythmic effects in atrial fibrillation or flutter and paroxysmal supraventricular tachycardia. In addition, CCBs reduced newly formed coronary lesions in atherosclerosis. In order to reach recommended blood pressure goals, there is a recent therapeutic move by combination of CCBs with other antihypertensive agents particularly with inhibitors acting at the level of the renin-angiotensin system. They are also combined with statins. Prevention of dementia has been reported in hypertensive patients treated with nitrendipine, opening a way for further studies on CCBs' beneficial effect in cognitive deterioration associated with aging.

  7. Optimal firm growth under the threat of entry.

    PubMed

    Kort, Peter M; Wrzaczek, Stefan

    2015-10-01

    The paper studies the incumbent-entrant problem in a fully dynamic setting. We find that under an open-loop information structure the incumbent anticipates entry by overinvesting, whereas in the Markov perfect equilibrium the incumbent slightly underinvests in the period before the entry. The entry cost level where entry accommodation passes into entry deterrence is lower in the Markov perfect equilibrium. Further we find that the incumbent's capital stock level needed to deter entry is hump shaped as a function of the entry time, whereas the corresponding entry cost, where the entrant is indifferent between entry and non-entry, is U-shaped.

  8. Preventing re-entry to foster care.

    PubMed

    Carnochan, Sarah; Rizik-Baer, Daniel; Austin, Michael J

    2013-01-01

    Re-entry to foster care generally refers to circumstances in which children who have been discharged from foster care to be reunified with their family of origin, adopted, or provided kinship guardianship are returned to foster care. In the context of the federal performance measurement system, re-entry refers specifically to a return to foster care following an unsuccessful reunification. The federal Children and Family Services Review measures re-entry to foster care with a single indicator, called the permanency of reunification indicator, one of four indicators comprising the reunification composite measure. This review focuses on research related to the re-entry indicator, including the characteristics of children, caregivers and families, as well as case and child welfare services that are associated with a higher or lower risk of re-entry to foster care. Promising post-reunification services designed to prevent re-entry to foster care are described.

  9. A Novel Calcium-Dependent Kinase Inhibitor, Bumped Kinase Inhibitor 1517, Cures Cryptosporidiosis in Immunosuppressed Mice.

    PubMed

    Castellanos-Gonzalez, Alejandro; Sparks, Hayley; Nava, Samantha; Huang, Wenlin; Zhang, Zhongsheng; Rivas, Kasey; Hulverson, Matthew A; Barrett, Lynn K; Ojo, Kayode K; Fan, Erkang; Van Voorhis, Wesley C; White, Arthur Clinton

    2016-12-15

    Cryptosporidium is recognized as one of the main causes of childhood diarrhea worldwide. However, the current treatment for cryptosporidiosis is suboptimal. Calcium flux is essential for entry in apicomplexan parasites. Calcium-dependent protein kinases (CDPKs) are distinct from protein kinases of mammals, and the CDPK1 of the apicomplexan Cryptosporidium lack side chains that typically block a hydrophobic pocket in protein kinases. We exploited this to develop bumped kinase inhibitors (BKIs) that selectively target CDPK1. We have shown that several BKIs of Cryptosporidium CDPK1 potently reduce enzymatic activity and decrease parasite numbers when tested in vitro. In the present work, we studied the anticryptosporidial activity of BKI-1517, a novel BKI. The half maximal effective concentration for Cryptosporidium parvum in HCT-8 cells was determined to be approximately 50 nM. Silencing experiments of CDPK1 suggest that BKI-1517 acts on CDPK1 as its primary target. In a mouse model of chronic infection, 5 of 6 SCID/beige mice (83.3%) were cured after treatment with a single daily dose of 120 mg/kg BKI-1517. No side effects were observed. These data support advancing BKI-1517 as a lead compound for drug development for cryptosporidiosis.

  10. Calcium fluoride window mounting

    NASA Astrophysics Data System (ADS)

    Berger, D. Douglas

    1982-10-01

    A technique has been developed for joining a large calcium fluoride crystal to a stainless-steel flange by means of a silver transition ring. The process involves both vacuum brazing using a copper-silver alloy and air brazing using silver chloride. This paper describes the procedure used in fabricating a high-vacuum leak-tight calcium fluoride window assembly.

  11. Calcium and bones (image)

    MedlinePlus

    ... for the growth, maintenance, and reproduction of the human body. Bones, like other tissues in the body, are continually being re-formed and incorporate calcium into their structure. Calcium is essential for the formation of and maintenance of healthy teeth.

  12. Microdamage induced calcium efflux from bone matrix activates intracellular calcium signaling in osteoblasts via L-type and T-type voltage-gated calcium channels.

    PubMed

    Jung, Hyungjin; Best, Makenzie; Akkus, Ozan

    2015-07-01

    Mechanisms by which bone microdamage triggers repair response are not completely understood. It has been shown that calcium efflux ([Ca(2+)]E) occurs from regions of bone undergoing microdamage. Such efflux has also been shown to trigger intracellular calcium signaling ([Ca(2+)]I) in MC3T3-E1 cells local to damaged regions. Voltage-gated calcium channels (VGCCs) are implicated in the entry of [Ca(2+)]E to the cytoplasm. We investigated the involvement of VGCC in the extracellular calcium induced intracellular calcium response (ECIICR). MC3T3-E1 cells were subjected to one dimensional calcium efflux from their basal aspect which results in an increase in [Ca(2+)]I. This increase was concomitant with membrane depolarization and it was significantly reduced in the presence of Bepridil, a non-selective VGCC inhibitor. To identify specific type(s) of VGCC in ECIICR, the cells were treated with selective inhibitors for different types of VGCC. Significant changes in the peak intensity and the number of [Ca(2+)]I oscillations were observed when L-type and T-type specific VGCC inhibitors (Verapamil and NNC55-0396, respectively) were used. So as to confirm the involvement of L- and T-type VGCC in the context of microdamage, cells were seeded on devitalized notched bone specimen, which were loaded to induce microdamage in the presence and absence of Verapamil and NNC55-0396. The results showed significant decrease in [Ca(2+)]I activity of cells in the microdamaged regions of bone when L- and T-type blockers were applied. This study demonstrated that extracellular calcium increase in association with damage depolarizes the cell membrane and the calcium ions enter the cell cytoplasm by L- and T-type VGCCs.

  13. Calcium signals activated by ghrelin and D-Lys(3)-GHRP-6 ghrelin antagonist in developing dorsal root ganglion glial cells.

    PubMed

    Erriquez, Jessica; Bernascone, Silvia; Ciarletta, Monica; Filigheddu, Nicoletta; Graziani, Andrea; Distasi, Carla

    2009-09-01

    Ghrelin is a hormone regulating energy homeostasis via interaction with its receptor, GHSR-1a. Ghrelin activities in dorsal root ganglia (DRG) cells are unknown. Herein we show that ghrelin induces a change of cytosolic calcium concentration in both glia and neurons of embryonic chick DRG. Both RT-PCR and binding studies performed with fluorescent ghrelin in the presence of either unlabeled ghrelin or GHSR-1a antagonist D-Lys(3)-GHRP-6, indicate that DRG cells express GHSR-1a. In glial cells the response is characterized by a rapid transient rise in [Ca(2+)](i) followed by a long lasting rise. The calcium elevation is dependent on calcium release from thapsigargin-sensitive intracellular stores and on activation of two distinct Ca(2+) entry pathways, a receptor activated calcium entry and a store operated calcium entry. Surprisingly, D-Lys(3)-GHRP-6 exerts several activities in the absence of exogenous ghrelin: (i) it activates calcium release from thapsigargin-sensitive intracellular stores and calcium entry via voltage-operated channels in non-neuronal cells; (ii) it inhibits calcium oscillations in non-neuronal cells exhibiting spontaneous Ca(2+) activity and iii) it promotes apoptosis of DRG cells, both neurons and glia. In summary, we provide the first evidence for ghrelin activity in DRG, and we also demonstrate that the widely used D-Lys(3)-GHRP-6 ghrelin antagonist features ghrelin independent activities.

  14. Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Caenorhabditis elegans Spermatheca

    PubMed Central

    Kovacevic, Ismar; Orozco, Jose M.; Cram, Erin J.

    2013-01-01

    The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue. PMID:23671426

  15. Hypersonic and Supersonic Static Aerodynamics of Mars Science Laboratory Entry Vehicle

    NASA Technical Reports Server (NTRS)

    Dyakonov, Artem A.; Schoenenberger, Mark; Vannorman, John W.

    2012-01-01

    This paper describes the analysis of continuum static aerodynamics of Mars Science Laboratory (MSL) entry vehicle (EV). The method is derived from earlier work for Mars Exploration Rover (MER) and Mars Path Finder (MPF) and the appropriate additions are made in the areas where physics are different from what the prior entry systems would encounter. These additions include the considerations for the high angle of attack of MSL EV, ablation of the heatshield during entry, turbulent boundary layer, and other aspects relevant to the flight performance of MSL. Details of the work, the supporting data and conclusions of the investigation are presented.

  16. Mixed results in the safety performance of computerized physician order entry.

    PubMed

    Metzger, Jane; Welebob, Emily; Bates, David W; Lipsitz, Stuart; Classen, David C

    2010-04-01

    Computerized physician order entry is a required feature for hospitals seeking to demonstrate meaningful use of electronic medical record systems and qualify for federal financial incentives. A national sample of sixty-two hospitals voluntarily used a simulation tool designed to assess how well safety decision support worked when applied to medication orders in computerized order entry. The simulation detected only 53 percent of the medication orders that would have resulted in fatalities and 10-82 percent of the test orders that would have caused serious adverse drug events. It is important to ascertain whether actual implementations of computerized physician order entry are achieving goals such as improved patient safety.

  17. State Policies Affecting the "Adult Re-Entry Pipeline" in Postsecondary Education: Results of a Fifty-State Inventory

    ERIC Educational Resources Information Center

    Boeke, Marianne; Zis, Stacey; Ewell, Peter

    2011-01-01

    With support from the Bill and Melinda Gates Foundation, the National Center for Higher Education Management Systems (NCHEMS) is engaged in a two year project centered on state policies that foster student progression and success in the "adult re-entry pipeline." The adult re-entry pipeline consists of the many alternative pathways to…

  18. But What Do They Really Expect? Employer Perceptions of the Skills of Entry-Level Instructional Designers

    ERIC Educational Resources Information Center

    Villachica, Steven W.; Marker, Anthony; Taylor, Kevin

    2010-01-01

    This descriptive study employed a convenience sample drawn from members of a professional organization supporting instructional designers (IDs) to investigate four research questions: What skills do potential employers expect entry-level instructional designers to possess? To what extent have their recently hired entry-level IDs met these…

  19. Evidence for a possible calcium flux dependent cardiomyopathy in hyperthyroidism

    SciTech Connect

    Barat, J.L.; Wicker, P.; Manley, W.; Brendel, A.J.; Lefort, G.; San Galli, F.; Commenges-Ducos, M.; Latapie, J.L.; Riviere, J.; Ducassou, D.

    1985-05-01

    This study was designed to test the hypothesis that the impaired functional cardiac reserve to exercise in hyperthyroidism is related to alterations in the regulation of calcium transport. In 2l hyperthyroid patients, the left ventricular ejection fraction (LVEF) was measured using equilibrium gated radionuclide angiocardiography at rest and during supine dynamic exercise. After a recovery period, the patients performed a second exercise study after random administration of Verapamil, a calcium entry blocker (11 pts), or propanolol, a beta adrenergic antagonist (10 pts) for comparison. The results showed i) normal resting LVEF with no significant change during exercise before any medication, ii) resting LVEF significantly decreased after Propanolol, and no significantly changed after Verapamil, iii) during exercise, significant increase of LVEF after Verapamil, and no significant change after Propanolol. These results are consistent with previous studies showing that abnormal change in LVEF during exercise in hyperthyroidism seems independent of beta adrenergic activation, and suggest a reversible functional cardiomyopathy dependent of calcium transporting systems.

  20. Communications Support for Flight Data Entry and Printout Terminals.

    DTIC Science & Technology

    1980-08-01

    SWITCHES 4-14 LINK: SWITCH-TO- NEAR-RANGE LONG-RANGE (b/s) (b/s) Average Center 478 574 New York Center 984 1,197 Indianapolis Center 411 524 TABLE 4-3: ONE...OKC - PWA - CSM 71 TUL 4 DFW - DAL - TYR - BAD - SHV MLU ’- TXK CIRCUIT SIZE CONSTRAINT 5 RCUs REMOTE DROPS Circuit No. 1 2 3 4 5 6 7 1 DYS - ABI - SJT...MAF - LBB 2 DFW - DAL - ACT 3 TIK OKC - PWA - CSM TULTYR 71 BAD - SHV - MLU TXK CIRCUIT SIZE CONSTRAINT 3 RCUs REMOTE DROPS Circuit No. 1 2 3 4 5 6

  1. Effect of glycoursodeoxycholate on precipitation of calcium carbonate.

    PubMed

    Marteau, C; Portugal, H; Pauli, A M; Gerolami, A

    1985-01-01

    The potential role of bile salts in preventing calcium carbonate precipitation was investigated by studying their interaction of Ca2+ and their inhibitory effects on calcium carbonate formation. Glycochenodeoxycholate micelles bound more calcium than did glycocholate. At bile salt concentrations exceeding 12.5 mM, glycoursodeoxycholate bound calcium as well as glycochenodexycholate did. Similar results for calcium binding were observed in mixed micelles of bile salts and lecithin. In bicarbonate (25 or 50 mM) and CaCl2 (10 mM) solutions, calcium carbonate formation was inhibited by the bile salts. Glycoursodeoxycholate and glycochenodeoxycholate (25 mM) prevented calcium carbonate formation which was delayed by glycocholate. This effect is not due to differences between both series of bile salts for calcium binding since glycoursodeoxycholate or glycochenodeoxycholate (25 mM) more efficiently prevented calcium carbonate precipitation than did 35 mM glycocholate in spite of the same Ca2+ binding. These results suggest that some bile salts may have a specific role in preventing calcium precipitation in bile. The mechanism is unknown. The physical properties of glycoursodeoxycholate and glycochenodeoxycholate do not support a role for CaCO3 precipitation in gallstone calcification during litholytic therapy.

