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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: mechanisms and modulation

    PubMed Central

    Hogan, Patrick G; Rao, Anjana

    2015-01-01

    Store-operated calcium entry is a central mechanism in cellular calcium signalling and in maintaining cellular calcium balance. This review traces the history of research on store-operated calcium entry, the discovery of STIM and ORAI as central players in calcium entry, and the role of STIM and ORAI in biology and human disease. It describes current knowledge of the basic mechanism of STIM-ORAI signalling and of the varied mechanisms by which STIM-ORAI signalling can be modulated. PMID:25998732

  3. Studies on endogenous circulating calcium entry blocker and stimulator

    SciTech Connect

    Pang, P.K.T.; Yang, M.C.M.

    1986-03-01

    Several synthetic compounds have been studied extensively for their calcium entry blockade and stimulation in smooth muscles. It is hypothesized that there should be endogenous substances which control calcium entry into cells. We recently investigated the effect of some vasoactive hormones on calcium entry. Our studies on rat tail artery helical strip showed that the in vitro vasoconstriction produced by arginine vasopressin (AVP) decreased stepwise with decreasing concentration of both calcium. After exposure of the tail artery to calcium-free Ringer's solution for 1 minute or longer, the tissue lost its ability to respond to AVP. Subsequent addition of calcium to the medium produced immediate contraction. Measurements of low affinity lanthanum resistant pool of calcium with /sup 45/Ca showed that AVP increased calcium uptake by tail artery in a dose-dependent manner. In another study rat tail artery helical strip indicated that the vasorelaxing action of parathyroid hormone (PTH) was related to an inhibition of calcium uptake. AVP or 60 mM potassium chloride increased the low affinity lanthanum resistant pool of calcium in rate tail artery and PTH inhibited the increase. In conclusion, AVP and PTH may behave like endogenous calcium entry stimulator and inhibitor respectively in vascular tissues.

  4. 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

    2016-07-01

    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 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. PMID:27189940

  5. 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.

  6. 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. PMID:27161240

  7. Store-operated calcium entry compensates fast ER calcium loss in resting hippocampal neurons.

    PubMed

    Samtleben, Samira; Wachter, Britta; Blum, Robert

    2015-08-01

    The endoplasmic reticulum (ER) acts as a dynamic calcium store and is involved in the generation of specific patterns of calcium signals in neurons. Calcium is mobilized from the ER store by multiple signaling cascades, and neuronal activity is known to regulate ER calcium levels. We asked how neurons regulate ER calcium levels in the resting state. Direct ER calcium imaging showed that ER calcium was lost quite rapidly from the somatic and dendritic ER when resting neurons were transiently kept under calcium-free conditions. Interestingly, free ER and free cytosolic calcium was lost continuously across the plasma membrane and was not held back in the cytosol, implying the presence of a prominent calcium influx mechanism to maintain ER calcium levels at rest. When neurons were treated acutely with inhibitors of store-operated calcium entry (SOCE), an immediate decline in ER calcium levels was observed. This continuous SOCE-like calcium entry did not require the activation of a signaling cascade, but was rather a steady-state phenomenon. The SOCE-like mechanism maintains medium-high ER calcium levels at rest and is essential for balanced resting calcium levels in the ER and cytosol.

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

    PubMed

    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. The heterogeneity of store-operated calcium entry in melanoma

    PubMed Central

    Hooper, Robert; Zaidi, M. Raza; Soboloff, Jonathan

    2016-01-01

    Calcium is a key regulator of many physiological processes that are perturbed in cancer, such as migration, proliferation and apoptosis. The proteins STIM and Orai mediate store-operated calcium entry (SOCE), the main pathway for calcium entry in non-excitable cells. Changes in the expression and function of STIM and Orai have been found in a range of cancer types and thus implicated in disease progression. Here we discuss the role of STIM, Orai and the SOCE pathway in the progression of melanoma and explore how the heterogeneous nature of melanoma may explain the lack of consensus in the field regarding the role of SOCE in the progression of this disease. PMID:27417567

  10. 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

  11. Depolarization and calcium entry in squid giant axons

    PubMed Central

    Baker, P. F.; Hodgkin, A. L.; Ridgway, E. B.

    1971-01-01

    stimulation was small it was proportional to the frequency of stimulation; if large to the square of the frequency. 11. Voltage-clamp experiments showed that the calcium entry associated with a depolarizing pulse could be divided into an early component which was abolished by tetrodotoxin (TTX), and a late component which was unaffected by this inhibitor. 12. The time relations of the early calcium entry were consistent with its being a leak of calcium ions through the sodium channel; the permeability of the sodium channel to calcium was about 1% of the permeability to sodium. 13. The late entry of calcium was little changed by injecting enough tetraethylammonium (TEA) to block the outward potassium current; it was greatly reduced by external concentrations of manganese which had little effect on the maximum potassium conductance. 14. The voltage—response curve for the late entry of calcium had a well defined maximum and was similar in shape to the curve relating calcium entry to depolarization at the presynaptic ending (Katz & Miledi, 1969, 1970). PMID:5133953

  12. Store-operated calcium entry in human oocytes and sensitivity to oxidative stress.

    PubMed

    Martín-Romero, Francisco Javier; Ortíz-de-Galisteo, Jose Ramón; Lara-Laranjeira, Javier; Domínguez-Arroyo, Jose Antonio; González-Carrera, Ernesto; Alvarez, Ignacio S

    2008-02-01

    Calcium signaling is a cellular event that plays a key role at many steps of fertilization and early development. However, little is known regarding the contribution of extracellular Ca(2+) influx into the cell to this signaling in gametes and early embryos. To better know the significance of calcium entry on oocyte physiology, we have evaluated the mechanism of store-operated calcium entry (SOCE) in human metaphase II (MII) oocytes and its sensitivity to oxidative stress, one of the major factors implicated in the outcome of in vitro fertilization (IVF) techniques. We show that depletion of intracellular Ca(2+) stores through inhibition of sarco(endo)plasmic Ca(2+)-ATPase with thapsigargin triggers Ca(2+) entry in resting human oocytes. Ba(2+) and Mn(2+) influx was also stimulated following inhibition, and Ca(2+) entry was sensitive to pharmacological inhibition because the SOCE blocker 2-aminoethoxydiphenylborate (2-APB) reduced calcium and barium entry. These results support the conclusion that there is a plasma membrane mechanism responsible for the capacitative divalent cation entry in human oocytes. Moreover, the Ca(2+) entry mechanism described in MII oocytes was found to be highly sensitive to oxidative stress. Hydrogen peroxide, at micromolar concentrations that could mimic culture conditions in IVF, elicited an increase of [Ca(2+)](i) that was dependent on the presence of extracellular Ca(2+). This rise was preventable by 2-APB, indicating that it was mainly due to the enhanced influx through store-operated calcium channels. In sum, our results demonstrate the occurrence of SOCE in human MII oocytes and the modification of this pathway due to oxidative stress, with possible consequences in IVF. PMID:18003943

  13. 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. PMID:27161238

  14. 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.

  15. Mitochondrial calcium uniporter MCU supports cytoplasmic Ca2+ oscillations, store-operated Ca2+ entry and Ca2+-dependent gene expression in response to receptor stimulation.

    PubMed

    Samanta, Krishna; Douglas, Sophie; Parekh, Anant B

    2014-01-01

    Ca2+ flux into mitochondria is an important regulator of cytoplasmic Ca2+ signals, energy production and cell death pathways. Ca2+ uptake can occur through the recently discovered mitochondrial uniporter channel (MCU) but whether the MCU is involved in shaping Ca2+ signals and downstream responses to physiological levels of receptor stimulation is unknown. Here, we show that modest stimulation of leukotriene receptors with the pro-inflammatory signal LTC4 evokes a series of cytoplasmic Ca2+ oscillations that are rapidly and faithfully propagated into mitochondrial matrix. Knockdown of MCU or mitochondrial depolarisation, to reduce the driving force for Ca2+ entry into the matrix, prevents the mitochondrial Ca2+ rise and accelerates run down of the oscillations. The loss of cytoplasmic Ca2+ oscillations appeared to be a consequence of enhanced Ca2+-dependent inactivation of InsP3 receptors, which arose from the loss of mitochondrial Ca2+ buffering. Ca2+ dependent gene expression in response to leukotriene receptor activation was suppressed following knockdown of the MCU. In addition to buffering Ca2+ release, mitochondria also sequestrated Ca2+ entry through store-operated Ca2+ channels and this too was prevented following loss of MCU. MCU is therefore an important regulator of physiological pulses of cytoplasmic Ca2+.

  16. Effects of calcium entry blockers on calcium-dependent contractions of rat portal vein.

    PubMed Central

    Dacquet, C.; Mironneau, C.; Mironneau, J.

    1987-01-01

    1 The effects of six calcium entry blockers belonging to the dihydropyridine (isradipine or PN 200-110, nifedipine, nicardipine), verapamil (D888 or desmethoxyverapamil, D600 or gallopamil) and diltiazem classes were investigated on isometric spontaneous contractions and contractions induced by high-K+ solutions, noradrenaline, acetylcholine and caffeine. 2 The rank order of potency was PN 200-110 greater than nicardipine = nifedipine = D888 greater than D600 greater than diltiazem from experiments on spontaneous contractions and high-K+ induced contractions. With depolarized preparations, the concentration-response curves for nicardipine, PN 200-110, nifedipine and D600 were significantly shifted to the left indicating that the calcium entry blockers show voltage-dependent inhibitory properties. This effect was not significant with D888 and diltiazem. 3 All the calcium entry blockers strongly reduced the noradrenaline (NA)- and acetylcholine (ACh)-induced contractions at concentrations which produced complete inhibition of spontaneous contractions. They had a slight effect on caffeine-induced contractions. 4 In Ca2+-free, EGTA-containing solutions, both ACh, NA and caffeine produced transient contractions, the amplitude of which could be taken as a measurement of the amount of internal calcium present in a drug-sensitive calcium store. The filling of the calcium store was maximal after 10-12 min of calcium loading in 2.1 mM Ca2+, while the depletion was complete after 4-6 min of perfusion in Ca2+-free solution. 5 At concentrations which abolished spontaneous contractions, PN 200-110, nifedipine, D888 and D600 had no appreciable effect on contractions evoked in Ca2+-free solutions by ACh, NA and caffeine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2959345

  17. 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.

  18. 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. PMID:27161226

  19. 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

  20. 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.

  1. 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.

  2. The serine-threonine phosphatase calcineurin is a regulator of endothelial store-operated calcium entry

    PubMed Central

    2014-01-01

    Abstract Disruption of the endothelium leads to increased permeability, allowing extravasation of macromolecules and other solutes from blood vessels. Calcium entry through a calcium-selective, store-operated calcium (SOC) channel, Isoc, contributes to barrier disruption. An understanding of the mechanisms surrounding the regulation of Isoc is far from complete. We show that the calcium/calmodulin-activated phosphatase calcineurin (CN) plays a role in regulation of SOC entry, possibly through the dephosphorylation of stromal interaction molecule 1 (STIM1). Phosphorylation has been implicated as a regulatory mechanism of activity for a number of canonical transient receptor potential (TRPC) and SOC channels, including Isoc. Our results show that STIM1 phosphorylation increases in pulmonary artery endothelial cells (PAECs) upon activation of SOC entry. However, the phosphatases involved in STIM1 dephosphorylation are unknown. We found that a CN inhibitor (calcineurin inhibitory peptide [CIP]) increases the phosphorylation pattern of STIM1. Using a fura 2-acetoxymethyl ester approach to measure cytosolic calcium in PAECs, we found that CIP decreases SOC entry following thapsigargin treatment in PAECs. Luciferase assays indicate that thapsigargin induces activation of CN activity and confirm inhibition of CN activity by CIP in PAECs. Also, Isoc is significantly attenuated in whole-cell patch-clamp studies of PAECs treated with CIP. Finally, PAECs pretreated with CIP exhibit decreased interendothelial cell gap formation in response to thapsigargin-induced SOC entry, as compared to control cells. Taken together, our data show that CN contributes to the phosphorylation status of STIM1, which is important in regulation of endothelial SOC entry and Isoc activity. PMID:25006427

  3. Relocalization of STIM1 in mouse oocytes at fertilization: early involvement of store-operated calcium entry.

    PubMed

    Gómez-Fernández, Carolina; Pozo-Guisado, Eulalia; Gañán-Parra, Miguel; Perianes, Mario J; Alvarez, Ignacio S; Martín-Romero, Francisco Javier

    2009-08-01

    Calcium waves represent one of the most important intracellular signaling events in oocytes at fertilization required for the exit from metaphase arrest and the resumption of the cell cycle. The molecular mechanism ruling this signaling has been described in terms of the contribution of intracellular calcium stores to calcium spikes. In this work, we considered the possible contribution of store-operated calcium entry (SOCE) to this signaling, by studying the localization of the protein STIM1 in oocytes. STIM1 has been suggested to play a key role in the recruitment and activation of plasma membrane calcium channels, and we show here that mature mouse oocytes express this protein distributed in discrete clusters throughout their periphery in resting cells, colocalizing with the endoplasmic reticulum marker calreticulin. However, immunolocalization of the endogenous STIM1 showed considerable redistribution over larger areas or patches covering the entire periphery of the oocyte during Ca(2+) store depletion induced with thapsigargin or ionomycin. Furthermore, pharmacological activation of endogenous phospholipase C induced a similar pattern of redistribution of STIM1 in the oocyte. Finally, fertilization of mouse oocytes revealed a significant and rapid relocalization of STIM1, similar to that found after pharmacological Ca(2+) store depletion. This particular relocalization supports a role for STIM1 and SOCE in the calcium signaling during early stages of fertilization.

  4. Relocalization of STIM1 in mouse oocytes at fertilization: early involvement of store-operated calcium entry.

    PubMed

    Gómez-Fernández, Carolina; Pozo-Guisado, Eulalia; Gañán-Parra, Miguel; Perianes, Mario J; Alvarez, Ignacio S; Martín-Romero, Francisco Javier

    2009-08-01

    Calcium waves represent one of the most important intracellular signaling events in oocytes at fertilization required for the exit from metaphase arrest and the resumption of the cell cycle. The molecular mechanism ruling this signaling has been described in terms of the contribution of intracellular calcium stores to calcium spikes. In this work, we considered the possible contribution of store-operated calcium entry (SOCE) to this signaling, by studying the localization of the protein STIM1 in oocytes. STIM1 has been suggested to play a key role in the recruitment and activation of plasma membrane calcium channels, and we show here that mature mouse oocytes express this protein distributed in discrete clusters throughout their periphery in resting cells, colocalizing with the endoplasmic reticulum marker calreticulin. However, immunolocalization of the endogenous STIM1 showed considerable redistribution over larger areas or patches covering the entire periphery of the oocyte during Ca(2+) store depletion induced with thapsigargin or ionomycin. Furthermore, pharmacological activation of endogenous phospholipase C induced a similar pattern of redistribution of STIM1 in the oocyte. Finally, fertilization of mouse oocytes revealed a significant and rapid relocalization of STIM1, similar to that found after pharmacological Ca(2+) store depletion. This particular relocalization supports a role for STIM1 and SOCE in the calcium signaling during early stages of fertilization. PMID:19470709

  5. Store-operated calcium entry and diabetic complications

    PubMed Central

    Chaudhari, Sarika

    2016-01-01

    Store-operated Ca2+ entry (SOCE) is mediated by the store-operated Ca2+ channel (SOC) that opens upon depletion of internal Ca2+ stores following activation of G protein-coupled receptors or receptor tyrosine kinases. Over the past two decades, the physiological and pathological relevance of SOCE has been extensively studied. Recently, accumulating evidence suggests associations of altered SOCE with diabetic complications. This review focuses on the implication of SOCE as it pertains to various complications resulting from diabetes. We summarize recent findings by us and others on the involvement of abnormal SOCE in the development of diabetic complications, such as diabetic nephropathy and diabetic vasculopathy. The underlying mechanisms that mediate the diabetes-associated alterations of SOCE are also discussed. The SOCE pathway may be considered as a potential therapeutic target for diabetes-associated diseases. PMID:26468167

  6. 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. PMID:26815481

  7. 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

  8. 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

  9. Calcium entry through nicotinic receptor channels and calcium channels in cultured rat superior cervical ganglion cells.

    PubMed Central

    Trouslard, J; Marsh, S J; Brown, D A

    1993-01-01

    1. Patch-clamp techniques in conjunction with indo-1 fluorescent measurements were used to measure increases in intracellular free calcium concentration and membrane conductance induced by the activation of nicotinic and calcium channels in cultured rat sympathetic neurons. 2. Under voltage-clamp conditions, pressure application of the nicotinic agonist DMPP (1,1-dimethyl-4-phenylpiperazinium iodide, 100 microM, 100 ms) increased [Ca2+]i by 193 +/- 26 nM at a clamp potential of -60 mV. This was accompanied by an inward current of -4.53 +/- 0.89 nA, giving a mean ratio of the delta (Ca2+]i to the total inward charge transfer of 42.7 nmoles per litre of free calcium per nanocoulomb of charge (M/q ratio). 3. The DMPP-induced current and associated delta [Ca2+]i were reduced by mecamylamine (100 nM-10 microM) but were unaffected by alpha-bungarotoxin (100 nM) or cadmium (100 microM). 4. The M/q ratio was not affected by the holding potential (from -80 to -40 mV) but was a function of the external calcium concentration. 5. The M/q ratio was reduced by increasing the intracellular calcium buffering capacity and increased by heparin but not affected by ryanodine or by depletion of the caffeine-sensitive calcium store. 6. Under the same recording conditions, we quantified the increase in [Ca2+]i associated with activation of the voltage-dependent calcium current. On average at -60 mV, the M/q ratio of this highly calcium-selective permeability was 1961 mM nC-1, which is 46 times that obtained for the nicotinic channel. 7. Assuming constant-field theory, ion-substitution experiments suggest that in 2.5 mM external calcium, the permeability sequence for the nicotinic conductance was Cs+ < Li+ < Na+ < K+ < Ca2+. 8. We conclude that the nicotinic channels in rat sympathetic neurones are significantly permeant to Ca2+ and that the influx of Ca2+ through these channels is the principal cause of the rise in [Ca2+]i seen under voltage clamp. PMID:8254522

  10. Protein kinase C activates non-capacitative calcium entry in human platelets

    PubMed Central

    Rosado, Juan A; Sage, Stewart O

    2000-01-01

    In many non-excitable cells Ca2+ influx is mainly controlled by the filling state of the intracellular Ca2+ stores. It has been suggested that this store-mediated or capacitative Ca2+ entry is brought about by a physical and reversible coupling of the endoplasmic reticulum with the plasma membrane. Here we provide evidence for an additional, non-capacitative Ca2+ entry mechanism in human platelets. Changes in cytosolic Ca2+ and Sr2+ were measured in human platelets loaded with the fluorescent indicator fura-2. Depletion of the internal Ca2+ stores with thapsigargin plus a low concentration of ionomycin stimulated store-mediated cation entry, as demonstrated upon Ca2+ or Sr2+ addition. Subsequent treatment with thrombin stimulated further divalent cation entry in a concentration-dependent manner. Direct activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate or 1-oleoyl-2-acetyl-sn-glycerol also stimulated divalent cation entry, without evoking the release of Ca2+ from intracellular stores. Cation entry evoked by thrombin or activators of PKC was abolished by the PKC inhibitor Ro-31-8220. Unlike store-mediated Ca2+ entry, jasplakinolide, which reorganises actin filaments into a tight cortical layer adjacent to the plasma membrane, did not inhibit divalent cation influx evoked by thrombin when applied after Ca2+ store depletion, or by activators of PKC. Thrombin also activated Ca2+ entry in platelets in which the release from intracellular stores and store-mediated Ca2+ entry were blocked by xestospongin C. These results indicate that the non-capacitative divalent cation entry pathway is regulated independently of store-mediated entry and does not require coupling of the endoplasmic reticulum and the plasma membrane. These results support the existence of a mechanism for receptor-evoked Ca2+ entry in human platelets that is independent of Ca2+ store depletion. This Ca2+ entry mechanism may be activated by occupation of G-protein-coupled receptors

  11. Store-operated calcium entry inactivates at the germinal vesicle breakdown stage of Xenopus meiosis.

    PubMed

    Machaca, K; Haun, S

    2000-12-01

    Store-operated calcium entry (SOCE) is the predominant Ca(2+) influx pathway in non-excitable cells and is activated in response to depletion of intracellular Ca(2+) stores. We have studied SOCE regulation during Xenopus oocyte meiosis. SOCE can be measured readily in stage VI Xenopus oocytes arrested at the G(2)-M transition of the cell cycle, either by Ca(2+) imaging or by recording the SOCE current. However, following meiotic maturation, SOCE can no longer be activated by store depletion. We have characterized the time course of SOCE inactivation during oocyte maturation, and show that SOCE inactivates almost completely, in a very short time period, at the germinal vesicle breakdown stage of meiosis. This acute inactivation offers an opportunity to better understand SOCE regulation.

  12. A STIM2 splice variant negatively regulates store-operated calcium entry

    PubMed Central

    Miederer, Anna-Maria; Alansary, Dalia; Schwär, Gertrud; Lee, Po-Hsien; Jung, Martin; Helms, Volkhard; Niemeyer, Barbara A.

    2015-01-01

    Cellular homeostasis relies upon precise regulation of Ca2+ concentration. Stromal interaction molecule (STIM) proteins regulate store-operated calcium entry (SOCE) by sensing Ca2+ concentration in the ER and forming oligomers to trigger Ca2+ entry through plasma membrane-localized Orai1 channels. Here we characterize a STIM2 splice variant, STIM2.1, which retains an additional exon within the region encoding the channel-activating domain. Expression of STIM2.1 is ubiquitous but its abundance relative to the more common STIM2.2 variant is dependent upon cell type and highest in naive T cells. STIM2.1 knockdown increases SOCE in naive CD4+ T cells, whereas knockdown of STIM2.2 decreases SOCE. Conversely, overexpression of STIM2.1, but not STIM2.2, decreases SOCE, indicating its inhibitory role. STIM2.1 interaction with Orai1 is impaired and prevents Orai1 activation, but STIM2.1 shows increased affinity towards calmodulin. Our results imply STIM2.1 as an additional player tuning Orai1 activation in vivo. PMID:25896806

  13. 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.

  14. Role of AQP2 in activation of calcium entry by hypotonicity: implications in cell volume regulation.

    PubMed

    Galizia, L; Flamenco, M P; Rivarola, V; Capurro, C; Ford, P

    2008-03-01

    We previously reported in a rat cortical collecting duct cell line (RCCD(1)) that the presence of aquaporin 2 (AQP2) in the cell membrane is critical for the rapid activation of regulatory volume decrease mechanisms (RVD) (Ford et al. Biol Cell 97: 687-697, 2005). The aim of our present work was to investigate the signaling pathway that links AQP2 to this rapid RVD activation. Since it has been previously described that hypotonic conditions induce intracellular calcium ([Ca(2+)](i)) increases in different cell types, we tested the hypothesis that AQP2 could have a role in activation of calcium entry by hypotonicity and its implication in cell volume regulation. Using a fluorescent probe technique, we studied [Ca(2+)](i) and cell volume changes in response to a hypotonic shock in WT-RCCD(1) (not expressing aquaporins) and in AQP2-RCCD(1) (transfected with AQP2) cells. We found that after a hypotonic shock only AQP2-RCCD(1) cells exhibit a substantial increase in [Ca(2+)](i). This [Ca(2+)](i) increase is strongly dependent on extracellular Ca(2+) and is partially inhibited by thapsigargin (1 muM) indicating that the rise in [Ca(2+)](i) reflects both influx from the extracellular medium and release from intracellular stores. Exposure of AQP2-RCCD(1) cells to 100 muM gadolinium reduced the increase in [Ca(2+)](i) suggesting the involvement of a mechanosensitive calcium channel. Furthermore, exposure of cells to all of the above described conditions impaired rapid RVD. We conclude that the expression of AQP2 in the cell membrane is critical to produce the increase in [Ca(2+)](i) which is necessary to activate RVD in RCCD(1) cells. PMID:18094031

  15. Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis.

    PubMed

    Müller, Margit S; Fox, Rebecca; Schousboe, Arne; Waagepetersen, Helle S; Bak, Lasse K

    2014-04-01

    Astrocytic glycogen, the only storage form of glucose in the brain, has been shown to play a fundamental role in supporting learning and memory, an effect achieved by providing metabolic support for neurons. We have examined the interplay between glycogenolysis and the bioenergetics of astrocytic Ca(2+) homeostasis, by analyzing interdependency of glycogen and store-operated Ca(2+) entry (SOCE), a mechanism in cellular signaling that maintains high endoplasmatic reticulum (ER) Ca(2+) concentration and thus provides the basis for store-dependent Ca(2+) signaling. We stimulated SOCE in primary cultures of murine cerebellar and cortical astrocytes, and determined glycogen content to investigate the effects of SOCE on glycogen metabolism. By blocking glycogenolysis, we tested energetic dependency of SOCE-related Ca(2+) dynamics on glycogenolytic ATP. Our results show that SOCE triggers astrocytic glycogenolysis. Upon inhibition of adenylate cyclase with 2',5'-dideoxyadenosine, glycogen content was no longer significantly different from that in unstimulated control cells, indicating that SOCE triggers astrocytic glycogenolysis in a cAMP-dependent manner. When glycogenolysis was inhibited in cortical astrocytes by 1,4-dideoxy-1,4-imino-D-arabinitol, the amount of Ca(2+) loaded into ER via sarco/endoplasmic reticulum Ca(2)-ATPase (SERCA) was reduced, which suggests that SERCA pumps preferentially metabolize glycogenolytic ATP. Our study demonstrates SOCE as a novel pathway in stimulating astrocytic glycogenolysis. We also provide first evidence for a new functional role of brain glycogen, in providing local ATP to SERCA, thus establishing the bioenergetic basis for astrocytic Ca(2+) signaling. This mechanism could offer a novel explanation for the impact of glycogen on learning and memory.

  16. Inhibition of Store-Operated Calcium Entry Protects Endothelial Progenitor Cells from H2O2-Induced Apoptosis

    PubMed Central

    Wang, Yan-Wei; Zhang, Ji-Hang; Yu, Yang; Yu, Jie; Huang, Lan

    2016-01-01

    Store-operated calcium entry (SOCE), a major mode of extracellular calcium entry, plays roles in a variety of cell activities. Accumulating evidence indicates that the intracellular calcium ion concentration and calcium signaling are critical for the responses induced by oxidative stress. The present study was designed to investigate the potential effect of SOCE inhibition on H2O2-induced apoptosis in endothelial progenitor cells (EPCs), which are the predominant cells involved in endothelial repair. The results showed that H2O2-induced EPC apoptosis was reversed by SOCE inhibition induced either using the SOCE antagonist ML-9 or via silencing of stromal interaction molecule 1 (STIM1), a component of SOCE. Furthermore, SOCE inhibition repressed the increases in intracellular reactive oxygen species (ROS) levels and endoplasmic reticulum (ER) stress and ameliorated the mitochondrial dysfunction caused by H2O2. Our findings provide evidence that SOCE inhibition exerts a protective effect on EPCs in response to oxidative stress induced by H2O2 and may serve as a potential therapeutic strategy against vascular endothelial injury. PMID:27169819

  17. Neuronal Store-Operated Calcium Entry and Mushroom Spine Loss in Amyloid Precursor Protein Knock-In Mouse Model of Alzheimer's Disease.

    PubMed

    Zhang, Hua; Wu, Lili; Pchitskaya, Ekaterina; Zakharova, Olga; Saito, Takashi; Saido, Takaomi; Bezprozvanny, Ilya

    2015-09-30

    Alzheimer's disease (AD) is the most common reason for elderly dementia in the world. We proposed that memory loss in AD is related to destabilization of mushroom postsynaptic spines involved in long-term memory storage. We demonstrated previously that stromal interaction molecule 2 (STIM2)-regulated neuronal store-operated calcium entry (nSOC) in postsynaptic spines play a key role in stability of mushroom spines by maintaining activity of synaptic Ca(2+)/calmodulin kinase II (CaMKII). Furthermore, we demonstrated previously that the STIM2-nSOC-CaMKII pathway is downregulated in presenilin 1 M146V knock-in (PS1-M146V KI) mouse model of AD, leading to loss of hippocampal mushroom spines in this model. In the present study, we demonstrate that hippocampal mushroom postsynaptic spines are also lost in amyloid precursor protein knock-in (APPKI) mouse model of AD. We demonstrated that loss of mushroom spines occurs as a result of accumulation of extracellular β-amyloid 42 in APPKI culture media. Our results indicate that extracellular Aβ42 acts by overactivating mGluR5 receptor in APPKI neurons, leading to elevated Ca(2+) levels in endoplasmic reticulum, compensatory downregulation of STIM2 expression, impaired synaptic nSOC, and reduced CaMKII activity. Pharmacological inhibition of mGluR5 or overexpression of STIM2 rescued synaptic nSOC and prevented mushroom spine loss in APPKI hippocampal neurons. Our results indicate that downregulation of synaptic STIM2-nSOC-CaMKII pathway causes loss of mushroom synaptic spines in both presenilin and APPKI mouse models of AD. We propose that modulators/activators of this pathway may have a potential therapeutic value for treatment of memory loss in AD. Significance statement: A direct connection between amyloid-induced synaptic mushroom spine loss and neuronal store-operated calcium entry pathway is shown. These results provide strong support for the calcium hypothesis of neurodegeneration and further validate the synaptic

  18. STIM1/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry

    PubMed Central

    Stathopulos, Peter B.; Schindl, Rainer; Fahrner, Marc; Zheng, Le; Gasmi-Seabrook, Geneviève M.; Muik, Martin; Romanin, Christoph; Ikura, Mitsuhiko

    2013-01-01

    Orai1 calcium channels in the plasma membrane are activated by stromal interaction molecule-1 (STIM1), an endoplasmic reticulum calcium sensor, to mediate store-operated calcium entry (SOCE). The cytosolic region of STIM1 contains a long putative coiled-coil (CC)1 segment and shorter CC2 and CC3 domains. Here we present solution nuclear magnetic resonance structures of a trypsin-resistant CC1–CC2 fragment in the apo and Orai1-bound states. Each CC1–CC2 subunit forms a U-shaped structure that homodimerizes through antiparallel interactions between equivalent α-helices. The CC2:CC2′ helix pair clamps two identical acidic Orai1 C-terminal helices at opposite ends of a hydrophobic/basic STIM–Orai association pocket. STIM1 mutants disrupting CC1:CC1′ interactions attenuate, while variants promoting CC1 stability spontaneously activate Orai1 currents. CC2 mutations cause remarkable variability in Orai1 activation because of a dual function in binding Orai1 and autoinhibiting STIM1 oligomerization via interactions with CC3. We conclude that SOCE is activated through dynamic interplay between STIM1 and Orai1 helices. PMID:24351972

  19. 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…

  20. 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…

  1. 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

  2. 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.

  3. 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

  4. New insights into store-independent Ca2+ entry: secretory pathway calcium ATPase 2 in normal physiology and cancer

    PubMed Central

    Feng, Ming-Ye; Rao, Rajini

    2013-01-01

    Recent studies in secretory pathway calcium ATPases (SPCA) revealed novel functions of SPCA2 in interacting with store-operated Ca2+ channel Orai1 and inducing Ca2+ influx at the cell surface. Importantly, SPCA2-mediated Ca2+ signaling is uncoupled from its conventional role of Ca2+-ATPase and independent of store-operated Ca2+ signaling pathway. SPCA2-induced store-independent Ca2+ entry (SICE) plays essential roles in many important physiological processes, while unbalanced SICE leads to enhanced cell proliferation and tumorigenesis. Finally, we have summarized the clinical implication of SICE in oral cancer prognosis and treatment. Inhibition of SICE may be a new target for the development of cancer therapeutics. PMID:23670239

  5. 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.