  2. Differential CaMKII regulation by voltage-gated calcium channels in the striatum.

    PubMed

    Pasek, Johanna G; Wang, Xiaohan; Colbran, Roger J

    2015-09-01

    Calcium signaling regulates synaptic plasticity and many other functions in striatal medium spiny neurons to modulate basal ganglia function. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a major calcium-dependent signaling protein that couples calcium entry to diverse cellular changes. CaMKII activation results in autophosphorylation at Thr286 and sustained calcium-independent CaMKII activity after calcium signals dissipate. However, little is known about the mechanisms regulating striatal CaMKII. To address this, mouse brain slices were treated with pharmacological modulators of calcium channels and punches of dorsal striatum were immunoblotted for CaMKII Thr286 autophosphorylation as an index of CaMKII activation. KCl depolarization increased levels of CaMKII autophosphorylation ~2-fold; this increase was blocked by an LTCC antagonist and was mimicked by treatment with pharmacological LTCC activators. The chelation of extracellular calcium robustly decreased basal CaMKII autophosphorylation within 5min and increased levels of total CaMKII in cytosolic fractions, in addition to decreasing the phosphorylation of CaMKII sites in the GluN2B subunit of NMDA receptors and the GluA1 subunit of AMPA receptors. We also found that the maintenance of basal levels of CaMKII autophosphorylation requires low-voltage gated T-type calcium channels, but not LTCCs or R-type calcium channels. Our findings indicate that CaMKII activity is dynamically regulated by multiple calcium channels in the striatum thus coupling calcium entry to key downstream substrates.

  3. Adaptable, Deployable Entry and Placement Technology (ADEPT) Overview of FY15 Accomplishments

    NASA Technical Reports Server (NTRS)

    Wercinski, P.; Brivkalns, C.; Cassell, A.; Chen, Y.-K.; Boghozian, T.; Chinnapongse, R.; Gasch, M.; Kruger, C.; Makino, A.; Milos, F.; Nishioka, O.; Smith, B.; Squire, T.; Venkatapathy, E.; Yount, B.; Zarchi, K.

    2015-01-01

    ADEPT is an atmospheric entry architecture for missions to most planetary bodies with atmospheres: Current Technology development project funded under STMD Game Changing Development Program (FY12 start); stowed inside the launch vehicle shroud and deployed in space prior to entry; low ballistic coefficient (less than 50 kilograms per square meter) provides a benign deceleration and thermal environment to the payload; High-temperature ribs support three dimensional woven carbon fabric to generate drag and withstand high heating.

  4. [Calcium and health].

    PubMed

    Ortega Anta, Rosa M; Jiménez Ortega, Ana I; López-Sobaler, Ana M

    2015-04-07

    An adequate intake of calcium is only not limited to avoid the risk of osteoporosis and its benefits in longterm bone health, but also it has been linked to protection against various major diseases, such as hypertension, cancer, kidney stones, insulin resistance, diabetes... and several investigations suggest its importance in preventing and controlling obesity. Studies conducted in Spanish representative samples show that a high percentage of adults and children (> 75%) don't achieve the recommended intake of calcium. Moreover, are growing trends among the population suggesting that calcium intake and dairy consumption (main food source of the mineral) are high, and even excessive, in many individuals. This misconception results in that the calcium intake is increasingly far from the recommended one. The maximum tolerable intake of the mineral is fixed at 2.500 mg/day, but this intake is unusual, and it's more disturbing and frequent, to find intakes below the recommended calcium intakes (1.000 and 1.200 mg/day in adults, men and women, respectively). Data from different studies highlight the risk of an inadequate calcium intake and the damages that may affect the health in a long term. It is not about transmitting indiscriminate guidelines in order to increase the intake of calcium / dairy, but the recommended intakes must be met to achieve both the nutritional and health benefits. Also activities for demystification of misconceptions are need, increasingly frequent, that may impair health population.

  5. 19 CFR 10.78 - Entry.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Entry. (a) No entry shall be required for fish or other marine products taken on the high seas by... or other products are brought into port by the taking vessel or are transferred at sea to another... enterprise conducted under the American flag by vessels of the United States on the high seas or in...

  6. 19 CFR 10.78 - Entry.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Entry. (a) No entry shall be required for fish or other marine products taken on the high seas by... or other products are brought into port by the taking vessel or are transferred at sea to another... enterprise conducted under the American flag by vessels of the United States on the high seas or in...

  7. 19 CFR 10.78 - Entry.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Entry. (a) No entry shall be required for fish or other marine products taken on the high seas by... or other products are brought into port by the taking vessel or are transferred at sea to another... enterprise conducted under the American flag by vessels of the United States on the high seas or in...

  8. 19 CFR 10.78 - Entry.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Entry. (a) No entry shall be required for fish or other marine products taken on the high seas by... or other products are brought into port by the taking vessel or are transferred at sea to another... enterprise conducted under the American flag by vessels of the United States on the high seas or in...

  9. 19 CFR 10.78 - Entry.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Entry. (a) No entry shall be required for fish or other marine products taken on the high seas by... or other products are brought into port by the taking vessel or are transferred at sea to another... enterprise conducted under the American flag by vessels of the United States on the high seas or in...

  10. 32 CFR 245.27 - Data entry.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Data entry. 245.27 Section 245.27 National... Under ESCAT § 245.27 Data entry. Aircraft will file IFR or VFR flight plans, assigned a discrete... entered in the remarks section of the flight plan. The EATPL number will be passed with flight plan...

  11. 32 CFR 245.27 - Data entry.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Data entry. 245.27 Section 245.27 National... Under ESCAT § 245.27 Data entry. Aircraft will file IFR or VFR flight plans, assigned a discrete... entered in the remarks section of the flight plan. The EATPL number will be passed with flight plan...

  12. 32 CFR 245.27 - Data entry.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Data entry. 245.27 Section 245.27 National... Under ESCAT § 245.27 Data entry. Aircraft will file IFR or VFR flight plans, assigned a discrete... entered in the remarks section of the flight plan. The EATPL number will be passed with flight plan...

  13. 32 CFR 245.27 - Data entry.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Data entry. 245.27 Section 245.27 National... Under ESCAT § 245.27 Data entry. Aircraft will file IFR or VFR flight plans, assigned a discrete... entered in the remarks section of the flight plan. The EATPL number will be passed with flight plan...

  14. 32 CFR 245.27 - Data entry.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Data entry. 245.27 Section 245.27 National... Under ESCAT § 245.27 Data entry. Aircraft will file IFR or VFR flight plans, assigned a discrete... entered in the remarks section of the flight plan. The EATPL number will be passed with flight plan...

  15. 21 CFR 1316.05 - Entry.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Entry. 1316.05 Section 1316.05 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE FUNCTIONS, PRACTICES, AND PROCEDURES Administrative Inspections § 1316.05 Entry. An inspection shall be carried out by an inspector. Any...

  16. 32 CFR 770.19 - Entry procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.19 Entry procedures. (a) Any person or group of persons desiring the advance consent of the... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  17. 32 CFR 770.19 - Entry procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.19 Entry procedures. (a) Any person or group of persons desiring the advance consent of the... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  18. 32 CFR 770.19 - Entry procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.19 Entry procedures. (a) Any person or group of persons desiring the advance consent of the... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  19. 32 CFR 770.19 - Entry procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.19 Entry procedures. (a) Any person or group of persons desiring the advance consent of the... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  20. 32 CFR 770.19 - Entry procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base, Bangor, Silverdale, Washington § 770.19 Entry procedures. (a) Any person or group of persons desiring the advance consent of the... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  1. Space X First Entry Sample Analysis

    NASA Technical Reports Server (NTRS)

    James, John T.

    2012-01-01

    The toxicological assessment of one sample collected on May 26, 2012 and returned to earth on May 31, 2012 was analyzed for pollutants that had offgassed into the Dragon capsule by the time of first entry operations performed by the ISS crew. The components identified in the first-entry sample and their contributions to the total T-value are shown.

  2. Specification of the Model 3 Entry Lexicon.

    ERIC Educational Resources Information Center

    Rhode, Mary

    The Model 3 communication skills lexicon consists of three lists of words developed by the Southwest Regional Laboratory (SWRL) for use in communication skills instruction in K-6. This report documents the procedures followed in compiling the entry lexicon, the first component of the Model 3 communication skills lexicon. The entry lexicon is…

  3. Modeling radon entry into Florida slab-on-grade houses.

    PubMed

    Revzan, K L; Fisk, W J; Sextro, R G

    1993-10-01

    Radon entry into a Florida house whose concrete slab is supported by a permeable concrete-block stem wall and a concrete footer is modeled. The slab rests on backfill material; the same material is used to fill the footer trench. A region of undisturbed soil is assumed to extend 10 m beyond and below the footer. The soil is assumed homogeneous and isotropic except for certain simulations in which soil layers of high permeability or radium content are introduced. Depressurization of the house induces a pressure field in the soil and backfill. The Laplace equation, resulting from Darcy's law and the continuity equation, is solved using a steady-state finite-difference model to determine this field. The mass-transport equation is then solved to obtain the diffusive and advective radon entry rates through the slab; the permeable stem wall; gaps at the intersections of the slab, stem wall, and footer; and gaps in the slab. These rates are determined for variable soil, backfill, and stem-wall permeability and radium content, slab-opening width and position, slab and stem-wall diffusivity, and water table depth. The variations in soil permeability and radium content include cases of horizontally stratified soil. We also consider the effect of a gap between the edge of the slab and the stem wall that restricts the passage of soil gas from the stem wall into the house. Calculations indicate that the total radon entry rate is relatively low unless the soil or backfill permeability or radium content is high. Variations in most of the factors, other than the soil permeability and radium content, have only a small effect on the total radon entry rate. However, for a fixed soil permeability, the total radon entry rate may be reduced by a factor of 2 or more by decreasing the backfill permeability, by making the stem wall impermeable and gap-free, (possibly by constructing a one-piece slab/stem-wall/footer), or by increasing the pressure in the interior of the stem wall (by

  4. Entry Pathways of Herpes Simplex Virus Type 1 into Human Keratinocytes Are Dynamin- and Cholesterol-Dependent

    PubMed Central

    Hsu, Mei-Ju; Rixon, Frazer J.; Knebel-Mörsdorf, Dagmar

    2011-01-01

    Herpes simplex virus type 1 (HSV-1) can enter cells via endocytic pathways or direct fusion at the plasma membrane depending on the cell line and receptor(s). Most studies into virus entry have used cultured fibroblasts but since keratinocytes represent the primary entry site for HSV-1 infection in its human host, we initiated studies to characterize the entry pathway of HSV-1 into human keratinocytes. Electron microscopy studies visualized free capsids in the cytoplasm and enveloped virus particles in vesicles suggesting viral uptake both by direct fusion at the plasma membrane and by endocytic vesicles. The ratio of the two entry modes differed in primary human keratinocytes and in the keratinocyte cell line HaCaT. Inhibitor studies further support a role for endocytosis during HSV-1 entry. Infection was inhibited by the cholesterol-sequestering drug methyl-β-cyclodextrin, which demonstrates the requirement for host cholesterol during virus entry. Since the dynamin-specific inhibitor dynasore and overexpression of a dominant-negative dynamin mutant blocked infection, we conclude that the entry pathways into keratinocytes are dynamin-mediated. Electron microscopy studies confirmed that virus uptake is completely blocked when the GTPase activity of dynamin is inhibited. Ex vivo infection of murine epidermis that was treated with dynasore further supports the essential role of dynamin during entry into the epithelium. Thus, we conclude that HSV-1 can enter human keratinocytes by alternative entry pathways that require dynamin and host cholesterol. PMID:22022400

  5. HADES PC network: an automated data entry system

    SciTech Connect

    Hegemann, D.L.

    1986-09-12

    Mound's Health Physics section is faced with an increasing need to store and retrieve radiological data. This need has been addressed by the Health Physics Automated Data Entry System (HADES) which assumed a full production status on April 1, 1986. Mound's Technical Computer Support group implemented HADES in a series of phases which allowed high priority needs to be immediately supported. As a result of the system's personal computer-based structure, additional capabilities such as automated data acquisition were easily brought on-line. Since its inception in the first quarter of 1984, HADES has matured into a cost-efficient automated data acquisition system for Mound's Health Physics section.

  6. Orion Entry Display Feeder and Interactions with the Entry Monitor System

    NASA Technical Reports Server (NTRS)

    Baird, Darren; Bernatovich, Mike; Gillespie, Ellen; Kadwa, Binaifer; Matthews, Dave; Penny, Wes; Zak, Tim; Grant, Mike; Bihari, Brian

    2010-01-01

    The Orion spacecraft is designed to return astronauts to a landing within 10 km of the intended landing target from low Earth orbit, lunar direct-entry, and lunar skip-entry trajectories. Al pile the landing is nominally controlled autonomously, the crew can fly precision entries manually in the event of an anomaly. The onboard entry displays will be used by the crew to monitor and manually fly the entry, descent, and landing, while the Entry Monitor System (EMS) will be used to monitor the health and status of the onboard guidance and the trajectory. The entry displays are driven by the entry display feeder, part of the Entry Monitor System (EMS). The entry re-targeting module, also part of the EMS, provides all the data required to generate the capability footprint of the vehicle at any point in the trajectory, which is shown on the Primary Flight Display (PFD). It also provides caution and warning data and recommends the safest possible re-designated landing site when the nominal landing site is no longer within the capability of the vehicle. The PFD and the EMS allow the crew to manually fly an entry trajectory profile from entry interface until parachute deploy having the flexibility to manually steer the vehicle to a selected landing site that best satisfies the priorities of the crew. The entry display feeder provides data from the ENIS and other components of the GNC flight software to the displays at the proper rate and in the proper units. It also performs calculations that are specific to the entry displays and which are not made in any other component of the flight software. In some instances, it performs calculations identical to those performed by the onboard primary guidance algorithm to protect against a guidance system failure. These functions and the interactions between the entry display feeder and the other components of the EMS are described.

  7. 21 CFR 184.1191 - Calcium carbonate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation process”; or (3) By precipitation of calcium carbonate from calcium chloride in the “Calcium...

  8. 21 CFR 184.1191 - Calcium carbonate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation process”; or (3) By precipitation of calcium carbonate from calcium chloride in the “Calcium...

  9. 21 CFR 184.1191 - Calcium carbonate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation process”; or (3) By precipitation of calcium carbonate from calcium chloride in the “Calcium...