  6. Sigma-1 receptors: a new pathway for the modulation of store-operated calcium entry.

    PubMed

    Rosado, Juan A

    2016-02-01

    SOCE (store-operated Ca(2+) entry) is a ubiquitous mechanism for Ca(2+) influx in animal cells. In a recent issue of the Biochemical Journal, Brailoiu and colleagues reported that cocaine attenuates SOCE in rat brain microvascular endothelial cells, via a mechanism that requires the expression and activation of the sigma-1 receptor, a chaperone located in the endoplasmic reticulum-mitochondrion interface that modulates intracellular Ca(2+) homoeostasis and cell survival. This study envisages a pathway through which cocaine modulates endothelial function via regulation of SOCE. The regulation of SOCE by sigma-1 receptors provides a novel and important pathway in Ca(2+) signalling.

  7. 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.

  8. 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

  9. 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

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

    PubMed

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

    2016-09-08

    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 Ca(2+) is an important signaling event in this process, yet the fundamental mechanism by which allergens induce Ca(2+) elevations in AECs remains poorly understood. Here we find that extracts from dust mite and cockroach induce sustained Ca(2+) elevations in AECs through the activation of Ca(2+) release-activated Ca(2+) (CRAC) channels encoded by Orai1 and STIM1. CRAC channel activation occurs, at least in part, through allergen mediated stimulation of PAR2 receptors. The ensuing Ca(2+) 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.

  11. Initial activation of STIM1, the regulator of store-operated calcium entry

    PubMed Central

    Zhou, Yubin; Srinivasan, Prasanna; Razavi, Shiva; Seymour, Sam; Meraner, Paul; Gudlur, Aparna; Stathopulos, Peter B; Ikura, Mitsuhiko; Rao, Anjana; Hogan, Patrick G

    2013-01-01

    Physiological Ca2+ signalling in T lymphocytes and other cells depends on the STIM-ORAI pathway of store-operated Ca2+ entry. STIM1 and STIM2 are Ca2+ sensors located in the endoplasmic reticulum (ER) membrane, with ER-luminal domains that monitor cellular Ca2+ stores and cytoplasmic domains that gate ORAI channels in the plasma membrane. The STIM ER-luminal domain dimerizes or oligomerizes upon dissociation of Ca2+, but the mechanism transmitting activation to the STIM cytoplasmic domain has not been defined. Here we demonstrate, using Tb3+–acceptor energy transfer, that dimerization of STIM1 ER-luminal domains can initiate an extensive conformational change in murine STIM1 cytoplasmic domains. The conformational change, triggered by apposition of the predicted coiled-coil 1 (CC1) regions, releases the ORAI-activating domains from their interaction with the CC1 regions and allows physical extension of the STIM1 cytoplasmic domain across the gap between ER and plasma membrane to communicate with ORAI channels. PMID:23851458

  12. Stanniocalcin 2 Is a Negative Modulator of Store-Operated Calcium Entry ▿ †

    PubMed Central

    Zeiger, William; Ito, Daisuke; Swetlik, Carol; Oh-hora, Masatsugu; Villereal, Mitchel L.; Thinakaran, Gopal

    2011-01-01

    The regulation of cellular Ca2+ homeostasis is essential for innumerable physiological and pathological processes. Stanniocalcin 1, a secreted glycoprotein hormone originally described in fish, is a well-established endocrine regulator of gill Ca2+ uptake during hypercalcemia. While there are two mammalian Stanniocalcin homologs (STC1 and STC2), their precise molecular functions remain unknown. Notably, STC2 is a prosurvival component of the unfolded protein response. Here, we demonstrate a cell-intrinsic role for STC2 in the regulation of store-operated Ca2+ entry (SOCE). Fibroblasts cultured from Stc2 knockout mice accumulate higher levels of cytosolic Ca2+ following endoplasmic reticulum (ER) Ca2+ store depletion, specifically due to an increase in extracellular Ca2+ influx through store-operated Ca2+ channels (SOC). The knockdown of STC2 expression in a hippocampal cell line also potentiates SOCE, and the overexpression of STC2 attenuates SOCE. Moreover, STC2 interacts with the ER Ca2+ sensor STIM1, which activates SOCs following ER store depletion. These results define a novel molecular function for STC2 as a negative modulator of SOCE and provide the first direct evidence for the regulation of Ca2+ homeostasis by mammalian STC2. Furthermore, our findings implicate the modulation of SOCE through STC2 expression as one of the prosurvival measures of the unfolded protein response. PMID:21746875

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

    PubMed

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

    2015-08-15

    Extracellular Ca(2+) influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca(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 (0-400mM) dose-dependently increased hepatocyte injury and 100mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca(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.

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

    PubMed

    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 Ca(2+) is an important signaling event in this process, yet the fundamental mechanism by which allergens induce Ca(2+) elevations in AECs remains poorly understood. Here we find that extracts from dust mite and cockroach induce sustained Ca(2+) elevations in AECs through the activation of Ca(2+) release-activated Ca(2+) (CRAC) channels encoded by Orai1 and STIM1. CRAC channel activation occurs, at least in part, through allergen mediated stimulation of PAR2 receptors. The ensuing Ca(2+) 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

  15. 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.

  16. Intragastric calcium infusions support flavor preference learning by calcium-deprived rats.

    PubMed

    Tordoff, Michael G

    2002-08-01

    We investigated whether rats can associate the flavor of ingested solutions with the postingestive delivery of calcium. In one series of experiments using the "electronic esophagus" preparation, calcium-deprived rats received pairs of daily one-bottle training trials in which they received intragastric infusions whenever they ingested an arbitrary flavor of Kool Aid. Rats later preferred the flavor associated with infusions of 50 mM CaCl(2) or 50 mM calcium lactate (CaLa), but not with water, 10, 100 or 250 mM CaCl(2) or 100 mM sodium lactate (NaLa). In another experiment, rats had simultaneous access to two arbitrary flavors, ingestion of one of which produced intragastric infusion of 50 mM CaCl(2), 75 mM NaCl or water. Only the rats given 50 mM CaCl(2) developed a preference for the flavor associated with the infusion. The preference for calcium infusions was not as large as that seen for orally ingested calcium. Nevertheless, these results show that 50 mM calcium infusions are rewarding to calcium-deprived rats. They thus suggest that rats can associate flavor ingestion with the postingestive benefits of consuming calcium. PMID:12126988

  17. 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.

  18. HL7 Structured Product Labeling - electronic prescribing information for provider order entry decision support.

    PubMed

    Schadow, Gunther

    2005-01-01

    Prescribing errors are an important cause of adverse events, and lack of knowledge of the drug is a root cause for prescribing errors. The FDA is issuing new regulations that will make the drug labels much more useful not only to physicians, but also to computerized order entry systems that support physicians to practice safe prescribing. For this purpose, FDA works with HL7 to create the Structured Product Label (SPL) standard that includes a document format as well as a drug knowledge representation, this poster introduces the basic concepts of SPL.

  19. Trifluoperazine, a calmodulin inhibitor, blocks secretion in cultured chromaffin cells at a step distal from calcium entry.

    PubMed

    Kenigsberg, R L; Côté, A; Trifaró, J M

    1982-01-01

    Trifluoperazine, a calmodulin antagonist, inhibited the secretory response of cultured bovine adrenal medullary chromaffin cells to acetylcholine (10(-4) M) or a depolarizing concentration of [K+] (56 mM KCl) in a dose-related fashion. The ID50s of this effect were 2 x 10(-7) M and 2.2 x 10(-6) M for acetylcholine and high [K+], respectively. A decrease in external [Ca2+] concentration of the incubation medium from 4.4 to 0.275 mM resulted in an increase in the percentage of inhibition produced by trifluoperazine on the acetylcholine-evoked secretory response from 20.7 to 96.5%, respectively. However, trifluoperazine inhibited the acetylcholine-evoked catecholamine output by a similar absolute magnitude for all [Ca2+] concentrations tested with the exception of 4.4 mM [Ca2+]. Trifluoperazine, unlike the [Ca2+] channel blocker Ni2+, in concentrations (10(-6)-10(-5) M) that were found to inhibit significantly [K+]-induced amine output did not modify [K+]-induced 45Ca uptake or 45Ca efflux. However, trifluoperazine at a concentration of 2.5 x 10(-5) M was found to produce a small decrease in the 45Ca efflux curve and a decrease in the [K+]-evoked 45Ca uptake of 30 +/- 14% (n = 6). In addition, 2.5 x 10(-6) M trifluoperazine, a concentration which was found to suppress high [K+]-induced amine release by 64 +/- 5%, did not inhibit the 45Ca2+-Ca2+ exchange mechanism. These results demonstrate that trifluoperazine, an antipsychotic agent with anticalmodulin activity, blocks catecholamine release from cultured chromaffin cells at a step distal from calcium entry and, consequently, suggests a role for calmodulin in the secretory process of these cells.

  20. 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.

  1. 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

  2. Hepatitis B virus PreS2-mutant large surface antigen activates store-operated calcium entry and promotes chromosome instability

    PubMed Central

    Yen, Tim Ting-Chung; Yang, Anderson; Chiu, Wen-Tai; Li, Tian-Neng; Wang, Lyu-Han; Wu, Yi-Hsuan; Wang, Hui-Chen; Chen, Linyi; Wang, Wen-Ching; Huang, Wenya; Chang, Chien-Wen; Chang, Margaret Dah-Tsyr; Shen, Meng-Ru; Su, Ih-Jen; Wang, Lily Hui-Ching

    2016-01-01

    Hepatitis B virus (HBV) is a driver of hepatocellular carcinoma, and two viral products, X and large surface antigen (LHBS), are viral oncoproteins. During chronic viral infection, immune-escape mutants on the preS2 region of LHBS (preS2-LHBS) are gain-of-function mutations that are linked to preneoplastic ground glass hepatocytes (GGHs) and early disease onset of hepatocellular carcinoma. Here, we show that preS2-LHBS provoked calcium release from the endoplasmic reticulum (ER) and triggered stored-operated calcium entry (SOCE). The activation of SOCE increased ER and plasma membrane (PM) connections, which was linked by ER- resident stromal interaction molecule-1 (STIM1) protein and PM-resident calcium release- activated calcium modulator 1 (Orai1). Persistent activation of SOCE induced centrosome overduplication, aberrant multipolar division, chromosome aneuploidy, anchorage-independent growth, and xenograft tumorigenesis in hepatocytes expressing preS2- LHBS. Chemical inhibitions of SOCE machinery and silencing of STIM1 significantly reduced centrosome numbers, multipolar division, and xenograft tumorigenesis induced by preS2-LHBS. These results provide the first mechanistic link between calcium homeostasis and chromosome instability in hepatocytes carrying preS2-LHBS. Therefore, persistent activation of SOCE represents a novel pathological mechanism in HBV-mediated hepatocarcinogenesis. PMID:26992221

  3. Tracking capability for entry, descent and landing and its support to NASA Mars Exploration Rovers

    NASA Technical Reports Server (NTRS)

    Pham, Timothy; Chang, Christine; Fort, David; Satorius, Edgar; Finley, Susan; White, Leslie; Estabrook, Polly

    2003-01-01

    This paper described a new capability recently deployed in the NASA Deep Space Network to support the entry, descent and landing of the two Mars Exploration Rovers - Spirit and Opportunity. This final segment of a 7-month journey was critical step in enabling successful mission operation. The EDL Data Analysis (EDA) equipment processed the open loop recording samples from the existing radio science receivers, extracted the MFSK-modulated tones, and provided information on the occurrence of associated events happened onboard spacecraft. The EDA software supported real-time as well as post pass processing. The design flexibility allowed the track to be divided into different segments, each could be processed with a configuration optimized for its signal conditions and uncertainties. The use of dynamic lock state concept enabled signal detection be done with minimum required computing power - less was spent when signal was steadily detected and more when signal fluctuated. With the server-client design, the EDA supported connections to different remote operation centers for monitor purpose. The paper also presented the field results from both Spirit and Opportunity landings. The detection were much better than anticipated. All critical event tones were seen in real time. Surprising detection of LCP signal was found with Spirit landing, resulted in a reconfiguration for Opportunity landing to maximize signal detection.

  4. 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 ...

  5. Calcium

    MedlinePlus

    ... supplements and fortified foods include gluconate, lactate, and phosphate. Calcium absorption is best when a person consumes ... also interfere with the body's ability to absorb iron and zinc, but this effect is not well ...

  6. 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

  7. Calcium.

    PubMed

    Williams, Robert J P

    2002-01-01

    This chapter describes the chemical and biological value of the calcium ion. In calcium chemistry, our main interest is in equilibria within static, nonflowing systems. Hence, we examined the way calcium formed precipitates and complex ions in solution. We observed thereafter its uses by humankind in a vast number of materials such as minerals, e.g., marble, concrete, mortars, which parallel the biological use in shells and bones. In complex formation, we noted that many combinations were of anion interaction with calcium for example in the uses of detergents and medicines. The rates of exchange of calcium from bound states were noted but they had little application. Calcium ions do not act as catalysts of organic reactions. In biological systems, interest is in the above chemistry, but extends to the fact that Ca2+ ions can carry information by flowing in one solution or from one solution to another through membranes. Hence, we became interested in the details of rates of calcium exchange. The fast exchange of this divalent ion from most organic binding sites has allowed it to develop as the dominant second messenger. Now the flow can be examined in vitro as calcium binds particular isolated proteins, which it activates as seen in physical mechanical changes or chemical changes and this piece-by-piece study of cells is common. Here, however, we have chosen to stress the whole circuit of Ca2+ action indicating that the cell is organized both at a basal and an activated state kinetic level by the steady state flow of the ion (see Fig. 11). Different time constants of exchange utilizing very similar binding constants lead to: 1) fast responses as in the muscle of an animal; or 2) slower change as in differentiation of an egg or seed. Many other changes of state may relate to Ca2+ steady-state levels of flow in the circuitry and here we point to two: 1) dormancy in reptiles and animals; and 2) sporulation in both bacteria and lower plants. In the other chapters of

  8. The health benefits of calcium citrate malate: a review of the supporting science.

    PubMed

    Reinwald, Susan; Weaver, Connie M; Kester, Jeffrey J

    2008-01-01

    There has been considerable investigation into the health benefits of calcium citrate malate (CCM) since it was first patented in the late 1980s. This chapter is a comprehensive summary of the supporting science and available evidence on the bioavailability and health benefits of consuming CCM. It highlights the important roles that CCM can play during various life stages. CCM has been shown to facilitate calcium retention and bone accrual in children and adolescents. In adults, it effectively promotes the consolidation and maintenance of bone mass. In conjunction with vitamin D, CCM also decreases bone fracture risk in the elderly, slows the rate of bone loss in old age, and is of benefit to the health and well-being of postmenopausal women. CCM is exceptional in that it confers many unique benefits that go beyond bone health. Unlike other calcium sources that necessitate supplementation be in conjunction with a meal to ensure an appreciable benefit is derived, CCM can be consumed with or without food and delivers a significant nutritional benefit to individuals of all ages. The chemistry of CCM makes it a particularly beneficial calcium source for individuals with hypochlorydia or achlorydia, which generally includes the elderly and those on medications that decrease gastric acid secretion. CCM is also recognized as a calcium source that does not increase the risk of kidney stones, and in fact it protects against stone-forming potential. The versatile nature of CCM makes it a convenient and practical calcium salt for use in moist foods and beverages. The major factor that may preclude selection of CCM as a preferred calcium source is the higher cost compared to other sources of calcium commonly used for fortification (e.g., calcium carbonate and tricalcium phosphate). However, formation of CCM directly within beverages or other fluid foods and/or preparations, and the addition of a concentrated CCM solution or slurry, are relatively cost-effective methods by

  9. Loss of primary cilia results in deregulated and unabated apical calcium entry in ARPKD collecting duct cells.

    PubMed

    Siroky, Brian J; Ferguson, William B; Fuson, Amanda L; Xie, Yi; Fintha, Attila; Komlosi, Peter; Yoder, Bradley K; Schwiebert, Erik M; Guay-Woodford, Lisa M; Bell, P Darwin

    2006-06-01

    Recent genetic analysis has identified a pivotal role of primary cilia in the pathogenesis of polycystic kidney disease (PKD). However, little is known regarding how cilia loss/dysfunction contributes to cyst development. In epithelial cells, changes in apical fluid flow induce cilia-mediated Ca2+ entry via polycystin-2 (PC2), a cation channel. The Oak Ridge Polycystic Kidney (orpk) mouse contains a mutated Tg737 gene that disrupts expression of polaris, a protein required for ciliogenesis. These studies examine the effect of cilia malformation on Ca2+ entry in orpk cilia(-) collecting duct principal cells, and in orpk cells in which wild-type Tg737 was reintroduced, orpk cilia(+). [Ca2+]i was monitored in confluent cell monolayers using fluorescence microscopy. Intrinsic apical Ca2+ entry was measured by Mn2+ quenching and Ca2+ depletion/readdition under flow conditions below the threshold for stimulation. We found that unstimulated apical Ca2+ entry was markedly increased in cilia(-) cells and was sensitive to Gd3+, an inhibitor of PC2. Electrophysiological measurements demonstrate increased abundance of an apical channel, consistent with PC2, in cilia(-) cells. Immunofluorescence studies revealed that PC2, normally expressed on and at the base of cilia in orpk cilia(+) cells, was observed throughout the apical membrane in cilia(-) cells. Furthermore, cilia(-) cells displayed elevated subapical Ca2+ levels measured with the near-membrane Ca2+ indicator FFP-18. We propose that cilia exert a tonic regulatory influence on apical Ca2+ entry, and absence of cilia results in loss of spatial organization of PC2, causing unregulated Ca2+ entry and elevations in subapical [Ca2+], a factor which may contribute to cyst formation. PMID:16396941

  10. 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…

  11. 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.

  12. Potentiation of the store-operated calcium entry (SOCE) induces phytohemagglutinin-activated Jurkat T cell apoptosis.

    PubMed

    Djillani, Alaeddine; Doignon, Isabelle; Luyten, Tomas; Lamkhioued, Bouchaib; Gangloff, Sophie C; Parys, Jan B; Nüße, Oliver; Chomienne, Christine; Dellis, Olivier

    2015-08-01

    Store-operated Ca(2+) entry (SOCE) is the main Ca(2+) entry pathway of non-excitable cells. In the past decade, the activation of this entry has been unveiled, with STIM1, a protein of the endoplasmic reticulum able to sense the intraluminal Ca(2+) content, and Orai1, the pore-forming unit of the Ca(2+) release activated Ca(2+) (CRAC) channels. When Ca(2+) ions are released from the endoplasmic reticulum, STIM1 proteins oligomerize and directly interact with Orai1 proteins, allowing the opening of the CRAC channels and a massive Ca(2+) ion influx known as SOCE. As Ca(2+) is involved in various cellular processes, the discovery of new drugs acting on the SOCE should be of interest to control the cell activity. By testing analogs of 2-aminoethyl diphenylborinate (2-APB), a well known, though not so selective effector of the SOCE, we identified methoxy diethylborinate (MDEB), a molecule able to potentiate the SOCE in three leukocyte and two breast cancer cell lines by increasing the Ca(2+) influx amplitude. Unlike 2-APB, MDEB does not affect the Ca(2+) pumps or the Ca(2+) release from the endoplasmic reticulum. MDEB could therefore represent the first member of a new group of molecules, specifically able to potentiate SOCE. Although not toxic for non-activated Jurkat T cells, it could induce the apoptosis of phytohemagglutinin-stimulated cells.

  13. Orai1-Orai2 complex is involved in store-operated calcium entry in chondrocyte cell lines.

    PubMed

    Inayama, Munenori; Suzuki, Yoshiaki; Yamada, Satoshi; Kurita, Takashi; Yamamura, Hisao; Ohya, Susumu; Giles, Wayne R; Imaizumi, Yuji

    2015-05-01

    Ca(2+) influx via store-operated Ca(2+) entry (SOCE) plays critical roles in many essential cellular functions. The Ca(2+) release-activated Ca(2+) (CRAC) channel complex, consisting of Orai and STIM, is one of the major components of store-operated Ca(2+) (SOC) channels. Our previous study demonstrated that histamine can cause sustained Ca(2+) entry through SOC channels in OUMS-27 cells derived from human chondrosarcoma. This SOCE was increased by low- and decreased by high-concentrations of 2-aminoethoxydiphenyl borate. Quantitative reverse transcription PCR and Western blot analyses revealed abundant expressions of Orai1, Orai2 and STIM1. Introduction of dominant negative mutant of Orai1, or siOrai1 knockdown significantly attenuated SOCE. Following histamine application, single molecule imaging using total internal reflection fluorescence (TIRF) microscopy demonstrated punctate Orai1-STIM1 complex formation in plasma membrane. In contrast, knockdown or over-expression of Orai2 resulted in an increase or a decrease in SOCE, respectively. Finally, TIRF imaging revealed direct coupling between Orai1 and Orai2, and suggested that Orai2 reduces Orai1 function by formation of a hetero-tetramer. These results provide substantial evidence that Orai1, Orai2 and STIM1 form functional CRAC channels in OUMS-27 cells and that these complexes are responsible for sustained Ca(2+) entry in response to agonist stimulation.

  14. 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

  15. 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.

  16. Integration of gene expression and GWAS results supports involvement of calcium signaling in Schizophrenia.

    PubMed

    Hertzberg, L; Katsel, P; Roussos, P; Haroutunian, V; Domany, E

    2015-05-01

    The number of Genome Wide Association Studies (GWAS) of schizophrenia is rapidly growing. However, the small effect of individual genes limits the number of reliably implicated genes, which are too few and too diverse to perform reliable pathway analysis; hence the biological roles of the genes implicated in schizophrenia are unclear. To overcome these limitations we combine GWAS with genome-wide expression data from human post-mortem brain samples of schizophrenia patients and controls, taking these steps: 1) Identify 36 GWAS-based genes which are expressed in our dataset. 2) Find a cluster of 19 genes with highly correlated expression. We show that this correlation pattern is robust and statistically significant. 3) GO-enrichment analysis of these 19 genes reveals significant enrichment of ion channels and calcium-related processes. This finding (based on analyzing a small number of coherently expressed genes) is validated and enhanced in two ways: First, the emergence of calcium channels and calcium signaling is corroborated by identifying proteins that interact with those encoded by the cluster of 19. Second, extend the 19 cluster genes into 1028 genes, whose expression is highly correlated with the cluster's average profile. When GO-enrichment analysis is performed on this extended set, many schizophrenia related pathways appear, with calcium-related processes enriched with high statistical significance. Our results give further, expression-based validation to GWAS results, support a central role of calcium-signaling in the pathogenesis of schizophrenia, and point to additional pathways potentially related to the disease.

  17. Plastibell circumcision supported by a calcium-alginate fibre dressing to reduce bleeding

    PubMed Central

    Pillai, Ravisankar G.; Al Naieb, Ziad

    2015-01-01

    Objective To assess the benefit of a new technique of a Plastibell circumcision supported by a ventral calcium-alginate fibre dressing, to reduce bleeding from the frenular vessels, the commonest complication of Plastibell circumcision. Patients and methods This was a retrospective study of 200 neonates circumcised in the Royal Bahrain Hospital over a 2-year period from 2012 to 2014. They had a standard Plastibell circumcision, but a calcium-alginate fibre dressing (Hypo-sorb, Plastod, Italy) was placed over the glans and under the foreskin, to help control bleeding from the frenular vessels. Results Circumcision using the calcium-alginate fibre dressing reduced the bleeding complication rate to zero. The delayed separation of the bell was 2.9% when using the new technique and 2.5% from our previous data. There were no cases of urinary retention reported, compared to two in the previous results. Conclusion A Plastibell circumcision supported by the calcium-alginate fibre dressing was a safe technique to reduce bleeding. PMID:26413343

  18. Re-Entry Women Students in Higher Education: A Model for Non-Traditional Support Programs in Counseling and Career Advisement.

    ERIC Educational Resources Information Center

    Karr-Kidwell, PJ

    A model program of support for non-traditional women students has been developed at Texas Woman's University (TWU). Based on a pilot study, several steps were taken to assist these re-entry students at TWU. For example, in spring semester of 1983, a committee for re-entry students was established, with a student organization--Women in…

  19. 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.

  20. 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.

  1. Azumolene inhibits a component of store-operated calcium entry coupled to the skeletal muscle ryanodine receptor.

    PubMed

    Zhao, Xiaoli; Weisleder, Noah; Han, Xuehai; Pan, Zui; Parness, Jerome; Brotto, Marco; Ma, Jianjie

    2006-11-01

    Dantrolene reduces the elevated myoplasmic Ca(2+) generated during malignant hyperthermia, a pharmacogenetic crisis triggered by volatile anesthetics. Although specific binding of dantrolene to the type 1 ryanodine receptor (RyR1), the Ca(2+) release channel of skeletal muscle sarcoplasmic reticulum, has been demonstrated, there is little evidence for direct dantrolene inhibition of RyR1 channel function. Recent studies suggest store-operated Ca(2+) entry (SOCE) contributes to skeletal muscle function, but the effect of dantrolene on this pathway has not been examined. Here we show that azumolene, an equipotent dantrolene analog, inhibits a component of SOCE coupled to activation of RyR1 by caffeine and ryanodine, whereas the SOCE component induced by thapsigargin is not affected. Our data suggest that azumolene distinguishes between two mechanisms of cellular signaling to SOCE in skeletal muscle, one that is coupled to and one independent from RyR1. PMID:16945924

  2. 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. PMID:17179638

  3. 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.

  4. Requirement for store-operated calcium entry in sodium butyrate-induced apoptosis in human colon cancer cells.

    PubMed

    Sun, Suxia; Li, Wenjun; Zhang, He; Zha, Longying; Xue, Yong; Wu, Xianbo; Zou, Fei

    2012-02-01

    The SOCE (store-operated Ca2+ entry) pathway plays a key role in both normal cells and cancerous cells. However, its molecular mechanism remains a long-lasting puzzle of Ca2+ signalling. In this paper, we provide evidence that butyric acid, a dietary fibre-derived short-chain fatty acid, induces apoptosis of colon cancer cells via SOCE signalling networks. We found that sodium butyrate (NaB) induces Ca2+ release from endoplasmic reticulum, which in turn causes extracellular Ca2+ influx in HCT-116 cells. The Ca2+ release and influx are important, because the addition of chelators, EGTA or BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)] respectively blocked NaB-induced apoptosis. Furthermore, down-regulation of STIM1 (stromal interaction molecule 1) by RNA interference or pharmacological blockade of the SOCC (store-operated Ca2+ channel) by 2-APB (2-aminoethoxydiphenyl borate) or SKF-96365 inhibited NaB-induced extracellular Ca2+ influx and apoptosis in HCT-116 cells. Thus we conclude that NaB triggers colon cancer cell apoptosis in an SOCE-dependent manner. This finding provides new insights into how butyric acid suppresses colon carcinogenesis.

  5. Ferulic Acid Suppresses Glutamate Release Through Inhibition of Voltage-Dependent Calcium Entry in Rat Cerebrocortical Nerve Terminals

    PubMed Central

    Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu-Kuei

    2013-01-01

    Abstract This study investigated the effects and possible mechanism of ferulic acid, a naturally occurring phenolic compound, on endogenous glutamate release in the nerve terminals of the cerebral cortex in rats. Results show that ferulic acid inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP). The effect of ferulic acid on the evoked glutamate release was prevented by chelating the extracellular Ca2+ ions, but was insensitive to the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate. Ferulic acid suppressed the depolarization-induced increase in a cytosolic-free Ca2+ concentration, but did not alter 4-AP–mediated depolarization. Furthermore, the effect of ferulic acid on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na+/Ca2+ exchange. These results show that ferulic acid inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca2+ entry. PMID:23342970

  6. Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice

    PubMed Central

    Wolf, Karen; Braun, Attila; Haining, Elizabeth J.; Tseng, Yu-Lun; Kraft, Peter; Schuhmann, Michael K.; Gotru, Sanjeev K.; Chen, Wenchun; Hermanns, Heike M.; Stoll, Guido; Lesch, Klaus-Peter; Nieswandt, Bernhard

    2016-01-01

    Background Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation. Objective To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke. Methods: 5-HT transporter knockout mice (5Htt-/-) were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke. Results In 5Htt-/- platelets, 5-HT uptake from the blood was completely abolished and agonist-induced Ca2+ influx through store operated Ca2+ entry (SOCE), integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) were reduced. These observed in vitro defects in 5Htt-/- platelets could be normalized by the addition of exogenous 5-HT. Moreover, reduced 5-HT levels in the plasma, an increased bleeding time and the formation of unstable thrombi were observed ex vivo under flow and in vivo in the abdominal aorta and carotid artery of 5Htt-/- mice. Surprisingly, in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke 5Htt-/- mice showed nearly normal infarct volume and the neurological outcome was comparable to control mice. Conclusion Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization. PMID:26800051

  7. Hemodynamic, renal, and humoral effects of the calcium entry blocker nicardipine and converting enzyme inhibitor captopril in hypertensive type II diabetic patients with nephropathy.

    PubMed

    Stornello, M; Valvo, E V; Scapellato, L

    1989-12-01

    We compared the effect of nicardipine, a dihydropiridine derivative calcium entry blocker (CEB), with that of captopril (CAP), a converting-enzyme inhibitor (CEI), and that of the two drugs combined, on blood pressure (BP), heart rate (HR), and renal function in 12 hypertensive type II diabetic outpatients with nephropathy (persistent proteinuria greater than 500 mg/24 h) according to a 2 x 2 factorial design. For 4-week treatments, the patients received nicardipine (NIC) 20 mg t.i.d., CAP 50 mg b.i.d., NIC plus CAP, and matched placebo. Each active treatment significantly reduced BP, with an additive effect of NIC and CAP combined versus either drug alone. HR did not change. Effective renal plasma flow (RPF) and glomerular filtration rate (GRF) were unmodified, but renal vascular resistances (RVRs) were significantly reduced by the three active treatments. Filtration fraction (FF) did not change with NIC or with NIC plus CAP and was significantly reduced with CAP. Urinary albumin excretion (UAE) was significantly reduced by each active treatment to a similar extent. Plasma renin activity (PRA) increased significantly with NIC plus CAP only and did not change when the drugs were administered singly. Plasma aldosterone, glucose, potassium, fructosamine, and urinary sodium and volume did not change during the trial. We conclude that the two drugs singly and combined are useful for treatment of hypertensive non-insulin-dependent diabetes (NIDD) patients with persistent proteinuria.

  8. 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,…

  9. Meteorological Predictions in Support of the Mars Science Laboratory Entry, Descent and Landing

    NASA Astrophysics Data System (ADS)

    Rothchild, A.; Rafkin, S. C.; Pielke, R. A., Sr.

    2010-12-01

    The Mars Science Laboratory (MSL) entry, descent, and landing (EDL) system employs a standard parachute strategy followed by a new sky crane concept where the rover is lowered to the ground via a tether from a hovering entry vehicle. As with previous missions, EDL system performance is sensitive to atmospheric conditions. While some observations characterizing the mean, large-scale atmospheric temperature and density data are available, there is effectively no information on the atmospheric conditions and variability at the scale that directly affects the spacecraft. In order to evaluate EDL system performance and to assess landing hazards and risk, it is necessary to simulate the atmosphere with a model that provides data at the appropriate spatial and temporal scales. Models also permit the study of the impact of the highly variable atmospheric dust loading on temperature, density and winds. There are four potential MSL landing sites: Mawrth Valle (22.3 N, 16.5W) , Gale Crater (5.4S, 137.7E), Holden Crater (26.1S, 34W), and Eberswalde Crater (24S, 33W). The final selection of the landing site will balance potential science return against landing and operational risk. Atmospheric modeling studies conducted with the Mars Regional Atmospheric Modeling System (MRAMS) is an integral part of the selection process. At each of the landing sites, a variety of simulations are conducted. The first type of simulations provide baseline predictions under nominal atmospheric dust loading conditions within the landing site window of ~Ls 150-170. The second type of simulation explores situations with moderate and high global atmospheric dust loading. The final type of simulation investigates the impact of local dust disturbances at the landing site. Mean and perturbation fields from each type of simulation at each of the potential landing sites are presented in comparison with the engineering performance limitations for the MSL EDL system. Within the lowest scale height, winds

  10. 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

  11. 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

    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

  12. 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.…

  13. Navigation support for the Salyut-7/Kosmos-1686 orbiting complex near re-entry

    NASA Astrophysics Data System (ADS)

    Lobachev, V.; Pochukaev, V.; Ivanov, N.; Dzesov, R.; Bidenko, N.; Iastrebov, V.; Glotov, V.; Zhukov, V.; Korsakov, V.; Kir'anov, V.

    In 1986, the 40 ton composite spacecraft (Salyut-7/Kosmos-1686) was raised to a higher altitude which was deemed sufficient to survive the peak solar activity of cycle 22. Atmospheric drag effects proved greater than expected and the vehicle reentered the earth's atmosphere on February 7, 1991. The navigation support provided by the mission control center in this final phase, during which the spacecraft complex was only partially controllable, is described.

  14. 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.

  15. Mitochondrial Genome Diversity of Native Americans Supports a Single Early Entry of Founder Populations into America

    PubMed Central

    Silva Jr., Wilson A.; Bonatto, Sandro L.; Holanda, Adriano J.; Ribeiro-dos-Santos, Andrea K.; Paixão, Beatriz M.; Goldman, Gustavo H.; Abe-Sandes, Kiyoko; Rodriguez-Delfin, Luis; Barbosa, Marcela; Paçó-Larson, Maria Luiza; Petzl-Erler, Maria Luiza; Valente, Valeria; Santos, Sidney E. B.; Zago, Marco A.

    2002-01-01

    There is general agreement that the Native American founder populations migrated from Asia into America through Beringia sometime during the Pleistocene, but the hypotheses concerning the ages and the number of these migrations and the size of the ancestral populations are surrounded by controversy. DNA sequence variations of several regions of the genome of Native Americans, especially in the mitochondrial DNA (mtDNA) control region, have been studied as a tool to help answer these questions. However, the small number of nucleotides studied and the nonclocklike rate of mtDNA control-region evolution impose several limitations to these results. Here we provide the sequence analysis of a continuous region of 8.8 kb of the mtDNA outside the D-loop for 40 individuals, 30 of whom are Native Americans whose mtDNA belongs to the four founder haplogroups. Haplogroups A, B, and C form monophyletic clades, but the five haplogroup D sequences have unstable positions and usually do not group together. The high degree of similarity in the nucleotide diversity and time of differentiation (i.e., ∼21,000 years before present) of these four haplogroups support a common origin for these sequences and suggest that the populations who harbor them may also have a common history. Additional evidence supports the idea that this age of differentiation coincides with the process of colonization of the New World and supports the hypothesis of a single and early entry of the ancestral Asian population into the Americas. PMID:12022039

  16. 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…

  17. Hydrogen production from steam reforming of acetic acid over Cu-Zn supported calcium aluminate.

    PubMed

    Mohanty, Pravakar; Patel, Madhumita; Pant, Kamal K

    2012-11-01

    Hydrogen can be produced by catalytic steam reforming (CSR) of biomass-derived oil. Typically bio oil contains 12-14% acetic acid; therefore, this acid was chosen as model compound for reforming of biooil with the help of a Cu-Zn/Ca-Al catalyst for high yield of H(2) with low CH(4) and CO content. Calcium aluminate support was prepared by solid-solid reaction at 1350°C. X-ray diffraction indicates 12CaO·7Al(2)O(3) as major, CaA(l4)O(7) and Ca(5)A(l6)O(14) as minor phases. Cu and Zn were loaded onto the support by wet-impregnation at 10 and 1wt.%, respectively. The catalysts were characterized by Brunauer-Emmett-Teller (BET), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy TEM and the surface area for both support and Cu-Zn were 10.5 and 5.8m(2)/g, respectively. CSR was carried out in a tubular fixed bed reactor (I.D.=19mm) at temperatures between 600 and 800°C with 3-g loadings and (H(2)O/acetic acid) wt. ratio of 9:1. Significantly high (80%) yield of hydrogen was obtained over Cu-Zn/Ca-Al catalyst, as incorporation of Zn enhanced the H(2) yield by reducing deactivation of the catalyst. The coke formation on the support (Ca-12/Al-7) surface was negligible due to the presence of excess oxygen in the 12CaO·7Al(2)O(3) phase.

  18. Hydrogen production from steam reforming of acetic acid over Cu-Zn supported calcium aluminate.

    PubMed

    Mohanty, Pravakar; Patel, Madhumita; Pant, Kamal K

    2012-11-01

    Hydrogen can be produced by catalytic steam reforming (CSR) of biomass-derived oil. Typically bio oil contains 12-14% acetic acid; therefore, this acid was chosen as model compound for reforming of biooil with the help of a Cu-Zn/Ca-Al catalyst for high yield of H(2) with low CH(4) and CO content. Calcium aluminate support was prepared by solid-solid reaction at 1350°C. X-ray diffraction indicates 12CaO·7Al(2)O(3) as major, CaA(l4)O(7) and Ca(5)A(l6)O(14) as minor phases. Cu and Zn were loaded onto the support by wet-impregnation at 10 and 1wt.%, respectively. The catalysts were characterized by Brunauer-Emmett-Teller (BET), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy TEM and the surface area for both support and Cu-Zn were 10.5 and 5.8m(2)/g, respectively. CSR was carried out in a tubular fixed bed reactor (I.D.=19mm) at temperatures between 600 and 800°C with 3-g loadings and (H(2)O/acetic acid) wt. ratio of 9:1. Significantly high (80%) yield of hydrogen was obtained over Cu-Zn/Ca-Al catalyst, as incorporation of Zn enhanced the H(2) yield by reducing deactivation of the catalyst. The coke formation on the support (Ca-12/Al-7) surface was negligible due to the presence of excess oxygen in the 12CaO·7Al(2)O(3) phase. PMID:22944490

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. The process of development of a prioritization tool for a clinical decision support build within a computerized provider order entry system: Experiences from St Luke's Health System.

    PubMed

    Wolf, Matthew; Miller, Suzanne; DeJong, Doug; House, John A; Dirks, Carl; Beasley, Brent

    2016-09-01

    To establish a process for the development of a prioritization tool for a clinical decision support build within a computerized provider order entry system and concurrently to prioritize alerts for Saint Luke's Health System. The process of prioritizing clinical decision support alerts included (a) consensus sessions to establish a prioritization process and identify clinical decision support alerts through a modified Delphi process and (b) a clinical decision support survey to validate the results. All members of our health system's physician quality organization, Saint Luke's Care as well as clinicians, administrators, and pharmacy staff throughout Saint Luke's Health System, were invited to participate in this confidential survey. The consensus sessions yielded a prioritization process through alert contextualization and associated Likert-type scales. Utilizing this process, the clinical decision support survey polled the opinions of 850 clinicians with a 64.7 percent response rate. Three of the top rated alerts were approved for the pre-implementation build at Saint Luke's Health System: Acute Myocardial Infarction Core Measure Sets, Deep Vein Thrombosis Prophylaxis within 4 h, and Criteria for Sepsis. This study establishes a process for developing a prioritization tool for a clinical decision support build within a computerized provider order entry system that may be applicable to similar institutions. PMID:25814483

  4. Design of an easy-to-use physician order entry system with support for nursing and ancillary departments.

    PubMed

    Teich, J M; Hurley, J F; Beckley, R F; Aranow, M

    1992-01-01

    The Brigham Integrated Computing System (BICS) provides a broad range of clinical and administrative data-management functions for Brigham and Women's Hospital (BWH), a 720-bed major urban teaching hospital. We describe here the development of an inpatient order-entry system (BICS-OE) which is fully integrated into the BICS clinical environment. BICS-OE uses direct entry of orders by physicians to improve order response time and minimize transcription problems. BICS-OE includes a number of novel features to enhance its acceptance by physician users and its benefit to clinical practice in the hospital. Dual-mode input gives users a choice of full-screen assistance with ordering, or an intelligent text mode which provides rapid entry of orders by direct typing. An automated primary/on-call coverage by direct typing. An automated primary/on-call coverage list directs patient alerts and cosigning requests to the proper physician. Variable order sets allow a large group of orders to be stored and entered rapidly, even when some of the orders may change for different conditions. Multitasking allows the user to check prior orders and labs while concurrently entering new orders. The system permits a wide range of order checking and alerts. PMID:1483016

  5. Design of an easy-to-use physician order entry system with support for nursing and ancillary departments.

    PubMed

    Teich, J M; Hurley, J F; Beckley, R F; Aranow, M

    1992-01-01

    The Brigham Integrated Computing System (BICS) provides a broad range of clinical and administrative data-management functions for Brigham and Women's Hospital (BWH), a 720-bed major urban teaching hospital. We describe here the development of an inpatient order-entry system (BICS-OE) which is fully integrated into the BICS clinical environment. BICS-OE uses direct entry of orders by physicians to improve order response time and minimize transcription problems. BICS-OE includes a number of novel features to enhance its acceptance by physician users and its benefit to clinical practice in the hospital. Dual-mode input gives users a choice of full-screen assistance with ordering, or an intelligent text mode which provides rapid entry of orders by direct typing. An automated primary/on-call coverage by direct typing. An automated primary/on-call coverage list directs patient alerts and cosigning requests to the proper physician. Variable order sets allow a large group of orders to be stored and entered rapidly, even when some of the orders may change for different conditions. Multitasking allows the user to check prior orders and labs while concurrently entering new orders. The system permits a wide range of order checking and alerts.

  6. Human ether à-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry.

    PubMed

    Hammadi, Mehdi; Chopin, Valérie; Matifat, Fabrice; Dhennin-Duthille, Isabelle; Chasseraud, Maud; Sevestre, Henri; Ouadid-Ahidouch, Halima

    2012-12-01

    Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development. PMID:22495877

  7. Human ether à-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry.

    PubMed

    Hammadi, Mehdi; Chopin, Valérie; Matifat, Fabrice; Dhennin-Duthille, Isabelle; Chasseraud, Maud; Sevestre, Henri; Ouadid-Ahidouch, Halima

    2012-12-01

    Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development.

  8. Cardiovascular characterization of pyrrolo[2,1-d][1,5]benzothiazepine derivatives binding selectively to the peripheral-type benzodiazepine receptor (PBR): from dual PBR affinity and calcium antagonist activity to novel and selective calcium entry blockers.

    PubMed

    Campiani, G; Fiorini, I; De Filippis, M P; Ciani, S M; Garofalo, A; Nacci, V; Giorgi, G; Sega, A; Botta, M; Chiarini, A; Budriesi, R; Bruni, G; Romeo, M R; Manzoni, C; Mennini, T

    1996-07-19

    The synthesis and cardiovascular characterization of a series of novel pyrrolo[2,1-d][1,5]-benzothiazepine derivatives (54-68) are described. Selective peripheral-type benzodiazepine receptor (PBR) ligands, such as PK 11195 and Ro 5-4864, have recently been found to possess low but significant inhibitory activity of L-type calcium channels, and this property is implicated in the cardiovascular effects observed with these compounds. In functional studies both PK 11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxa mide) and Ro 5-4864 (4'-chlorodiazepam) did not display selectivity between cardiac and vascular tissue. Therefore, several 7-(acyloxy)-6-arylpyrrolo[2,1-d][1,5]benzothiazepines, potent and selective peripheral-type benzodiazepine receptor ligands recently developed by us (3, 7-20), were subjected to calcium channel receptor binding assay. Some of these compounds showed an unexpected potency in displacing the binding of [3H]nitrendipine from L-type calcium channels, much higher than that reported for PK 11195 and Ro 5-4864 and equal to or higher than that of reference calcium antagonists such as verapamil and (+)-cis-diltiazem. Specifically, in rat cortex homogenate, our prototypic PBR ligand 7-acetoxy-6-(p-methoxyphenyl)pyrrolo[2,1-d][1,5]benzothiazepine (3) showed an IC50 equal to 0.13 nM for inhibition of [3H]nitrendipine binding. Furthermore, in functional studies this compound displayed a clear-cut selectivity for cardiac over vascular tissue. Comparison of calcium antagonist activity on guinea pig aorta strips with the negative inotropic activity, determined by using isolated guinea pig left atria, revealed that 3 displayed higher selectivity than the reference (+)-cis-diltiazem. Thus, the pyrrolobenzothiazepine 3 might represent a new tool for characterizing the relationship between the PBR and cardiac function. Furthermore, we have also investigated the structural dependence of binding to PBR and L-type calcium channels, and

  9. 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)

  10. Evaluation of medium-term consequences of implementing commercial computerized physician order entry and clinical decision support prescribing systems in two ‘early adopter’ hospitals

    PubMed Central

    Cresswell, Kathrin M; Bates, David W; Williams, Robin; Morrison, Zoe; Slee, Ann; Coleman, Jamie; Robertson, Ann; Sheikh, Aziz

    2014-01-01

    Objective To understand the medium-term consequences of implementing commercially procured computerized physician order entry (CPOE) and clinical decision support (CDS) systems in ‘early adopter’ hospitals. Materials and methods In-depth, qualitative case study in two hospitals using a CPOE or a CDS system for at least 2 years. Both hospitals had implemented commercially available systems. Hospital A had implemented a CPOE system (with basic decision support), whereas hospital B invested additional resources in a CDS system that facilitated order entry but which was integrated with electronic health records and offered more advanced CDS. We used a combination of documentary analysis of the implementation plans, audiorecorded semistructured interviews with system users, and observations of strategic meetings and systems usage. Results We collected 11 documents, conducted 43 interviews, and conducted a total of 21.5 h of observations. We identified three major themes: (1) impacts on individual users, including greater legibility of prescriptions, but also some accounts of increased workloads; (2) the introduction of perceived new safety risks related to accessibility and usability of hardware and software, with users expressing concerns that some problems such as duplicate prescribing were more likely to occur; and (3) realizing organizational benefits through secondary uses of data. Conclusions We identified little difference in the medium-term consequences of a CPOE and a CDS system. It is important that future studies investigate the medium- and longer-term consequences of CPOE and CDS systems in a wider range of hospitals. PMID:24431334

  11. 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.

  12. 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. PMID:26787486

  13. Time course and mechanism of hippocampal neuronal death in an in vitro model of status epilepticus: Role of NMDA receptor activation and NMDA dependent calcium entry

    PubMed Central

    Deshpande, Laxmikant S.; Lou, Jeffrey K.; Mian, Ali; Blair, Robert E.; Sombati, Sompong; Attkisson, Elisa; DeLorenzo, Robert J.

    2008-01-01

    The hippocampus is especially vulnerable to seizure-induced damage and excitotoxic neuronal injury. This study examined the time course of neuronal death in relationship to seizure duration and the pharmacological mechanisms underlying seizure-induced cell death using low magnesium (Mg2+) induced continuous high frequency epileptiform discharges (in vitro status epilepticus) in hippocampal neuronal cultures. Neuronal death was assessed using cell morphology and Fluorescein diacetate-Propidium iodide staining. Effects of low Mg2+ and various receptor antagonists on spike frequency were assessed using patch clamp electrophysiology. We observed a linear and time-dependent increase in neuronal death with increasing durations of status epilepticus. This cell death was dependent upon extracellular calcium that entered primarily through the N-methyl-D-aspartate (NMDA) glutamate receptor channel subtype. Neuronal death was significantly decreased by co-incubation with the NMDA receptor antagonists and was also inhibited by reduction of extracellular calcium (Ca2+) during status epilepticus. In contrast, neuronal death from in vitro status epilepticus was not significantly prevented by inhibition of other glutamate receptor subtypes or voltage-gated Ca2+ channels. Interestingly this NMDA-Ca2+ dependent neuronal death was much more gradual in onset compared to cell death from excitotoxic glutamate exposure. The results provide evidence that in vitro status epilepticus results in increased activation of the NMDA-Ca2+ transduction pathway leading to neuronal death in a time dependent fashion. The results also indicate that there is a significant window of opportunity during the initial time of continuous seizure activity to be able to intervene, protect neurons and decrease the high morbidity and mortality associated with status epilepticus. PMID:18289526

  14. Influence of the alkylsulfonylamino substituent located at the 6-position of 2,2-dimethylchromans structurally related to cromakalim: from potassium channel openers to calcium entry blockers?

    PubMed

    Florence, Xavier; Desvaux, Vincent; Goffin, Eric; de Tullio, Pascal; Pirotte, Bernard; Lebrun, Philippe

    2014-06-10

    The present study described the synthesis of original R/S-6-alkylsulfonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyrans bearing a 3- or 4-substituted phenylthiourea or phenylurea moiety at the 4-position. Their biological effects were evaluated both on insulin-secreting and smooth muscle cells and were compared to those of reference KATP channel activators such as (±)-cromakalim, diazoxide and previously synthesized cromakalim analogues. The study aimed at exploring the influence of the introduction of an alkylsulfonylamino substituent at the 6-position of 2,2-dimethylchromans in order to improve biological activity, tissue selectivity but also hydrophilicity of dihydrobenzopyran derivatives. Several compounds were found to be equipotent or even more potent than (±)-cromakalim and diazoxide at inhibiting the insulin releasing process. Most of the newly synthesized and more hydrophilic dihydrobenzopyrans also exhibited a marked vasorelaxant activity although they were less potent than (±)-cromakalim. Additional pharmacological and radioisotopic investigations suggested that R/S-N-3-chlorophenyl-N'-(3,4-dihydro-6-methylsulfonylamino-2,2-dimethyl-2H-1-benzopyran-4-yl)thiourea (21) did not act as a potassium channel opener but rather as a Ca(2+) entry blocker.

  15. Neuroprotection induced by N-acetylcysteine and selenium against traumatic brain injury-induced apoptosis and calcium entry in hippocampus of rat.

    PubMed

    Nazıroğlu, Mustafa; Senol, Nilgün; Ghazizadeh, Vahid; Yürüker, Vehbi

    2014-08-01

    Neurodegeneration associated with acute central nervous system injuries and diseases such as spinal cord injury and traumatic brain injury (TBI) are reported to be mediated by the regulation of apoptosis and oxidative stress through Ca(2+) influx. The thiol redox system antioxidants, such as N-acetylcysteine (NAC) and selenium (Se), display neuroprotective activities mediated at least in part by their antioxidant and anti-inflammatory properties. However, there are no reports on hippocampal apoptosis, cytosolic reactive oxygen species (ROS), or Ca(2+) values in rats with an induced TBI. Therefore, we tested the effects of Se and NAC administration on apoptosis, oxidative stress, and Ca(2+) influx through TRPV1 channel activations in the hippocampus of TBI-induced rats. The 32 rats were divided into four groups: control, TBI, TBI + NAC, and TBI + Se groups. Intraperitoneal administrations of NAC and Se were performed at 1, 24, 48, and 72 h after TBI induction. After 3 days, the hippocampal neurons were freshly isolated from the rats. In cytosolic-free Ca(2+) analyses, the neurons were stimulated with the TRPV1 channel agonist capsaicin, a pungent compound found in hot chili peppers. Cytosolic-free Ca(2+), apoptosis, cytosolic ROS levels, and caspase-3 and -9 activities were higher in the TBI group than control. The values in the hippocampus were decreased by Se and NAC administrations. In conclusion, we observed that NAC and Se have protective effects on oxidative stress, apoptosis, and Ca(2+) entry via TRPV1 channel activation in the hippocampus of this TBI model, but the effect of NAC appears to be much greater than that of Se. They are both interesting candidates for studying the amelioration of TBIs. PMID:24842665

  16. Neuroprotection induced by N-acetylcysteine and selenium against traumatic brain injury-induced apoptosis and calcium entry in hippocampus of rat.

    PubMed

    Nazıroğlu, Mustafa; Senol, Nilgün; Ghazizadeh, Vahid; Yürüker, Vehbi

    2014-08-01

    Neurodegeneration associated with acute central nervous system injuries and diseases such as spinal cord injury and traumatic brain injury (TBI) are reported to be mediated by the regulation of apoptosis and oxidative stress through Ca(2+) influx. The thiol redox system antioxidants, such as N-acetylcysteine (NAC) and selenium (Se), display neuroprotective activities mediated at least in part by their antioxidant and anti-inflammatory properties. However, there are no reports on hippocampal apoptosis, cytosolic reactive oxygen species (ROS), or Ca(2+) values in rats with an induced TBI. Therefore, we tested the effects of Se and NAC administration on apoptosis, oxidative stress, and Ca(2+) influx through TRPV1 channel activations in the hippocampus of TBI-induced rats. The 32 rats were divided into four groups: control, TBI, TBI + NAC, and TBI + Se groups. Intraperitoneal administrations of NAC and Se were performed at 1, 24, 48, and 72 h after TBI induction. After 3 days, the hippocampal neurons were freshly isolated from the rats. In cytosolic-free Ca(2+) analyses, the neurons were stimulated with the TRPV1 channel agonist capsaicin, a pungent compound found in hot chili peppers. Cytosolic-free Ca(2+), apoptosis, cytosolic ROS levels, and caspase-3 and -9 activities were higher in the TBI group than control. The values in the hippocampus were decreased by Se and NAC administrations. In conclusion, we observed that NAC and Se have protective effects on oxidative stress, apoptosis, and Ca(2+) entry via TRPV1 channel activation in the hippocampus of this TBI model, but the effect of NAC appears to be much greater than that of Se. They are both interesting candidates for studying the amelioration of TBIs.

  17. Hydrogen peroxide generation induces pp60src activation in human platelets: evidence for the involvement of this pathway in store-mediated calcium entry.

    PubMed

    Rosado, Juan A; Redondo, Pedro C; Salido, Ginés M; Gómez-Arteta, Emilio; Sage, Stewart O; Pariente, Jose A

    2004-01-16

    Reactive oxygen species, such as H2O2, have been recognized as intracellular messengers involved in several cell functions. Here we report the activation of the tyrosine kinase pp60(src) by H2O2, a mechanism required for the activation of store-mediated Ca2+ entry (SMCE) in human platelets. Treatment of platelets with H2O2 resulted in a time- and concentration-dependent activation of pp60(src). Incubation with GF 109203X, a protein kinase C (PKC) inhibitor, prevented H2O2-induced pp60(src) activation. In contrast, dimethyl-BAPTA loading did not affect this response, suggesting that activation of pp60(src) by H2O2 is independent of increases in [Ca2+](i). Cytochalasin D, an inhibitor of actin polymerization, significantly reduced H2O2-induced pp60(src) activation. We found that platelet stimulation with thapsigargin (TG) plus ionomycin (Iono) or thrombin induced rapid H2O2 production, a mechanism independent of elevations in [Ca2+](i). Treatment of platelets with catalase attenuated TG plus Iono- and thrombin-induced activation of pp60(src). In addition, catalase as well as the pp60(src) inhibitor, PP1, reduced both the activation of SMCE and the coupling between the hTrp1 and the IP(3)R type II without having any effect on the maintenance of SMCE. Consistent with the role of PKC in the activation of pp60(src) by H2O2, the PKC inhibitors GF 109202X and Ro-31-8220 were found to reduced SMCE in platelets. This study suggests that platelet activation with TG plus Iono or thrombin is associated with H2O2 production, which acts as a second messenger by stimulating pp60(src) by a PKC-dependent pathway and is involved in the activation of SMCE in these cells.

  18. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    SciTech Connect

    Davidson, J.S.; Wakefield, I.K.; King, J.A.; Mulligan, G.P.; Millar, R.P.

    1988-04-01

    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release.

  19. 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.

  20. 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…

  1. 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.

  2. 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.

  3. 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. ...

  4. The influence of cellular source on periodontal regeneration using calcium phosphate coated polycaprolactone scaffold supported cell sheets.

    PubMed

    Dan, Hongxia; Vaquette, Cédryck; Fisher, Anthony G; Hamlet, Stephen M; Xiao, Yin; Hutmacher, Dietmar W; Ivanovski, Saso

    2014-01-01

    Cell-based therapy is considered a promising approach to achieving predictable periodontal regeneration. In this study, the regenerative potential of cell sheets derived from different parts of the periodontium (gingival connective tissue, alveolar bone and periodontal ligament) were investigated in an athymic rat periodontal defect model. Periodontal ligament (PDLC), alveolar bone (ABC) and gingival margin-derived cells (GMC) were obtained from human donors. The osteogenic potential of the primary cultures was demonstrated in vitro. Cell sheets supported by a calcium phosphate coated melt electrospun polycaprolactone (CaP-PCL) scaffold were transplanted to denuded root surfaces in surgically created periodontal defects, and allowed to heal for 1 and 4 weeks. The CaP-PCL scaffold alone was able to promote alveolar bone formation within the defect after 4 weeks. The addition of ABC and PDLC sheets resulted in significant periodontal attachment formation. The GMC sheets did not promote periodontal regeneration on the root surface and inhibited bone formation within the CaP-PCL scaffold. In conclusion, the combination of either PDLC or ABC sheets with a CaP-PCL scaffold could promote periodontal regeneration, but ABC sheets were not as effective as PDLC sheets in promoting new attachment formation.

  5. Calcium-dependent binding of rabbit C-reactive protein to supported lipid monolayers containing exposed phosphorylcholine group.

    PubMed Central

    Sui, S F; Sun, Y T; Mi, L Z

    1999-01-01

    The interaction of rabbit C-reactive protein (rCRP) with a supported monolayer containing a phosphorylcholine moiety was studied. Three types of phospholipids were synthesized, each containing a insertion spacer of eight, six, or three atoms between the phosphorylcholine group and hydrophobic tail. By varying the length of the insertion spacer, we can vary the extension of the phosphorylcholine group from the membrane surface. By varying the monolayer composition, we can control the lateral distance between the exposed phosphorylcholine groups. Using the surface plasmon resonance technique (SPR), we demonstrated that the calcium-dependent binding of rCRP to the model membrane is governed not only by the ability of the ligand to access the binding pocket fully (spacer length), but also by lateral hindrance within the two-dimensional plane of the membrane. The value of the apparent binding constant was estimated by theoretical analysis, which is obviously dependent on the composition of the lipid mixture, and a maximum of (9.9 +/- 1.5) x 10(6) M-1 was obtained. PMID:9876145

  6. 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

  7. Degradation of complex carbohydrate: immobilization of pectinase from Bacillus licheniformis KIBGE-IB21 using calcium alginate as a support.

    PubMed

    Rehman, Haneef Ur; Aman, Afsheen; Silipo, Alba; Qader, Shah Ali Ul; Molinaro, Antonio; Ansari, Asma

    2013-08-15

    Pectinases are heterogeneous group of enzymes that catalyse the hydrolysis of pectin substances which is responsible for the turbidity and undesirable cloudiness in fruits juices. In current study, partially purified pectinase from Bacillus licheniformis KIBGE-IB21 was immobilized in calcium alginate beads. The effect of sodium alginate and calcium chloride concentration on immobilization was studied and it was found that the optimal sodium alginate and calcium chloride concentration was 3.0% and 0.2 M, respectively. It was found that immobilization increases the optimal reaction time for pectin degradation from 5 to 10 min and temperature from 45 to 55°C, whereas, the optimal pH remained same with reference to free enzyme. Thermal stability of enzyme increased after immobilization and immobilized pectinase retained more than 80% of its initial activity after 5 days at 30°C as compared with free enzyme which showed only 30% of residual activity. The immobilized enzyme also exhibited good operational stability and 65% of its initial activity was observed during third cycle. In term of pectinase immobilization efficiency and stability, this calcium alginate beads approach seemed to permit good results and can be used to make a bioreactor for various applications in food industries.

  8. Calcium sensing receptor function supports osteoblast survival and acts as a co-factor in PTH anabolic actions in bone

    PubMed Central

    Al-Dujaili, Saja A.; Koh, Amy J.; Dang, Ming; Mi, Xue; Chang, Wenhan; Ma, Peter X.; McCauley, Laurie K.

    2016-01-01

    Anabolic actions of PTH in bone involve increased deposition of mineralizing matrix. Regulatory feedback of the process may be important to maintain calcium homeostasis and, in turn, calcium may inform the process. This investigation clarified the role of calcium availability and the calcium sensing receptor (CaSR) in the anabolic actions of PTH. CaSR function promoted osteoblastic cell numbers, with lower cell numbers in post-confluent cultures of primary calvarial cells from Col1-CaSR knock-out (KO) mice, and for calvarial cells from wild-type (WT) mice treated with a calcilytic. Increased apoptosis of calvarial cells with calcilytic treatment suggested CaSR is critical for protection against stage-dependent cell death. Whole and cortical, but not trabecular, bone parameters were significantly lower in Col1-CaSR KO mice versus WT littermates. Intact Col1-CaSR KO mice had lower serum P1NP levels relative to WT. PTH treatment displayed anabolic actions in WT and, to a lesser degree, KO mice, and rescued the lower P1NP levels in KO mice. Furthermore, PTH effects on whole tibiae were inhibited by osteoblast-specific CaSR ablation. Vertebral body implants (vossicles) from untreated Col1-CaSR KO and WT mice had similar bone volumes after 4 weeks of implantation in athymic mice. These findings suggest that trabecular bone formation can occur independently of the CaSR, and that the CaSR plays a collaborative role in the PTH anabolic effects on bone. PMID:26579618

  9. Calcium Sensing Receptor Function Supports Osteoblast Survival and Acts as a Co-Factor in PTH Anabolic Actions in Bone.

    PubMed

    Al-Dujaili, Saja A; Koh, Amy J; Dang, Ming; Mi, Xue; Chang, Wenhan; Ma, Peter X; McCauley, Laurie K

    2016-07-01

    Anabolic actions of PTH in bone involve increased deposition of mineralizing matrix. Regulatory feedback of the process may be important to maintain calcium homeostasis and, in turn, calcium may inform the process. This investigation clarified the role of calcium availability and the calcium sensing receptor (CaSR) in the anabolic actions of PTH. CaSR function promoted osteoblastic cell numbers, with lower cell numbers in post-confluent cultures of primary calvarial cells from Col1-CaSR knock-out (KO) mice, and for calvarial cells from wild-type (WT) mice treated with a calcilytic. Increased apoptosis of calvarial cells with calcilytic treatment suggested CaSR is critical for protection against stage-dependent cell death. Whole and cortical, but not trabecular, bone parameters were significantly lower in Col1-CaSR KO mice versus WT littermates. Intact Col1-CaSR KO mice had lower serum P1NP levels relative to WT. PTH treatment displayed anabolic actions in WT and, to a lesser degree, KO mice, and rescued the lower P1NP levels in KO mice. Furthermore, PTH effects on whole tibiae were inhibited by osteoblast-specific CaSR ablation. Vertebral body implants (vossicles) from untreated Col1-CaSR KO and WT mice had similar bone volumes after 4 weeks of implantation in athymic mice. These findings suggest that trabecular bone formation can occur independently of the CaSR, and that the CaSR plays a collaborative role in the PTH anabolic effects on bone. J. Cell. Biochem. 117: 1556-1567, 2016. © 2015 Wiley Periodicals, Inc.

  10. Immobilization of cellulase from newly isolated strain Bacillus subtilis TD6 using calcium alginate as a support material.

    PubMed

    Andriani, Dian; Sunwoo, Changshin; Ryu, Hwa-Won; Prasetya, Bambang; Park, Don-Hee

    2012-01-01

    Bacillus subtilis TD6 was isolated from Takifugu rubripes, also known as puffer fish. Cellulase from this strain was partially purified by ammonium sulphate precipitation up to 80% saturation, entrapped in calcium alginate beads, and finally characterized using CMC as the substrate. For optimization, various parameters were observed, including pH maximum, temperature maximum, sodium alginate, and calcium chloride concentration. pH maximum of the enzyme showed no changes before and after immobilization and remained stable at 6.0. The temperature maximum showed a slight increase to 60 °C. Two percent sodium alginate and a 0.15 M calcium chloride solution were the optimum conditions for acquisition of enzyme with greater stability. K (m) and V (max) values for the immobilized enzyme were slightly increased, compared with those of free enzyme, 2.9 mg/ml and 32.1 μmol/min/mL, respectively. As the purpose of immobilization, reusability and storage stability of the enzyme were also observed. Immobilized enzyme retained its activity for a longer period of time and can be reused up to four times. The storage stability of entrapped cellulase at 4 °C was found to be up to 12 days, while at 30 °C, the enzyme lost its activity within 3 days.