  10. 21 CFR 184.1191 - Calcium carbonate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation process”; or (3) By precipitation of calcium carbonate from calcium chloride in the “Calcium...

  11. CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING ON LEFT, ...

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

    CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING ON LEFT, CALCIUM CHLORIDE STORAGE BUILDING ON RIGHT OF CENTER WITH TOP OF SA (SODA ASH) BUILDING IN RIGHT BACKGROUND. - Solvay Process Company, Calcium Chloride Plant, Between Willis & Milton Avenues, Solvay, Onondaga County, NY

  12. 19 CFR 143.35 - Procedure for electronic entry summary.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Procedure for electronic entry summary. 143.35...; DEPARTMENT OF THE TREASURY (CONTINUED) SPECIAL ENTRY PROCEDURES Electronic Entry Filing § 143.35 Procedure for electronic entry summary. In order to obtain entry summary processing electronically, the...

  13. 19 CFR 142.3 - Entry documentation required.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry documentation required. 142.3 Section 142.3... TREASURY (CONTINUED) ENTRY PROCESS Entry Documentation § 142.3 Entry documentation required. (a) Contents. Except as provided in paragraph (b) of this section, the entry documentation required to secure...

  14. 19 CFR 143.35 - Procedure for electronic entry summary.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Procedure for electronic entry summary. 143.35...; DEPARTMENT OF THE TREASURY (CONTINUED) SPECIAL ENTRY PROCEDURES Electronic Entry Filing § 143.35 Procedure for electronic entry summary. In order to obtain entry summary processing electronically, the...

  15. 50 CFR 91.22 - Display of contest entries.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Display of contest entries. 91.22 Section... Administering the Contest § 91.22 Display of contest entries. The Federal Duck Stamp Office assigns all eligible entries a number as entries are received. That office displays the entries in numerical order at...

  16. 50 CFR 91.22 - Display of contest entries.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Display of contest entries. 91.22 Section... Administering the Contest § 91.22 Display of contest entries. The Federal Duck Stamp Office assigns all eligible entries a number as entries are received. That office displays the entries in numerical order at...

  17. 50 CFR 91.22 - Display of contest entries.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Display of contest entries. 91.22 Section... Administering the Contest § 91.22 Display of contest entries. The Federal Duck Stamp Office assigns all eligible entries a number as entries are received. That office displays the entries in numerical order at...

  18. 50 CFR 91.22 - Display of contest entries.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Display of contest entries. 91.22 Section... Administering the Contest § 91.22 Display of contest entries. The Federal Duck Stamp Office assigns all eligible entries a number as entries are received. That office displays the entries in numerical order at...

  19. 50 CFR 91.22 - Display of contest entries.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Display of contest entries. 91.22 Section... Administering the Contest § 91.22 Display of contest entries. The Federal Duck Stamp Office assigns all eligible entries a number as entries are received. That office displays the entries in numerical order at...

  20. 50 CFR 679.83 - Rockfish Program entry level fishery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Rockfish Program entry level fishery. 679... ALASKA Rockfish Program § 679.83 Rockfish Program entry level fishery. (a) Rockfish entry level fishery—(1) General. A rockfish entry level harvester and rockfish entry level processor may participate...

  1. 50 CFR 679.83 - Rockfish Program entry level fishery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Rockfish Program entry level fishery. 679... ALASKA Rockfish Program § 679.83 Rockfish Program entry level fishery. (a) Rockfish entry level fishery—(1) General. A rockfish entry level harvester and rockfish entry level processor may participate...

  2. Effects of dietary vitamin D on calcium and magnesium levels in mice with abnormal calcium metabolism

    SciTech Connect

    Spurlock, B.G.; West, W.L.; Knight, E.M. )

    1991-03-11

    In previous studies vitamin D has been used to induce cardiac calcium overload in laboratory animals. Interrelationships between calcium and magnesium metabolism are also documented. The authors have investigated the effect of varying vitamin D in the diet on calcium and magnesium levels in plasma, kidney and heart of DBA mice which exhibit genetic abnormalities in cardiac calcium metabolism. Weanling DBA mice were maintained for 28 days on an AIN-76 diet containing either 1,000 I.U. of vitamin D{sub 3} per kg of diet (control); 4,000 I.U. of vitamin D{sub 3} per kg of diet; or no vitamin D. When compared to controls, supplemented animals showed significantly higher plasma magnesium, kidney calcium and kidney magnesium levels; animals receiving the vitamin D-deficient diet exhibited increases in cardiac calcium levels. The authors results support previous findings that vitamin D deficiency increases cardiac calcium uptake and suggest a possible role of vitamin D in magnesium metabolism.

  3. Thermal Soak Analysis of Earth Entry Vehicles

    NASA Technical Reports Server (NTRS)

    Agrawal, Parul; Sepka, Steven A.; Aliaga, Jose F.; Venkatapathy, Ethiraj; Samareh, Jamshid A.

    2012-01-01

    The Multi-Mission Earth Entry Vehicle project is developing an integrated tool called Multi Mission System Analysis for Planetary Entry Descent and Landing that will provide key technology solutions including mass sizing, aerodynamics, aerothermodynamics, and thermal and structural analysis for any given sample return mission. Thermal soak analysis and temperature predictions of various components including the payload container of the entry vehicle are part of the solution that this tool will offer to mission designers. The present paper focuses on the thermal soak analysis of an entry vehicle design based on the Mars Sample Return entry vehicle geometry and discusses a technical approach to develop parametric models for thermal soak analysis that will be integrated into the tool.

  4. Trajectory and atmospheric structure from entry probes: Demonstration of a real-time reconstruction technique using a simple direct-to-Earth radio link

    NASA Astrophysics Data System (ADS)

    Withers, Paul

    2010-12-01

    The reconstruction of the trajectory and atmospheric structure associated with an entry probe has traditionally relied upon onboard accelerometer measurements. Here we outline an equivalent reconstruction technique that uses Doppler-shifted direct-to-Earth transmissions instead. A critical assumption is that the entry probe's angle of attack is zero. The technique is successfully demonstrated on the atmospheric entry of the Mars Exploration Rover Opportunity, terminating at parachute deployment. This technique can be applied in real-time, which supports mission operations and public engagement. It can also be applied to entry probes that fail during their high-risk atmospheric entry.

  5. Trajectory And Atmospheric Structure From Entry Probes: Demonstration Of A Real-time Reconstruction Technique Using A Simple Direct-to-earth Radio Link

    NASA Astrophysics Data System (ADS)

    Withers, Paul

    2010-10-01

    The reconstruction of the trajectory and atmospheric structure associated with an entry probe has traditionally relied upon onboard accelerometer measurements. Here we outline an equivalent reconstruction technique that uses Doppler-shifted direct-to-Earth transmissions instead. A critical assumption is that the entry probe's angle of attack is zero. The technique is successfully demonstrated on the atmospheric entry of the Mars Exploration Rover Opportunity, terminating at parachute deployment. This technique can be applied in real-time, which supports mission operations and public engagement. It can also be applied to entry probes that fail during their high-risk atmospheric entry.

  6. Calcium trafficking integrates endoplasmic reticulum function with mitochondrial bioenergetics

    PubMed Central

    Kaufman, Randal J.; Malhotra, Jyoti D.

    2014-01-01

    Calcium homeostasis is central to all cellular functions and has been studied for decades. Calcium acts as a critical second messenger for both extracellular and intracellular signaling and is fundamental in cell life and death decisions [1]. The calcium gradient in the cell is coupled with an inherent ability of the divalent cation to reversibly bind multiple target biological molecules to generate an extremely versatile signaling system [2]. Calcium signals are used by the cell to control diverse processes as development, neurotransmitter release, muscle contraction, metabolism, autophagy and cell death. “Cellular calcium overload” is detrimental to cellular health, resulting in massive activation of proteases and phospholipases leading to cell death [3]. Historically, cell death associated with calcium ion perturbations has been primarily recognized as necrosis. Recent evidence clearly associate changes in calcium ion concentrations with more sophisticated forms of cellular demise, including apoptosis [4] [5] [6] [7]. Although the endoplasmic reticulum (ER) serves as the primary calcium store in the metazoan cell, dynamic calcium release to the cytosol, mitochondria, nuclei and other organelles orchestrate diverse coordinated responses. Most evidence supports that calcium transport from the ER to mitochondria plays a significant role in regulating cellular bioenergetics, production of reactive oxygen species, induction of autophagy and apoptosis. Recently, molecular identities that mediate calcium traffic between the ER and mitochondria have been discovered [8] [9] [10]. The next questions are how they are regulated for exquisite tight control of ER – mitochondrial calcium dynamics. This review attempts to summarize recent advances in the role of calcium in regulation of ER and mitochondrial function. PMID:24690484

  7. Electric-field-driven polymer entry into asymmetric nanoscale channels.

    PubMed

    Nikoofard, Narges; Fazli, Hossein

    2012-02-01

    The electric-field-driven entry process of flexible charged polymers such as single-stranded DNA (ssDNA) into asymmetric nanoscale channels such as the α-hemolysin protein channel is studied theoretically and using molecular dynamics simulations. Dependence of the height of the free-energy barrier on the polymer length, the strength of the applied electric field, and the channel entrance geometry is investigated. It is shown that the squeezing effect of the driving field on the polymer and the lateral confinement of the polymer before its entry to the channel crucially affect the barrier height and its dependence on the system parameters. The attempt frequency of the polymer for passing the channel is also discussed. Our theoretical and simulation results support each other and describe related data sets of polymer translocation experiments through the α-hemolysin protein channel reasonably well.

  8. Assisted entry mitigates text messaging-based driving detriment.

    PubMed

    Sawyer, Benjamin D; Hancock, Peter A

    2012-01-01

    Previous research using cell phones indicates that manual manipulation is not a principal component of text messaging relating driving detriment. This paper suggests that manipulation of a phone in conjunction with the cognitive need to compose the message itself co-act to contribute to driving degradation. This being so, drivers sending text messages might experience reduced interference to the driving task if the text messaging itself were assisted through the predictive T9 system. We evaluated undergraduate drivers in a simulator who drove and texted using either Assisted Text entry, via Nokia's T9 system, or unassisted entry via the multitap interface. Results supported the superiority of the T9 system over the multitap system implying that specific assistive technologies can modulate the degradation of capacity which texting tragically induces.

  9. Calcium, obesity, and the role of the calcium-sensing receptor.

    PubMed

    Villarroel, Pia; Villalobos, Elisa; Reyes, Marcela; Cifuentes, Mariana

    2014-10-01

    The elevated prevalence of obesity worldwide is a challenging public health problem. Dietary calcium intake is frequently below recommendations, and evidence gathered for more than a decade suggests that inadequate calcium intake may be related to increased body weight and/or body fat, although a consensus has yet to be reached. Whole-body energy balance and the cellular mechanisms involved have been proposed to explain this relationship, and increasing evidence from epidemiological, clinical, and basic research lends support to the hypothesis that calcium is linked to the regulation of body weight. This review provides a critical appraisal of evidence from studies that examined several different aspects of this issue. Different mechanisms are highlighted and, based on recent work, new perspectives are offered, which incorporate the concept of obesity-associated inflammation and the possible role of the extracellular calcium-sensing receptor.

  10. Basal and Activated Calcium Sensitization Mediated by RhoA/Rho Kinase Pathway in Rats with Genetic and Salt Hypertension.

    PubMed

    Behuliak, Michal; Bencze, Michal; Vaněčková, Ivana; Kuneš, Jaroslav; Zicha, Josef

    2017-01-01

    Calcium sensitization mediated by RhoA/Rho kinase pathway can be evaluated either in the absence (basal calcium sensitization) or in the presence of endogenous vasoconstrictor systems (activated calcium sensitization). Our aim was to compare basal and activated calcium sensitization in three forms of experimental hypertension with increased sympathetic tone and enhanced calcium entry-spontaneously hypertensive rats (SHR), heterozygous Ren-2 transgenic rats (TGR), and salt hypertensive Dahl rats. Activated calcium sensitization was determined as blood pressure reduction induced by acute administration of Rho kinase inhibitor fasudil in conscious rats with intact sympathetic nervous system (SNS) and renin-angiotensin system (RAS). Basal calcium sensitization was studied as fasudil-dependent difference in blood pressure response to calcium channel opener BAY K8644 in rats subjected to RAS and SNS blockade. Calcium sensitization was also estimated from reduced development of isolated artery contraction by Rho kinase inhibitor Y-27632. Activated calcium sensitization was enhanced in all three hypertensive models (due to the hyperactivity of vasoconstrictor systems). In contrast, basal calcium sensitization was reduced in SHR and TGR relative to their controls, whereas it was augmented in salt-sensitive Dahl rats relative to their salt-resistant controls. Similar differences in calcium sensitization were seen in femoral arteries of SHR and Dahl rats.

  11. HTCC: Broad Range Inhibitor of Coronavirus Entry

    PubMed Central

    Milewska, Aleksandra; Kaminski, Kamil; Ciejka, Justyna; Kosowicz, Katarzyna; Zeglen, Slawomir; Wojarski, Jacek; Nowakowska, Maria; Szczubiałka, Krzysztof; Pyrc, Krzysztof

    2016-01-01

    To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobically-modified derivative (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses. PMID:27249425

  12. Calcium Channel Blockers

    MedlinePlus

    ... such as high blood pressure, chest pain and Raynaud's disease. Find out more about this class of medication. ... Irregular heartbeats (arrhythmia) Some circulatory conditions, such as Raynaud's disease For black people and older people, calcium channel ...

  13. Stoichiometry of Calcium Medicines

    ERIC Educational Resources Information Center

    Pinto, Gabriel

    2005-01-01

    The topic of calcium supplement and its effects on human lives is presented in the way of questions to the students. It enables the students to realize the relevance of chemistry outside the classroom surrounding.

  14. Calcium-D-glucarate.

    PubMed

    2002-08-01

    Calcium-D-glucarate is the calcium salt of D-glucaric acid, a substance produced naturally in small amounts by mammals, including humans. Glucaric acid is also found in many fruits and vegetables with the highest concentrations to be found in oranges, apples, grapefruit, and cruciferous vegetables. Oral supplementation of calcium-D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme produced by colonic microflora and involved in Phase II liver detoxification. Elevated beta-glucuronidase activity is associated with an increased risk for various cancers, particularly hormone-dependent cancers such as breast, prostate, and colon cancers. Other potential clinical applications of oral calcium-D-glucarate include regulation of estrogen metabolism and as a lipid-lowering agent.

  15. Do calcium buffers always slow down the propagation of calcium waves?

    PubMed

    Tsai, Je-Chiang

    2013-12-01

    Calcium buffers are large proteins that act as binding sites for free cytosolic calcium. Since a large fraction of cytosolic calcium is bound to calcium buffers, calcium waves are widely observed under the condition that free cytosolic calcium is heavily buffered. In addition, all physiological buffered excitable systems contain multiple buffers with different affinities. It is thus important to understand the properties of waves in excitable systems with the inclusion of buffers. There is an ongoing controversy about whether or not the addition of calcium buffers into the system always slows down the propagation of calcium waves. To solve this controversy, we incorporate the buffering effect into the generic excitable system, the FitzHugh-Nagumo model, to get the buffered FitzHugh-Nagumo model, and then to study the effect of the added buffer with large diffusivity on traveling waves of such a model in one spatial dimension. We can find a critical dissociation constant (K = K(a)) characterized by system excitability parameter a such that calcium buffers can be classified into two types: weak buffers (K ∈ (K(a), ∞)) and strong buffers (K ∈ (0, K(a))). We analytically show that the addition of weak buffers or strong buffers but with its total concentration b(0)(1) below some critical total concentration b(0,c)(1) into the system can generate a traveling wave of the resulting system which propagates faster than that of the origin system, provided that the diffusivity D1 of the added buffers is sufficiently large. Further, the magnitude of the wave speed of traveling waves of the resulting system is proportional to √D1 as D1 --> ∞. In contrast, the addition of strong buffers with the total concentration b(0)(1) > b(0,c)(1) into the system may not be able to support the formation of a biologically acceptable wave provided that the diffusivity D1 of the added buffers is sufficiently large.

  16. Viral cell recognition and entry.

    PubMed Central

    Rossmann, M. G.

    1994-01-01

    Rhinovirus infection is initiated by the recognition of a specific cell-surface receptor. The major group of rhinovirus serotypes attach to intercellular adhesion molecule-1 (ICAM-1). The attachment process initiates a series of conformational changes resulting in the loss of genomic RNA from the virion. X-ray crystallography and sequence comparisons suggested that a deep crevice or canyon is the site on the virus recognized by the cellular receptor molecule. This has now been verified by electron microscopy of human rhinovirus 14 (HRV14) and HRV16 complexed with a soluble component of ICAM-1. A hydrophobic pocket underneath the canyon is the site of binding of various hydrophobic drug compounds that can inhibit attachment and uncoating. This pocket is also associated with an unidentified, possibly cellular in origin, "pocket factor." The pocket factor binding site overlaps the binding site of the receptor. It is suggested that competition between the pocket factor and receptor regulates the conformational changes required for the initiation of the entry of the genomic RNA into the cell. PMID:7849588

  17. LABORATORY VOICE DATA ENTRY SYSTEM.

    SciTech Connect

    PRAISSMAN,J.L.SUTHERLAND,J.C.

    2003-04-01

    We have assembled a system using a personal computer workstation equipped with standard office software, an audio system, speech recognition software and an inexpensive radio-based wireless microphone that permits laboratory workers to enter or modify data while performing other work. Speech recognition permits users to enter data while their hands are holding equipment or they are otherwise unable to operate a keyboard. The wireless microphone allows unencumbered movement around the laboratory without a ''tether'' that might interfere with equipment or experimental procedures. To evaluate the potential of voice data entry in a laboratory environment, we developed a prototype relational database that records the disposal of radionuclides and/or hazardous chemicals Current regulations in our laboratory require that each such item being discarded must be inventoried and documents must be prepared that summarize the contents of each container used for disposal. Using voice commands, the user enters items into the database as each is discarded. Subsequently, the program prepares the required documentation.

  18. Calcium-sensing receptors.

    PubMed

    Goodman, William G

    2004-01-01

    It is now known that variations in extracellular calcium concentration exert diverse physiologic effects in a variety of tissues that are mediated by a calcium-sensing receptor (CaSRs). In parathyroid tissue, the CaSR represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration, modulate parathyroid hormone (PTH) secretion accordingly, and thus maintain serum calcium levels within a narrow physiologic range. In the kidney, the CaSR regulates renal calcium excretion and influences the transepithelial movement of water and other electrolytes. More generally, activation of the CaSR represents an important signal transduction pathway in intestine, placenta, brain, and perhaps bone. Some of these actions involve cell cycle regulation, changes that may be relevant to understanding the pathogenesis of parathyroid gland hyperplasia in secondary hyperparathyroidism caused by chronic kidney disease. The CaSR represents an appealing target for therapeutic agents designed to modify parathyroid gland function in vivo, offering the prospect of novel therapies for selected disorders of bone and mineral metabolism. Other receptors capable of responding to extracellular calcium ions also have been identified, but the functional importance of these interactions remains to be determined.

  19. Stoichiometry of Envelope Glycoprotein Trimers in the Entry of Human Immunodeficiency Virus Type 1

    PubMed Central

    Yang, Xinzhen; Kurteva, Svetla; Ren, Xinping; Lee, Sandra; Sodroski, Joseph

    2005-01-01

    The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Envs) function as a trimer, mediating virus entry by promoting the fusion of the viral and target cell membranes. HIV-1 Env trimers induce membrane fusion through a pH-independent pathway driven by the interaction between an Env trimer and its cellular receptors, CD4 and CCR5/CXCR4. We studied viruses with mixed heterotrimers of wild-type and dominant-negative Envs to determine the number (T) of Env trimers required for HIV-1 entry. To our surprise, we found that a single Env trimer is capable of supporting HIV-1 entry; i.e., T = 1. A similar approach was applied to investigate the entry stoichiometry of envelope glycoproteins from amphotropic murine leukemia virus (A-MLV), avian sarcoma/leukosis virus type A (ASLV-A), and influenza A virus. When pseudotyped on HIV-1 virions, the A-MLV and ASLV-A Envs also exhibit a T = 1 entry stoichiometry. In contrast, eight to nine influenza A virus hemagglutinin trimers function cooperatively to achieve membrane fusion and virus entry, using a pH-dependent pathway. The different entry requirements for cooperativity among Env trimers for retroviruses and influenza A virus may influence viral strategies for replication and evasion of the immune system. PMID:16160141

  20. Oxidative calcium release from catechol.

    PubMed

    Riley, Patrick A; Stratford, Michael R L

    2015-04-01

    Oxidation of 4-methylcatechol previously exposed to aqueous calcium chloride was shown by ion chromatography to be associated with release of calcium ions. The catechol was oxidised to the corresponding orthoquinone by the use of tyrosinase from Agaricus bisporus. The oxidative release of calcium from the catechol is ascribed to the diminution of the available hydroxyl functions able to act as chelating groups. Our results suggest that the redox status of melanin may regulate calcium binding and influence calcium levels in pigmented cells.

  1. Entry Guidance for the Reusable Launch Vehicle

    NASA Technical Reports Server (NTRS)

    Lu, Ping

    1999-01-01

    The X-33 Advanced Technology Demonstrator is a half-scale prototype developed to test the key technologies needed for a full-scale single-stage reusable launch vehicle (RLV). The X-33 is a suborbital vehicle that will be launched vertically, and land horizontally. The goals of this research were to develop an alternate entry guidance scheme for the X-33 in parallel to the actual X-33 entry guidance algorithms, provide comparative and complementary study, and identify potential new ways to improve entry guidance performance. Toward these goals, the nominal entry trajectory is defined by a piecewise linear drag-acceleration-versus-energy profile, which is in turn obtained by the solution of a semi-analytical parameter optimization problem. The closed-loop guidance is accomplished by tracking the nominal drag profile with primarily bank-angle modulation on-board. The bank-angle is commanded by a single full-envelope nonlinear trajectory control law. Near the end of the entry flight, the guidance logic is switched to heading control in order to meet strict conditions at the terminal area energy management interface. Two methods, one on ground-track control and the other on heading control, were proposed and examined for this phase of entry guidance where lateral control is emphasized. Trajectory dispersion studies were performed to evaluate the effectiveness of the entry guidance algorithms against a number of uncertainties including those in propulsion system, atmospheric properties, winds, aerodynamics, and propellant loading. Finally, a new trajectory-regulation method is introduced at the end as a promising precision entry guidance method. The guidance principle is very different and preliminary application in X-33 entry guidance simulation showed high precision that is difficult to achieve by existing methods.

  2. Advances in spacecraft atmospheric entry guidance

    NASA Astrophysics Data System (ADS)

    Benito Manrique, Joel

    In order to advance entry guidance technology two different research areas have been explored with the objective of increasing the reachable landing area and the landing accuracy for future Mars missions. Currently only the northern hemisphere of Mars is available for landing due to its low elevation. Only low elevation landing sites have the necessary atmospheric density to allow landing using current Entry, Descent and Landing (EDL) technology. In order to reach most of the Ancient Highlands, the majority of the southern hemisphere, advanced EDL technology is needed in multiple fields, including entry guidance. The first research area is the definition and applications of reachable and controllable sets for entry. The definition of the reachable and controllable sets provides a framework for the study of the capabilities of an entry vehicle in a given planet. Reachable and controllable sets can be used to comprehensively characterize the envelope of trajectories that a vehicle can fly, the sites it can reach and the entry states that can be accommodated. The sets can also be used for the evaluation of trajectory planning algorithms and to assist in the selection of the entry or landing sites. In essence, the reachable and controllable sets offer a powerful vehicle and trajectory analysis and design framework that allows for better mission design choices. In order to illustrate the use of the sets, they are computed for a representative Mars mission using two different vehicle configurations. The sets characterize the impact of the vehicle configuration on the entry capability. Furthermore, the sets are used to find the best skip-entry trajectory for a return from the Moon mission, highlighting the utility of the sets in atmospheric maneuvers other than entry. The second research area is the development of the components of an entry guidance algorithm that allow high elevation landing and provide as well high landing accuracy. The approach taken follows the

  3. Entry, Descent, and Landing With Propulsive Deceleration

    NASA Technical Reports Server (NTRS)

    Palaszewski, Bryan

    2012-01-01

    The future exploration of the Solar System will require innovations in transportation and the use of entry, descent, and landing (EDL) systems at many planetary landing sites. The cost of space missions has always been prohibitive, and using the natural planetary and planet s moons atmospheres for entry, descent, and landing can reduce the cost, mass, and complexity of these missions. This paper will describe some of the EDL ideas for planetary entry and survey the overall technologies for EDL that may be attractive for future Solar System missions.

  4. Adjustable Bracket For Entry Of Welding Wire

    NASA Technical Reports Server (NTRS)

    Gilbert, Jeffrey L.; Gutow, David A.

    1993-01-01

    Wire-entry bracket on welding torch in robotic welding system provides for adjustment of angle of entry of welding wire over range of plus or minus 30 degrees from nominal entry angle. Wire positioned so it does not hide weld joint in view of through-the-torch computer-vision system part of robot-controlling and -monitoring system. Swiveling bracket also used on nonvision torch on which wire-feed-through tube interferes with workpiece. Angle simply changed to one giving sufficient clearance.

  5. Parachute design for Galileo Jupiter entry probe

    NASA Technical Reports Server (NTRS)

    Rodier, R. W.; Thuss, R. C.; Terhune, J. E.

    1981-01-01

    This paper discusses the parachute subsystem used on an atmospheric entry probe that will descend through the clouds of Jupiter. The entry probe is a part of the Galileo Project to be launched in 1985 aboard the Space Shuttle; the entry probe will encounter the planet in 1988. The parachute subsystem consists of a pilot parachute and a main parachute, and both are of conventional conical ribbon design. Key considerations in the design of the parachutes and a summary of the parachute subsystem test program, which includes two air drop tests and a systems drop test (balloon launched), are presented.

  6. Available hardware for automated entry control

    SciTech Connect

    Holmes, J.P.

    1990-11-01

    Automated entry control has become an increasingly important issue at facilities where budget constraints are limiting options for manned entry control points. Three questions are immediately raised when automated entry control is considered: What hardware is available How much does it cost How effective is it in maintaining security Ongoing work at Sandia National Labs is attempting to answer these questions and establish a data base for use by facility security managers working the problem of how to maintain security on a limited budget. 14 refs.

  7. Texting while driving: is speech-based text entry less risky than handheld text entry?

    PubMed

    He, J; Chaparro, A; Nguyen, B; Burge, R J; Crandall, J; Chaparro, B; Ni, R; Cao, S

    2014-11-01

    Research indicates that using a cell phone to talk or text while maneuvering a vehicle impairs driving performance. However, few published studies directly compare the distracting effects of texting using a hands-free (i.e., speech-based interface) versus handheld cell phone, which is an important issue for legislation, automotive interface design and driving safety training. This study compared the effect of speech-based versus handheld text entries on simulated driving performance by asking participants to perform a car following task while controlling the duration of a secondary text-entry task. Results showed that both speech-based and handheld text entries impaired driving performance relative to the drive-only condition by causing more variation in speed and lane position. Handheld text entry also increased the brake response time and increased variation in headway distance. Text entry using a speech-based cell phone was less detrimental to driving performance than handheld text entry. Nevertheless, the speech-based text entry task still significantly impaired driving compared to the drive-only condition. These results suggest that speech-based text entry disrupts driving, but reduces the level of performance interference compared to text entry with a handheld device. In addition, the difference in the distraction effect caused by speech-based and handheld text entry is not simply due to the difference in task duration.

  8. 9 CFR 93.806 - Animals refused entry.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Elephants, Hippopotami, Rhinoceroses, and Tapirs § 93.806 Animals refused entry. Any elephant, hippopotamus, rhinoceros, or tapir refused entry into...

  9. 9 CFR 93.806 - Animals refused entry.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Elephants, Hippopotami, Rhinoceroses, and Tapirs § 93.806 Animals refused entry. Any elephant, hippopotamus, rhinoceros, or tapir refused entry into...

  10. 9 CFR 93.806 - Animals refused entry.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Elephants, Hippopotami, Rhinoceroses, and Tapirs § 93.806 Animals refused entry. Any elephant, hippopotamus, rhinoceros, or tapir refused entry into...

  11. 9 CFR 93.806 - Animals refused entry.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Elephants, Hippopotami, Rhinoceroses, and Tapirs § 93.806 Animals refused entry. Any elephant, hippopotamus, rhinoceros, or tapir refused entry into...