  11. Calcium Carbonate

    MedlinePlus

    Calcium carbonate is a dietary supplement used when the amount of calcium taken in the diet is not ... for healthy bones, muscles, nervous system, and heart. Calcium carbonate also is used as an antacid to relieve ...

  12. Calcium - urine

    MedlinePlus

    High levels of urine calcium (above 300 mg/day) may be due to: Chronic kidney disease High vitamin D levels Leaking of calcium from the kidneys into the urine, which causes calcium kidney stones Sarcoidosis Taking ...

  13. 30 CFR 877.13 - Entry and consent to reclaim.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INTERIOR ABANDONED MINE LAND RECLAMATION RIGHTS OF ENTRY § 877.13 Entry and consent to reclaim. (a) OSM... supporting reasons that— (1) Land or water resources have been or may be adversely affected by past...

  14. 30 CFR 877.14 - Entry for emergency reclamation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INTERIOR ABANDONED MINE LAND RECLAMATION RIGHTS OF ENTRY § 877.14 Entry for emergency reclamation. (a) OSM... shall make a written finding with supporting reasons that the situation qualifies as an emergency...

  15. 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

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

    PubMed

    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

  17. Components of Visual Prior Entry

    ERIC Educational Resources Information Center

    Schneider, Keith A.; Bavelier, Daphne

    2003-01-01

    The prior entry hypothesis contends that attention accelerates sensory processing, shortening the time to perception. Typical observations supporting the hypothesis may be explained equally well by response biases, changes in decision criteria, or sensory facilitation. In a series of experiments conducted to discriminate among the potential…

  18. Biliary calcium and gallstone formation.

    PubMed

    Moore, E W

    1990-09-01

    The purpose of this paper is to present a brief overview of the current status of the field of biliary calcium and the role of calcium in the formation and maturation of gallstones. The study of free Ca+(+) ions in bile by electrochemical potentiometric measurements using Ca+(+)-selective ion-exchange electrodes is a relatively new field, but much progress has been made in the past few years. Using this powerful analytical tool, new concepts and findings have arisen in almost every aspect of biliary calcium. Although the current symposium is targeted primarily toward cholesterol gallstones, there are several areas in which understanding of biliary calcium may significantly contribute to a better understanding of the pathogenesis of cholesterol, as well as "pigment" (calcium salt), gallstones. Five broad areas are considered in relation to biliary calcium: (a) physiology (calcium entry into bile), (b) biophysics (the regulation of biliary free [Ca+(+)] as related to Gibbs-Donnan equilibria, (c) physical chemistry (the physicochemical state of calcium in bile, (d) thermodynamics (calcium solubility in bile), and (e) kinetics (pronucleating and antinucleating factors and metastable states). With more specific reference to cholesterol stones, consideration is also made of (a) the calcium salt "seed" hypothesis in cholesterol stone pathogenesis; (b) the interactions of Ca+(+) with phospholipid-cholesterol vesicles, with consideration of possible structural requirements and (c) thermodynamic and kinetic factors as related to peripheral or "eggshell" calcification of existing cholesterol stones. PMID:2210651

  19. 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.

  20. 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.

  1. Reconstruction of the Genesis Entry

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

    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 aftbody. Through this investigation, an overall assertion can be made that all the data gathered from the Genesis entry is consistent with flight performance that was close to the nominal preentry prediction. Consequently, the design principles and methodologies utilized for the flight dynamics, aerodynamics, and aerothermodynamics analyses have been corroborated.

  2. Computerized Physician Order Entry

    PubMed Central

    Khanna, Raman; Yen, Tony

    2014-01-01

    Computerized physician order entry (CPOE) has been promoted as an important component of patient safety, quality improvement, and modernization of medical practice. In practice, however, CPOE affects health care delivery in complex ways, with benefits as well as risks. Every implementation of CPOE is associated with both generally recognized and unique local factors that can facilitate or confound its rollout, and neurohospitalists will often be at the forefront of such rollouts. In this article, we review the literature on CPOE, beginning with definitions and proceeding to comparisons to the standard of care. We then proceed to discuss clinical decision support systems, negative aspects of CPOE, and cultural context of CPOE implementation. Before concluding, we follow the experiences of a Chief Medical Information Officer and neurohospitalist who rolled out a CPOE system at his own health care organization and managed the resulting workflow changes and setbacks. PMID:24381708

  3. 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

  4. CaO-based pellets supported by calcium aluminate cements for high-temperature CO2 capture.

    PubMed

    Manovic, Vasilije; Anthony, Edward J

    2009-09-15

    The development of highly efficient CaO-based pellet sorbents, using inexpensive raw materials (limestones) or the spent sorbent from CO2 capture cycles, and commercially available calcium aluminate cements (CA-14, CA-25, Secar 51, and Secar 80), is described here. The pellets were prepared using untreated powdered limestones or their corresponding hydrated limes and were tested for their CO2 capture carrying capacities for 30 carbonation/calcination cycles in a thermogravimetric analyzer (TGA). Their morphology was also investigated by scanning electron microscopy (SEM) and their compositions before and after carbonation/calcination cycleswere determined by X-ray diffraction (XRD). Pellets prepared in this manner showed superior behavior during CO2 capture cycles compared to natural sorbents, with the highest conversions being > 50% after 30 cycles. This improved performance was attributed to the resulting substructure of the sorbent particles, i.e., a porous structure with nanoparticles incorporated. During carbonation/calcination cycles mayenite (Ca12Al14O33) was formed, which is believed to be responsible for the favorable performance of synthetic CaO-based sorbents doped with alumina compounds. An added advantage of the pellets produced here is their superior strength, offering the possibility of using them in fluidized bed combustion (FBC) systems with minimal sorbent loss due to attrition. PMID:19806751

  5. B Lymphocyte Calcium InFlux

    PubMed Central

    King, Leslie B.; Freedman, Bruce D.

    2014-01-01

    Dynamic changes in cytoplasmic calcium concentration dictate the immunological fate and functions of lymphocytes. During the past few years important details have been revealed about the mechanism of store-operated calcium entry in lymphocytes, including the molecular identity of calcium-release activated (CRAC) channels and the ER calcium sensor (STIM1) responsible for CRAC channel activation following calcium depletion of stores. However, details of the potential fine regulation of CRAC channel activation that may be imposed on lymphocytes following physiologic stimulation within an inflammatory environment have not been fully addressed. In this review, we discuss several underexplored aspects of store-operated (CRAC-mediated) and store-independent calcium signaling in B lymphocytes. First, we discuss the potential novel requirement for antigen-receptor linked pathways in initiating CRAC channel activation. Second, we will discuss results suggesting that coupling between stores and CRAC channels may be regulated, allowing for graded activation in response to partial depletion of ER stores. Third, we will discuss mechanisms that sustain the duration of calcium entry via CRAC channels. Finally, we discuss distinct calcium permeant non-selective cation channels (NSCCs) that are activated by innate stimuli in B cells, potential means by which these innate calcium signaling pathways and CRAC channels crossregulate one another and the mechanistic basis and physiologic consequences of innate calcium signaling. PMID:19754903

  6. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    PubMed

    de Jonge, H J M Henk-Marijn; Gans, R O B Rijk; Huls, Gerwin

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate absorption. No convincing scientific evidence supporting the advice to prescribe calcium citrate instead of calcium carbonate to patients who also take antacids is available, and therefore deserves further investigation. On the contrary, the fact that calcium carbonate does not need acid in order to be absorbed, has also not been proven. In clinical practise, it appears important that calcium is taken with meals in order to improve its absorption. PMID:22914054

  7. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    PubMed

    de Jonge, H J M Henk-Marijn; Gans, R O B Rijk; Huls, Gerwin

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate absorption. No convincing scientific evidence supporting the advice to prescribe calcium citrate instead of calcium carbonate to patients who also take antacids is available, and therefore deserves further investigation. On the contrary, the fact that calcium carbonate does not need acid in order to be absorbed, has also not been proven. In clinical practise, it appears important that calcium is taken with meals in order to improve its absorption.

  8. 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.

  9. Improvement of cardiac sarcoplasmic reticulum calcium cycling in dogs with heart failure following long-term therapy with the Acorn Cardiac Support Device.

    PubMed

    Gupta, Ramesh C; Mishra, Sudhish; Rastogi, Sharad; Sharov, Victor G; Sabbah, Hani N

    2005-06-01

    Abnormal Ca(2+)-homeostasis is a hall-marked characteristic of the failing heart. In the normal myocardium, the sarcoplasmic reticulum (SR) is a principal organelle that controls intracellular Ca(2+) concentration during the cardiac cycle. The SR consists of longitudinal and terminal cisternea regions. The former contains the Ca(2+)-ATPase pump or SERCA-2a whose function is to transport cytosolic Ca(2+) into the lumen of the SR during diastole and whose activity is regulated by reversible phosphorylation of the endogenously SR-bound phospholamban (PLB). The SR's terminal cisternea region contains ryanodine-sensitive Ca(2+)-release channels (RR), the activity of which is regulated by direct and indirect reversible phosphorylation. These channels release the SR-stored Ca(2+) during contraction. We have shown that in left ventricular (LV) myocardium from dogs with coronary microembolization-induced heart failure, ability of the SR to sequester and release Ca(2+) during the cardiac cycles is impaired. This abnormality was associated with reduced expression (protein and mRNA) levels of Ca(2+)-ATPase, PLB, and reduced PLB phosphorylation. Long-term therapy with the Acorn Cardiac Support Device (CSD) is associated with restoration of the ability of the SR to sequester Ca(2+). This improvement in SR function following chronic CSD therapy was due primarily to increased affinity of the SERCA-2a for calcium. The later was associated with (1) increased phosphorylation of PLB at serine 16 and threonine 17, (2) unchanged protein expression of PLB and (3) unchanged protein expression of SERCA-2a in LV myocardium of CSD-treated dogs compared to controls. This review summarizes our current understanding of the role of the CSD in modulating SR calcium cycling in an experimental canine model of chronic heart failure produced by multiple sequential intracoronary microembolizations. PMID:16258722

  10. 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.

  11. 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. PMID:26034201

  12. Paraeducator Entry-Level Training for Supporting Students with Disabilities. Field Test Version 2.0. Instructor's Manual [and] Participant's Manual.

    ERIC Educational Resources Information Center

    CichoskiKelly, Eileen; Backus, Linda; Giangreco, Michael F.; Sherman-Tucker, Priscilla

    These instructor and participant manuals provide a basic training program curriculum for paraeducators supporting students with disabilities in inclusive educational settings. The course requires approximately 18 hours of instruction and 12 hours of practicum, can be offered in a variety of formats (intensively or over a number of weeks), and does…

  13. 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…

  14. 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

  15. Laboratory studies supporting cooling-water treatment tests at a power plant with calcium-limited water. Final report

    SciTech Connect

    Aronson, J.T.; Campbell, K.S.

    1985-07-01

    The Electric Power Research Institute is sponsoring a three phase research project to develop a design and operating methodology for recirculating cooling water systems at high concentration factors. As part of this program, a portable field test (FTU) has been designed and fabricated for operation at sites with different makeup water qualities. Phase II testing at the first site, Comanche Generating Station in Pueblo, Colorado, started February 1981 and stopped December 1981. During the field testing, several cooling water treatment options were used to increase the concentration factor for operating the FTU. In addition to the field test program, additional activities were conducted to supplement and support the data compiled from the field program. These additional activities included a literature survey, laboratory studies, and an independent makeup softener test. This report presents the results of these supplemental activities. 61 refs., 57 figs., 37 tabs.

  16. 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…

  17. Lesion-specific coronary artery calcium quantification for predicting cardiac event with multiple instance support vector machines.

    PubMed

    Liu, Qingshan; Qian, Zhen; Marvasty, Idean; Rinehart, Sarah; Voros, Szilard; Metaxas, Dimitris N

    2010-01-01

    Conventional whole-heart CAC quantification has been demonstrated to be insufficient in predicting coronary events, especially in accurately predicting near-term coronary events in high-risk adults. In this paper, we propose a lesion-specific CAC quantification framework to improve CAC's near-term predictive value in intermediate to high-risk populations with a novel multiple instance support vector machines (MISVM) approach. Our method works on data sets acquired with clinical imaging protocols on conventional CT scanners without modifying the CT hardware or updating the imaging protocol. The calcific lesions are quantified by geometric information, density, and some clinical measurements. A MISVM model is built to predict cardiac events, and moreover, to give a better insight of the characterization of vulnerable or culprit lesions in CAC. Experimental results on 31 patients showed significant improvement of the predictive value with the ROC analysis, the net reclassification improvement evaluation, and the leave-one-out validation against the conventional methods. PMID:20879266

  18. Osteoblasts detect pericellular calcium concentration increase via neomycin-sensitive voltage gated calcium channels.

    PubMed

    Sun, Xuanhao; Kishore, Vipuil; Fites, Kateri; Akkus, Ozan

    2012-11-01

    The mechanisms underlying the detection of critically loaded or micro-damaged regions of bone by bone cells are still a matter of debate. Our previous studies showed that calcium efflux originates from pre-failure regions of bone matrix and MC3T3-E1 osteoblasts respond to such efflux by an increase in the intracellular calcium concentration. The mechanisms by which the intracellular calcium concentration increases in response to an increase in the pericellular calcium concentration are unknown. Elevation of the intracellular calcium may occur via release from the internal calcium stores of the cell and/or via the membrane bound channels. The current study applied a wide range of pharmaceutical inhibitors to identify the calcium entry pathways involved in the process: internal calcium release from endoplasmic reticulum (ER, inhibited by thapsigargin and TMB-8), calcium receptor (CaSR, inhibited by calhex), stretch-activated calcium channel (SACC, inhibited by gadolinium), voltage-gated calcium channels (VGCC, inhibited by nifedipine, verapamil, neomycin, and ω-conotoxin), and calcium-induced-calcium-release channel (CICRC, inhibited by ryanodine and dantrolene). These inhibitors were screened for their effectiveness to block intracellular calcium increase by using a concentration gradient induced calcium efflux model which mimics calcium diffusion from the basal aspect of cells. The inhibitor(s) which reduced the intracellular calcium response was further tested on osteoblasts seeded on mechanically loaded notched cortical bone wafers undergoing damage. The results showed that only neomycin reduced the intracellular calcium response in osteoblasts, by 27%, upon extracellular calcium stimulus induced by concentration gradient. The inhibitory effect of neomycin was more pronounced (75% reduction in maximum fluorescence) for osteoblasts seeded on notched cortical bone wafers loaded mechanically to damaging load levels. These results imply that the increase in

  19. Modelling the coupling between intracellular calcium release and the cell cycle during cortical brain development.

    PubMed

    Barrack, Duncan S; Thul, Rüdiger; Owen, Markus R

    2014-04-21

    Most neocortical neurons formed during embryonic brain development arise from radial glial cells which communicate, in part, via ATP mediated calcium signals. Although the intercellular signalling mechanisms that regulate radial glia proliferation are not well understood, it has recently been demonstrated that ATP dependent intracellular calcium release leads to an increase of nearly 100% in overall cellular proliferation. It has been hypothesised that cytoplasmic calcium accelerates entry into S phase of the cell cycle and/or acts to recruit otherwise quiescent cells onto the cell cycle. In this paper we study this cell cycle acceleration and recruitment by forming a differential equation model for ATP mediated calcium-cell cycle coupling via Cyclin D in a single radial glial cell. Bifurcation analysis and numerical simulations suggest that the cell cycle period depends only weakly on cytoplasmic calcium. Therefore, the accelerative impact of calcium on the cell cycle can only account for a small fraction of the large increase in proliferation observed experimentally. Crucially however, our bifurcation analysis reveals that stable fixed point and stable limit cycle solutions can coexist, and that calcium dependent Cyclin D dynamics extend the oscillatory region to lower Cyclin D synthesis rates, thus rendering cells more susceptible to cycling. This supports the hypothesis that cycling glial cells recruit quiescent cells (in G0 phase) onto the cell cycle, via a calcium signalling mechanism, and that this may be the primary means by which calcium augments proliferation rates at the population scale. Numerical simulations of two coupled cells demonstrate that such a scenario is indeed feasible.

  20. Calcium and osteoporosis.

    PubMed

    Nordin, B E

    1997-01-01

    pregnancy and lactation and for children and adolescents, taking into account the additional needs of the fetus, of milk production, and of growth. There is a rise in obligatory calcium excretion at menopause, which increases the theoretical calcium requirement in postmenopausal women to about 25 mmol (1000 mg) and implies an allowance of perhaps 30 mmol (1200 mg) or even more if calcium absorption declines at the same time. At issue here, however, is whether menopausal changes in calcium metabolism are the cause or the result of postmenopausal bone loss. The first interpretation relies on evidence of a positive action of estrogen on the gastrointestinal absorption and renal tubular reabsorption of calcium; the latter interpretation relies on evidence of a direct inhibitory effect of estrogen on bone resorption. The calcium model for postmenopausal bone loss tends to be supported by the effect of calcium therapy. An analysis of the 20 major calcium trials in postmenopausal women reported in the last 20 years yielded a mean rate of bone loss of 1.00% per annum (p.a.) in the controls and 0.014% p.a. (NS) in the treated subjects (P < 0.001). However, trials in which calcium and estrogen have been directly compared have shown that the latter is generally more effective than calcium in that it produces a small, but often significant bone gain. This superiority of estrogen over calcium could be due to the former's dual action on calcium absorption and excretion or to a direct action of estrogen on bone itself. In older women, the importance of calcium intake is overshadowed by the strong association between vitamin D insufficiency and hip fracture. Whether this insufficiency arises primarily from lack of exposure to sunlight or to a progressive failure to activate the vitamin D precursor in the skin or both is uncertain but it is compounded by a general decline in dietary vitamin D intake with age. The biological effect is probably an impairment of calcium absorption and c PMID

  1. Harm reduction services as a point-of-entry to and source of end-of-life care and support for homeless and marginally housed persons who use alcohol and/or illicit drugs: a qualitative analysis

    PubMed Central

    2012-01-01

    Background Homeless and marginally housed persons who use alcohol and/or illicit drugs often have end-of-life care needs that go unmet due to barriers that they face to accessing end-of-life care services. Many homeless and marginally housed persons who use these substances must therefore rely upon alternate sources of end-of-life care and support. This article explores the role of harm reduction services in end-of-life care services delivery to homeless and marginally housed persons who use alcohol and/or illicit drugs. Methods A qualitative case study design was used to explore end-of-life care services delivery to homeless and marginally housed persons in six Canadian cities. A key objective was to explore the role of harm reduction services. 54 health and social services professionals participated in semi-structured qualitative interviews. All participants reported that they provided care and support to this population at end-of-life. Results Harm reduction services (e.g., syringe exchange programs, managed alcohol programs, etc.) were identified as a critical point-of-entry to and source of end-of-life care and support for homeless and marginally housed persons who use alcohol and/or illicit drugs. Where possible, harm reduction services facilitated referrals to end-of-life care services for this population. Harm reduction services also provided end-of-life care and support when members of this population were unable or unwilling to access end-of-life care services, thereby improving quality-of-life and increasing self-determination regarding place-of-death. Conclusions While partnerships between harm reduction programs and end-of-life care services are identified as one way to improve access, it is noted that more comprehensive harm reduction services might be needed in end-of-life care settings if they are to engage this underserved population. PMID:22545586

  2. Calcium signaling and cell proliferation.

    PubMed

    Pinto, Mauro Cunha Xavier; Kihara, Alexandre Hiroaki; Goulart, Vânia A M; Tonelli, Fernanda M P; Gomes, Katia N; Ulrich, Henning; Resende, Rodrigo R

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review.

  3. 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.

  4. 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 ...

  5. Calcium-dependent and calcium-sensitizing pathways in the mature and immature ductus arteriosus.

    PubMed

    Clyman, Ronald I; Waleh, Nahid; Kajino, Hiroki; Roman, Christine; Mauray, Francoise

    2007-10-01

    Studies performed in sheep and baboons have shown that after birth, the normoxic muscle media of ductus arteriosus (DA) becomes profoundly hypoxic as it constricts and undergoes anatomic remodeling. We used isolated fetal lamb DA (pretreated with inhibitors of prostaglandin and nitric oxide production) to determine why the immature DA fails to remain tightly constricted during the hypoxic phase of remodeling. Under normoxic conditions, mature DA constricts to 70% of its maximal active tension (MAT). Half of its normoxic tension is due to Ca(2+) entry through calcium L-channels and store-operated calcium (SOC) channels. The other half is independent of extracellular Ca(2+) and is unaffected by inhibitors of sarcoplasmic reticulum (SR) Ca(2+) release (ryanodine) or reuptake [cyclopiazonic acid (CPA)]. The mature DA relaxes slightly during hypoxia (to 60% MAT) due to decreases in calcium L-channel-mediated Ca(2+) entry. Inhibitors of Rho kinase and tyrosine kinase inhibit both Ca(2+)-dependent and Ca(2+)-independent DA tension. Although Rho kinase activity may increase during gestation, immature DA develop lower tensions than mature DA, primarily because of differences in the way they process Ca(2+). Calcium L-channel expression increases with advancing gestation. Under normoxic conditions, differences in calcium L-channel-mediated Ca(2+) entry account for differences in tension between immature (60% MAT) and mature (70% MAT) DA. Under hypoxic conditions, differences in both calcium L-channel-dependent and calcium L-channel-independent Ca(2+) entry, account for differences in tension between immature (33% MAT) and mature (60% MAT) DA. Stimulation of Ca(2+) entry through reverse-mode Na(+)/Ca(2+) exchange or CPA-induced SOC channel activity constrict the DA and eliminate differences between immature and mature DA during both hypoxia and normoxia.

  6. Calcium Test

    MedlinePlus

    ... as thyroid disease , parathyroid disorder , malabsorption , cancer, or malnutrition An ionized calcium test may be ordered when ... albumin , which can result from liver disease or malnutrition , both of which may result from alcoholism or ...

  7. Calcium Calculator

    MedlinePlus

    ... with Sarcopenia Skeletal Rare Disorders Data & Publications Facts and Statistics Vitamin D map Fracture Risk Map Hip Fracture ... Training Courses Working Groups Regional Audits Reports Facts and Statistics Popular content Calcium content of common foods What ...

  8. 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.

  9. 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.

  10. 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. PMID:26940168

  11. 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

  12. Viral Entry into Cells

    NASA Astrophysics Data System (ADS)

    D'Orsogna, Maria R.

    2010-09-01

    Successful viral infection of a healthy cell requires complex host-pathogen interactions. In this talk we focus on the dynamics specific to the HIV virus entering a eucaryotic cell. We model viral entry as a stochastic engagement of receptors and coreceptors on the cell surface. We also consider the transport of virus material to the cell nucleus by coupling microtubular motion to the concurrent biochemical transformations that render the viral material competent for nuclear entry. We discuss both mathematical and biological consequences of our model, such as the formulation of an effective integrodifferential boundary condition embodying a memory kernel and optimal timing in maximizing viral probabilities.

  13. Double-Entry Bookkeeping.

    ERIC Educational Resources Information Center

    Snyder, Herbert

    1999-01-01

    Explains the principles and mechanics of double-entry bookkeeping as a part of the accounting cycle to produce a functioning set of accounting records. Suggests that libraries need to have accurate and timely information about their spending to gain financial control and protect against fraud and abuse. (LRW)

  14. 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 planning…

  15. Flavivirus Entry Inhibitors.

    PubMed

    Wang, Qing-Yin; Shi, Pei-Yong

    2015-09-11

    Many flaviviruses are significant human pathogens that are transmitted by mosquitoes and ticks. Although effective vaccines are available for yellow fever virus, Japanese encephalitic virus, and tick-borne encephalitis virus, these and other flaviviruses still cause thousands of human deaths and millions of illnesses each year. No clinically approved antiviral therapy is available for flavivirus treatment. To meet this unmet medical need, industry and academia have taken multiple approaches to develop antiflavivirus therapy, among which targeting viral entry has been actively pursued in the past decade. Here we review the current knowledge of flavivirus entry and its use for small molecule drug discovery. Inhibitors of two major steps of flaviviral entry have been reported: (i) molecules that block virus-receptor interaction; (ii) compounds that prevent conformational change of viral envelope protein during virus-host membrane fusion. We also discuss the advantages and disadvantages of targeting viral entry for treatment of flavivirus infection as compared to targeting viral replication proteins. PMID:27617926

  16. Globalisation and temporary entry.

    PubMed

    Birrell, B; Healy, E

    1997-01-01

    "Beginning on 1 August 1996 the Australian Government implemented a radical deregulation of temporary entry provisions governing foreign persons working in Australia on contracts of three months to four years. The result has been a significant increase in the numbers visaed, particularly on-shore, plus evidence that the program is being exploited in ways inconsistent with the Government's objectives."

  17. 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.

  18. INTERIOR OF ENTRY HALLWAY AND STEEL ENTRY DOOR ON SOUTH ...

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

    INTERIOR OF ENTRY HALLWAY AND STEEL ENTRY DOOR ON SOUTH SIDE, VIEW FACING NORTHEAST. - Naval Air Station Barbers Point, Telephone Exchange, Coral Sea Road north of Bismarck Sea Road, Ewa, Honolulu County, HI

  19. The Calcium Signaling Toolkit of the Apicomplexan Parasites Toxoplasma gondii and Plasmodium spp

    PubMed Central

    Lourido, Sebastian; Moreno, Silvia N.J.

    2015-01-01

    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 (Ca2+) 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 Ca2+ 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 Ca2+ 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 Ca2+-ATPases are present in apicomplexans and a putative mitochondrial Ca2+/H+ exchanger has been identified. Apicomplexan genomes contain numerous genes encoding Ca2+-binding proteins, with the notable expansion of calcium-dependent protein kinases (CDPKs), whose study has revealed novel 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 Ca2+ 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 Ca2+ in these parasites. PMID:25605521

  20. Calcium-induced calcium release and gap junctions mediate large-scale calcium waves in olfactory ensheathing cells in situ.

    PubMed

    Stavermann, Maren; Meuth, Patrick; Doengi, Michael; Thyssen, Anne; Deitmer, Joachim W; Lohr, Christian

    2015-08-01

    Olfactory ensheathing cells (OECs) are a specialised type of glial cells, supporting axon growth and guidance during development and regeneration of the olfactory nerve and the nerve layer of the olfactory bulb. We measured calcium signalling in OECs in olfactory bulb in-toto preparations using confocal and epifluorescence microscopy and the calcium indicator Fluo-4. We identified two subpopulations of olfactory bulb OECs: OECs in the outer sublamina of the nerve layer responded to purinergic neurotransmitters such as adenosine triphosphate with calcium transients, while OECs in the inner sublamina of the nerve layer did not respond to neurotransmitters. However, the latter generated spontaneous calcium waves that covered hundreds of cells. These calcium waves persisted in the presence of tetrodotoxin and in calcium-free saline, but were abolished after calcium store depletion with cyclopiazonic acid or inositol trisphosphate receptor blockage with 2-APB. Calcium waves could be triggered by laser photolysis of caged inositol trisphosphate. Blocking purinoceptors with PPADS had no effect on calcium wave propagation, whereas blocking gap junctions with carbenoxolone or meclofenamic acid entirely suppressed calcium waves. Increasing calcium buffer capacity in OECs with NP-EGTA ("caged" Ca(2+)) prevented calcium wave generation, and laser photolysis of NP-EGTA in a small group of OECs resulted in a calcium increase in the irradiated cells followed by a calcium wave. We conclude that calcium waves in OECs can be initiated by calcium-induced calcium release via InsP3 receptors and propagate through gap junctions, while purinergic signalling is not involved.

  1. Get Enough Calcium

    MedlinePlus

    ... Calcium Print This Topic En español Get Enough Calcium Browse Sections The Basics Overview Foods and Vitamins ... 2 of 4 sections Take Action! Take Action: Calcium Sources Protect your bones – get plenty of calcium ...

  2. Calcium carbonate overdose

    MedlinePlus

    Tums overdose; Calcium overdose ... Calcium carbonate can be dangerous in large amounts. ... Some products that contain calcium carbonate are certain: ... and mineral supplements Other products may also contain calcium ...

  3. 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

  4. Poxvirus host cell entry.

    PubMed

    Schmidt, Florian Ingo; Bleck, Christopher Karl Ernst; Mercer, Jason

    2012-02-01

    Poxviruses are characterized by their large size, complex composition, and cytoplasmic life cycle. They produce two types of infectious particles: mature virions (MVs) and extracellular virions (EVs). Both MVs and EVs of vaccinia virus, the model poxvirus, take advantage of host cell endocytosis for internalization: they activate macropinocytosis-the most suitable form of endocytosis for large particles. Although largely dependent on the same cellular machinery, MV and EV entry differs with regard to the mechanisms used to trigger macropinocytosis and to undergo fusion. While EVs have to shed an additional membrane to expose the fusion complex, MV fusion requires the inactivation of fusion inhibitory proteins absent in EVs. This review highlights recent advances in the understanding of poxvirus MV and EV cell entry. PMID:22440962

  5. Depletion of calcium stores regulates calcium influx and signal transmission in rod photoreceptors

    PubMed Central

    Szikra, Tamas; Cusato, Karen; Thoreson, Wallace B; Barabas, Peter; Bartoletti, Theodore M; Krizaj, David

    2008-01-01

    Tonic synapses are specialized for sustained calcium entry and transmitter release, allowing them to operate in a graded fashion over a wide dynamic range. We identified a novel plasma membrane calcium entry mechanism that extends the range of rod photoreceptor signalling into light-adapted conditions. The mechanism, which shares molecular and physiological characteristics with store-operated calcium entry (SOCE), is required to maintain baseline [Ca2+]i in rod inner segments and synaptic terminals. Sustained Ca2+ entry into rod cytosol is augmented by store depletion, blocked by La3+ and Gd3+ and suppressed by organic antagonists MRS-1845 and SKF-96365. Store depletion and the subsequent Ca2+ influx directly stimulated exocytosis in terminals of light-adapted rods loaded with the activity-dependent dye FM1–43. Moreover, SOCE blockers suppressed rod-mediated synaptic inputs to horizontal cells without affecting presynaptic voltage-operated Ca2+ entry. Silencing of TRPC1 expression with small interference RNA disrupted SOCE in rods, but had no effect on cone Ca2+ signalling. Rods were immunopositive for TRPC1 whereas cone inner segments immunostained with TRPC6 channel antibodies. Thus, SOCE modulates Ca2+ homeostasis and light-evoked neurotransmission at the rod photoreceptor synapse mediated by TRPC1. PMID:18755743

  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. 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

  8. Time Card Entry System

    1996-05-07

    The Time Card Entry System was developed for the Department of Enegy, Idaho Operations Office (DOE-ID) to interface with the DOE headquarters (DOE-HQ) Electronic Time and Attendance (ETA) system for payroll. It features pop-up window pick lists for Work Breakdown Structure numbers and Hour Codes and has extensive processing that ensures that time and attendance reported by the employee fulfills U.S. Government/OMB requirements before Timekeepers process the data at the end of the two weekmore » payroll cycle using ETA. A tour of duty profile (e.g., ten hour day, four day week with Sunday, friday and Saturday off), previously established in the ETA system, is imported into the Time Card Entry System by the timekeepers. An individual''s profile establishes the basis for validation of time of day and number of hours worked per day. At the end of the two cycle, data is exported by the timekeepers from the Time Card Entry System into ETA files.« less

  9. Mechanosensitive calcium entry and mobilization in renal A6 cells.

    PubMed

    Urbach, V; Leguen, I; O'Kelly, I; Harvey, B J

    1999-03-01

    Using spectrofluorescence imaging of fura-2 loaded renal A6 cells, we have investigated the generation of the cytosolic Ca2+ signal in response to osmotic shock and localized membrane stretch. Upon hypotonic exposure, the cells began to swell prior to a transient increase in [Ca2+]i and the cells remained swollen after [Ca2+]i had returned towards basal levels. Exposure to 2/3rd strength Ringer produced a cell volume increase within 3 min, followed by a slow regulatory volume decrease (RVD). The hypotonic challenge also produced a transient increase in [Ca2+] after a delay of 22 sec. Both the RVD and [Ca2+]i response to hypotonicity were inhibited in a Ca2+-free bathing solution and by gadolinium (10 microm), an inhibitor of stretch-activated channels. Stretching the membrane by application of subatmospheric pressure (-2 kPa) inside a cell-attached patch-pipette induced a similar global increase in [Ca2+]i as occurred after hypotonic shock. A stretch-sensitive [Ca2+]i increase was also observed in a Ca2+-free bathing solution, provided the patch-pipette contained Ca2+. The mechanosensitive [Ca2+]i response was by gadolinium (10 microm) or Ca2+-free pipette solutions, even when Ca2+ (2 mm) was present in the bath. Long-term (>10 min) pretreatment of the cells with thapsigargin inhibited the [Ca2+]i response to hypotonicity. These results provide evidence that cell swelling or mechanical stimulation can activate a powerful amplification system linked to intracellular Ca2+ release mechanisms.

  10. 19 CFR 148.6 - Entry of unaccompanied shipments of effects subject to personal exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry of unaccompanied shipments of effects... General Provisions § 148.6 Entry of unaccompanied shipments of effects subject to personal exemptions. (a) Declaration to support free entry. When effects claimed to be free of duty under subheadings 9804.00.10,...

  11. 19 CFR 148.6 - Entry of unaccompanied shipments of effects subject to personal exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Entry of unaccompanied shipments of effects... General Provisions § 148.6 Entry of unaccompanied shipments of effects subject to personal exemptions. (a) Declaration to support free entry. When effects claimed to be free of duty under subheadings 9804.00.10,...

  12. 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.

  13. 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.

  14. [Chronic kidney disease and cellular calcium homeostasis].

    PubMed

    Lajdová, I; Okša, A; Spustová, A; Dzúrik, R

    2012-01-01

    Free intracellular calcium represents a critical signaling mediator in a number of biological systems. Calcium cations (Ca2+) are an important ubiquitous messenger, controlling a broad range of cellular processes. Free cytosolic calcium concentration ([Ca2+]i) is controlled by mechanisms that regulate Ca2+ entry from the extracellular space and Ca2+ release from intracellular stores, and by the activity of ATP-dependent Ca2+ pumps and antiporters that move Ca2+ back into stores or out of cells. Chronic kidney disease is associated with a significant elevation in [Ca2+]i which is toxic to the cells and may be responsible for a multiple organ dysfunction. Disturbances in cellular calcium homeostasis in patients with chronic kidney disease represent a complex process. Our studies elucidate pathophysiological mechanisms of altered cellular calcium homeostasis in the peripheral blood mononuclear cells which represent the model of nonexcitable cells in patients with chronic kidney disease. The results demonstrate that [Ca2+]i is significantly increased in peripheral blood mononuclear cells already in early stages of chronic kidney disease. The calcium concentration of intracellular stores and the capacitative calcium entry into the cells of these patients are significantly higher in comparison with healthy volunteers. Also the pore-forming P2X7 receptors participate in increased [Ca2+]i in peripheral blood mononuclear cells of patients with chronic kidney disease. An altered P2X7 receptor function and increased P2X7 receptor expression may contribute to the complex disturbances in intracellular calcium homeostasis in chronic kidney disease. On the other hand, the activity of plasmatic membrane Ca2+-ATPases which is responsible for removing excessive calcium out of the cell, was found to be decreased by 25 % when compared to healthy subjects. It means that not only the mechanisms of entry, but also of the removal are impaired by the disease. All these alterations in

  15. Oxygen increases ductus arteriosus smooth muscle cytosolic calcium via release of calcium from inositol triphosphate-sensitive stores.

    PubMed

    Keck, Maggie; Resnik, Ernesto; Linden, Bradley; Anderson, Franklin; Sukovich, David J; Herron, Jean; Cornfield, David N

    2005-05-01

    In utero, blood shunts away from the lungs via the ductus arteriosus (DA) and the foramen ovale. After birth, the DA closes concomitant with increased oxygen tension. The present experimental series tests the hypothesis that oxygen directly increases DA smooth muscle cell (SMC) cytosolic calcium ([Ca(2+)](i)) through inactivation of a K(+) channel, membrane depolarization, and entry of extracellular calcium. To test the hypothesis, DA SMC were isolated from late-gestation fetal lambs and grown to subconfluence in primary culture in low oxygen tension (25 Torr). DA SMC were loaded with the calcium-sensitive fluorophore fura-2 under low oxygen tension conditions and studied using microfluorimetry while oxygen tension was acutely increased (120 Torr). An acute increase in oxygen tension progressively increased DA SMC [Ca(2+)](i) by 11.7 +/- 1.4% over 40 min. The effect of acute normoxia on DA SMC [Ca(2+)](i) was mimicked by pharmacological blockade of the voltage-sensitive K(+) channel. Neither removal of extracellular calcium nor voltage-operated calcium channel blockade prevented the initial increase in DA SMC [Ca(2+)](i). Manganese quenching experiments demonstrated that acute normoxia initially decreases the rate of extracellular calcium entry. Pharmacological blockade of inositol triphosphate-sensitive, but not ryanodine-sensitive, intracellular calcium stores prevented the oxygen-induced increase in [Ca(2+)](i). Endothelin increased [Ca(2+)](i) in acutely normoxic, but not hypoxic, DA SMC. Thus acute normoxia 1) increases DA SMC [Ca(2+)](i) via release of calcium from intracellular calcium stores, and subsequent entry of extracellular calcium, and 2) potentiates the effect of contractile agonists. Prolonged patency of the DA may result from disordered intracellular calcium homeostasis.

  16. Emerging evidence for specific neuronal functions of auxiliary calcium channel α2δ subunits

    PubMed Central

    Obermair, Gerald J.

    2015-01-01

    In nerve cells the ubiquitous second messenger calcium regulates a variety of vitally important functions including neurotransmitter release, gene regulation, and neuronal plasticity. The entry of calcium into cells is tightly regulated by voltage-gated calcium channels, which consist of a heteromultimeric complex of a pore forming α1, and the auxiliary β and α2δ subunits. Four genes (Cacna2d1-4) encode for the extracellular membrane-attached α2δ subunits (α2δ-1 to α2δ-4), out of which three isoforms (α2δ-1 to -3) are strongly expressed in the central nervous system. Over the years a wealth of studies has demonstrated the classical role of α2δ subunits in channel trafficking and calcium current modulation. Recent studies in specialized neuronal cell systems propose roles of α2δ subunits beyond the classical view and implicate α2δ subunits as important regulators of synapse formation. These findings are supported by the identification of novel human disease mutations associated with α2δ subunits and by the fact that α2δ subunits are the target of the anti-epileptic and anti-allodynic drugs gabapentin and pregabalin. Here we review the recently emerging evidence for specific as well as redundant neuronal roles of α2δ subunits and discuss the mechanisms for establishing and maintaining specificity. PMID:25504062

  17. 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

  18. 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

  19. 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 ...

  20. Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse.

    PubMed Central

    Llinás, R; McGuinness, T L; Leonard, C S; Sugimori, M; Greengard, P

    1985-01-01

    Synapsin I and calcium/calmodulin-dependent protein kinase II were pressure-injected into the preterminal digit of the squid giant synapse to test directly the possible regulation of neurotransmitter release by these substances. Neurotransmitter release was determined by measuring the amplitude, rate of rise, and latency of the postsynaptic potential generated in response to presynaptic depolarizing steps under voltage clamp conditions. Injection of dephosphosynapsin I decreased the amplitude and rate of rise of the postsynaptic potential, whereas injection of either phosphosynapsin I or heat-treated dephosphosynapsin I was without effect. Conversely, injection of calcium/calmodulin-dependent protein kinase II, which phosphorylates synapsin I on site II, increased the rate of rise and amplitude and decreased the latency of the postsynaptic potential. The effects of these proteins were observed without any detectable change in the initial phase of the presynaptic calcium current. A synapsin I-like protein and calcium/calmodulin-dependent protein kinase II were demonstrated by biochemical and immunochemical techniques to be present in squid nervous tissue. The data support the hypothesis that synapsin I regulates the availability of synaptic vesicles for release; we propose that calcium entry into the nerve terminal activates calcium/calmodulin-dependent protein kinase II, which phosphorylates synapsin I on site II, dissociating it from the vesicles and thereby removing a constraint in the release process. Images PMID:2859595

  1. 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

  2. Calcium Release-Activated Calcium (CRAC) Channels Mediate the β2-Adrenergic Regulation of Na,K-ATPase

    PubMed Central

    Keller, Michael J.; Lecuona, Emilia; Prakriya, Murali; Cheng, Yuan; Soberanes, Saul; Scott Budinger, G.R.; Sznajder, Jacob I.

    2014-01-01

    β2-adrenergic agonists have been shown to regulate Na,K-ATPase in the alveolar epithelium by recruiting Na,K-ATPase-containing vesicles to the plasma membrane of alveolar epithelial cells (AEC). Here, we provide evidence that β2-agonists induce store-operated calcium entry (SOCE) in AECs. This calcium entry is necessary for β2-agonist-induced recruitment of Na,K-ATPase to the plasma membrane of AECs. Specifically, we show that β2-agonists induce SOCE via stromal interaction molecule 1 (STIM1)-associated calcium release-activated calcium (CRAC) channels. We also demonstrate that the magnitude of SOCE affects the abundance of Na,K-ATPase at the plasma membrane of AECs. PMID:25447523

  3. Entry charges on immigrants.

    PubMed

    Clarke, H R

    1994-01-01

    The author analyzes "the various arguments that can be advanced for imposing fees on immigrants to optimize...resident gains.... This article discusses cost recovery and emphasizes the costs of multiculturalism as a possible basis for fees. It then analyzes the effects of inelastic immigrant supplies in providing an optimal tariff motivation for monopsonistically restricting labor flows and deals with the second-best problem of devising an optimal fee policy to accompany a possibly suboptimal immigration quota. Next, attention turns to the role of priceable externalities. Externalities which are expensive to price because of transactions costs are analyzed. Finally, along with summarization of major conclusions, the author considers if, even in the economic interests of existing residents, entry rights should be sold."

  4. [Voltage gated calcium channels: structure, characteristics and terminology].

    PubMed

    Veizerová, L; Svetlík, J; Kettmann, V

    2007-07-01

    Voltage-gated Ca2+ channels are the major pathway of Ca2+ entry into the cells. Their activity is essential to couple electrical signals from the cell surface to physiological events in cells. Several pharmacologically, structurally and kinetically distinct calcium channel types have been identified at the electrophysiological and molecular levels. This review aims to describe the functional, structural and pharmacological properties of voltage-gated calcium channels.

  5. Coronary Calcium Scan

    MedlinePlus

    ... the NHLBI on Twitter. What Is a Coronary Calcium Scan? A coronary calcium scan is a test ... you have calcifications in your coronary arteries. Coronary Calcium Scan Figure A shows the position of the ...

  6. Calcium and bones (image)

    MedlinePlus

    Calcium is one of the most important minerals for the growth, maintenance, and reproduction of the human ... body, are continually being re-formed and incorporate calcium into their structure. Calcium is essential for the ...

  7. Calcium hydroxide poisoning

    MedlinePlus

    Hydrate - calcium; Lime milk; Slaked lime ... Calcium hydroxide ... These products contain calcium hydroxide: Cement Limewater Many industrial solvents and cleaners (hundreds to thousands of construction products, flooring strippers, brick cleaners, cement ...

  8. Calcium source (image)

    MedlinePlus

    Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has ... as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also effects the ...

  9. Comparable Stocks, Boundedly Rational Stock Markets and IPO Entry Rates

    PubMed Central

    Chok, Jay; Qian, Jifeng

    2013-01-01

    In this study, we examine how initial public offerings (IPO) entry rates are affected when stock markets are boundedly rational and IPO firms infer information from their counterparts in the market. We hypothesize a curvilinear relationship between the number of comparable stocks and initial public offerings (IPO) entry rates into the NASDAQ Stock Exchange. Furthermore, we argue that trading volume and changes in stock returns partially mediates the relationship between the number of comparable stocks and IPO entry rates. The statistical evidence provides strong support for the hypotheses. PMID:23690924

  10. Double-Entry Expectancy Tables.

    ERIC Educational Resources Information Center

    Wesman, Alexander G.

    1966-01-01

    Double-entry expectancy tables are used to make admissions, guidance, or employment decisions based on two predictors. Examples of their use in showing relationships between high school and college performance are explained. The advantages of double-entry expectacy tables given are: (1) relative simplicity of preparation requiring no formal…

  11. 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.

  12. Viking entry aerodynamics and heating

    NASA Technical Reports Server (NTRS)

    Polutchko, R. J.

    1974-01-01

    The characteristics of the Mars entry including the mission sequence of events and associated spacecraft weights are described along with the Viking spacecraft. Test data are presented for the aerodynamic characteristics of the entry vehicle showing trimmed alpha, drag coefficient, and trimmed lift to drag ratio versus Mach number; the damping characteristics of the entry configuration; the angle of attack time history of Viking entries; stagnation heating and pressure time histories; and the aeroshell heating distribution as obtained in tests run in a shock tunnel for various gases. Flight tests which demonstrate the aerodynamic separation of the full-scale aeroshell and the flying qualities of the entry configuration in an uncontrolled mode are documented. Design values selected for the heat protection system based on the test data and analysis performed are presented.

  13. Reconstruction of the Genesis Entry

    NASA Technical Reports Server (NTRS)

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

    2005-01-01

    This paper provides an overview of the findings from a reconstruction analysis of the Genesis capsule entry. First, a comparison of the atmospheric properties (density and winds) encountered during the entry to the pre-entry profile is presented. The analysis that was performed on the video footage (obtained from the tracking stations at UTTR) during the descent is then described from which the Mach number at the onset of the capsule tumble was estimated following the failure of the drogue parachute deployment. Next, an assessment of the Genesis capsule aerodynamics that was extracted from the video footage is discussed, followed by a description of the capsule hypersonic attitude that must have occurred during the entry based on examination of the recovered capsule heatshield. Lastly, the entry trajectory reconstruction that was performed is presented.

  14. 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.

  15. 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

  16. Calcium, iron and neuronal function.

    PubMed

    Hidalgo, Cecilia; Núñez, Marco T

    2007-01-01

    Calcium and iron play dual roles in neuronal function: they are both essential but when present in excess they cause neuronal damage and may even induce neuronal death. Calcium signals are required for synaptic plasticity, a neuronal process that entails gene expression and which is presumably the cellular counterpart of cognitive brain functions such as learning and memory. Neuronal activity generates cytoplasmic and nuclear calcium signals that in turn stimulate pathways that promote the transcription of genes known to participate in synaptic plasticity. In addition, evidence discussed in this article shows that iron deficiency causes learning and memory impairments that persist following iron repletion, indicating that iron is necessary for normal development of cognitive functions. Recent results from our group indicate that iron is required for long-term potentiation in hippocampal CA1 neurons and that iron stimulates ryanodine receptor-mediated calcium release through ROS produced via the Fenton reaction leading to stimulation of the ERK signaling pathway. These combined results support a coordinated action between iron and calcium in synaptic plasticity and raise the possibility that elevated iron levels may contribute to neuronal degeneration through excessive intracellular calcium increase caused by iron-induced oxidative stress. PMID:17505966

  17. 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.

  18. 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.

  19. 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.

  20. DLMS voice data entry

    NASA Astrophysics Data System (ADS)

    Scott, P. B.

    1980-06-01

    This report describes the design, principles of operation, and performance characteristics of an Advanced Development Model of a voice recognition system (VRS) which can serve to input cartographic data to a computer. The completed system has been installed at the Defense Mapping Agency Aerospace Center (DMAAC) at St. Louis, MO, for evaluation and testing. The VRS is intended for use in entering by voice cartographic data to the Digital Landmass System (DLMS) Data Base. It was designed to satisfy the DMAAC product specifications. The software developed for the VRS includes two complete stand-alone programs. Performance tests conducted at TTI disclosed an average system word recognition accuracy of just under 99 percent for five talkers. The recognition tests were conducted by the use of tape recordings. These tape recordings were made during a previous contract involving cartographic data entry. Each person spoke approximately 536 words after uttering five training repetitions. The test results were virtually identical to those obtained during the previous contract.

  1. Long-term behavior of CaO-based pellets supported by calcium aluminate cements in a long series of CO{sub 2} capture cycles

    SciTech Connect

    Manovic, V.; Anthony, E.J.

    2009-10-15

    A series of carbonation/calcination tests consisting of 1000 cycles was performed with CaO-based pellets prepared using hydrated lime and calcium aluminate cement. The change in CO{sub 2} carrying capacity of the sorbent was investigated in a thermogravimetric analyzer (TGA) apparatus and the morphology of residues after those cycles in the TGA was examined by scanning electron microscopy (SEM). Larger quantities of sorbent pellets underwent 300 carbonation/calcination cycles in a tube furnace (TF), and their properties were examined by nitrogen physisorption tests (BET and BJH). The crushing strength of the pellets before and after the CO{sub 2} cycles was determined by means of a custom-made strength testing apparatus. The results showed high CO{sub 2} carrying capacity in long series of cycles with an extremely high residual activity of the order of 28%. This superior performance is a result of favorable morphology due to the existence of large numbers of nanosized pores suitable for carbonation. This morphology is relatively stable during cycles due to the presence of mayenite (Ca{sub 12}Al{sub 14}O{sub 33}) in the CaO structure. However, the crushing tests showed that pellets lost strength after 300 carbonation/calcination cycles, and this appears to be due to the cracks formed in the pellets. This effect was not observed in smaller particles suitable for use in fluidized bed (FBC) systems.

  2. Effects of dihydropyridines and inorganic calcium blockers on aggregation and on intracellular free calcium in platelets.

    PubMed

    Palés, J; Palacios-Araus, L; López, A; Gual, A

    1991-05-01

    [Ca2+]i increase is necessary in physiological platelet activity, particularly aggregation and release. The increase of [Ca2+]i observed during platelet activation depends in part on Ca2+ influx from the extracellular medium. The participation of voltage-operated Ca2+ channels as a pathway for Ca2+ entry is controversial. In the present study we have attempted to reinvestigate this problem by measuring aggregation and [Ca2+]i changes in platelets activated by ADP or thrombin and incubated with organic or inorganic blockers of calcium channels. The main findings of the present paper can be summarized as follows: (i) Ni2+, Co2+ and Mn2+, well known inorganic blockers of Ca2+ channels, inhibited platelet aggregation induced by ADP or thrombin in a dose-dependent manner, Ni2+ being the most effective agent. (ii) Thrombin induced a rise in free [Ca2+]i in platelets incubated both in 1 mmol/l Ca(2+)-containing medium and in nominally Ca(2+)-free medium; the rise of free [Ca2+]i was in the first case up to 370 +/- 31 nmol/l and in the second case up to 242 +/- 26 nmol/l, indicating that this observed difference was due to Ca2+ entry from the extracellular medium. Co2+ and Ni2+ abolished that difference by inhibiting Ca2+ influx. (iii) Nisoldipine, nitrendipine and nimodipine (10-50 nmol/l) inhibited in a dose-dependent manner platelet aggregation induced by either ADP or thrombin in platelets incubated in normal-Ca2+ normal-K+ medium, also, aggregation was inhibited to a similar extent in platelets incubated in normal-Ca2+ high-K+ medium. (iv) Nisoldipine--the most effective dihydropyridine to inhibit platelet aggregation--also inhibited Ca2+ influx in platelets incubated in normal-Ca2+ medium, either in normal-K+ or high-K+ media. Our data support the existence of voltage-operated, dihydropyridine-sensitive calcium channels (L-type) and a physiological role for them in platelet function.

  3. 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

  4. 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.

  5. 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

  6. Dietary perturbation of calcium metabolism in normal man: compartmental analysis

    PubMed Central

    Phang, James M.; Berman, Mones; Finerman, Gerald A.; Neer, Robert M.; Rosenberg, Leon E.; Hahn, Theodore J.

    1969-01-01

    The effect of dietary calcium intake on calcium metabolism was studied in eight normal volunteers by multicompartmental analysis of radiocalcium and balance data. In paired studies of six normal subjects on normal and high or low calcium intakes, necessary and sufficient criteria were used to determine changes in calcium metabolic parameters produced by alterations in dietary calcium. These changes involved gastrointestinal calcium absorption rate, renal and endogenous fecal rate constants, and bone resorption rate. Bone accretion rate and compartment sizes need not change between the paired studies. The changes of parameters involving kidney, gut, and bone were in a direction to support calcium homeostasis and were compatible with the pattern of changes produced by parathyroid hormone. However, the source of the stimulus for hormone secretion was not apparent since plasma calcium concentrations showed no significant difference between paired studies. The implications of these findings relative to control of hormone secretion, calcium regulatory mechanisms, and metabolic bone disease are discussed. PMID:5765028

  7. Calcium-dependent inactivation of L-type calcium channels in planar lipid bilayers.

    PubMed Central

    Haack, J A; Rosenberg, R L

    1994-01-01

    Intracellular Ca2+ can inhibit the activity of voltage-gated Ca channels by modulating the rate of channel inactivation. Ca(2+)-dependent inactivation of these channels may be a common negative feedback process important for regulating Ca2+ entry under physiological and pathological conditions. This article demonstrates that the inactivation of cardiac L-type Ca channels, reconstituted into planar lipid bilayers and studied in the presence of a dihydropyridine agonist, is sensitive to Ca2+. The rates and extents of inactivation, determined from ensemble averages of unitary Ba2+ currents, decreased when the calcium concentration facing the intracellular surface of the channel ([Ca2+]i) was lowered from approximately 10 microM to 20 nM by the addition of Ca2+ chelators. The rates and extents of Ba2+ current inactivation could also be increased by subsequent addition of Ca2+ raising the [Ca2+]i to 15 microM, thus demonstrating that the Ca2+ dependence of inactivation could be reversibly regulated by changes in [Ca2+]i. In addition, reconstituted Ca channels inactivated more quickly when the inward current was carried by Ca2+ than when it was carried by Ba2+, suggesting that local increases in [Ca2+]i could activate Ca(2+)-dependent inactivation. These data support models in which Ca2+ binds to the channel itself or to closely associated regulatory proteins to control the rate of channel inactivation, and are inconsistent with purely enzymatic models for channel inactivation. PMID:8038377

  8. 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...

  9. Electrical power requirements analysis. Single failure tolerant entry

    NASA Technical Reports Server (NTRS)

    Pipher, M. D.; Green, P. A.; Wolfgram, D. F.

    1977-01-01

    The results of an analysis of the orbiter electrical power system for the case of a single failure tolerant (SFT) entry are presented. The analysis was performed using the shuttle electrical power system analysis computer program. It was performed to permit assessment of the capability of the orbiter systems to support the proposed entry configuration and to provide the data necessary to identify potential constraints and limitations. Three contingency modes have been identified which would require an SFT entry. This analysis addresses an SFT entry resulting from the loss of two fuel cell powerplants, while on orbit. The results of the analysis indicate that, even under near optimum conditions, the fuel cell power demand will exceed the tested operating capacity of 16 kw, and that various electrical components may experience voltages below 24 VDC.

  10. Overview of the Mars Sample Return Earth Entry Vehicle

    NASA Technical Reports Server (NTRS)

    Dillman, Robert; Corliss, James

    2008-01-01

    NASA's Mars Sample Return (MSR) project will bring Mars surface and atmosphere samples back to Earth for detailed examination. Langley Research Center's MSR Earth Entry Vehicle (EEV) is a core part of the mission, protecting the sample container during atmospheric entry, descent, and landing. Planetary protection requirements demand a higher reliability from the EEV than for any previous planetary entry vehicle. An overview of the EEV design and preliminary analysis is presented, with a follow-on discussion of recommended future design trade studies to be performed over the next several years in support of an MSR launch in 2018 or 2020. Planned topics include vehicle size for impact protection of a range of sample container sizes, outer mold line changes to achieve surface sterilization during re-entry, micrometeoroid protection, aerodynamic stability, thermal protection, and structural materials selection.

  11. 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.

  12. 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.

  13. 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...

  14. Stimulation of calcium-sodium exchange in dog red blood cells by hemolysis and resealing.

    PubMed

    Parker, J C

    1988-09-01

    Osmotic hemolysis and resealing greatly increase calcium influx in dog red blood cells. The resealed ghosts show a saturable calcium entry pathway with complex kinetics. As expected for a calcium-sodium exchanger, calcium uptake is stimulated by internal sodium and inhibited by external sodium. Compared to fresh, intact red cells the resealed ghost calcium-sodium exchanger is less responsive to quinidine and to alterations in medium tonicity. The differences in calcium uptake rate among cells from different donors are minimized in the ghost preparation. There are several ways to stimulate sodium-dependent calcium movements in these cells, of which hemolysis-resealing is the most potent. The results of these and previous studies suggest that dog red blood cells have a latent capacity for calcium-sodium exchange. PMID:3415988

  15. Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter.

    PubMed

    Holmström, Kira M; Pan, Xin; Liu, Julia C; Menazza, Sara; Liu, Jie; Nguyen, Tiffany T; Pan, Haihui; Parks, Randi J; Anderson, Stasia; Noguchi, Audrey; Springer, Danielle; Murphy, Elizabeth; Finkel, Toren

    2015-08-01

    Mitochondrial calcium is thought to play an important role in the regulation of cardiac bioenergetics and function. The entry of calcium into the mitochondrial matrix requires that the divalent cation pass through the inner mitochondrial membrane via a specialized pore known as the mitochondrial calcium uniporter (MCU). Here, we use mice deficient of MCU expression to rigorously assess the role of mitochondrial calcium in cardiac function. Mitochondria isolated from MCU(-/-) mice have reduced matrix calcium levels, impaired calcium uptake and a defect in calcium-stimulated respiration. Nonetheless, we find that the absence of MCU expression does not affect basal cardiac function at either 12 or 20months of age. Moreover, the physiological response of MCU(-/-) mice to isoproterenol challenge or transverse aortic constriction appears similar to control mice. Thus, while mitochondria derived from MCU(-/-) mice have markedly impaired mitochondrial calcium handling, the hearts of these animals surprisingly appear to function relatively normally under basal conditions and during stress.

  16. 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

  17. Analysis of Ebola Virus Entry Into Macrophages.

    PubMed

    Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

    2015-10-01

    Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)-driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells.

  18. Analysis of Ebola Virus Entry Into Macrophages

    PubMed Central

    Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B.; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A.; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

    2015-01-01

    Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)–driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. PMID:25877552

  19. Analysis of Ebola Virus Entry Into Macrophages.

    PubMed

    Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

    2015-10-01

    Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)-driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. PMID:25877552

  20. Market entry and exit by biotech and device companies funded by venture capital.

    PubMed

    Burns, Lawton R; Housman, Michael G; Robinson, Charles A

    2009-01-01

    Start-up companies in the biotechnology and medical device sectors are important sources of health care innovation. This paper describes the role of venture capital in supporting these companies and charts the growth in venture capital financial support. The paper then uses longitudinal data to describe market entry and exit by these companies. Similar factors are associated with entry and exit in the two sectors. Entries and exits in one sector also appear to influence entry in the other. These findings have important implications for developing innovative technologies and ensuring competitive markets in the life sciences.

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. Calcium signaling and T-type calcium channels in cancer cell cycling

    PubMed Central

    Taylor, James T; Zeng, Xiang-Bin; Pottle, Jonathan E; Lee, Kevin; Wang, Alun R; Yi, Stephenie G; Scruggs, Jennifer A S; Sikka, Suresh S; Li, Ming

    2008-01-01

    Regulation of intracellular calcium is an important signaling mechanism for cell proliferation in both normal and cancerous cells. In normal epithelial cells, free calcium concentration is essential for cells to enter and accomplish the S phase and the M phase of the cell cycle. In contrast, cancerous cells can pass these phases of the cell cycle with much lower cytoplasmic free calcium concentrations, indicating an alternative mechanism has developed for fulfilling the intracellular calcium requirement for an increased rate of DNA synthesis and mitosis of fast replicating cancerous cells. The detailed mechanism underlying the altered calcium loading pathway remains unclear; however, there is a growing body of evidence that suggests the T-type Ca2+ channel is abnormally expressed in cancerous cells and that blockade of these channels may reduce cell proliferation in addition to inducing apoptosis. Recent studies also show that the expression of T-type Ca2+ channels in breast cancer cells is proliferation state dependent, i.e. the channels are expressed at higher levels during the fast-replication period, and once the cells are in a non-proliferation state, expression of this channel is minimal. Therefore, selectively blocking calcium entry into cancerous cells may be a valuable approach for preventing tumor growth. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2+ channel blockers may be useful in the treatment of certain types of cancers. PMID:18763278

  7. 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

  8. 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.

  9. Atmospheric entry heating of micrometeorites

    NASA Technical Reports Server (NTRS)

    Flynn, G. J.

    1989-01-01

    A computer simulation of the atmospheric entry deceleration and heating of cosmic dust particles has been developed and the predicted peak temperatures are compared to the earlier closed-form mathematical solutions of Whipple (195) and Fraundorf (1980). A 20-micron diameter particle of density 1 gm/cu cm having a velocity of 10 km/s at infinity and entering the atmosphere at normal incidence reaches a peak temperature of 1159 K. The duration of the heating pulse is about 8 s but the particle remains within 100 K of the peak temperature for only 1.0 s. As the angle of incidence decreases, the peak temperature reached on entry also decreases, and the duration of the temperature pulse increases. Comparison with the Whipple amd Fraundorf models indicates that they accurately assess the entry heating for cosmic dust particles of moderate or higher densities and entry angles near normal incidence. As particle density decreases or the entry angle nears grazing incidence, they overestimate the peak temperature.

  10. 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... for multiple entries. (a) Requirements. Except as provided in paragraph (b) of this section, the port... summary. (b) Merchandise not eligible. One entry summary shall not be used for multiple entries of...

  11. 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.

  12. Calcium and Vitamin D

    MedlinePlus

    ... to your weekly shopping list. Produce Serving Size Estimated Calcium* Collard greens, frozen 8 oz 360 mg ... Oranges 1 whole 55 mg Seafood Serving Size Estimated Calcium* Sardines, canned with bones 3 oz 325 ...

  13. Fenoprofen calcium overdose

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002649.htm Fenoprofen calcium overdose To use the sharing features on this page, please enable JavaScript. Fenoprofen calcium is a type of medicine called a nonsteroidal ...

  14. Calcium and bones

    MedlinePlus

    ... only gets the calcium it needs through the food you eat, or from supplements. If you do ... materials it needs to build bones. High-calcium foods include: Milk Cheese Ice cream Leafy green vegetables, ...

  15. Calcium signaling mediates cold sensing in insect tissues.

    PubMed

    Teets, Nicholas M; Yi, Shu-Xia; Lee, Richard E; Denlinger, David L

    2013-05-28

    The ability to rapidly respond to changes in temperature is a critical adaptation for insects and other ectotherms living in thermally variable environments. In a process called rapid cold hardening (RCH), insects significantly enhance cold tolerance following brief (i.e., minutes to hours) exposure to nonlethal chilling. Although the ecological relevance of RCH is well-established, the underlying physiological mechanisms that trigger RCH are poorly understood. RCH can be elicited in isolated tissues ex vivo, suggesting cold-sensing and downstream hardening pathways are governed by brain-independent signaling mechanisms. We previously provided preliminary evidence that calcium is involved in RCH, and here we firmly establish that calcium signaling mediates cold sensing in insect tissues. In tracheal cells of the freeze-tolerant goldenrod gall fly, Eurosta solidaginis, chilling to 0 °C evoked a 40% increase in intracellular calcium concentration as determined by live-cell confocal imaging. Downstream of calcium entry, RCH conditions significantly increased the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) while reducing phosphorylation of the inhibitory Thr306 residue. Pharmacological inhibitors of calcium entry, calmodulin activation, and CaMKII activity all prevented ex vivo RCH in midgut and salivary gland tissues, indicating that calcium signaling is required for RCH to occur. Similar results were obtained for a freeze-intolerant species, adults of the flesh fly, Sarcophaga bullata, suggesting that calcium-mediated cold sensing is a general feature of insects. Our results imply that insect tissues use calcium signaling to instantly detect decreases in temperature and trigger downstream cold-hardening mechanisms.