  12. 9 CFR 93.806 - Animals refused entry.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Elephants, Hippopotami, Rhinoceroses, and Tapirs § 93.806 Animals refused entry. Any elephant, hippopotamus, rhinoceros, or tapir refused entry into...

  13. Structure and Function of a Genetically Engineered Mimic of a Nonenveloped Virus Entry Intermediate

    SciTech Connect

    Banerjee, Manidipa; Speir, Jeffrey A.; Kwan, Maggie H.; Huang, Rick; Aryanpur, Peyman P.; Bothner, Brian; Johnson, John E.

    2010-04-07

    Divalent metal ions are components of numerous icosahedral virus capsids. Flock House virus (FHV), a small RNA virus of the family Nodaviridae, was utilized as an accessible model system with which to address the effects of metal ions on capsid structure and on the biology of virus-host interactions. Mutations at the calcium-binding sites affected FHV capsid stability and drastically reduced virus infectivity, without altering the overall architecture of the capsid. The mutations also altered the conformation of gamma, a membrane-disrupting, virus-encoded peptide usually sequestered inside the capsid, by increasing its exposure under neutral pH conditions. Our data demonstrate that calcium binding is essential for maintaining a pH-based control on gamma exposure and host membrane disruption, and they reveal a novel rationale for the metal ion requirement during virus entry and infectivity. In the light of the phenotypes displayed by a calcium site mutant of FHV, we suggest that this mutant corresponds to an early entry intermediate formed in the endosomal pathway.

  14. Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

    SciTech Connect

    Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

    1989-01-01

    Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release.

  15. Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance

    PubMed Central

    Oh-hora, Masatsugu; Yamashita, Megumi; Hogan, Patrick G; Sharma, Sonia; Lamperti, Ed; Chung, Woo; Prakriya, Murali; Feske, Stefan; Rao, Anjana

    2009-01-01

    Store-operated Ca2+ entry through calcium release–activated calcium channels is the chief mechanism for increasing intracellular Ca2+ in immune cells. Here we show that mouse T cells and fibroblasts lacking the calcium sensor STIM1 had severely impaired store-operated Ca2+ influx, whereas deficiency in the calcium sensor STIM2 had a smaller effect. However, T cells lacking either STIM1 or STIM2 had much less cytokine production and nuclear translocation of the transcription factor NFAT. T cell–specific ablation of both STIM1 and STIM2 resulted in a notable lymphoproliferative phenotype and a selective decrease in regulatory T cell numbers. We conclude that both STIM1 and STIM2 promote store-operated Ca2+ entry into T cells and fibroblasts and that STIM proteins are required for the development and function of regulatory T cells. PMID:18327260

  16. [The electronic health record: computerised provider order entry and the electronic instruction document as new functionalities].

    PubMed

    Derikx, Joep P M; Erdkamp, Frans L G; Hoofwijk, A G M

    2013-01-01

    An electronic health record (EHR) should provide 4 key functionalities: (a) documenting patient data; (b) facilitating computerised provider order entry; (c) displaying the results of diagnostic research; and (d) providing support for healthcare providers in the clinical decision-making process.- Computerised provider order entry into the EHR enables the electronic receipt and transfer of orders to ancillary departments, which can take the place of handwritten orders.- By classifying the computer provider order entries according to disorders, digital care pathways can be created. Such care pathways could result in faster and improved diagnostics.- Communicating by means of an electronic instruction document that is linked to a computerised provider order entry facilitates the provision of healthcare in a safer, more efficient and auditable manner.- The implementation of a full-scale EHR has been delayed as a result of economic, technical and legal barriers, as well as some resistance by physicians.

  17. [Microbial geochemical calcium cycle].

    PubMed

    Zavarzin, G A

    2002-01-01

    The participation of microorganisms in the geochemical calcium cycle is the most important factor maintaining neutral conditions on the Earth. This cycle has profound influence on the fate of inorganic carbon, and, thereby, on the removal of CO2 from the atmosphere. The major part of calcium deposits was formed in the Precambrian, when prokaryotic biosphere predominated. After that, calcium recycling based on biogenic deposition by skeletal organisms became the main process. Among prokaryotes, only a few representatives, e.g., cyanobacteria, exhibit a special calcium function. The geochemical calcium cycle is made possible by the universal features of bacteria involved in biologically mediated reactions and is determined by the activities of microbial communities. In the prokaryotic system, the calcium cycle begins with the leaching of igneous rock predominantly through the action of the community of organotrophic organisms. The release of carbon dioxide to the soil air by organotrophic aerobes leads to leaching with carbonic acid and soda salinization. Under anoxic conditions, of major importance is the organic acid production by primary anaerobes (fermentative microorganisms). Calcium carbonate is precipitated by secondary anaerobes (sulfate reducers) and to a smaller degree by methanogens. The role of the cyanobacterial community in carbonate deposition is exposed by stromatolites, which are the most common organo-sedimentary Precambrian structures. Deposition of carbonates in cyanobacterial mats as a consequence of photoassimilation of CO2 does not appear to be a significant process. It is argued that carbonates were deposited at the boundary between the "soda continent", which emerged as a result of subaerial leaching with carbonic acid, and the ocean containing Ca2+. Such ecotones provided favorable conditions for the development of the benthic cyanobacterial community, which was a precursor of stromatolites.

  18. Osteoclast cytosolic calcium, regulated by voltage-gated calcium channels and extracellular calcium, controls podosome assembly and bone resorption

    NASA Technical Reports Server (NTRS)

    Miyauchi, A.; Hruska, K. A.; Greenfield, E. M.; Duncan, R.; Alvarez, J.; Barattolo, R.; Colucci, S.; Zambonin-Zallone, A.; Teitelbaum, S. L.; Teti, A.

    1990-01-01

    The mechanisms of Ca2+ entry and their effects on cell function were investigated in cultured chicken osteoclasts and putative osteoclasts produced by fusion of mononuclear cell precursors. Voltage-gated Ca2+ channels (VGCC) were detected by the effects of membrane depolarization with K+, BAY K 8644, and dihydropyridine antagonists. K+ produced dose-dependent increases of cytosolic calcium ([Ca2+]i) in osteoclasts on glass coverslips. Half-maximal effects were achieved at 70 mM K+. The effects of K+ were completely inhibited by dihydropyridine derivative Ca2+ channel blocking agents. BAY K 8644 (5 X 10(-6) M), a VGCC agonist, stimulated Ca2+ entry which was inhibited by nicardipine. VGCCs were inactivated by the attachment of osteoclasts to bone, indicating a rapid phenotypic change in Ca2+ entry mechanisms associated with adhesion of osteoclasts to their resorption substrate. Increasing extracellular Ca2+ ([Ca2+]e) induced Ca2+ release from intracellular stores and Ca2+ influx. The Ca2+ release was blocked by dantrolene (10(-5) M), and the influx by La3+. The effects of [Ca2+]e on [Ca2+]i suggests the presence of a Ca2+ receptor on the osteoclast cell membrane that could be coupled to mechanisms regulating cell function. Expression of the [Ca2+]e effect on [Ca2+]i was similar in the presence or absence of bone matrix substrate. Each of the mechanisms producing increases in [Ca2+]i, (membrane depolarization, BAY K 8644, and [Ca2+]e) reduced expression of the osteoclast-specific adhesion structure, the podosome. The decrease in podosome expression was mirrored by a 50% decrease in bone resorptive activity. Thus, stimulated increases of osteoclast [Ca2+]i lead to cytoskeletal changes affecting cell adhesion and decreasing bone resorptive activity.

  19. Coronas-F Orbit Monitoring and Re-Entry Prediction

    NASA Technical Reports Server (NTRS)

    Ivanov, N. M.; Kolyuka, Yu. F.; Afanasieva, T. I.; Gridchina, T. A.

    2007-01-01

    Russian scientific satellite CORONAS-F was launched on July, 31, 2001. The object was inserted in near-circular orbit with the inclination 82.5deg and a mean altitude approx. 520 km. Due to the upper atmosphere drag CORONAS-F was permanently descended and as a result on December, 6, 2005 it has finished the earth-orbital flight, having lifetime in space approx. 4.5 years. The satellite structural features and its flight attitude control led to the significant variations of its ballistic coefficient during the flight. It was a cause of some specific difficulties in the fulfillment of the ballistic and navigation support of this space vehicle flight. Besides the main mission objective CORONAS-F also has been selected by the Inter-Agency Space Debris Coordination Committee (IADC) as a target object for the next regular international re-entry test campaign on a program of surveillance and re-entry prediction for the hazard space objects within their de-orbiting phases. Spacecraft (S/C) CORONAS-F kept its working state right up to the end of the flight - down to the atmosphere entry. This fact enabled to realization of the additional research experiments, concerning with an estimation of the atmospheric density within the low earth orbits (LEO) of the artificial satellites, and made possible to continue track the S/C during final phase of its flight by means of Russian regular command & tracking system, used for it control. Thus there appeared a unique possibility of using for tracking S/C at its de-orbiting phase not only passive radar facilities, belonging to the space surveillance systems and traditionally used for support of the IADC re-entry test campaigns, but also more precise active trajectory radio-tracking facilities from the ground control complex (GCC) applied for this object. Under the corresponding decision of the Russian side such capability of additional high-precise tracking control of the CORONAS-F flight in this period of time has been implemented

  20. Generic aerocapture atmospheric entry study, volume 1

    NASA Technical Reports Server (NTRS)

    1980-01-01

    An atmospheric entry study to fine a generic aerocapture vehicle capable of missions to Mars, Saturn, and Uranus is reported. A single external geometry was developed through atmospheric entry simulations. Aerocapture is a system design concept which uses an aerodynamically controlled atmospheric entry to provide the necessary velocity depletion to capture payloads into planetary orbit. Design concepts are presented which provide the control accuracy required while giving thermal protection for the mission payload. The system design concepts consist of the following elements: (1) an extendable biconic aerodynamic configuration with lift to drag ratio between 1.0 and 2.0; (2) roll control system concepts to control aerodynamic lift and disturbance torques; (3) aeroshell design concepts capable of meeting dynamic pressure loads during aerocapture; and (4) entry thermal protection system design concepts to meet thermodynamic loads during aerocapture.

  1. Multiscale perspectives of virus entry via endocytosis.

    PubMed

    Barrow, Eric; Nicola, Anthony V; Liu, Jin

    2013-06-05

    Most viruses take advantage of endocytic pathways to gain entry into host cells and initiate infections. Understanding of virus entry via endocytosis is critically important for the design of antiviral strategies. Virus entry via endocytosis is a complex process involving hundreds of cellular proteins. The entire process is dictated by events occurring at multiple time and length scales. In this review, we discuss and evaluate the available means to investigate virus endocytic entry, from both experimental and theoretical/numerical modeling fronts, and highlight the importance of multiscale features. The complexity of the process requires investigations at a systems biology level, which involves the combination of different experimental approaches, the collaboration of experimentalists and theorists across different disciplines, and the development of novel multiscale models.

  2. Aerocapture Inflatable Decelerator for Planetary Entry

    NASA Technical Reports Server (NTRS)

    Reza, Sajjad; Hund, Richard; Kustas, Frank; Willcockson, William; Songer, Jarvis; Brown, Glen

    2007-01-01

    Forward Attached Inflatable Decelerators, more commonly known as inflatable aeroshells, provide an effective, cost efficient means of decelerating spacecrafts by using atmospheric drag for aerocapture or planetary entry instead of conventional liquid propulsion deceleration systems. Entry into planetary atmospheres results in significant heating and aerodynamic pressures which stress aeroshell systems to their useful limits. Incorporation of lightweight inflatable decelerator surfaces with increased surface-area footprints provides the opportunity to reduce heat flux and induced temperatures, while increasing the payload mass fraction. Furthermore, inflatable aeroshell decelerators provide the needed deceleration at considerably higher altitudes and Mach numbers when compared with conventional rigid aeroshell entry systems. Inflatable aeroshells also provide for stowage in a compact space, with subsequent deployment of a large-area, lightweight heatshield to survive entry heating. Use of a deployable heatshield decelerator enables an increase in the spacecraft payload mass fraction and may eliminate the need for a spacecraft backshell.

  3. Tyrosine kinases activate store-mediated Ca2+ entry in human platelets through the reorganization of the actin cytoskeleton.

    PubMed Central

    Rosado, J A; Graves, D; Sage, S O

    2000-01-01

    We have recently reported that store-mediated Ca(2+) entry in platelets is likely to be mediated by a reversible trafficking and coupling of the endoplasmic reticulum with the plasma membrane, a model termed 'secretion-like coupling'. In this model the actin cytoskeleton plays a key regulatory role. Since tyrosine kinases have been shown to be important for Ca(2+) entry in platelets and other cells, we have now investigated the possible involvement of tyrosine kinases in the secretion-like-coupling model. Treatment of platelets with thrombin or thapsigargin induced actin polymerization by a calcium-independent pathway. Methyl 2,5-dihydroxycinnamate, a tyrosine kinase inhibitor, prevented thrombin- or thapsigargin-induced actin polymerization. The effects of tyrosine kinases in store-mediated Ca(2+) entry were found to be entirely dependent on the actin cytoskeleton. PP1, an inhibitor of the Src family of proteins, partially inhibited store-mediated Ca(2+) entry. In addition, depletion of intracellular Ca(2+) stores stimulated cytoskeletal association of the cytoplasmic tyrosine kinase pp60(src), a process that was sensitive to treatment with cytochalasin D and PP1, but not to inhibition of Ras proteins using prenylcysteine analogues. Finally, combined inhibition of both Ras proteins and tyrosine kinases resulted in complete inhibition of Ca(2+) entry, suggesting that these two families of proteins have independent effects in the activation of store-mediated Ca(2+) entry in human platelets. PMID:11023829

  4. A Review of Aerothermal Modeling for Mars Entry Missions

    NASA Technical Reports Server (NTRS)

    Wright, Michael J; Tang, Chun Y.; Edquist, Karl T.; Hollis, Brian R.; Krasa, Paul

    2009-01-01

    The current status of aerothermal analysis for Mars entry missions is reviewed. The aeroheating environment of all Mars missions to date has been dominated by convective heating. Two primary uncertainties in our ability to predict forebody convective heating are turbulence on a blunt lifting cone and surface catalysis in a predominantly CO2 environment. Future missions, particularly crewed vehicles, will encounter additional heating from shock-layer radiation due to a combination of larger size and faster entry velocity. Localized heating due to penetrations or other singularities on the aeroshell must also be taken into account. The physical models employed to predict these phenomena are reviewed, and key uncertainties or deficiencies inherent in these models are explored. Capabilities of existing ground test facilities to support aeroheating validation are also summarized. Engineering flight data from the Viking and Pathfinder missions, which may be useful for aerothermal model validation, are discussed, and an argument is presented for obtaining additional flight data. Examples are taken from past, present, and future Mars entry missions, including the twin Mars Exploration Rovers and the Mars Science Laboratory, scheduled for launch by NASA in 2011.