  16. Calcium signaling mediates cold sensing in insect tissues

    PubMed Central

    Teets, Nicholas M.; Yi, Shu-Xia; Lee, Richard E.; Denlinger, David L.

    2013-01-01

    The ability to rapidly respond to changes in temperature is a critical adaptation for insects and other ectotherms living in thermally variable environments. In a process called rapid cold hardening (RCH), insects significantly enhance cold tolerance following brief (i.e., minutes to hours) exposure to nonlethal chilling. Although the ecological relevance of RCH is well-established, the underlying physiological mechanisms that trigger RCH are poorly understood. RCH can be elicited in isolated tissues ex vivo, suggesting cold-sensing and downstream hardening pathways are governed by brain-independent signaling mechanisms. We previously provided preliminary evidence that calcium is involved in RCH, and here we firmly establish that calcium signaling mediates cold sensing in insect tissues. In tracheal cells of the freeze-tolerant goldenrod gall fly, Eurosta solidaginis, chilling to 0 °C evoked a 40% increase in intracellular calcium concentration as determined by live-cell confocal imaging. Downstream of calcium entry, RCH conditions significantly increased the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) while reducing phosphorylation of the inhibitory Thr306 residue. Pharmacological inhibitors of calcium entry, calmodulin activation, and CaMKII activity all prevented ex vivo RCH in midgut and salivary gland tissues, indicating that calcium signaling is required for RCH to occur. Similar results were obtained for a freeze-intolerant species, adults of the flesh fly, Sarcophaga bullata, suggesting that calcium-mediated cold sensing is a general feature of insects. Our results imply that insect tissues use calcium signaling to instantly detect decreases in temperature and trigger downstream cold-hardening mechanisms. PMID:23671084

  17. Calcium signaling mediates cold sensing in insect tissues.

    PubMed

    Teets, Nicholas M; Yi, Shu-Xia; Lee, Richard E; Denlinger, David L

    2013-05-28

    The ability to rapidly respond to changes in temperature is a critical adaptation for insects and other ectotherms living in thermally variable environments. In a process called rapid cold hardening (RCH), insects significantly enhance cold tolerance following brief (i.e., minutes to hours) exposure to nonlethal chilling. Although the ecological relevance of RCH is well-established, the underlying physiological mechanisms that trigger RCH are poorly understood. RCH can be elicited in isolated tissues ex vivo, suggesting cold-sensing and downstream hardening pathways are governed by brain-independent signaling mechanisms. We previously provided preliminary evidence that calcium is involved in RCH, and here we firmly establish that calcium signaling mediates cold sensing in insect tissues. In tracheal cells of the freeze-tolerant goldenrod gall fly, Eurosta solidaginis, chilling to 0 °C evoked a 40% increase in intracellular calcium concentration as determined by live-cell confocal imaging. Downstream of calcium entry, RCH conditions significantly increased the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) while reducing phosphorylation of the inhibitory Thr306 residue. Pharmacological inhibitors of calcium entry, calmodulin activation, and CaMKII activity all prevented ex vivo RCH in midgut and salivary gland tissues, indicating that calcium signaling is required for RCH to occur. Similar results were obtained for a freeze-intolerant species, adults of the flesh fly, Sarcophaga bullata, suggesting that calcium-mediated cold sensing is a general feature of insects. Our results imply that insect tissues use calcium signaling to instantly detect decreases in temperature and trigger downstream cold-hardening mechanisms. PMID:23671084

  18. HIV: Cell Binding and Entry

    PubMed Central

    Wilen, Craig B.; Tilton, John C.; Doms, Robert W.

    2012-01-01

    The first step of the human immunodeficiency virus (HIV) replication cycle—binding and entry into the host cell—plays a major role in determining viral tropism and the ability of HIV to degrade the human immune system. HIV uses a complex series of steps to deliver its genome into the host cell cytoplasm while simultaneously evading the host immune response. To infect cells, the HIV protein envelope (Env) binds to the primary cellular receptor CD4 and then to a cellular coreceptor. This sequential binding triggers fusion of the viral and host cell membranes, initiating infection. Revealing the mechanism of HIV entry has profound implications for viral tropism, transmission, pathogenesis, and therapeutic intervention. Here, we provide an overview into the mechanism of HIV entry, provide historical context to key discoveries, discuss recent advances, and speculate on future directions in the field. PMID:22908191

  19. 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.

  20. Reduced calcium-dependent mitochondrial damage underlies the reduced vulnerability of excitotoxicity-tolerant hippocampal neurons.

    PubMed

    Pivovarova, Natalia B; Stanika, Ruslan I; Watts, Charlotte A; Brantner, Christine A; Smith, Carolyn L; Andrews, S Brian

    2008-03-01

    In central neurons, over-stimulation of NMDA receptors leads to excessive mitochondrial calcium accumulation and damage, which is a critical step in excitotoxic death. This raises the possibility that low susceptibility to calcium overload-induced mitochondrial damage might characterize excitotoxicity-resistant neurons. In this study, we have exploited two complementary models of preconditioning-induced excitotoxicity resistance to demonstrate reduced calcium-dependent mitochondrial damage in NMDA-tolerant hippocampal neurons. We have further identified adaptations in mitochondrial calcium handling that account for enhanced mitochondrial integrity. In both models, enhanced tolerance was associated with improved preservation of mitochondrial membrane potential and structure. In the first model, which exhibited modest neuroprotection, mitochondria-dependent calcium deregulation was delayed, even though cytosolic and mitochondrial calcium loads were quantitatively unchanged, indicating that enhanced mitochondrial calcium capacity accounts for reduced injury. In contrast, the second model, which exhibited strong neuroprotection, displayed further delayed calcium deregulation and reduced mitochondrial damage because downregulation of NMDA receptor surface expression depressed calcium loading. Reducing calcium entry also modified the chemical composition of the calcium-buffering precipitates that form in calcium-loaded mitochondria. It thus appears that reduced mitochondrial calcium loading is a major factor underlying the robust neuroprotection seen in highly tolerant cells. PMID:18036152

  1. 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

  2. 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

  3. 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…

  4. 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.

  5. 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)

  6. 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.

  7. Delayed School Entry in Uganda

    ERIC Educational Resources Information Center

    Moyi, Peter

    2011-01-01

    Since 1997 Uganda has seen a large increase in school enrolment. Despite this increased enrolment, universal education has remained elusive. Many children enrol in school, but not at the recommended age, and they drop out before completing school. This article focuses on one of these problems--delayed school entry. What household factors are…

  8. Poxvirus entry and membrane fusion

    SciTech Connect

    Moss, Bernard . E-mail: bmoss@nih.gov

    2006-01-05

    The study of poxvirus entry and membrane fusion has been invigorated by new biochemical and microscopic findings that lead to the following conclusions: (1) the surface of the mature virion (MV), whether isolated from an infected cell or by disruption of the membrane wrapper of an extracellular virion, is comprised of a single lipid membrane embedded with non-glycosylated viral proteins; (2) the MV membrane fuses with the cell membrane, allowing the core to enter the cytoplasm and initiate gene expression; (3) fusion is mediated by a newly recognized group of viral protein components of the MV membrane, which are conserved in all members of the poxvirus family; (4) the latter MV entry/fusion proteins are required for cell to cell spread necessitating the disruption of the membrane wrapper of extracellular virions prior to fusion; and furthermore (5) the same group of MV entry/fusion proteins are required for virus-induced cell-cell fusion. Future research priorities include delineation of the roles of individual entry/fusion proteins and identification of cell receptors.

  9. Multiple effects of opiates on intracellular calcium level and on calcium uptake in three neuronal cell lines.

    PubMed

    Fields, A; Gafni, M; Oron, Y; Sarne, Y

    1995-07-31

    The present study examines the modulation by opiates of intracellular calcium levels and calcium entry, using fura-2 imaging and 45Ca2+ uptake, in three neuronal cell lines. We show that opiates (10(-7)-10(-5) M morphine and 10(-9)-10(-7) M etorphine) exert both inhibitory and excitatory effects on KCl-induced elevation in intracellular calcium level in SK-N-SH, NG108-15 and NMB cell lines. In addition, opiates elevate basal (non KCl-stimulated) intracellular calcium level in all three cell cultures. 45Ca2+ uptake is augmented by opiates in SK-N-SH cells and this stimulatory effect is not blocked by pertussis toxin. In NMB cells, an additional inhibitory effect of opiates on basal calcium takes place: opiates reduce intracellular calcium level as measured by fura-2, and decrease calcium influx as detected by 45Ca2+ uptake. The heterogeneity in the opioid regulation of calcium could not be attributed to the type of opioid drug, neither to its concentration nor to the experimental conditions, since neighboring cells within the same culture responded differently.

  10. Mitochondria: the calcium connection.

    PubMed

    Contreras, Laura; Drago, Ilaria; Zampese, Enrico; Pozzan, Tullio

    2010-01-01

    Calcium handling by mitochondria is a key feature in cell life. It is involved in energy production for cell activity, in buffering and shaping cytosolic calcium rises and also in determining cell fate by triggering or preventing apoptosis. Both mitochondria and the mechanisms involved in the control of calcium homeostasis have been extensively studied, but they still provide researchers with long-standing or even new challenges. Technical improvements in the tools employed for the investigation of calcium dynamics have been-and are still-opening new perspectives in this field, and more prominently for mitochondria. In this review we present a state-of-the-art toolkit for calcium measurements, with major emphasis on the advantages of genetically encoded indicators. These indicators can be efficiently and selectively targeted to specific cellular sub-compartments, allowing previously unavailable high-definition calcium dynamic studies. We also summarize the main features of cellular and, in more detail, mitochondrial calcium handling, especially focusing on the latest breakthroughs in the field, such as the recent direct characterization of the calcium microdomains that occur on the mitochondrial surface upon cellular stimulation. Additionally, we provide a major example of the key role played by calcium in patho-physiology by briefly describing the extensively reported-albeit highly controversial-alterations of calcium homeostasis in Alzheimer's disease, casting lights on the possible alterations in mitochondrial calcium handling in this pathology.

  11. Calcium signaling and epilepsy.

    PubMed

    Steinlein, Ortrud K

    2014-08-01

    Calcium signaling is involved in a multitude of physiological and pathophysiological mechanisms. Over the last decade, it has been increasingly recognized as an important factor in epileptogenesis, and it is becoming obvious that the excess synchronization of neurons that is characteristic for seizures can be linked to various calcium signaling pathways. These include immediate effects on membrane excitability by calcium influx through ion channels as well as delayed mechanisms that act through G-protein coupled pathways. Calcium signaling is able to cause hyperexcitability either by direct modulation of neuronal activity or indirectly through calcium-dependent gliotransmission. Furthermore, feedback mechanisms between mitochondrial calcium signaling and reactive oxygen species are able to cause neuronal cell death and seizures. Unravelling the complexity of calcium signaling in epileptogenesis is a daunting task, but it includes the promise to uncover formerly unknown targets for the development of new antiepileptic drugs.

  12. 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.

  13. Cell entry of enveloped viruses.

    PubMed

    Cosset, François-Loic; Lavillette, Dimitri

    2011-01-01

    Enveloped viruses penetrate their cell targets following the merging of their membrane with that of the cell. This fusion process is catalyzed by one or several viral glycoproteins incorporated on the membrane of the virus. These envelope glycoproteins (EnvGP) evolved in order to combine two features. First, they acquired a domain to bind to a specific cellular protein, named "receptor." Second, they developed, with the help of cellular proteins, a function of finely controlled fusion to optimize the replication and preserve the integrity of the cell, specific to the genus of the virus. Following the activation of the EnvGP either by binding to their receptors and/or sometimes the acid pH of the endosomes, many changes of conformation permit ultimately the action of a specific hydrophobic domain, the fusion peptide, which destabilizes the cell membrane and leads to the opening of the lipidic membrane. The comprehension of these mechanisms is essential to develop medicines of the therapeutic class of entry inhibitor like enfuvirtide (Fuzeon) against human immunodeficiency virus (HIV). In this chapter, we will summarize the different envelope glycoprotein structures that viruses develop to achieve membrane fusion and the entry of the virus. We will describe the different entry pathways and cellular proteins that viruses have subverted to allow infection of the cell and the receptors that are used. Finally, we will illustrate more precisely the recent discoveries that have been made within the field of the entry process, with a focus on the use of pseudoparticles. These pseudoparticles are suitable for high-throughput screenings that help in the development of natural or artificial inhibitors as new therapeutics of the class of entry inhibitors.

  14. Urinary calcium, sodium, and bone mass of young females.

    PubMed

    Matkovic, V; Ilich, J Z; Andon, M B; Hsieh, L C; Tzagournis, M A; Lagger, B J; Goel, P K

    1995-08-01

    Calcium is an important determinant of peak bone mass in young adults because of its influence on skeletal development during growth. Attainment of maximum peak bone mass requires optimal positive balance between calcium intake and obligatory losses of calcium, primarily in urine and feces. Urinary excretion is an important determinant of calcium retention in the body. Accordingly, the purpose of this study was to evaluate the influence of various nutrients on urinary calcium excretion, and to assess their impact on bone mass of young females, aged 8-13 y, during early puberty. The study was conducted in 381 healthy white females in pubertal stage 2. From each participant we collected basic anthropometric measurements, a 3-d food record, blood, a 24-h urine sample, and bone mass measurements of the total body and forearm by dual X-ray absorptiometry. Urinary sodium was found to be one of the most important determinants of urinary calcium excretion: [urinary calcium (mmol/d) = 0.01154 x urinary sodium (mmol/d) + 0.823], whereas calcium intake had relatively little impact: [urinary calcium (mmol/d) = 0.02252 x calcium intake (mmol/d) + 1.5261]. Urinary calcium was much higher at a calcium intake of approximately 37.5 mmol/d (1500 mg/d), supporting the notion that calcium is a threshold nutrient. Calcium intake had a significant positive influence on the bone mineral content and density of the whole body and radius shaft whereas urinary calcium had a negative influence, presumably by reducing calcium accretion into the skeleton.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. TMEM203 Is a Novel Regulator of Intracellular Calcium Homeostasis and Is Required for Spermatogenesis

    PubMed Central

    Shambharkar, Prashant B.; Bittinger, Mark; Latario, Brian; Xiong, ZhaoHui; Bandyopadhyay, Somnath; Davis, Vanessa; Lin, Victor; Yang, Yi; Valdez, Reginald; Labow, Mark A.

    2015-01-01

    Intracellular calcium signaling is critical for initiating and sustaining diverse cellular functions including transcription, synaptic signaling, muscle contraction, apoptosis and fertilization. Trans-membrane 203 (TMEM203) was identified here in cDNA overexpression screens for proteins capable of modulating intracellular calcium levels using activation of a calcium/calcineurin regulated transcription factor as an indicator. Overexpression of TMEM203 resulted in a reduction of Endoplasmic Reticulum (ER) calcium stores and elevation in basal cytoplasmic calcium levels. TMEM203 protein was localized to the ER and found associated with a number of ER proteins which regulate ER calcium entry and efflux. Mouse Embryonic Fibroblasts (MEFs) derived from Tmem203 deficient mice had reduced ER calcium stores and altered calcium homeostasis. Tmem203 deficient mice were viable though male knockout mice were infertile and exhibited a severe block in spermiogenesis and spermiation. Expression profiling studies showed significant alternations in expression of calcium channels and pumps in testes and concurrently Tmem203 deficient spermatocytes demonstrated significantly altered calcium handling. Thus Tmem203 is an evolutionarily conserved regulator of cellular calcium homeostasis, is required for spermatogenesis and provides a causal link between intracellular calcium regulation and spermiogenesis. PMID:25996873

  16. 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... the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  17. 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... the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  18. 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... the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  19. 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... the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  20. 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... the United States in the performance of their official duties, entry upon Naval Submarine Base,...

  1. Smoking, calcium, calcium antagonists, and aging.

    PubMed

    Nicita-Mauro, V

    1990-01-01

    Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action. PMID:2226675

  2. Calcium signals and oocyte maturation in marine invertebrates.

    PubMed

    Deguchi, Ryusaku; Takeda, Noriyo; Stricker, Stephen A

    2015-01-01

    In various oocytes and eggs of animals, transient elevations in cytoplasmic calcium ion concentrations are known to regulate key processes during fertilization and the completion of meiosis. However, whether or not calcium transients also help to reinitiate meiotic progression at the onset of oocyte maturation remains controversial. This article summarizes reports of calcium signals playing essential roles during maturation onset (=germinal vesicle breakdown, GVBD) in several kinds of marine invertebrate oocytes. Conversely, other data from the literature, as well as previously unpublished findings for jellyfish oocytes, fail to support the view that calcium signals are required for GVBD. In addition to assessing the effects of calcium transients on GVBD in marine invertebrate oocytes, the ability of maturing oocytes to enhance their calcium-releasing capabilities after GVBD is also reviewed. Furthermore, possible explanations are proposed for the contradictory results that have been obtained regarding calcium signals during oocyte maturation in marine invertebrates. PMID:26679945

  3. Calcium signals and oocyte maturation in marine invertebrates.

    PubMed

    Deguchi, Ryusaku; Takeda, Noriyo; Stricker, Stephen A

    2015-01-01

    In various oocytes and eggs of animals, transient elevations in cytoplasmic calcium ion concentrations are known to regulate key processes during fertilization and the completion of meiosis. However, whether or not calcium transients also help to reinitiate meiotic progression at the onset of oocyte maturation remains controversial. This article summarizes reports of calcium signals playing essential roles during maturation onset (=germinal vesicle breakdown, GVBD) in several kinds of marine invertebrate oocytes. Conversely, other data from the literature, as well as previously unpublished findings for jellyfish oocytes, fail to support the view that calcium signals are required for GVBD. In addition to assessing the effects of calcium transients on GVBD in marine invertebrate oocytes, the ability of maturing oocytes to enhance their calcium-releasing capabilities after GVBD is also reviewed. Furthermore, possible explanations are proposed for the contradictory results that have been obtained regarding calcium signals during oocyte maturation in marine invertebrates.

  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. 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...

  6. 10 CFR 1048.3 - Unauthorized entry.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ENTRY POLICY, CIVIL DISTURBANCE INTERVENTION AND DISASTER ASSISTANCE Installation Entry Policy § 809a.3... by the commander of a military installation or facility, which includes the parameters for authorized entry to or exit from a military installation, is legally enforceable against all persons whether or...

  8. 32 CFR 809a.3 - Unauthorized entry.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ENTRY POLICY, CIVIL DISTURBANCE INTERVENTION AND DISASTER ASSISTANCE Installation Entry Policy § 809a.3... by the commander of a military installation or facility, which includes the parameters for authorized entry to or exit from a military installation, is legally enforceable against all persons whether or...

  9. 19 CFR 159.7 - Rewarehouse entries.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Rewarehouse entries. 159.7 Section 159.7 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) LIQUIDATION OF DUTIES General Provisions § 159.7 Rewarehouse entries. The liquidation of the original warehouse entry shall be...

  10. 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...

  11. 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... 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...

  12. 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...

  13. 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...

  14. 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...

  15. Calcium supplements: benefits and risks.

    PubMed

    Reid, I R; Bristow, S M; Bolland, M J

    2015-10-01

    Calcium is an essential element in the diet, but there is continuing controversy regarding its optimal intake, and its role in the pathogenesis of osteoporosis. Most studies show little evidence of a relationship between calcium intake and bone density, or the rate of bone loss. Re-analysis of data from the placebo group from the Auckland Calcium Study demonstrates no relationship between dietary calcium intake and rate of bone loss over 5 years in healthy older women with intakes varying from <400 to >1500 mg day(-1) . Thus, supplements are not needed within this range of intakes to compensate for a demonstrable dietary deficiency, but might be acting as weak anti-resorptive agents via effects on parathyroid hormone and calcitonin. Consistent with this, supplements do acutely reduce bone resorption and produce small short-term effects on bone density, without evidence of a cumulative density benefit. As a result, anti-fracture efficacy remains unproven, with no evidence to support hip fracture prevention (other than in a cohort with severe vitamin D deficiency) and total fracture numbers are reduced by 0-10%, depending on which meta-analysis is considered. Five recent large studies have failed to demonstrate fracture prevention in their primary analyses. This must be balanced against an increase in gastrointestinal side effects (including a doubling of hospital admissions for these problems), a 17% increase in renal calculi and a 20-40% increase in risk of myocardial infarction. Each of these adverse events alone neutralizes any possible benefit in fracture prevention. Thus, calcium supplements appear to have a negative risk-benefit effect, and so should not be used routinely in the prevention or treatment of osteoporosis. PMID:26174589

  16. Calcium supplements: benefits and risks.

    PubMed

    Reid, I R; Bristow, S M; Bolland, M J

    2015-10-01

    Calcium is an essential element in the diet, but there is continuing controversy regarding its optimal intake, and its role in the pathogenesis of osteoporosis. Most studies show little evidence of a relationship between calcium intake and bone density, or the rate of bone loss. Re-analysis of data from the placebo group from the Auckland Calcium Study demonstrates no relationship between dietary calcium intake and rate of bone loss over 5 years in healthy older women with intakes varying from <400 to >1500 mg day(-1) . Thus, supplements are not needed within this range of intakes to compensate for a demonstrable dietary deficiency, but might be acting as weak anti-resorptive agents via effects on parathyroid hormone and calcitonin. Consistent with this, supplements do acutely reduce bone resorption and produce small short-term effects on bone density, without evidence of a cumulative density benefit. As a result, anti-fracture efficacy remains unproven, with no evidence to support hip fracture prevention (other than in a cohort with severe vitamin D deficiency) and total fracture numbers are reduced by 0-10%, depending on which meta-analysis is considered. Five recent large studies have failed to demonstrate fracture prevention in their primary analyses. This must be balanced against an increase in gastrointestinal side effects (including a doubling of hospital admissions for these problems), a 17% increase in renal calculi and a 20-40% increase in risk of myocardial infarction. Each of these adverse events alone neutralizes any possible benefit in fracture prevention. Thus, calcium supplements appear to have a negative risk-benefit effect, and so should not be used routinely in the prevention or treatment of osteoporosis.

  17. Measurement of shear stress-mediated intracellular calcium dynamics in human dermal lymphatic endothelial cells

    PubMed Central

    Jafarnejad, M.; Cromer, W. E.; Kaunas, R. R.; Zhang, S. L.; Zawieja, D. C.

    2015-01-01

    The shear stress applied to lymphatic endothelial cells (LEC) by lymph flow changes dramatically under normal conditions as well as in response to disease conditions and immune reactions. In general, LEC are known to regulate the contraction frequency and strength of lymphatic pumping in response to shear stress. Intracellular calcium concentration ([Ca2+]i) is an important factor that regulates lymphatic contraction characteristics. In this study, we measured changes in the [Ca2+]i under different shear stress levels and determined the source of this calcium signal. Briefly, human dermal LEC were cultured in custom-made microchannels for 3 days before loading with 2 µM fura-2 AM, a ratiometric calcium dye to measure [Ca2+]i. Step changes in shear stress resulted in a rapid increase in [Ca2+]i followed by a gradual return to the basal level and sometimes below the initial baseline (45.2 ± 2.2 nM). The [Ca2+]i reached a peak at 126.2 ± 5.6 nM for 10 dyn/cm2 stimulus, whereas the peak was only 71.8 ± 5.4 nM for 1 dyn/cm2 stimulus, indicating that the calcium signal depends on the magnitude of shear stress. Removal of the extracellular calcium from the buffer or pharmocological blockade of calcium release-activated calcium (CRAC) channels significantly reduced the peak [Ca2+]i, demonstrating a role of extracellular calcium entry. Inhibition of endoplasmic reticulum (ER) calcium pumps showed the importance of intracellular calcium stores in the initiation of this signal. In conclusion, we demonstrated that the shear-mediated calcium signal is dependent on the magnitude of the shear and involves ER store calcium release and extracellular calcium entry. PMID:25617358

  18. Planetary-Entry Gas Dynamics

    NASA Astrophysics Data System (ADS)

    Gnoffo, Peter A.

    A review of planetary-entry gas dynamics is presented. Evolution of a blunt-body flowfield from a free molecular flow environment to a continuum environment is described. Simulations of near-wake flow phenomena, important for defining aerobrake payload environments, are also discussed. Some topics to be highlighted include aerodynamic coefficient predictions with emphasis on high-temperature gas effects; surface heating and temperature predictions for thermal protection system (TPS) design in a high-temperature, thermochemical nonequilibrium environment; and thermochemical models required for numerical flow simulation. Recent applications involving atmospheric entry into Jupiter (Galileo), Mars (Pathfinder and Global Surveyor), and a planned mission in which dust from the tail of a comet will be returned to Earth (Stardust) will provide context for this discussion.

  19. Highly constrained entry trajectory generation

    NASA Astrophysics Data System (ADS)

    Xie, Yu; Liu, Luhua; Tang, Guojian; Zheng, Wei

    2013-07-01

    An entry trajectory planning algorithm that generates flyable trajectories satisfying waypoints, no-fly zones, and other path and terminal constraints is presented. The algorithm tactically divides the entry trajectory into the initial and glide phases. In the initial phase, a nominal angle of attack and a constant bank angle are used to generate the 3-D trajectory. In the glide phase, a planner is developed based on the evolved acceleration guidance logic for entry (EAGLE). The planner is divided into a longitudinal sub-planner and a lateral sub-planner. For longitudinal planning, the drag-energy profile is represented as five piecewise linear functions of the normalized non-conventional energy to make it consistent with both the desired trajectory length and the lateral maneuverability required to meet waypoint and no-fly zone constraints. The longitudinal sub-planner determines the magnitude of the bank angle, whereas the lateral sub-planner determines the appropriate sign of the bank angle for passing waypoints, avoiding no-fly zones, and minimizing the final heading error. The longitudinal and lateral sub-planners are iteratively employed until all path and terminal constraints are satisfied. Then, a tracker is employed to follow both the reference drag acceleration and the heading angle profiles to generate a feasible closed-loop entry trajectory. The approach is tested using the Common Aero Vehicle model. Simulations demonstrate that the generated trajectories can pass the predetermined waypoints, avoid no-fly zones, and achieve the desired target conditions within allowable tolerances.

  20. Cellular receptors and HCV entry.

    PubMed

    Flint, Mike; Tscherne, Donna M

    2009-01-01

    After attachment to specific receptors on the surfaces of target cells, hepatitis C virus (HCV) particles are thought to be internalized to endosomes, where low pH induces fusion between the viral and cellular membranes, delivering the HCV genome into the cytoplasm. Here, we describe methods to study the early events in HCV infection; the interactions with cellular receptors and the mechanism of entry.

  1. 19 CFR 143.36 - Form of immediate delivery, entry and entry summary.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Form of immediate delivery, entry and entry summary. (a) Electronic form of data. If Customs determines that the immediate delivery, entry or entry summary data is satisfactory under §§ 143.34 and 143.35... responsible for the accuracy of the data submitted electronically to the same extent as if the documents...

  2. 19 CFR 141.64 - Review and correction of entry and entry summary documentation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Review and correction of entry and entry summary documentation. 141.64 Section 141.64 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Presentation of Entry Papers §...

  3. 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.

  4. 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.

  5. 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.

  6. Entry decisions in the generic pharmaceutical industry.

    PubMed

    Morton, F M

    1999-01-01

    Data on all generic drug entries in the period 1984-1994 are used to estimate which markets heterogeneous potential entrants will decide to enter. I find that organizational experience predicts entry. Firms tend to enter markets with supply and demand characteristics similar to the firm's existing drugs. Larger revenue markets, markets with more hospital sales, and products that treat chronic conditions attract more entry. The simultaneous nature of entry leads to an additional interpretation: specialization is profitable because of the severe risk to profits when a market is "overentered." However, I am unable to make any conclusions about the efficiency of entry decisions. PMID:10558596

  7. Characterizing Functional Domains for TIM-Mediated Enveloped Virus Entry

    PubMed Central

    Moller-Tank, Sven; Albritton, Lorraine M.; Rennert, Paul D.

    2014-01-01

    ABSTRACT T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members were recently identified as phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance entry of Ebola virus (EBOV) and other viruses by binding PtdSer on the viral envelope, concentrating virus on the cell surface, and promoting subsequent internalization. The PtdSer-binding activity of the immunoglobulin-like variable (IgV) domain is essential for both virus binding and internalization by TIM-1. However, TIM-3, whose IgV domain also binds PtdSer, does not effectively enhance virus entry, indicating that other domains of TIM proteins are functionally important. Here, we investigate the domains supporting enhancement of enveloped virus entry, thereby defining the features necessary for a functional PVEER. Using a variety of chimeras and deletion mutants, we found that in addition to a functional PtdSer-binding domain PVEERs require a stalk domain of sufficient length, containing sequences that promote an extended structure. Neither the cytoplasmic nor the transmembrane domain of TIM-1 is essential for enhancing virus entry, provided the protein is still plasma membrane bound. Based on these defined characteristics, we generated a mimic lacking TIM sequences and composed of annexin V, the mucin-like domain of α-dystroglycan, and a glycophosphatidylinositol anchor that functioned as a PVEER to enhance transduction of virions displaying Ebola, Chikungunya, Ross River, or Sindbis virus glycoproteins. This identification of the key features necessary for PtdSer-mediated enhancement of virus entry provides a basis for more effective recognition of unknown PVEERs. IMPORTANCE T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members are recently identified phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance virus entry by binding the phospholipid, PtdSer, present on the viral

  8. 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.

  9. Structural aspects of calcium-release activated calcium channel function

    PubMed Central

    Stathopulos, Peter B; Ikura, Mitsuhiko

    2013-01-01

    Store-operated calcium (Ca2+) entry is the process by which molecules located on the endo/sarcoplasmic reticulum (ER/SR) respond to decreased luminal Ca2+ levels by signaling Ca2+ release activated Ca2+ channels (CRAC) channels to open on the plasma membrane (PM). This activation of PM CRAC channels provides a sustained cytosolic Ca2+ elevation associated with myriad physiological processes. The identities of the molecules which mediate SOCE include stromal interaction molecules (STIMs), functioning as the ER/SR luminal Ca2+ sensors, and Orai proteins, forming the PM CRAC channels. This review examines the current available high-resolution structural information on these CRAC molecular components with particular focus on the solution structures of the luminal STIM Ca2+ sensing domains, the crystal structures of cytosolic STIM fragments, a closed Orai hexameric crystal structure and a structure of an Orai1 N-terminal fragment in complex with calmodulin. The accessible structural data are discussed in terms of potential mechanisms of action and cohesiveness with functional observations. PMID:24213636

  10. Calcium hydroxyapatite fillers.

    PubMed

    Tansavatdi, Kristina; Mangat, Devinder S

    2011-12-01

    Calcium hydroxyapatite fillers have unique advantages over other fillers in regards to duration of action and volume of product required for augmentation, especially in the midface and lower face. In this article, we describe our experience with calcium hydroxyapatite fillers and compare them with other available filler products.

  11. Management of calcium channel antagonist overdose.

    PubMed

    Salhanick, Steven D; Shannon, Michael W

    2003-01-01

    Calcium channel antagonists are used primarily for the treatment of hypertension and tachyarrhythmias. Overdose of calcium channel antagonists can be lethal. Calcium channel antagonists act at the L-type calcium channels primarily in cardiac and vascular smooth muscle preventing calcium influx into cells with resultant decreases in vascular tone and cardiac inotropy and chronotropy. The L-type calcium channel is a complex structure and is thus affected by a large number of structurally diverse antagonists. In the setting of overdose, patients may experience vasodilatation and bradycardia leading to a shock state. Patients may also be hyperglycaemic and acidotic due to the blockade of L-type calcium channels in the pancreatic islet cells that affect insulin secretion. Aggressive therapy is warranted in the setting of toxicity. Gut decontamination with charcoal, or whole bowel irrigation or multiple-dose charcoal in the setting of extended-release products is indicated. Specific antidotes include calcium salts, glucagon and insulin. Calcium salts may be given in bolus doses or may be employed as a continuous infusion. Care should be exercised to avoid the administration of calcium in the setting of concomitant digoxin toxicity. Insulin administration has been used effectively to increase cardiac inotropy and survival. The likely mechanism involves a shift to carbohydrate metabolism in the setting of decreased availability of carbohydrates due to decreased insulin secretion secondary to blockade of calcium channels in pancreatic islet cells. Glucose should be administered as well to maintain euglycaemia. Supportive care including the use of phosphodiesterase inhibitors, adrenergic agents, cardiac pacing, balloon pump or extracorporeal bypass is frequently indicated if antidotal therapy is not effective. Careful evaluation of asymptomatic patients, including and electrocardiogram and a period of observation, is indicated. Patients ingesting a nonsustained

  12. 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.

  13. Calcium signaling in trypanosomatid parasites.

    PubMed

    Docampo, Roberto; Huang, Guozhong

    2015-03-01

    Calcium ion (Ca(2+)) is an important second messenger in trypanosomatids and essential for their survival although prolonged high intracellular Ca(2+) levels lead to cell death. As other eukaryotic cells, trypanosomes use two sources of Ca(2+) for generating signals: Ca(2+) release from intracellular stores and Ca(2+) entry across the plasma membrane. Ca(2+) release from intracellular stores is controlled by the inositol 1,4,5-trisphosphate receptor (IP3R) that is located in acidocalcisomes, acidic organelles that are the primary Ca(2+) reservoir in these cells. A plasma membrane Ca(2+)-ATPase controls the cytosolic Ca(2+) levels and a number of pumps and exchangers are responsible for Ca(2+) uptake and release from intracellular compartments. The trypanosomatid genomes contain a wide variety of signaling and regulatory proteins that bind Ca(2+) as well as many Ca(2+)-binding proteins that await further characterization. The mitochondrial Ca(2+) transporters of trypanosomatids have an important role in the regulation of cell bioenergetics and flagellar Ca(2+) appears to have roles in sensing the environment. In trypanosomatids in which an intracellular life cycle is present, Ca(2+) signaling is important for host cell invasion. PMID:25468729

  14. Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum.

    PubMed

    Budu, Alexandre; Gomes, Mayrim M; Melo, Pollyana M; El Chamy Maluf, Sarah; Bagnaresi, Piero; Azevedo, Mauro F; Carmona, Adriana K; Gazarini, Marcos L

    2016-03-01

    Calcium and calmodulin (CaM) are important players in eukaryote cell signaling. In the present study, by using a knockin approach, we demonstrated the expression and localization of CaM in all erythrocytic stages of Plasmodium falciparum. Under extracellular Ca(2+)-free conditions, calmidazolium (CZ), a potent CaM inhibitor, promoted a transient cytosolic calcium ([Ca(2+)]cyt) increase in isolated trophozoites, indicating that CZ mobilizes intracellular sources of calcium. In the same extracellular Ca(2+)-free conditions, the [Ca(2+)]cyt rise elicited by CZ treatment was ~3.5 fold higher when the endoplasmic reticulum (ER) calcium store was previously depleted ruling out the mobilization of calcium from the ER by CZ. The effects of the Ca(2+)/H(+) ionophore ionomycin (ION) and the Na(+)/H(+) ionophore monensin (MON) suggest that the [Ca(2+)]cyt-increasing effect of CZ is driven by the removal of Ca(2+) from at least one Ca(2+)-CaM-related (CaMR) protein as well as by the mobilization of Ca(2+) from intracellular acidic calcium stores. Moreover, we showed that the mitochondrion participates in the sequestration of the cytosolic Ca(2+) elicited by CZ. Finally, the modulation of membrane Ca(2+) channels by CZ and thapsigargin (THG) was demonstrated. The opened channels were blocked by the unspecific calcium channel blocker Co(2+) but not by 2-APB (capacitative calcium entry inhibitor) or nifedipine (L-type Ca(2+) channel inhibitor). Taken together, the results suggested that one CaMR protein is an important modulator of calcium signaling and homeostasis during the Plasmodium intraerythrocytic cell cycle, working as a relevant intracellular Ca(2+) reservoir in the parasite.

  15. 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.

  16. Architecture of the Mitochondrial Calcium Uniporter

    PubMed Central

    Oxenoid, Kirill; Dong, Ying; Cao, Chan; Cui, Tanxing; Sancak, Yasemin; Markhard, Andrew L.; Grabarek, Zenon; Kong, Liangliang; Liu, Zhijun; Ouyang, Bo; Cong, Yao; Mootha, Vamsi K.; Chou, James J.

    2016-01-01

    Mitochondria from multiple, eukaryotic clades uptake and buffer large amounts of calcium (Ca2+) via an inner membrane transporter called the uniporter. Early studies demonstrated that this transport requires a mitochondrial membrane potential and that the uniporter is itself Ca2+ activated, and blocked by ruthenium red or Ru3601. Later, electrophysiological studies demonstrated that the uniporter is an ion channel with remarkably high conductance and selectivity2. Ca2+ entry into mitochondria is also known to activate the TCA cycle and appears to be critical for matching ATP production in mitochondria with its cytosolic demand3. MCU (mitochondrial calcium uniporter) is the pore forming and Ca2+ conducting subunit of the uniporter, but its primary sequence does not resemble any calcium channel known to date. Here, we report the structure of the core region of MCU, determined using nuclear magnetic resonance (NMR) and electron microscopy (EM). MCU is a homo-oligomer with the second transmembrane helix forming a hydrophilic pore across the membrane. The channel assembly represents a new solution of ion channel architecture and is stabilized by a coiled coil motif protruding in the mitochondrial matrix. The critical DxxE motif forms the pore entrance featuring two carboxylate rings, which appear to be the selectivity filter based on the ring dimensions and functional mutagenesis. To our knowledge, this is one of the largest structures characterized by NMR, which provides a structural blueprint for understanding the function of this channel. PMID:27135929

  17. 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.

  18. Optimal firm growth under the threat of entry

    PubMed Central

    Kort, Peter M.; Wrzaczek, Stefan

    2015-01-01

    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. PMID:26435573

  19. The activation wave of calcium in the ascidian egg and its role in ooplasmic segregation

    PubMed Central

    1990-01-01

    We have studied egg activation and ooplasmic segregation in the ascidian Phallusia mammillata using an imaging system that let us simultaneously monitor egg morphology and calcium-dependent aequorin luminescence. After insemination, a wave of highly elevated free calcium crosses the egg with a peak velocity of 8-9 microns/s. A similar wave is seen in egg fertilized in the absence of external calcium. Artificial activation via incubation with WGA also results in a calcium wave, albeit with different temporal and spatial characteristics than in sperm-activated eggs. In eggs in which movement of the sperm nucleus after entry is blocked with cytochalasin D, the sperm aster is formed at the site where the calcium wave had previously started. This indicates that the calcium wave starts where the sperm enters. In 70% of the eggs, the calcium wave starts in the animal hemisphere, which confirms previous observations that there is a preference for sperm to enter this part of the egg (Speksnijder, J. E., L. F. Jaffe, and C. Sardet. 1989. Dev. Biol. 133:180-184). About 30-40 s after the calcium wave starts, a slower (1.4 microns/s) wave of cortical contraction starts near the animal pole. It carries the subcortical cytoplasm to a contraction pole, which forms away from the side of sperm entry and up to 50 degrees away from the vegetal pole. We propose that the point of sperm entry may affect the direction of ooplasmic segregation by causing it to tilt away from the vegetal pole, presumably via some action of the calcium wave. PMID:2335565

  20. The activation wave of calcium in the ascidian egg and its role in ooplasmic segregation.

    PubMed

    Speksnijder, J E; Sardet, C; Jaffe, L F

    1990-05-01

    We have studied egg activation and ooplasmic segregation in the ascidian Phallusia mammillata using an imaging system that let us simultaneously monitor egg morphology and calcium-dependent aequorin luminescence. After insemination, a wave of highly elevated free calcium crosses the egg with a peak velocity of 8-9 microns/s. A similar wave is seen in egg fertilized in the absence of external calcium. Artificial activation via incubation with WGA also results in a calcium wave, albeit with different temporal and spatial characteristics than in sperm-activated eggs. In eggs in which movement of the sperm nucleus after entry is blocked with cytochalasin D, the sperm aster is formed at the site where the calcium wave had previously started. This indicates that the calcium wave starts where the sperm enters. In 70% of the eggs, the calcium wave starts in the animal hemisphere, which confirms previous observations that there is a preference for sperm to enter this part of the egg (Speksnijder, J. E., L. F. Jaffe, and C. Sardet. 1989. Dev. Biol. 133:180-184). About 30-40 s after the calcium wave starts, a slower (1.4 microns/s) wave of cortical contraction starts near the animal pole. It carries the subcortical cytoplasm to a contraction pole, which forms away from the side of sperm entry and up to 50 degrees away from the vegetal pole. We propose that the point of sperm entry may affect the direction of ooplasmic segregation by causing it to tilt away from the vegetal pole, presumably via some action of the calcium wave.

  1. [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.

  2. 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.

  3. Receptor usage and cell entry of porcine epidemic diarrhea coronavirus.

    PubMed

    Liu, Chang; Tang, Jian; Ma, Yuanmei; Liang, Xueya; Yang, Yang; Peng, Guiqing; Qi, Qianqian; Jiang, Shibo; Li, Jianrong; Du, Lanying; Li, Fang

    2015-06-01

    Porcine epidemic diarrhea coronavirus (PEDV) has significantly damaged America's pork industry. Here we investigate the receptor usage and cell entry of PEDV. PEDV recognizes protein receptor aminopeptidase N from pig and human and sugar coreceptor N-acetylneuraminic acid. Moreover, PEDV infects cells from pig, human, monkey, and bat. These results support the idea of bats as an evolutionary origin for PEDV, implicate PEDV as a potential threat to other species, and suggest antiviral strategies to control its spread. PMID:25787280

  4. Calcium and iron absorption: mechanism of action and nutritional importance.

    PubMed

    Hallberg, L; Rossander-Hultén, L; Brune, M; Gleerup, A

    1992-05-01

    We investigated the inhibitory effect of calcium on iron absorption in 57 human subjects. Three studies suggested that the effect is not located in the gastrointestinal tract. The presence of phytate in a meal and formation of calcium-iron-phytate complexes is not a prerequisite for the inhibition. The relative increase in iron absorption by ascorbic acid was the same in meals with and without calcium, suggesting that calcium did not influence the balance between enhancing and inhibiting ligands in the gastrointestinal lumen. No inhibiting effect on iron absorption was seen when adding 3 mg calcium to 0.01 mg iron (molar ratio Ca/Fe = 420). Previous studies showing a marked inhibition by calcium had a lower molar ratio, but greater amounts of calcium were given. This suggests that a minimal concentration of calcium is needed to achieve an effect. The present results indirectly support our original hypothesis that the inhibitory effect of calcium on iron absorption is situated within the intestinal mucosal cells. The practical nutritional implications of the inhibitory effect of calcium are considerable since addition of milk, milkshake or cheese to common meals such as pizza or hamburger meals reduced iron absorption by 50-60%. It is recommended to reduce the intake of dairy products with the main meals providing most of the dietary iron, especially for those having the highest iron requirements i.e. children, teenagers and women at childbearing age.

  5. 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

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. Text entry on handheld computers by older users.

    PubMed

    Wright, P; Bartram, C; Rogers, N; Emslie, H; Evans, J; Wilson, B; Belt, S

    2000-06-01

    Small pocket computers offer great potential in workplaces where mobility is needed to collect data or access reference information while carrying out tasks such as maintenance or customer support. This paper reports on three studies examining the hypothesis that data entry by older workers is easier when the pocket computer has a physical keyboard, albeit a small one, rather than a touch-screen keyboard. Using a counter-balanced, within-subjects design the accuracy and speed with which adults over 55 years of age could make or modify short text entries was measured for both kinds of pocket computer. The keyboard computer was the Hewlett Packard 360LX (HP), but the touch-screen computers varied across studies (experiment 1: Apple Newton and PalmPilot; experiment 2: Philips Nino; experiment 3: Casio E10). All studies showed significant decrements in accuracy and speed when entering text via the touch-screen. Across studies, most participants preferred using the HP's small physical keyboard. Even after additional practice with the touch screen (experiments 2 and 3) many entries still contained errors. Experiment 3 showed that younger people were faster but not more accurate than older people at using the touch-screen keyboard. It is concluded that satisfactory text entry on palm-size computers awaits improvements to the touch-screen keyboard or alternative input methods such as handwriting or voice. Interface developments that assist older people typically benefit younger users too. PMID:10902881

  11. 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... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  12. 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... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  13. 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... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  14. 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... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  15. 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... Commanding Officer, Naval Submarine Base, Bangor, 1100 Hunley Road, Silverdale, WA 98315. (b) Each...

  16. Meteorite Atmospheric Entry Reproduced in Plasmatron

    NASA Astrophysics Data System (ADS)

    Pittarello, L.; McKibbin, S.; Goderis, S.; Soens, B.; Bariselli, F.; Barros Dias, B. R.; Zavalan, F. L.; Magin, T.; Claeys, Ph.

    2016-08-01

    Plasmatron facility allows experimental conditions that reproduce atmospheric entry of meteorites. Tests on basalt, as meteorite analogue, have been performed. Preliminary results have highlighted melting and evaporation effects.

  17. 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.

  18. Cytosolic free calcium in platelets: relationships to blood pressure and indices of systemic calcium metabolism.

    PubMed

    Hvarfner, A; Larsson, R; Mörlin, C; Rastad, J; Wide, L; Akerström, G; Ljunghall, S

    1988-01-01

    Relationships between cytosolic free calcium ([Ca2+]i) in platelets, indices of systemic calcium metabolism and blood pressure were examined in 86 subjects; 29 patients with untreated and 29 patients with treated essential hypertension, six patients with borderline hypertension and 22 healthy reference subjects. In order to analyse interactions between the variables, multivariate statistical analyses were employed. The patients with untreated hypertension had higher [Ca2+]i values in non-activated platelets (P = 0.04) and lower levels of plasma ionized calcium (P = 0.02) than the reference subjects. In multivariate models analysing platelet [Ca2+]i mean blood pressure (MBP), plasma ionized calcium, serum parathyroid hormone (PTH) and body mass index (BMI), the relationship between platelet [Ca2+]i and blood pressure was attenuated (P = 0.13), whereas the inverse relationships between plasma ionized calcium and MBP (P = 0.01) and between platelet [Ca2+]i and serum PTH (P = 0.06) seen in univariate analyses persisted. According to the multivariate models the [Ca2+]i value explained only 5% of the MBP variability. Thus, the data from this investigation do not support a close relationship between basal platelet [Ca2+]i and blood pressure. The inverse relationship between plasma ionized calcium and blood pressure, independent of platelet [Ca2+]i and serum PTH, suggests a direct interaction between plasma ionized calcium and blood pressure regulation.

  19. [Calcium-supplementation in pregnancy--is it a must?].

    PubMed

    Beinder, E

    2007-05-01

    The pregnant woman's body provides daily doses between 50 and 330 mg to support the developing fetal skeleton. This high fetal demand for calcium in pregnancy is facilitated by profound physiological interactions between mother and fetus. The D-A-CH organization (which represents the German, Austrian and Swiss Nutrition Offices) and the Institute of Medicine (IOM) of the US recommend a daily consumption of 1000 mg calcium for pregnant and lactating women at an age over 19 years. The average consumption of calcium in western countries is about 800 mg in young women. Therefore calcium consumption in pregnancy should be encouraged, especially during the second and third trimester of pregnancy and during lactation. Proper calcium consumption can be attained by diet with healthy nourishment including 3-4 snacks of milk or milk-derived products such as yogurt and cheese and calcium-rich mineral waters. In these women calcium-supplementation in pregnancy is not necessary. In women with chronic autoimmunologic disorders, low-molecular-weight-heparin therapy during pregnancy, lactose intolerance or in women who prefer to skip milk and milk products due to personal preference the supplementation of 500 to 1000 mg calcium in addition to dietary measures is recommended. Calcium supplementation in pregnancy has been associated with a reduced risk of pregnancy-induced hypertension, but this effect is only seen in persons with a low basal calcium intake. There are reports in literature that calcium supplementation in pregnancy protects against low-birthweight in newborns, which is defined as a birthweight of < 2500 g or that calcium supplementation lowers offspring blood pressure thus helping to prevent hypertension in the next generation. These reports are either preliminary or are not applicable to the Swiss population or need confirmation. Therefore calcium supplementation is only recommended in order to achieve a daily uptake of at least 1000 mg/day in pregnant women.

  20. 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.

  1. Calcium channel blocker overdose

    MedlinePlus

    ... Goldschlager N. Cardiovascular toxicology. In: Shannon MW, Borron SW, Burns MJ, eds. Haddad and Winchester's Clinical Management ... SD. Calcium channel antagonists. In: Shannon MW, Borron SW, Burns MJ, eds. Haddad and Winchester's Clinical Management ...

  2. Calcium blood test

    MedlinePlus

    ... failure Low blood level of albumin Liver disease Magnesium deficiency Pancreatitis Vitamin D deficiency ... PA: Elsevier; 2013:chap 66. Leone KA. Calcium, magnesium, and phosphorus. In: Adams JG, ed. Emergency Medicine: ...

  3. Calcium-mediated inactivation of calcium current in Paramecium.

    PubMed

    Brehm, P; Eckert, R; Tillotson, D

    1980-09-01

    1. The Ca current seen in response to depolarization was investigated in Paramecium caudatum under voltage clamp. Inactivation of the current was measured with the double pulse method; a fixed test pulse of an amplitude sufficient to evoke maximal inward current was preceded by a conditioning pulse of variable amplitude (0-120 mV).2. The amplitude of the current recorded during the test pulse was related to the potential of the conditioning pulse. Reduction of test pulse current was taken as an index of Ca current inactivation. The current recorded during a test pulse showed a progressive decrease to a minimum as the potential of the conditioning pulse approached +10 to +30 mV. Further increase in conditioning pulse amplitude was accompanied by a progressive restoration of the test pulse current. Conditioning pulses near the calcium equilibrium potential had only a slight inactivating effect on the test pulse current.3. Injection of a mixture of Cs and TEA which blocked late outward current had essentially no effect on the inward current or its inactivation.4. Elevation of external Ca from 0.5 to 5 mM was accompanied by increased inactivation of the test pulse current. The enhanced inactivation of the test pulse current was approximately proportional to the increase in current recorded during the conditioning pulse.5. Following injection of the Ca chelating agent, EGTA, the inactivation of the test pulse current was diminished; in addition, the transient inward current relaxed slightly more slowly, and the transient was followed by a steady net inward current.6. The time course of recovery from inactivation in the double pulse experiment approximated a single exponential having a time constant of 80-110 msec. Injection of EGTA shortened the time constant by as much as 50%.7. It is concluded that interference with the entry of Ca or enhanced removal of intracellular free Ca(2+) interferes with the process of Ca current inactivation, while enhanced entry of Ca

  4. 19 CFR 10.112 - Filing free entry documents or reduced duty documents after entry.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., form, or statement required to be filed in connection with the entry is not filed at the time of the... time prior to liquidation of the entry or, if the entry was liquidated, before the liquidation becomes final. See § 113.43(c) of this chapter for satisfaction of the bond and cancellation of the bond...

  5. 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.

  6. Herpesvirus Entry into Host Cells Mediated by Endosomal Low pH.

    PubMed

    Nicola, Anthony V

    2016-09-01

    Herpesviral pathogenesis stems from infection of multiple cell types including the site of latency and cells that support lytic replication. Herpesviruses utilize distinct cellular pathways, including low pH endocytic pathways, to enter different pathophysiologically relevant target cells. This review details the impact of the mildly acidic milieu of endosomes on the entry of herpesviruses, with particular emphasis on herpes simplex virus 1 (HSV-1). Epithelial cells, the portal of primary HSV-1 infection, support entry via low pH endocytosis mechanisms. Mildly acidic pH triggers reversible conformational changes in the HSV-1 class III fusion protein glycoprotein B (gB). In vitro treatment of herpes simplex virions with a similar pH range inactivates infectivity, likely by prematurely activating the viral entry machinery in the absence of a target membrane. How a given herpesvirus mediates both low pH and pH-independent entry events is a key unresolved question. PMID:27126894

  7. 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.

  8. 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 obtain a…

  9. Calcium channel structural determinants of synaptic transmission between identified invertebrate neurons.

    PubMed

    Spafford, J David; Munno, David W; Van Nierop, Pim; Feng, Zhong-Ping; Jarvis, Scott E; Gallin, Warren J; Smit, August B; Zamponi, Gerald W; Syed, Naweed I

    2003-02-01

    We report here that unlike what was suggested for many vertebrate neurons, synaptic transmission in Lymnaea stagnalis occurs independent of a physical interaction between presynaptic calcium channels and a functional complement of SNARE proteins. Instead, synaptic transmission in Lymnaea requires the expression of a C-terminal splice variant of the Lymnaea homolog to mammalian N- and P/Q-type calcium channels. We show that the alternately spliced region physically interacts with the scaffolding proteins Mint1 and CASK, and that synaptic transmission is abolished following RNA interference knockdown of CASK or after the injection of peptide sequences designed to disrupt the calcium channel-Mint1 interactions. Our data suggest that Mint1 and CASK may serve to localize the non-L-type channels at the active zone and that synaptic transmission in invertebrate neurons utilizes a mechanism for optimizing calcium entry, which occurs independently of a physical association between calcium channels and SNARE proteins.

  10. 46 CFR 147A.25 - Entry.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... During Fumigation § 147A.25 Entry. (a) No person may enter the spaces that immediately adjoin the space that is fumigated during fumigation unless entry is for emergency purposes or the space is tested and... space that is fumigated or any adjoining spaces during fumigation unless he wears the...

  11. 46 CFR 147A.25 - Entry.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... During Fumigation § 147A.25 Entry. (a) No person may enter the spaces that immediately adjoin the space that is fumigated during fumigation unless entry is for emergency purposes or the space is tested and... space that is fumigated or any adjoining spaces during fumigation unless he wears the...

  12. 46 CFR 147A.25 - Entry.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... During Fumigation § 147A.25 Entry. (a) No person may enter the spaces that immediately adjoin the space that is fumigated during fumigation unless entry is for emergency purposes or the space is tested and... space that is fumigated or any adjoining spaces during fumigation unless he wears the...

  13. 32 CFR 245.27 - Data entry.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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 data... 32 National Defense 2 2010-07-01 2010-07-01 false Data entry. 245.27 Section 245.27...

  14. 32 CFR 245.27 - Data entry.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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 data... 32 National Defense 2 2014-07-01 2014-07-01 false Data entry. 245.27 Section 245.27...

  15. 32 CFR 245.27 - Data entry.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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 data... 32 National Defense 2 2011-07-01 2011-07-01 false Data entry. 245.27 Section 245.27...

  16. 32 CFR 245.27 - Data entry.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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 data... 32 National Defense 2 2013-07-01 2013-07-01 false Data entry. 245.27 Section 245.27...

  17. 27 CFR 19.306 - Entry.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Production of Distilled Spirits Rules for Production of Spirits § 19.306 Entry. (a) Following completion of the production gauge, a proprietor must make the... proprietor may use the production gauge as the entry gauge when spirits are: (1) Deposited for storage...

  18. 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...

  19. 19 CFR 163.3 - Entry records.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Entry records. 163.3 Section 163.3 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) RECORDKEEPING § 163.3 Entry records. Any person described in § 163.2(a) with reference to...

  20. 19 CFR 163.3 - Entry records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry records. 163.3 Section 163.3 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) RECORDKEEPING § 163.3 Entry records. Any person described in § 163.2(a) with reference to...

  1. 19 CFR 163.3 - Entry records.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Entry records. 163.3 Section 163.3 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) RECORDKEEPING § 163.3 Entry records. Any person described in § 163.2(a) with reference to...

  2. 19 CFR 163.3 - Entry records.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Entry records. 163.3 Section 163.3 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) RECORDKEEPING § 163.3 Entry records. Any person described in § 163.2(a) with reference to...

  3. Maternal calcium metabolic stress and fetal growth123

    PubMed Central

    Scholl, Theresa O; Chen, Xinhua; Stein, T Peter

    2014-01-01

    Background: Suboptimal maternal calcium intake and vitamin D status may or may not adversely influence fetal growth. Objective: It was hypothesized that maternal calcium metabolic stress in early pregnancy, rather than suboptimal calcium intake or insufficient vitamin D, influences the risk of small-for-gestational-age (SGA) births and other aspects of fetal growth. Stress to calcium metabolism was defined as elevated intact parathyroid hormone (PTH) (>62 pg/mL) accompanied by a very low calcium intake [<60% of the Estimated Average Requirement (EAR)] or insufficient 25-hydroxyvitamin D [25(OH)D] (<20 ng/mL). Design: This was a prospective cohort study of 1116 low-income and minority gravidae at entry to care of 13.8 ± 5.6 wk (mean ± SD). Results: The PTH concentration depended on circulating 25(OH)D and total calcium intake. When 25(OH)D was insufficient, even a high calcium intake (which equaled or exceeded the Recommended Dietary Allowance) was unable to maintain PTH or to moderate the proportion of patients with an elevated PTH. When examined one at a time, very low calcium intake (<60% of EAR), very low 25(OH)D (<12 ng/mL), and elevated PTH (>62 pg/mL) each had a small but significant association with birth weight. Elevated PTH was also related to birth length and risk of SGA birth. Elevated PTH accompanied by insufficient 25(OH)D or very low calcium intake was associated with a 2- to 3-fold increased risk of SGA birth and a significantly lower birth weight, birth length, and head circumference, even after women who developed preeclampsia were excluded. Infants born to gravidae with insufficient 25(OH)D or very low calcium intake without elevated PTH or with elevated PTH alone were unaffected. Conclusion: Maternal calcium metabolic stress, rather than low calcium intake or insufficient vitamin D, has an adverse influence on fetal growth. This trial was registered at clinicaltrials.gov as NIH 0320070046. PMID:24500145

  4. 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.

  5. 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.

  6. Intelligent Visual Input: A Graphical Method for Rapid Entry of Patient-Specific Data

    PubMed Central

    Bergeron, Bryan P.; Greenes, Robert A.

    1987-01-01

    Intelligent Visual Input (IVI) provides a rapid, graphical method of data entry for both expert system interaction and medical record keeping purposes. Key components of IVI include: a high-resolution graphic display; an interface supportive of rapid selection, i.e., one utilizing a mouse or light pen; algorithm simplification modules; and intelligent graphic algorithm expansion modules. A prototype IVI system, designed to facilitate entry of physical exam findings, is used to illustrates the potential advantages of this approach.

  7. PICK1/calcineurin suppress ASIC1-mediated Ca2+ entry in rat pulmonary arterial smooth muscle cells.

    PubMed

    Herbert, Lindsay M; Nitta, Carlos H; Yellowhair, Tracylyn R; Browning, Carly; Gonzalez Bosc, Laura V; Resta, Thomas C; Jernigan, Nikki L

    2016-03-01

    Acid-sensing ion channel 1 (ASIC1) contributes to Ca(2+) influx and contraction in pulmonary arterial smooth muscle cells (PASMC). ASIC1 binds the PDZ (PSD-95/Dlg/ZO-1) domain of the protein interacting with C kinase 1 (PICK1), and this interaction is important for the subcellular localization and/or activity of ASIC1. Therefore, we first hypothesized that PICK1 facilitates ASIC1-dependent Ca(2+) influx in PASMC by promoting plasma membrane localization. Using Duolink to determine protein-protein interactions and a biotinylation assay to assess membrane localization, we demonstrated that the PICK1 PDZ domain inhibitor FSC231 diminished the colocalization of PICK1 and ASIC1 but did not limit ASIC1 plasma membrane localization. Although stimulation of store-operated Ca(2+) entry (SOCE) greatly enhanced colocalization between ASIC1 and PICK1, both FSC231 and shRNA knockdown of PICK1 largely augmented SOCE. These data suggest PICK1 imparts a basal inhibitory effect on ASIC1 Ca(2+) entry in PASMC and led to an alternative hypothesis that PICK1 facilitates the interaction between ASIC1 and negative intracellular modulators, namely PKC and/or the calcium-calmodulin-activated phosphatase calcineurin. FSC231 limited PKC-mediated inhibition of SOCE, supporting a potential role for PICK1 in this response. Additionally, we found PICK1 inhibits ASIC1-mediated SOCE through an effect of calcineurin to dephosphorylate the channel. Furthermore, it appears PICK1/calcineurin-mediated regulation of SOCE opposes PKA phosphorylation and activation of ASIC1. Together our data suggest PKA and PICK1/calcineurin differentially regulate ASIC1-mediated SOCE and these modulatory complexes are important in determining downstream Ca(2+) signaling. PMID:26702130

  8. 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.

  9. 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...

  10. 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...

  11. Abort-once-around entry corridor analysis program document

    NASA Technical Reports Server (NTRS)

    Kyle, H. C.

    1975-01-01

    The abort once around entry target corridor analysis program (ABECAP) was studied. The allowable range of flight path angles at entry interface for acceptable entry trajectories from a shuttle abort once around (AOA) situation was established. The solutions thus determined may be shown as corridor plots of entry interface flight path angle versus range from entry interface (EI) to the target.

  12. 19 CFR 141.91 - Entry without required invoice.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Entry without required invoice. 141.91 Section 141... THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Invoices § 141.91 Entry without required invoice. If a required invoice is not available in proper form at the time the entry or entry summary documentation...

  13. 19 CFR 141.91 - Entry without required invoice.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Entry without required invoice. 141.91 Section 141... THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Invoices § 141.91 Entry without required invoice. If a required invoice is not available in proper form at the time the entry or entry summary documentation...

  14. 19 CFR 141.91 - Entry without required invoice.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Entry without required invoice. 141.91 Section 141... THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Invoices § 141.91 Entry without required invoice. If a required invoice is not available in proper form at the time the entry or entry summary documentation...

  15. 19 CFR 141.91 - Entry without required invoice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry without required invoice. 141.91 Section 141... THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Invoices § 141.91 Entry without required invoice. If a required invoice is not available in proper form at the time the entry or entry summary documentation...

  16. Calcium store-mediated signaling in sustentacular cells of the mouse olfactory epithelium.

    PubMed

    Hegg, Colleen Cosgrove; Irwin, Mavis; Lucero, Mary T

    2009-04-15

    Sustentacular cells have structural features that allude to functions of secretion, absorption, phagocytosis, maintenance of extracellular ionic gradients, metabolism of noxious chemicals, and regulation of cell turnover. We present data detailing their dynamic activity. We show, using a mouse olfactory epithelium slice model, that sustentacular cells are capable of generating two types of calcium signals: intercellular calcium waves where elevations in intracellular calcium propagate between neighboring cells, and intracellular calcium oscillations consisting of repetitive elevations in intracellular calcium confined to single cells. Sustentacular cells exhibited rapid, robust increases in intracellular calcium in response to G-protein coupled muscarinic and purinergic receptor stimulation. In a subpopulation of sustentacular cells, oscillatory calcium transients were evoked. We pharmacologically characterized the properties of purinergic-evoked increases in intracellular calcium. Calcium transients were elicited by release from intracellular stores and were not dependent on extracellular calcium. BAPTA-AM, a cytosolic calcium chelator, and cyclopiazonic acid, an endoplasmic reticulum Ca(2+)-ATPase inhibitor irreversibly blocked the purinergic-induced calcium transient. Phospholipase C antagonist U73122 inhibited the purinergic-evoked calcium transient. 2-Aminoethoxydiphenyl borate, an inositol-1,4,5-trisphosphate (IP(3)) receptor antagonist, and the ryanodine receptor (RyR) antagonists tetracaine and ryanodine, inhibited the UTP-induced calcium transients. Collectively, these data suggest that activation of the phospholipase C pathway, IP(3)-mediated calcium release, and subsequent calcium-induced-calcium release is involved in ATP-elicited increases in intracellular calcium. Our findings indicate that sustentacular cells are not static support cells, and, like glia in the central nervous system, have complex calcium signaling.