  5. Entry/Exit Port testing, test report

    SciTech Connect

    Winkelman, R.H.

    1993-05-01

    The Waste Receiving and Processing Module I (WRAP-1) facility must have the ability to allow 55-gallon drums to enter and exit glovebox enclosures. An Entry/Exit Port (Appendix 1, Figure 1), designed by United Engineers and Constructors (UE&C), is one method chosen for drum transfer. The Entry/Exit Port is to be used for entry of 55-gallon drums into both process entry gloveboxes, exit of 55-gallon drum waste pucks from the low-level waste (LLW) glovebox, and loadout of waste from the restricted waste management glovebox. The Entry/Exit Port relies on capture velocity air flow and a neoprene seal to provide alpha confinement when the Port is in the open and closed positions, respectively. Since the glovebox is in a slight vacuum, air flow is directed into the glovebox through the space between the overpack drum and glovebox floor. The air flow is to direct any airborne contamination into the glovebox. A neoprene seal is used to seal the Port door to the glovebox floor, thus maintaining confinement in the closed position. Entry/Exit Port testing took place February 17, 1993, through April 14, 1993, in the 305 building of Westinghouse Hanford Company. Testing was performed in accordance with the Entry/Exit Port Testing Test Plan, document number WHC-SD-WO26-TP-005. A prototype Entry/Exit Port built at the Hanford Site was tested using fluorescent paint pigment and smoke candles as simulant contaminants. This test report is an interim test report. Further developmental testing is required to test modifications made to the Port as the original design of the Port did not provide complete confinement during all stages of operation.

  6. Binding of ( sup 125 I)iodipine to parathyroid cell membranes: Evidence of a dihydropyridine-sensitive calcium channel

    SciTech Connect

    Jones, J.I.; Fitzpatrick, L.A. )

    1990-04-01

    The parathyroid cell is unusual, in that an increase in extracellular calcium concentrations inhibits PTH release. Calcium channels are glycoproteins that span cell membranes and allow entry of extracellular calcium into cells. We have demonstrated that the calcium channel agonist (+)202-791, which opens calcium channels, inhibits PTH release and that the antagonist (-)202-791, which closes calcium channels, stimulates PTH release. To identify the calcium channels responsible for these effects, we used a radioligand that specifically binds to calcium channels. Bovine parathyroid cell membranes were prepared and incubated under reduced lighting with (125I) iodipine (SA, 2000 Ci/mmol), which recognizes 1,4-dihydropyridine-sensitive calcium channels. Bound ligand was separated from free ligand by rapid filtration through Whatman GF/B filters. Nonspecific binding was measured by the inclusion of nifedipine at 10 microM. Specific binding represented approximately 40% of the total binding. The optimal temperature for (125I) iodipine binding was 4 C, and binding reached equilibrium by 30 min. The equilibrium dissociation constant (Kd) was approximately 550 pM, and the maximum number of binding sites was 780 fmol/mg protein. Both the calcium channel agonist (+)202-791 and antagonist (-)202-791 competitively inhibited (125I) iodipine binding, with 50% inhibition concentrations of 20 and 300 nM, respectively. These data indicate the presence of dihydropyridine-sensitive calcium channels on parathyroid cell membranes.

  7. Calcium metabolism and correcting calcium deficiencies.

    PubMed

    Emkey, Ronald D; Emkey, Gregory R

    2012-09-01

    Calcium is the most abundant cation in the human body, of which approximately 99% occurs in bone, contributing to its rigidity and strength. Bone also functions as a reservoir of Ca for its role in multiple physiologic and biochemical processes. This article aims to provide a thorough understanding of the absorptive mechanisms and factors affecting these processes to enable one to better appreciate an individual's Ca needs, and to provide a rationale for correcting Ca deficiencies. An overview of Ca requirements and suggested dosing regimens is presented, with discussion of various Ca preparations and potential toxicities of Ca treatment.

  8. Orion Capsule Handling Qualities for Atmospheric Entry

    NASA Technical Reports Server (NTRS)

    Tigges, Michael A.; Bihari, Brian D.; Stephens, John-Paul; Vos, Gordon A.; Bilimoria, Karl D.; Mueller, Eric R.; Law, Howard G.; Johnson, Wyatt; Bailey, Randall E.; Jackson, Bruce

    2011-01-01

    Two piloted simulations were conducted at NASA's Johnson Space Center using the Cooper-Harper scale to study the handling qualities of the Orion Command Module capsule during atmospheric entry flight. The simulations were conducted using high fidelity 6-DOF simulators for Lunar Return Skip Entry and International Space Station Return Direct Entry flight using bank angle steering commands generated by either the Primary (PredGuid) or Backup (PLM) guidance algorithms. For both evaluations, manual control of bank angle began after descending through Entry Interface into the atmosphere until drogue chutes deployment. Pilots were able to use defined bank management and reversal criteria to accurately track the bank angle commands, and stay within flight performance metrics of landing accuracy, g-loads, and propellant consumption, suggesting that the pilotability of Orion under manual control is both achievable and provides adequate trajectory performance with acceptable levels of pilot effort. Another significant result of these analyses is the applicability of flying a complex entry task under high speed entry flight conditions relevant to the next generation Multi Purpose Crew Vehicle return from Mars and Near Earth Objects.

  9. Hypersonic and planetary entry flight mechanics

    NASA Technical Reports Server (NTRS)

    Vinh, N. X.; Busemann, A.; Culp, R. D.

    1980-01-01

    The book treats hypersonic flight trajectories and atmospheric entry flight mechanics in light of their importance for space shuttle entry. Following a review of the structures of planetary atmospheres and aerodynamic forces, equations are derived for flight over a spherical planet, and the performance of long-range hypervelocity vehicles in extra-atmospheric flight is analyzed. Consideration is then given to vehicle trajectories in the powered and atmospheric reentry phases of flight, and several first-order solutions are derived for various planetary entry situations. The second-order theory of Loh for entry trajectories is presented along with the classical theories of Yaroshevskii and Chapman for entry into planetary atmospheres, and the thermal problems encountered in hypersonic flight are analyzed. A unified theory for entry into planetary atmospheres is then introduced which allows the performance of a general type of lifting vehicle to be studied, and applied to the analysis of orbit contraction due to atmospheric drag, flight with lift modulation and lateral maneuvers.

  10. Models of radon entry: A review

    SciTech Connect

    Gadgil, A.J.

    1991-08-01

    This paper reviews existing models of radon entry into houses. The primary mechanism of radon entry in houses with high indoor concentrations is, in most cases, convective entry of radon bearing soil-gas from the surrounding soil. The driving force for this convective entry is the small indoor-outdoor pressure difference arising from the stack effect and other causes. Entry points for the soil-gas generally are the cracks or gaps in the building substructure, or though other parts of the building shell in direct contact with the soil, although entry may also occur by flow though permeable concrete or cinder block walls of the substructure. Models using analytical solutions to idealized geometrical configurations with simplified boundary conditions obtain analytical tractability of equations to be solved at the cost of severe approximations; their strength is in the insights they offer with their solutions. Models based on lumped parameters attempt to characterize the significant physical behavioral characteristics of the soil-gas and radon flow. When realistic approximations are desired for the boundary conditions and terms in the governing equations, numerical models must be used; these are usually based on finite difference or finite element solutions to the governing equations. Limited data are now available for experimental verification of model predictions. The models are briefly reviewed and their strengths and limitations are discussed.

  11. Well engineering for re-entry operations

    SciTech Connect

    1996-10-01

    Oil and gas operators are constantly looking at their existing assets for ways to increase their value. Several operators consider a re-entry program as the principle leveraging technology in strategic acquisitions. Much of the current re-entry operations effort targets the longer reach sidetrack and multilateral well markets. The key to this effort, whether it involves coiled tubing drilling, short radius drilling or multilateral well technologies, is re-entry well engineering. The engineer evaluating a re-entry prospect must apply significant levels of reservoir engineering, rock mechanics, completion engineering and drilling engineering to properly design the well and develop successful procedures. Re-entry drilling means that the operator is working with proven or probable reserves. Completion design and engineering are the most important aspects of well design once the target has been selected. Ultimately, the completion design selected will dictate the type of re-entry program: slot recovery, drilling out below the current casing shoe, or section milling and whipstock sidetracking. It can also dictate the principle aspects of the drilling program. The acceptable wellbore inclination build rates (dogleg severity), wellbore length, and drilling fluid selection are commonly influenced and even dictated by the completion design. These factors are discussed.

  12. Nipah virus entry can occur by macropinocytosis

    SciTech Connect

    Pernet, Olivier; Pohl, Christine; Ainouze, Michelle; Kweder, Hasan; Buckland, Robin

    2009-12-20

    Nipah virus (NiV) is a zoonotic biosafety level 4 paramyxovirus that emerged recently in Asia with high mortality in man. NiV is a member, with Hendra virus (HeV), of the Henipavirus genus in the Paramyxoviridae family. Although NiV entry, like that of other paramyxoviruses, is believed to occur via pH-independent fusion with the host cell's plasma membrane we present evidence that entry can occur by an endocytic pathway. The NiV receptor ephrinB2 has receptor kinase activity and we find that ephrinB2's cytoplasmic domain is required for entry but is dispensable for post-entry viral spread. The mutation of a single tyrosine residue (Y304F) in ephrinB2's cytoplasmic tail abrogates NiV entry. Moreover, our results show that NiV entry is inhibited by constructions and drugs specific for the endocytic pathway of macropinocytosis. Our findings could potentially permit the rapid development of novel low-cost antiviral treatments not only for NiV but also HeV.

  13. Inositol trisphosphate and calcium signalling

    NASA Astrophysics Data System (ADS)

    Berridge, Michael J.

    1993-01-01

    Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals. It operates through receptors whose molecular and physiological properties closely resemble the calcium-mobilizing ryanodine receptors of muscle. This family of intracellular calcium channels displays the regenerative process of calcium-induced calcium release responsible for the complex spatiotemporal patterns of calcium waves and oscillations. Such a dynamic signalling pathway controls many cellular processes, including fertilization, cell growth, transformation, secretion, smooth muscle contraction, sensory perception and neuronal signalling.

  14. Planetary/DOD entry technology flight experiments. Volume 2: Planetary entry flight experiments

    NASA Technical Reports Server (NTRS)

    Christensen, H. E.; Krieger, R. J.; Mcneilly, W. R.; Vetter, H. C.

    1976-01-01

    The technical feasibility of launching a high speed, earth entry vehicle from the space shuttle to advance technology for the exploration of the outer planets' atmospheres was established. Disciplines of thermodynamics, orbital mechanics, aerodynamics propulsion, structures, design, electronics and system integration focused on the goal of producing outer planet environments on a probe shaped vehicle during an earth entry. Major aspects of analysis and vehicle design studied include: planetary environments, earth entry environment capability, mission maneuvers, capabilities of shuttle upper stages, a comparison of earth entry planetary environments, experiment design and vehicle design.

  15. The Impact of Vitamin D3 Supplementation on Mechanisms of Cell Calcium Signaling in Chronic Kidney Disease.

    PubMed

    Lajdova, Ingrid; Spustova, Viera; Oksa, Adrian; Kaderjakova, Zuzana; Chorvat, Dusan; Morvova, Marcela; Sikurova, Libusa; Marcek Chorvatova, Alzbeta

    2015-01-01

    Intracellular calcium concentration in peripheral blood mononuclear cells (PBMCs) of patients with chronic kidney disease (CKD) is significantly increased, and the regulatory mechanisms maintaining cellular calcium homeostasis are impaired. The purpose of this study was to examine the effect of vitamin D3 on predominant regulatory mechanisms of cell calcium homeostasis. The study involved 16 CKD stages 2-3 patients with vitamin D deficiency treated with cholecalciferol 7000-14000 IU/week for 6 months. The regulatory mechanisms of calcium signaling were studied in PBMCs and red blood cells. After vitamin D3 supplementation, serum concentration of 25(OH)D3 increased (P < 0.001) and [Ca(2+)]i decreased (P < 0.001). The differences in [Ca(2+)]i were inversely related to differences in 25(OH)D3 concentration (P < 0.01). Vitamin D3 supplementation decreased the calcium entry through calcium release activated calcium (CRAC) channels and purinergic P2X7 channels. The function of P2X7 receptors was changed in comparison with their baseline status, and the expression of these receptors was reduced. There was no effect of vitamin D3 on P2X7 pores and activity of plasma membrane Ca(2+)-ATPases. Vitamin D3 supplementation had a beneficial effect on [Ca(2+)]i decreasing calcium entry via CRAC and P2X7 channels and reducing P2X7 receptors expression.

  16. Differential regulation of calcium signalling pathways by components of Piper methysticum (‘Awa)

    PubMed Central

    Shimoda, L.M.N; Showman, A.; Baker, J.D.; Lange, I.; Koomoa, D.L.; Stokes, A.J.; Borris, R.P.; Turner, H.

    2015-01-01

    Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA-ergic effects of the well-characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS-targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally-prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium-mobilizing activity of traditionally-prepared and partially HPLC-purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin-sensitive and –insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non-store-operated pathways. Together with the pepper-like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP-like conductances are observed in kava-treated cells under patch clamp. Thus TRP-mediated cellular effects may be responsible for some of the reported pharmacology of kava. PMID:25640812

  17. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    ERIC Educational Resources Information Center

    Henrickson, Charles H.; Robinson, Paul R.

    1979-01-01

    The gravimetric determination of calcium as calcium carbonate is described. This experiment is suitable for undergraduate quantitative analysis laboratories. It is less expensive than determination of chloride as silver chloride. (BB)

  18. Subcellular propagation of calcium waves in Müller glia does not require autocrine/paracrine purinergic signaling.

    PubMed

    Phuong, Tam T T; Yarishkin, Oleg; Križaj, David

    2016-09-02

    The polarized morphology of radial glia allows them to functionally interconnect different layers of CNS tissues including the retina, cerebellum, and cortex. A likely mechanism involves propagation of transcellular Ca(2+) waves which were proposed to involve purinergic signaling. Because it is not known whether ATP release is required for astroglial Ca(2+) wave propagation we investigated this in mouse Müller cells, radial astroglia-like retinal cells in which in which waves can be induced and supported by Orai/TRPC1 (transient receptor potential isoform 1) channels. We found that depletion of endoplasmic reticulum (ER) stores triggers regenerative propagation of transcellular Ca(2+) waves that is independent of ATP release and activation of P2X and P2Y receptors. Both the amplitude and kinetics of transcellular, depletion-induced waves were resistant to non-selective purinergic P2 antagonists such as pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). Thus, store-operated calcium entry (SOCE) is itself sufficient for the initiation and subcellular propagation of calcium waves in radial glia.

  19. Role of homocysteine and folic acid on the altered calcium homeostasis of platelets from rats with biliary cirrhosis.

    PubMed

    Romecín, Paola; Atucha, Noemí M; Navarro, Esther G; Clara Ortiz, M; Iyú, David; Rosado, Juan Antonio; García-Estañ, Joaquín

    2017-02-02

    Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state. Different studies indicate that cholestatic diseases are associated with hyperhomocysteinemia; thus, we hypothetized that it could contribute to those platelet alterations. In the present study, we have investigated the role of homocysteine (HCY) in platelet aggregation and calcium signaling in the BDL model. The effect of chronic folic acid treatment was also analyzed. Acute treatment with HCY increased the aggregation response to ADP and calcium responses to thrombin in platelets of control and BDL rats. Capacitative calcium entry was not altered by HCY. Chronic treatment with folic acid decreased platelet aggregation in control and BDL rats, but this decrease was greater in BDL rats. In folic acid-treated rats, thrombin-induced calcium entry and release were decreased in platelet of control rats but unaltered in BDL rats; however, capacitative calcium entry was decreased in platelets of control and BDL rats treated with folic acid. Reactive oxygen species were produced at higher levels by BDL platelets after stimulation with HCY or thrombin and folic acid normalized these responses. HCY plays a role in the enhanced platelet aggregation response of BDL rats, probably through an enhanced formation of ROS. Folic acid pretreatment normalizes many of the platelet alterations shown by BDL rats.

  20. Purinergic stimulation of rabbit ciliated airway epithelia: control by multiple calcium sources.

    PubMed Central

    Korngreen, A; Priel, Z

    1996-01-01

    1. Simultaneous measurements of average intracellular calcium concentration ([Ca2+]i) and ciliary beat frequency (CBF) were carried out on ciliated rabbit tracheal cells in order to determine quantitatively the role of calcium in the regulation of mucus-transporting cilia. 2. Extracellular ATP caused a rapid increase in both [Ca2+]i and CBF in the 0.1-1000 microM concentration range. The rise in [Ca2+]i levelled off to an elevated [Ca2+]i plateau while the cilia remained in a high activation state. The magnitude of the rise in [Ca2+]i and CBF as well as the value of the elevated [Ca2+]i plateau and the value of the sustained CBF were dependent on the concentration of ATP in the solution. 3. No correlation was found between the mean values of [Ca2+]i and CBF at rest but a sigmoidal relationship was found to exist between the maximal rises of these parameters following excitation with extracellular ATP. This sigmoidal correlation incorporated the experiments where [Ca2+]i rise was induced by depletion of internal calcium stores with thapsigargin or by entry of calcium induced by ionomycin. 4. Extracellular ATP caused both the release of calcium from internal stores and calcium influx from the extracellular solution. The release of calcium was identified as originating from a thapsigargin-sensitive and a thapsigargin-insensitive calcium store. It is suggested that the release of calcium from these stores induces the initial rise in CBF. 5. The sustained activation of the cilia and elevated calcium plateau were found to be the result of the extracellular ATP-induced calcium influx. This calcium influx was insensitive to the voltage-gated calcium channel inhibitors verapamil and diltiazem, but was completely eliminated by lowering the extracellular calcium concentration to 0.1 microM. 6. We propose that the initial jump in the CBF is mediated by the calcium released from a thapsigargin-insensitive calcium store adjacent to the cilia, while the later, and longer, rise in

  1. Calcium Handling and Arrhythmogenesis.

    PubMed

    Bompotis, Georgios C; Pappas, Loukas K; Angelidis, Christos; Kossyvakis, Charalampos; Giannopoulos, Georgios; Deftereos, Spyridon

    2016-01-01

    Intracellular calcium homeostasis plays a fundamental role in the electric and mechanical function of the heart by modulating action potential pattern and duration, by linking cell membrane depolarization to myocardial contraction and by regulating cardiac automaticity. Abnormalities of intracellular calcium regulation disrupt the electrophysiological properties of the heart and create an arrhythmogenic milieu, which promotes atrial and ventricular arrhythmogenesis and impairs cardiac automaticity and atrioventricular conduction. In this brief review, we summarize the basic genetic, molecular and electrophysiological mechanisms linking inherited or acquired intracellular Ca(2+) dysregulation to arrhythmogenesis.

  2. Calcium metabolism in microgravity.

    PubMed

    Heer, M; Kamps, N; Biener, C; Korr, C; Boerger, A; Zittermann, A; Stehle, P; Drummer, C

    1999-09-09

    Unloading of weight bearing bones as induced by microgravity or immobilization has significant impacts on the calcium and bone metabolism and is the most likely cause for space osteoporosis. During a 4.5 to 6 month stay in space most of the astronauts develop a reduction in bone mineral density in spine, femoral neck, trochanter, and pelvis of 1%-1.6% measured by Dual Energy X-ray Absorption (DEXA). Dependent on the mission length and the individual turnover rates of the astronauts it can even reach individual losses of up to 14% in the femoral neck. Osteoporosis itself is defined as the deterioration of bone tissue leading to enhanced bone fragility and to a consequent increase in fracture risk. Thinking of long-term missions to Mars or interplanetary missions for years, space osteoporosis is one of the major concerns for manned spaceflight. However, decrease in bone density can be initiated differently. It either can be caused by increases in bone formation and bone resorption resulting in a net bone loss, as obtained in fast looser postmenopausal osteoporosis. On the other hand decrease in bone formation and increase in bone resorption also leads to bone losses as obtained in slow looser postmenopausal osteoporosis or in Anorexia Nervosa patients. Biomarkers of bone turnover measured during several missions indicated that the pattern of space osteoporosis is very similar to the pattern of Anorexia Nervosa patients or slow looser postmenopausal osteoporosis. However, beside unloading, other risk factors for space osteoporosis exist such as stress, nutrition, fluid shifts, dehydration and bone perfusion. Especially nutritional factors may contribute considerably to the development of osteoporosis. From earthbound studies it is known that calcium supplementation in women and men can prevent bone loss of 1% bone per year. Based on these results we studied the calcium intake during several European missions and performed an experiment during the German MIR 97 mission

  3. Localised calcium release events in cells from the muscle of guinea-pig gastric fundus

    PubMed Central

    Parsons, S P; Bolton, T B

    2004-01-01

    After enzymatic dispersion of the muscle of the guinea-pig gastric fundus, single elongated cells were observed which differed from archetypal smooth muscle cells due to their knurled, tuberose or otherwise irregular surface morphology. These, but not archetypal smooth muscle cells, consistently displayed spontaneous localized (i.e. non-propagating) intracellular calcium ([Ca2+]i) release events. Such calcium events were novel in their magnitude and kinetic profiles. They included short transient events, plateau events and events which coalesced spatially or temporally (compound events). Quantitative analysis of the events with an automatic detection programme showed that their spatio-temporal characteristics (full width and full duration at half-maximum amplitude) were approximately exponentially distributed. Their amplitude distribution suggested the presence of two release modes. Carbachol application caused an initial cell-wide calcium transient followed by an increase in localized calcium release events. Pharmacological analysis suggested that localized calcium release was largely dependent on external calcium entry acting on both inositol trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) to release stored calcium. Nominally calcium-free external solution immediately and reversibly abolished all localized calcium release without blocking the initial transient calcium release response to carbachol. This was inhibited by 2-APB (100 μm), ryanodine (10 or 50 μm) or U-73122 (1 μm). 2-APB (100 μm), xestospongin C (XeC, 10 μm) or U-73122 (1 μm) blocked both spontaneous localized calcium release and localized release stimulated by 10 μm carbachol. Ryanodine (50 μm) also inhibited spontaneous release, but enhanced localized release in response to carbachol. This study represents the first characterization of localized calcium release events in cells from the gastric fundus. PMID:14608011

  4. A case study of multi-seam coal mine entry stability analysis with strength reduction method

    PubMed Central

    Tulu, Ihsan Berk; Esterhuizen, Gabriel S; Klemetti, Ted; Murphy, Michael M.; Sumner, James; Sloan, Michael

    2017-01-01

    In this paper, the advantage of using numerical models with the strength reduction method (SRM) to evaluate entry stability in complex multiple-seam conditions is demonstrated. A coal mine under variable topography from the Central Appalachian region is used as a case study. At this mine, unexpected roof conditions were encountered during development below previously mined panels. Stress mapping and observation of ground conditions were used to quantify the success of entry support systems in three room-and-pillar panels. Numerical model analyses were initially conducted to estimate the stresses induced by the multiple-seam mining at the locations of the affected entries. The SRM was used to quantify the stability factor of the supported roof of the entries at selected locations. The SRM-calculated stability factors were compared with observations made during the site visits, and the results demonstrate that the SRM adequately identifies the unexpected roof conditions in this complex case. It is concluded that the SRM can be used to effectively evaluate the likely success of roof supports and the stability condition of entries in coal mines. PMID:28239503

  5. Calcium channels, external calcium concentration and cell proliferation.

    PubMed

    Borowiec, Anne-Sophie; Bidaux, Gabriel; Pigat, Natascha; Goffin, Vincent; Bernichtein, Sophie; Capiod, Thierry

    2014-09-15

    Evidence for a role for calcium channel proteins in cell proliferation is numerous suggesting that calcium influx is essential in this physiological process. Several studies in the past thirty years have demonstrated that calcium channel expression levels are determinant in cell proliferation. Voltage-gated, store-operated, second messengers and receptor-operated calcium channels have been associated to cell proliferation. However, the relationship between calcium influx and cell proliferation can be uncoupled in transformed and cancer cells, resulting in an external calcium-independent proliferation. Thus, protein expression could be more important than channel function to trigger cell proliferation suggesting that additional channel functions may be responsible to reconcile calcium channel expression and cell proliferation. When needed, external calcium concentration is obviously important for calcium channel function but it also regulates calcium sensing receptor (CaSR) activity. CaSR can up- or down-regulate cell proliferation depending on physiological conditions. CaSR sensitivity to external calcium is within the 0.5 to 5 mM range and therefore, the role of these receptors in cell proliferation must be taken into account. We therefore suggest here that cell proliferation rates could depend on the relative balance between calcium influx and CaSR activation.

  6. 19 CFR 142.44 - Entry number range.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry number range. 142.44 Section 142.44 Customs... (CONTINUED) ENTRY PROCESS Line Release § 142.44 Entry number range. After an application for Line Release has received final approval, filers must provide the port director, in writing, with a range of entry...

  7. 19 CFR 142.44 - Entry number range.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Entry number range. 142.44 Section 142.44 Customs... (CONTINUED) ENTRY PROCESS Line Release § 142.44 Entry number range. After an application for Line Release has received final approval, filers must provide the port director, in writing, with a range of entry...

  8. 19 CFR 142.44 - Entry number range.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Entry number range. 142.44 Section 142.44 Customs... (CONTINUED) ENTRY PROCESS Line Release § 142.44 Entry number range. After an application for Line Release has received final approval, filers must provide the port director, in writing, with a range of entry...

  9. 19 CFR 142.44 - Entry number range.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Entry number range. 142.44 Section 142.44 Customs... (CONTINUED) ENTRY PROCESS Line Release § 142.44 Entry number range. After an application for Line Release has received final approval, filers must provide the port director, in writing, with a range of entry...

  10. 19 CFR 142.44 - Entry number range.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Entry number range. 142.44 Section 142.44 Customs... (CONTINUED) ENTRY PROCESS Line Release § 142.44 Entry number range. After an application for Line Release has received final approval, filers must provide the port director, in writing, with a range of entry...

  11. 7 CFR 319.24-5 - Condition of entry.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Corn Diseases Regulations Governing Entry of Indian Corn Or Maize § 319.24-5 Condition of entry. The corn shall not be removed from the port of entry... Quarantine Programs, that the corn has been properly sterilized and released for entry without...

  12. 7 CFR 319.24-5 - Condition of entry.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Corn Diseases Regulations Governing Entry of Indian Corn Or Maize § 319.24-5 Condition of entry. The corn shall not be removed from the port of entry... Quarantine Programs, that the corn has been properly sterilized and released for entry without...

  13. 7 CFR 319.24-5 - Condition of entry.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Corn Diseases Regulations Governing Entry of Indian Corn Or Maize § 319.24-5 Condition of entry. The corn shall not be removed from the port of entry... Quarantine Programs, that the corn has been properly sterilized and released for entry without...

  14. 7 CFR 319.24-5 - Condition of entry.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Corn Diseases Regulations Governing Entry of Indian Corn Or Maize § 319.24-5 Condition of entry. The corn shall not be removed from the port of entry... Quarantine Programs, that the corn has been properly sterilized and released for entry without...

  15. 7 CFR 319.24-5 - Condition of entry.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... SERVICE, DEPARTMENT OF AGRICULTURE FOREIGN QUARANTINE NOTICES Corn Diseases Regulations Governing Entry of Indian Corn Or Maize § 319.24-5 Condition of entry. The corn shall not be removed from the port of entry... Quarantine Programs, that the corn has been properly sterilized and released for entry without...

  16. 7 CFR 319.8-26 - Material refused entry.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., or other expenses incidental to the safeguarding or disposal of material refused entry by the... 7 Agriculture 5 2014-01-01 2014-01-01 false Material refused entry. 319.8-26 Section 319.8-26... Provisions § 319.8-26 Material refused entry. Any material refused entry for noncompliance with...

  17. 7 CFR 319.8-26 - Material refused entry.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., or other expenses incidental to the safeguarding or disposal of material refused entry by the... 7 Agriculture 5 2011-01-01 2011-01-01 false Material refused entry. 319.8-26 Section 319.8-26... Provisions § 319.8-26 Material refused entry. Any material refused entry for noncompliance with...

  18. 7 CFR 319.8-26 - Material refused entry.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., or other expenses incidental to the safeguarding or disposal of material refused entry by the... 7 Agriculture 5 2012-01-01 2012-01-01 false Material refused entry. 319.8-26 Section 319.8-26... Provisions § 319.8-26 Material refused entry. Any material refused entry for noncompliance with...

  19. 7 CFR 319.8-26 - Material refused entry.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., or other expenses incidental to the safeguarding or disposal of material refused entry by the... 7 Agriculture 5 2010-01-01 2010-01-01 false Material refused entry. 319.8-26 Section 319.8-26... Provisions § 319.8-26 Material refused entry. Any material refused entry for noncompliance with...

  20. 48 CFR 52.225-8 - Duty-Free Entry.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Duty-Free Entry. 52.225-8...-Free Entry. As prescribed in 25.1101(e), insert the following clause: Duty-Free Entry (OCT 2010) (a... accorded duty-free entry. (c) Except as provided in paragraph (d) of this clause or elsewhere in...

  1. 48 CFR 52.225-8 - Duty-Free Entry.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Duty-Free Entry. 52.225-8...-Free Entry. As prescribed in 25.1101(e), insert the following clause: Duty-Free Entry (OCT 2010) (a... accorded duty-free entry. (c) Except as provided in paragraph (d) of this clause or elsewhere in...

  2. 48 CFR 52.225-8 - Duty-Free Entry.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Duty-Free Entry. 52.225-8...-Free Entry. As prescribed in 25.1101(e), insert the following clause: Duty-Free Entry (OCT 2010) (a... accorded duty-free entry. (c) Except as provided in paragraph (d) of this clause or elsewhere in...

  3. 48 CFR 52.225-8 - Duty-Free Entry.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Duty-Free Entry. 52.225-8...-Free Entry. As prescribed in 25.1101(e), insert the following clause: Duty-Free Entry (OCT 2010) (a... accorded duty-free entry. (c) Except as provided in paragraph (d) of this clause or elsewhere in...

  4. 7 CFR 319.8-26 - Material refused entry.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., or other expenses incidental to the safeguarding or disposal of material refused entry by the... 7 Agriculture 5 2013-01-01 2013-01-01 false Material refused entry. 319.8-26 Section 319.8-26... Provisions § 319.8-26 Material refused entry. Any material refused entry for noncompliance with...

  5. Testing, time limits, and English learners: does age of school entry affect how quickly students can learn English?

    PubMed

    Conger, Dylan

    2009-06-01

    Using data on young English learners (EL) who enroll in the New York City public school system, I examine how long it takes students to become minimally proficient in English and how the time to proficiency differs for students by their age of school entry. Specifically, I follow four recent entry cohorts of ELs ages 5-10 and use discrete-time survival analysis to model the rate at which different age groups acquire proficiency. I find that approximately half of the students become proficient within three years after school entry and that younger students learn more quickly than older students. Age of entry differences are robust to controls for observed differences between age of entry groups in their economic and demographic characteristics, their disabilities, and the schools they attend. The results lend support to the theory that older students face developmental barriers to learning new languages quickly.

  6. Diet and calcium stones.

    PubMed Central

    Hughes, J; Norman, R W

    1992-01-01

    OBJECTIVE: To review the current literature on the dietary modification of urinary risk factors as a means of reducing the likelihood of recurrent stone formation and to develop practical dietary recommendations that might be useful to this end. DATA SOURCES: MEDLINE was searched for English-language articles published from 1983 to 1990. Additional references were selected from the bibliographies of identified articles. STUDY SELECTION: Nonrandomized trials and retrospective reviews were included because of a paucity of randomized controlled trials. DATA SYNTHESIS: Information on the dietary intake of calcium, oxalate, protein, sodium and fibre and on alcohol and fluid intake was used to develop practical guidelines on dietary modification. CONCLUSION: Dietary modification plays an important role in the reduction of urinary risk factors in patients with calcium stone disease of the urinary tract. As an initial form of prevention attention should be directed toward moderating the intake of calcium, oxalate, protein, sodium and alcohol and increasing the intake of fibre and water. Future research should include an assessment of the long-term reduction of dietary and urinary risk factors and the rates of recurrence of calcium stones. PMID:1310430

  7. Calcium silicate insulation structure

    DOEpatents

    Kollie, Thomas G.; Lauf, Robert J.

    1995-01-01

    An insulative structure including a powder-filled evacuated casing utilizes a quantity of finely divided synthetic calcium silicate having a relatively high surface area. The resultant structure-provides superior thermal insulating characteristics over a broad temperature range and is particularly well-suited as a panel for a refrigerator or freezer or the insulative barrier for a cooler or a insulated bottle.

  8. Calcium biofortification of crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    More than half of the world's population is deficient in calcium (Ca), iron (Fe), iodine (I), magnesium (Mg), selenium (Se), or zinc (Zn). The consumption of plants, directly or via livestock, containing inadequate concentrations of particular minerals causes these deficiencies. Agronomic and geneti...

  9. High Blood Calcium (Hypercalcemia)

    MedlinePlus

    ... as sarcoidosis • Hormone disorders, such as overactive thyroid (hyperthyroidism) • A genetic condition called familial hypocalciuric hypercalcemia • Kidney ... topics: www.hormone.org (search for PHPT, calcium, hyperthyroidism, or osteoporosis) • MedlinePlus (National Institutes of Health-NIH): ...

  10. Assay for calcium channels

    SciTech Connect

    Glossmann, H.; Ferry, D.R.

    1985-01-01

    This chapter focuses on biochemical assays for Ca/sup 2 +/-selective channels in electrically excitable membranes which are blocked in electrophysiological and pharmacological experiments by verapamil, 1,4-dihydropyridines, diltiazen (and various other drugs), as well as inorganic di- or trivalent cations. The strategy employed is to use radiolabeled 1,4-dihydropyridine derivatives which block calcium channels with ED/sub 50/ values in the nanomolar range. Although tritiated d-cis-diltiazem and verapamil can be used to label calcium channels, the 1,4-dihydropyridines offer numerous advantages. The various sections cover tissue specificity of channel labeling, the complex interactions of divalent cations with the (/sup 3/H)nimodipine-labeled calcium channels, and the allosteric regulation of (/sup 3/H)nimodipine binding by the optically pure enantiomers of phenylalkylamine and benzothiazepine calcium channel blockers. A comparison of the properties of different tritiated 1,4-dihydropyridine radioligands and the iodinated channel probe (/sup 125/I)iodipine is given.

  11. Entry Year Pilot Project: A Reflective Approach to Mentoring Ohio's Entry Year Teachers.

    ERIC Educational Resources Information Center

    Murray, Susan R.; Hillkirk, Keith

    This monograph describes Ohio University College of Education's Entry Year Pilot Project. The College of Education was awarded grant money to create and implement a mentoring program to help entry-year teachers through their first year and through the Praxis III assessment. The project involved beginning teachers, school-level mentors, and…

  12. 76 FR 66875 - Informal Entry Limit and Removal of a Formal Entry Requirement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... reduced the value of that amount in real terms. Consequently, CBP proposes to raise the current informal... reduce the administrative burden on importers and other entry filers. Moreover, CBP proposes to remove... proposed change will reduce the overall administrative burden on importers and ] other entry filers...

  13. Atmospheric Entry Studies for Venus Missions: 45 Sphere-Cone Rigid Aeroshells and Ballistic Entries

    NASA Technical Reports Server (NTRS)

    Prabhu, Dinesh K.; Spilker, Thomas R.; Allen, Gary A., Jr.; Hwang, Helen H.; Cappuccio, Gelsomina; Moses, Robert W.

    2013-01-01

    The present study considers direct ballistic entries into the atmosphere of Venus using a 45deg sphere-cone rigid aeroshell, a legacy shape that has been used successfully in the past in the Pioneer Venus Multiprobe Mission. For a number of entry mass and heatshield diameter combinations (i.e., various ballistic coefficients) and entry velocities, the trajectory space in terms of entry flight path angles between skip out and -30deg is explored with a 3DoF trajectory code, TRAJ. From these trajectories, the viable entry flight path angle space is determined through the use of mechanical and thermal performance limits on the thermal protection material and science payload; the thermal protection material of choice is entry-grade carbon phenolic, for which a material thermal response model is available. For mechanical performance, a 200 g limit is placed on the peak deceleration load experienced by the science instruments, and 10 bar is assumed as the pressure limit for entry-grade carbon-phenolic material. For thermal performance, inflection points in the total heat load distribution are used as cut off criteria. Analysis of the results shows the existence of a range of critical ballistic coefficients beyond which the steepest possible entries are determined by the pressure limit of the material rather than the deceleration load limit.

  14. Effect of Cognitive Entry Behaviors and Affective Entry Characteristics on Learning Level

    ERIC Educational Resources Information Center

    Çaliskan, Muhittin

    2014-01-01

    In this study, the effect of cognitive entry behaviors and affective entry characteristics on learning level was investigated. The study was conducted on 258 first year students attending the Faculty of Education in the autumn semester of the 2011-2012 academic year. The study was conducted using the relational survey model and data was collected…

  15. The Plasma Membrane Calcium Pump

    NASA Technical Reports Server (NTRS)

    Rasmussen, H.

    1983-01-01

    Three aspect of cellular calcium metabolism in animal cells was discussed including the importance of the plasma membrane in calcium homeostasis, experiments dealing with the actual mechanism of the calcium pump, and the function of the pump in relationship to the mitochondria and to the function of calmodulin in the intact cell.

  16. Impregnating Coal With Calcium Carbonate

    NASA Technical Reports Server (NTRS)

    Sharma, Pramod K.; Voecks, Gerald E.; Gavalas, George R.

    1991-01-01

    Relatively inexpensive process proposed for impregnating coal with calcium carbonate to increase rates of gasification and combustion of coal and to reduce emission of sulfur by trapping sulfur in calcium sulfide. Process involves aqueous-phase reactions between carbon dioxide (contained within pore network of coal) and calcium acetate. Coal impregnated with CO2 by exposing it to CO2 at high pressure.

  17. Thermal Analysis Methods For Earth Entry Vehicle

    NASA Technical Reports Server (NTRS)

    Amundsen, Ruth M.; Dec, John A.; Lindell, Michael C.

    2000-01-01

    Thermal analysis of a vehicle designed to return samples from another planet, such as the Earth Entry vehicle for the Mars Sample Return mission, presents several unique challenges. The Earth Entry Vehicle (EEV) must contain Martian material samples after they have been collected and protect them from the high heating rates of entry into the Earth's atmosphere. This requirement necessitates inclusion of detailed thermal analysis early in the design of the vehicle. This paper will describe the challenges and solutions for a preliminary thermal analysis of an Earth Entry Vehicle. The aeroheating on the vehicle during entry would be the main driver for the thermal behavior, and is a complex function of time, spatial position on the vehicle, vehicle temperature, and trajectory parameters. Thus, the thermal analysis must be closely tied to the aeroheating analysis in order to make accurate predictions. Also, the thermal analysis must account for the material response of the ablative thermal protection system (TPS). For the exo-atmospheric portion of the mission, the thermal analysis must include the orbital radiation fluxes on the surfaces. The thermal behavior must also be used to predict the structural response of the vehicle (the thermal stress and strains) and whether they remain within the capability of the materials. Thus, the thermal analysis requires ties to the three-dimensional geometry, the aeroheating analysis, the material response analysis, the orbital analysis, and the structural analysis. The goal of this paper is to describe to what degree that has been achieved.

  18. Feasibility study of low angle planetary entry. [probe design for Jovian entry

    NASA Technical Reports Server (NTRS)

    Defrees, R. E.

    1975-01-01

    The feasibility of a Jovian entry by a probe originally designed for Saturn and Uranus entries is examined. An entry probe is described which is capable of release near an outer planet's sphere of influence and descent to a predetermined target entry point in the planet's atmosphere. The probe is designed so as to survive the trapped particle radiation belts and an entry heating pulse. Data is gathered and relayed to an overflying spacecraft bus during descent. Probe variations for two similar missions are described. In the first flyby of Jupiter by a Pioneer spacecraft launched during the 1979 opportunity is examined parametrically. In the second mission an orbiter based on Pioneer and launched in 1980 is defined in specific terms. The differences rest in the science payloads and directly affected wiring and electronics packages.

  19. MCC level C formulation requirements. Entry guidance and entry autopilot, optional TAEM targeting

    NASA Technical Reports Server (NTRS)

    Harpold, J. C.

    1980-01-01

    The level C software formulations requirements for the entry guidance and the simplified autopilot to be used by the Mission Control Center (MCC) entry processor are presented. The modifications required to functionally simulate optional Terminal Area Energy Management (TAEM) targeting capability (OTT) are incorporated. Implementation of this logic in the MCC must be coordinated with flight software OTT implementation and MCC TAEM guidance OTT. The entry guidance logic is based on the orbiter avionics entry guidance software. Descriptions of the entry guidance detailed formulation requirements, the detailed autopilot formulation requirements, and the targeting routine are given. Also included are a definition of coordinate systems, a list of parameter definitions for the software formulations, and a set of formulation flow charts.

  20. Shuttle program. MCC Level C formulation requirements: Entry guidance and entry autopilot

    NASA Technical Reports Server (NTRS)

    Harpold, J. C.; Hill, O.

    1980-01-01

    A set of preliminary entry guidance and autopilot software formulations is presented for use in the Mission Control Center (MCC) entry processor. These software formulations meet all level B requirements. Revision 2 incorporates the modifications required to functionally simulate optimal TAEM targeting capability (OTT). Implementation of this logic in the MCC must be coordinated with flight software OTT implementation and MCC TAEM guidance OTT. The entry guidance logic is based on the Orbiter avionics entry guidance software. This MCC requirements document contains a definition of coordinate systems, a list of parameter definitions for the software formulations, a description of the entry guidance detailed formulation requirements, a description of the detailed autopilot formulation requirements, a description of the targeting routine, and a set of formulation flow charts.