  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. 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.

  19. Spatiotemporal calcium signaling in a Drosophila melanogaster cell line stably expressing a Drosophila muscarinic acetylcholine receptor.

    PubMed

    Cordova, D; Delpech, V Raymond; Sattelle, D B; Rauh, J J

    2003-11-01

    A muscarinic acetylcholine receptor (mAChR), DM1, expressed in the nervous system of Drosophila melanogaster, has been stably expressed in a Drosophila S2 cell line (S2-DM1) and used to investigate spatiotemporal calcium changes following agonist activation. Carbamylcholine (CCh) and oxotremorine are potent agonists, whereas application of the vertebrate M1 mAChR agonist, McN-A-343, results in a weak response. Activation of S2-DM1 receptors using CCh resulted in an increase in intracellular calcium ([Ca(2+)](i)) that was biphasic. Two distinct calcium sources were found to contribute to calcium signaling: (1) internal stores that are sensitive to both thapsigargin and 2-aminoethoxydiphenyl borate and (2) capacitative calcium entry. Spatiotemporal imaging of individual S2-DM1 cells showed that the CCh-induced [Ca(2+)](i) transient resulted from a homogeneous calcium increase throughout the cell, indicative of calcium release from internal stores. In contrast, ionomycin induced the formation of a "calcium ring" at the cell periphery, consistent with external calcium influx. PMID:12827518

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. On the conservation of fast calcium wave speeds.

    PubMed

    Jaffe, L

    2002-10-01

    Calcium waves were first seen about 25 years ago as the giant, 10 micro m/s wave or tsunami which crosses the cytoplasm of an activating medaka fish egg [J Cell Biol 76 (1978) 448]. By 1991, reports of such waves with approximately 10 micro m/s velocities through diverse, activating eggs and with approximately 30 micro m/s velocities through diverse, fully active systems had been compiled to form a class of what are now called fast calcium waves [Proc Natl Acad Sci USA 88 (1991) 9883; Bioessays 21 (1999) 657]. This compilation is now updated to include organisms from algae and sponges up to blowflies, squid and men and organizational levels from mammalian brains and hearts as well as chick embryos down to muscle, nerve, epithelial, blood and cancer cells and even cell-free extracts. Plots of these data confirm the narrow, 2-3-fold ranges of fast wave speeds through activating eggs and 3-4-fold ones through fully active systems at a given temperature. This also indicate Q(10)'s of 2.7-fold per 10 degrees C for both activating eggs and for fully activated cells.Speeds through some ultraflat preparations which are a few-fold above the conserved range are attributed to stretch propagated calcium entry (SPCE) rather than calcium-induced calcium release (CICR).

  5. Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI

    PubMed Central

    Hogan, Patrick G.; Lewis, Richard S.; Rao, Anjana

    2010-01-01

    Ca2+ entry into cells of the peripheral immune system occurs through highly Ca2+-selective channels known as CRAC (calcium release-activated calcium) channels. CRAC channels are a very well-characterized example of store-operated Ca2+ channels, so designated because they open when the endoplasmic reticulum (ER) Ca2+ store becomes depleted. Physiologically, Ca2+ is released from the ER lumen into the cytoplasm when activated receptors couple to phospholipase C and trigger production of the second messenger inositol 1,4,5-trisphosphate (IP3). IP3 binds to IP3 receptors in the ER membrane and activates Ca2+ release. The proteins STIM and ORAI were discovered through limited and genome-wide RNAi screens, respectively, performed in Drosophila cells and focused on identifying modulators of store-operated Ca2+ entry. STIM1 and STIM2 sense the depletion of ER Ca2+ stores, whereas ORAI1 is a pore subunit of the CRAC channel. In this review, we discuss selected aspects of Ca2+ signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store-operated Ca2+ entry. PMID:20307213

  6. 19 CFR 142.3 - Entry documentation required.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TREASURY (CONTINUED) ENTRY PROCESS Entry Documentation § 142.3 Entry documentation required. (a) Contents... required, a pro forma invoice or other acceptable documentation listed in that section may be submitted...

  7. 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.

  8. 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)

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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. PMID:25089769

  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. SPCA2 regulates Orai1 trafficking and store independent Ca2+ entry in a model of lactation.

    PubMed

    Cross, Brandie M; Hack, Anniesha; Reinhardt, Timothy A; Rao, Rajini

    2013-01-01

    An unconventional interaction between SPCA2, an isoform of the Golgi secretory pathway Ca(2+)-ATPase, and the Ca(2+) influx channel Orai1, has previously been shown to contribute to elevated Ca(2+) influx in breast cancer derived cells. In order to investigate the physiological role of this interaction, we examined expression and localization of SPCA2 and Orai1 in mouse lactating mammary glands. We observed co-induction and co-immunoprecipitation of both proteins, and isoform-specific differences in the localization of SPCA1 and SPCA2. Three-dimensional cultures of normal mouse mammary epithelial cells were established using lactogenic hormones and basement membrane. The mammospheres displayed elevated Ca(2+) influx by store independent mechanisms, consistent with upregulation of both SPCA2 and Orai1. Knockdown of either SPCA2 or Orai1 severely depleted Ca(2+) influx and interfered with mammosphere differentiation. We show that SPCA2 is required for plasma membrane trafficking of Orai1 in mouse mammary epithelial cells and that this function can be replaced, at least in part, by a membrane-anchored C-terminal domain of SPCA2. These findings clearly show that SPCA2 and Orai1 function together to regulate Store-independent Ca(2+) entry (SICE), which mediates the massive basolateral Ca(2+) influx into mammary epithelia to support the large calcium transport requirements for milk secretion.

  17. Nanoscale patterning of STIM1 and Orai1 during store-operated Ca2+ entry

    PubMed Central

    Perni, Stefano; Dynes, Joseph L.; Yeromin, Andriy V.; Cahalan, Michael D.; Franzini-Armstrong, Clara

    2015-01-01

    Stromal interacting molecule (STIM) and Orai proteins constitute the core machinery of store-operated calcium entry. We used transmission and freeze–fracture electron microscopy to visualize STIM1 and Orai1 at endoplasmic reticulum (ER)–plasma membrane (PM) junctions in HEK 293 cells. Compared with control cells, thin sections of STIM1-transfected cells possessed far more ER elements, which took the form of complex stackable cisternae and labyrinthine structures adjoining the PM at junctional couplings (JCs). JC formation required STIM1 expression but not store depletion, induced here by thapsigargin (TG). Extended molecules, indicative of STIM1, decorated the cytoplasmic surface of ER, bridged a 12-nm ER-PM gap, and showed clear rearrangement into small clusters following TG treatment. Freeze–fracture replicas of the PM of Orai1-transfected cells showed extensive domains packed with characteristic “particles”; TG treatment led to aggregation of these particles into sharply delimited “puncta” positioned upon raised membrane subdomains. The size and spacing of Orai1 channels were consistent with the Orai crystal structure, and stoichiometry was unchanged by store depletion, coexpression with STIM1, or an Orai1 mutation (L273D) affecting STIM1 association. Although the arrangement of Orai1 channels in puncta was substantially unstructured, a portion of channels were spaced at ∼15 nm. Monte Carlo analysis supported a nonrandom distribution for a portion of channels spaced at ∼15 nm. These images offer dramatic, direct views of STIM1 aggregation and Orai1 clustering in store-depleted cells and provide evidence for the interaction of a single Orai1 channel with small clusters of STIM1 molecules. PMID:26351694

  18. CALCIUM-INDUCED SUPRAMOLECULAR STRUCTURES IN THE CALCIUM CASEINATE SYSTEM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The molecular details deciphering the spontaneous calcium-induced protein aggregation process in the calcium caseinate system remain obscure. Understanding this complex process could lead to potential new applications of this important food ingredient. In this work, we studied calcium-induced supra...

  19. 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

  20. [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.

  1. Calcium Content of Common Foods

    MedlinePlus

    ... 130 Waffle 80 g 47 Meat, fish and eggs Food Serving Size Calcium (mg) Egg 50 g 27 Red meat 120 g 7 ... foods Food Serving Size Calcium (mg) Quiche (cheese, eggs) 200 g 212 Omelette with cheese 120 g ...

  2. Children's Bone Health and Calcium

    MedlinePlus

    ... Trials Resources and Publications Children's Bone Health and Calcium: Condition Information Skip sharing on social media links ... straight, walk, run, and lead an active life. Calcium is one of the key dietary building blocks ...

  3. Intestinal Stem Cells: Got Calcium?

    PubMed

    Nászai, Máté; Cordero, Julia B

    2016-02-01

    Calcium ions are well-known intracellular signalling molecules. A new study identifies local cytoplasmic calcium as a central integrator of metabolic and proliferative signals in Drosophila intestinal stem cells. PMID:26859268

  4. Calcium carbonate with magnesium overdose

    MedlinePlus

    The combination of calcium carbonate and magnesium is commonly found in antacids. These medicines provide heartburn relief. Calcium carbonate with magnesium overdose occurs when someone takes more than the ...

  5. 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

  6. Submerged Entry Nozzles that Resist Clogging

    SciTech Connect

    2001-04-01

    Development Of Submerged Entry Nozzles (SENs) Can Incrase Yields, Improve Product Quality, And Increase Productivity In Continuous Casting Of Steel, A Process Used For The Production Of 95% Of Steel In The U.S.

  7. Multiscale perspectives of virus entry via endocytosis

    PubMed Central

    2013-01-01

    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. PMID:23734580

  8. 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.

  9. 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.

  10. 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

  11. Entry, Descent, and Landing Operations Analysis for the Genesis Re-Entry Capsule

    NASA Technical Reports Server (NTRS)

    Desai, Prasun N.; Lyons, Dan T.

    2005-01-01

    On September 8, 2004, the Genesis spacecraft returned to Earth after spending 29 months about the sun-Earth libration point collecting solar wind particles. Four hours prior to Earth arrival, the entry capsule containing the samples was released for entry and subsequent landing at the Utah Test and Training Range. This paper provides an overview of the entry, descent, and landing trajectory analysis that was performed during the Mission Operations Phase leading up to final approach to Earth. The operations effort accurately delivered the entry capsule to the desired landing site. The final landing location was 8.3 km from the target, and was well within the allowable landing area. Preliminary reconstruction analyses indicate that the actual entry trajectory was very close to the pre-entry prediction.

  12. Supplementation trials with calcium citrate malate: evidence in favor of increasing the calcium RDA during childhood and adolescence.

    PubMed

    Andon, M B; Lloyd, T; Matkovic, V

    1994-08-01

    The vast majority of peak adult bone mass is accumulated by the time longitudinal growth is complete. As peak bone mass is an important determinant of future fracture risk, the goal of the current calcium recommended dietary allowance during youth is to provide a calcium intake that allows individuals to reach their full genetic potential for acquiring skeletal mass. The advent of controlled trials of calcium supplementation and total body bone mass measurements in children and adolescents provide the first direct way of determining the amount of calcium necessary to achieve optimal skeletal accretion. These studies indicate that the current RDAs are insufficient to support optimal bone mass gain during growth and development. Based on the recent intervention trials, recommendations are made for an RDA of 1250 mg during childhood and 1450 mg during adolescence. These values are consistent with established calcium balance intake thresholds for growth during pre-adolescence and adolescence.

  13. FLPP IXV Re-Entry Vehicle, Aerodynamic Characterisation

    NASA Astrophysics Data System (ADS)

    Belmont, J.-P.; Cantinaud, O.; Tribot, J.-P.; Walloschek, T.

    2009-01-01

    The European Space Agency ESA, has engaged in 2004, the IXV project (Intermediate eXperimental Vehicle) which is part of the FLPP (Future Launcher Preparatory Programme) aiming at answering to critical technological issues, while supporting the future generation launchers and improving in general European capabilities in the strategic field of atmospheric re-entry for space transportation, exploration, and scientific applications. The IXV key mission and system objectives are the design, development, manufacturing, assembling and on- ground to in-flight verification of an autonomous European lifting and aerodynamically controlled re- entry system, integrating the critical re-entry technologies at the system level. The current IXV vehicle is a slender body type exhibiting rounded shape and thick body. Since the beginning of the IXV project, an aerodynamic data base (AEDB) has been built up and continuously updated integrating the additional information mainly provided by means of CFD. The AEDB includes nominal aerodynamic data, a new set of free molecular aerodynamic coefficients as well as aerodynamic uncertainties. Through the phase B2/C1, complementary computations were performed (CFSE, EPFL, ASTRIUM, TAS, DAA) as well as wind tunnel tests such as ONERA S4ma, DLR H2K, DNW/NLR SST, FOI T1500. All data were analyzed and compared enabling the consolidation of the nominal aerodynamic and aerodynamic uncertainties as well. The paper presents the logic of work based on the system engineering plan with emphasis on the different prediction tools used aiming the final aerodynamic characterization of the IXV configuration.

  14. 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.

  15. Calcium and phosphorus fluxes during hemodialysis with low calcium dialysate.

    PubMed

    Hou, S H; Zhao, J; Ellman, C F; Hu, J; Griffin, Z; Spiegel, D M; Bourdeau, J E

    1991-08-01

    We evaluated the acute effects of varying dialysate calcium concentration on plasma concentrations and dialyzer fluxes of calcium and phosphorus in adult hemodialysis patients. Seven individuals with stable end-stage renal failure were dialyzed 4 hours, three times weekly. The effects of dialysates containing 1.75, 1.25, or 0.75 mmol/L (70.1, 50.1, or 30.1 mg/L) of calcium were compared. Each patient was studied once at each bath calcium concentration. Compared with the predialysis mean value of 2.27 mmol/L (9.1 mg/dL), plasma total calcium concentration increased, remained constant, or decreased with the 1.75-, 1.25-, or 0.75-mmol/L calcium dialysates, respectively. The 0.75-mmol/L calcium dialysate did not cause signs or symptoms of hypocalcemia (and the plasma calcium concentration did not fall below 1.80 mmol/L [7.2 mg/dL]). Plasma phosphorus concentrations decreased equally from a predialysis mean value of 2.16 mmol/L (6.7 mg/dL), regardless of the dialysate calcium concentration. After 4 hours of treatment with the three different dialysates, the cumulative calcium fluxes were significantly different. With 1.75 mmol/L calcium, mean bodily calcium accumulation was 21.9 mmol (879 mg). With 1.25 mmol/L, there was no net calcium flux. With 0.75 mmol/L, mean patient calcium loss was 5.8 mmol (231 mg). Mean phosphorus removal after 4 hours was 32.5 mmol (1,006 mg) and was unaffected by dialysate calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1867178

  16. Entry into the American Labor Force.

    ERIC Educational Resources Information Center

    Ornstein, Michael D.

    This analysis of entry into the labor force by American men between the ages of 30 and 39 was based on a set of about 1,600 retrospective life history interviews, approximately half from whites and half from blacks. At the time of entry the mean level of whites' education was higher than that of blacks and this was translated into jobs with higher…

  17. Transmission strategies for atmospheric entry probes.

    NASA Technical Reports Server (NTRS)

    Butman, S.

    1972-01-01

    In this article we shall be concerned with the question of how to maximize the expected data return when the channel capacity cannot be predicted in advance. An example of this type is a planetary entry probe to Venus or Jupiter, whose atmospheric transmission characteristics are not yet fully known. And even if they were known, these transmission characteristics would be subject to unpredictable changes due to planet weather and/or entry trajectory.

  18. 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...

  19. 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

  20. 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.

  1. 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): ...

  2. Calcium aluminate in alumina

    NASA Astrophysics Data System (ADS)

    Altay, Arzu

    The properties of ceramic materials are determined not only by the composition and structure of the phases present, but also by the distribution of impurities, intergranular films and second phases. The phase distribution and microstructure both depend on the fabrication techniques, the raw materials used, the phase-equilibrium relations, grain growth and sintering processes. In this dissertation research, various approaches have been employed to understand fundamental phenomena such as grain growth, impurity segregation, second-phase formation and crystallization. The materials system chosen was alumina intentionally doped with calcium. Atomic-scale structural analyses of grain boundaries in alumina were carried on the processed samples. It was found that above certain calcium concentrations, CA6 precipitated as a second phase at all sintering temperatures. The results also showed that abnormal grain growth can occur after precipitation and it is not only related to the calcium level, but it is also temperature dependent. In order to understand the formation mechanism of CA6 precipitates in calcium doped alumina samples, several studies have been carried out using either bulk materials or thin films The crystallization of CA2 and CA6 powders has been studied. Chemical processing techniques were used to synthesize the powders. It was observed that CA2 powders crystallized directly, however CA6 powders crystallized through gamma-Al 2O3 solid solution. The results of energy-loss near-edge spectrometry confirmed that gamma-Al2O3 can dissolve calcium. Calcium aluminate/alumina reaction couples have also been investigated. All reaction couples were heat treated following deposition. It was found that gamma-Al2O3 was formed at the interface as a result of the interfacial reaction between the film and the substrate. gamma-Al 2O3 at the interface was stable at much higher temperatures compared to the bulk gamma-Al2O3 formed prior to the CA6 crystallization. In order to

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. New reference values for calcium.

    PubMed

    2013-01-01

    The nutrition societies of Germany, Austria and Switzerland are the joint editors of the 'reference values for nutrient intake'. They have revised the reference values for the intake of calcium and published them in June 2013. The reference values for the calcium intake for infants are derived from the calcium content of breast milk. For infants from 4 to <12 months of age, the calcium intake from solid foods is included in addition to the calcium intake from breast milk. Thus, the reference values for infants are estimated values; they are 220 mg/day for infants to <4 months and 330 mg/day for infants from 4 to <12 months of age. As a parameter for determining the calcium requirement in children and adolescents, calcium retention is taken into account. The average requirement is calculated by the factorial method. A balanced calcium metabolism is calculated based upon calcium balance studies and used as a parameter for the determination of the calcium requirement in adults. On the basis of the average requirement, recommended calcium intake levels for children, adolescents and adults are derived. Depending on age, the recommended calcium intake ranges between 600 mg/day for children aged 1 to <4 years and 1,200 mg/day for adolescents aged 13 to <19 years; for adults, it is 1,000 mg/day. PMID:24356454

  8. Data on calcium increases depending on stretch in dystrophic cardiomyocytes.

    PubMed

    Aguettaz, E; Lopez, J J; Krzesiak, A; Constantin, B; Cognard, C; Sebille, S

    2016-09-01

    In this data article, intracellular Ca(2+) concentration ([Ca(2+)]i) was measured in isolated ventricular Wild Type (WT) and mdx cardiomyocytes in two different conditions: at rest and during the application of an axial stretch. Using a carbon microfibers technique, axial stretch was applied to mimic effects of physiological conditions of ventricular filling. A study of cation entry with the same experimental model and the manganese quenching method reported (i) a constitutive cation entry in mdx cardiomyocytes and (ii) the involvement of TRPV2 channels in axial-stretch dependant cation entry, "Axial stretch-dependent cation entry in dystrophic cardiomyopathy: involvement of several TRPs channels" (Aguettaz et al., 2016) [1]. Here, the Ca(2+) dye fluo-8 was used for [Ca(2+)]i measurement, in both resting and stretching conditions, using a perfusion protocol starting initially with a calcium free Tyrode solution followed by the perfusion of 1.8 mM Ca(2+) Tyrode solution. The variation of [Ca(2+)]i was found higher in mdx cardiomyocytes. PMID:27617280

  9. Micronutrients and the premenstrual syndrome: the case for calcium.

    PubMed

    Thys-Jacobs, S

    2000-04-01

    Premenstrual syndrome afflicts millions of premenopausal women and has been described as one of the most common disorders in women. Research over the past few years suggests that a variety of nutrients may have an important role in the phase related mood and behavioral disturbances of the premenstrual syndrome. There is scientific evidence, at least for a few of these micronutrients, specifically calcium and vitamin D, supporting cyclic fluctuations during the menstrual cycle that may help explain some features of PMS. Ovarian hormones influence calcium, magnesium and vitamin D metabolism. Estrogen regulates calcium metabolism, intestinal calcium absorption and parathyroid gene expression and secretion, triggering fluctuations across the menstrual cycle. Alterations in calcium homeostasis (hypocalcemia and hypercalcemia) have long been associated with many affective disturbances. PMS shares many features of depression, anxiety and the dysphoric states. The similarity between the symptoms of PMS and hypocalcemia is remarkable. Clinical trials in women with PMS have found that calcium supplementation effectively alleviates the majority of mood and somatic symptoms. Evidence to date indicates that women with luteal phase symptomatology have an underlying calcium dysregulation with a secondary hyperparathyroidism and vitamin D deficiency. This strongly suggests that PMS represents the clinical manifestation of a calcium deficiency state that is unmasked following the rise of ovarian steroid hormone concentrations during the menstrual cycle. PMID:10763903

  10. 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.

  11. Wnt-induced calcium signaling mediates axon growth and guidance in the developing corpus callosum.

    PubMed

    Hutchins, B Ian; Li, Li; Kalil, Katherine

    2012-01-10

    Wnt5a gradients guide callosal axons by repulsion through Ryk receptors in vivo. We recently found that Wnt5a repels cortical axons and promotes axon outgrowth through calcium signaling in vitro. Here, using cortical slices, we show that Wnt5a signals through Ryk to guide and promote outgrowth of callosal axons after they cross the midline. Calcium transient frequencies in callosal growth cones positively correlate with axon outgrowth rates in vitro. In cortical slices, calcium release through inositol 1,4,5-trisphosphate (IP(3)) receptors and calcium entry through transient receptor potential channels modulate axon growth and guidance. Knocking down Ryk inhibits calcium signaling in cortical axons, reduces rates of axon outgrowth subsequent to midline crossing, and causes axon guidance defects. Calcium- and calmodulin-dependent protein kinase II (CaMKII) is required downstream of Wnt-induced calcium signaling for postcrossing callosal axon growth and guidance. Taken together, these results suggest that growth and guidance of postcrossing callosal axons by Wnt-Ryk-calcium signaling involves axon repulsion through CaMKII.

  12. Disturbed calcium signaling in spinocerebellar ataxias and Alzheimer's disease.

    PubMed

    Egorova, Polina; Popugaeva, Elena; Bezprozvanny, Ilya

    2015-04-01

    Neurodegenerative disorders, such as spinocerebellar ataxias (SCAs) and Alzheimer's disease (AD) represent a huge scientific and medical question, but the molecular mechanisms of these diseases are still not clear. There is increasing evidence that neuronal calcium signaling is abnormal in many neurodegenerative disorders. Abnormal neuronal calcium release from the endoplasmic reticulum may result in disturbances of cell homeostasis, synaptic dysfunction, and eventual cell death. Neuronal loss is observed in most cases of neurodegenerative diseases. Recent experimental evidence supporting the role of neuronal calcium signaling in the pathogenesis of SCAs and AD is discussed in this review.

  13. Neutron-Induced Cross Sections Measurements of Calcium

    SciTech Connect

    Guber, Klaus H; Kopecky, S.; Schillebeeckx, P.; Kauwenberghs, K.; Siegler, P.

    2013-01-01

    To support the US Department of Energy Nuclear Criticality Safety Program neutron induced cross section experiments were performed at the Geel Electron Linear Accelerator of the Institute for Reference Material and Measurements of the Joint Research Centers, European Union. Neutron capture and transmission measurements were carried out using a metallic calcium sample. The obtained data will be used for a new calcium evaluation, which will be submitted with its covariances to the ENDBF/B nuclear data base.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 19 CFR 143.11 - Merchandise eligible for appraisement entry.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Merchandise eligible for appraisement entry. 143.11 Section 143.11 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) SPECIAL ENTRY PROCEDURES Appraisement Entry § 143.11 Merchandise eligible for appraisement entry. (a)...

  20. 30 CFR 877.13 - Entry and consent to reclaim.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...; and (3) The owner of the land or water resources where entry must be made to restore, reclaim, abate... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Entry and consent to reclaim. 877.13 Section... INTERIOR ABANDONED MINE LAND RECLAMATION RIGHTS OF ENTRY § 877.13 Entry and consent to reclaim. (a)...

  1. 30 CFR 877.13 - Entry and consent to reclaim.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...; and (3) The owner of the land or water resources where entry must be made to restore, reclaim, abate... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Entry and consent to reclaim. 877.13 Section... INTERIOR ABANDONED MINE LAND RECLAMATION RIGHTS OF ENTRY § 877.13 Entry and consent to reclaim. (a)...

  2. 46 CFR 109.433 - Logbook entries. 1

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Logbook entries. 1 109.433 Section 109.433 Shipping... Reports, Notifications, and Records Records § 109.433 Logbook entries. 1 1 Note: 46 U.S.C. 11301 requires that certain entries be made in an official logbook, in addition to the entries required by...

  3. 30 CFR 877.13 - Entry and consent to reclaim.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...; and (3) The owner of the land or water resources where entry must be made to restore, reclaim, abate... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Entry and consent to reclaim. 877.13 Section... INTERIOR ABANDONED MINE LAND RECLAMATION RIGHTS OF ENTRY § 877.13 Entry and consent to reclaim. (a)...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Calcium signaling in taste cells.

    PubMed

    Medler, Kathryn F

    2015-09-01

    The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

  10. [Progress in calcium regulation in myocardial and vascular ischemia-reperfusion injury].

    PubMed

    He, Xi; Bi, Xue-Yuan; Wang, Hao; Yu, Xiao-Jiang; Zang, Wei-Jin

    2012-06-25

    Ischemia-reperfusion injury (IRI) has been recognized as a serious problem for therapy of cardiovascular diseases. Calcium regulation appears to be an important issue in the study of IRI. This article reviews calcium regulation in myocardial and vascular IRI, including the calcium overload and calcium sensitivity in IRI. This review is focused on the key players in Ca(2+) handling in IRI, including membrane damage resulting in increase in Ca(2+) influx, reverse-mode of Na(+)-Ca(2+) exchangers leading to increased Ca(2+) entry, the decreased activity of sarcoplasmic reticulum (SR) Ca(2+)-ATPase causing SR Ca(2+) uptake dysfunction, and increased activity of Rho kinase. These key players in Ca(2+) homeostasis will provide promising strategies and potential targets for therapy of cardiovascular IRI. PMID:22717637

  11. Fruit Calcium: Transport and Physiology.

    PubMed

    Hocking, Bradleigh; Tyerman, Stephen D; Burton, Rachel A; Gilliham, Matthew

    2016-01-01

    Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium

  12. Fruit Calcium: Transport and Physiology

    PubMed Central

    Hocking, Bradleigh; Tyerman, Stephen D.; Burton, Rachel A.; Gilliham, Matthew

    2016-01-01

    Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium

  13. 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.

  14. Complexometric Determination of Calcium

    NASA Astrophysics Data System (ADS)

    Nielsen, S. Suzanne

    Ethylenediaminetetraacetate (EDTA) complexes with numerous mineral ions, including calcium and magnesium. This reaction can be used to determine the amount of these minerals in a sample by a complexometric titration. Endpoints in the titration are detected using indicators that change color when they complex with mineral ions. Calmagite and eriochrome black T (EBT) are such indicators that change from blue to pink when they complex with calcium and magnesium. In the titration of a mineral-containing solution with EDTA, the solution turns from pink to blue at the endpoint with either indicator. The pH affects a complexometric EDTA titration in several ways, and must be carefully controlled. A major application of EDTA titration is testing the hardness of water, for which the method described is an official one (Standard Methods for the Examination of Water and Wastewater, Method 2340C; AOAC Method 920.196).

  15. DISTILLATION OF CALCIUM

    DOEpatents

    Barton, J.

    1954-07-27

    This invention relates to an improvement in the process for the purification of caicium or magnesium containing an alkali metal as impurity, which comprises distiiling a batch of the mixture in two stages, the first stage distillation being carried out in the presence of an inert gas at an absolute pressure substantially greater than the vapor pressure of calcium or maguesium at the temperature of distillation, but less than the vaper pressure at that temperature of the alkali metal impurity so that only the alkali metal is vaporized and condensed on a condensing surface. A second stage distilso that substantially only the calcium or magnesium distills under its own vapor pressure only and condenses in solid form on a lower condensing surface.

  16. Synthesis of calcium superoxide

    NASA Technical Reports Server (NTRS)

    Rewick, R. T.; Blucher, W. G.; Estacio, P. L.

    1972-01-01

    Efforts to prepare Ca(O2) sub 2 from reactions of calcium compounds with 100% O3 and with O(D-1) atoms generated by photolysis of O3 at 2537 A are described. Samples of Ca(OH) sub 2, CaO, CaO2, Ca metal, and mixtures containing suspected impurities to promote reaction have been treated with excess O3 under static and flow conditions in the presence and absence of UV irradiation. Studies with KO2 suggest that the superoxide anion is stable to radiation at 2537 A but reacts with oxygen atoms generated by the photolysis of O3 to form KO3. Calcium superoxide is expected to behave in an analogous.

  17. 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.

  18. 75 FR 82241 - Technical Correction: Completion of Entry and Entry Summary-Declaration of Value

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-30

    ... Correction: Completion of Entry and Entry Summary-- Declaration of Value AGENCY: Customs and Border...(g) has expired and that this regulation is no longer necessary. ] Accordingly, part 141 of the CBP... summary documentation must be completed. Within Sec. 141.61, paragraph (g) requires an importer...

  19. 76 FR 66875 - Informal Entry Limit and Removal of a Formal Entry Requirement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... the language requiring formal entry for certain articles, because with the elimination of absolute... proposes to remove language stating that formal entry is required for certain ``articles valued in excess... States (HTSUS). We propose to remove this language because CBP no longer needs to require formal...

  20. Lessons learned from planetary entry probe missions

    NASA Astrophysics Data System (ADS)

    Niemann, Hasso; Atreya, Sushil K.; Kasprzak, Wayne

    Probing the atmospheres and surfaces of the planets and their moons with fast moving entry probes has been a very useful and essential technique to obtain in situ or quasi in situ scientific data (ground truth) which could not otherwise be obtained from fly by or orbiter only missions and where balloon, aircraft or lander missions are too complex and too costly. Planetary entry probe missions have been conducted successfully on Venus, Mars, Jupiter and Titan after having been first demonstrated in the Earth's atmosphere. Future planetary missions should also include more entry probe missions back to Venus and to the outer planets. The success of and science returns from past missions, the need for more and unique data, and a continuously advancing technology generate confidence that future missions will be even more successful with respect to science return and technical performance. There are, however, unique challenges associated with entry probe missions and with building instruments for an entry probe, as compared to orbiters, landers, or rovers. Conditions during atmospheric entry are extreme. There are operating time constraints due to the usually short duration of the probe descent, and the instruments experience rapid environmental changes in temperature and pressure. In addition, there are resource limitations, i.e. mass, power, size and bandwidth. Because of the protective heat shield and the high acceleration the probe experiences during entry, the ratio of payload to total probe mass is usually much smaller than in other missions. Finally, the demands on the instrument design are determined in large part by conditions (pressure, temperature, composition) unique to the particular body under study, and as a result, there is no one-size-fits-all instrument for an atmospheric probe. Many of these requirements are more easily met by miniaturizing the probe instrumentation and consequently reducing the required size of the probe. Improved heat shield

  1. Calcium hydroxylapatite: Radiesse.

    PubMed

    Ahn, Min S

    2007-02-01

    Among the array of choices for aesthetic soft tissue fillers, Radiesse occupies a unique niche as a safe, easily administered, "semi-permanent" material. Composed of calcium hydroxylapatite in a gel matrix, it has a proven safety profile and has been approved by the US Food and Drug Administration for use in the nasolabial folds and for HIV lipoatrophy. Radiesse have evolved quickly into a effective filler for moderately deep facial folds with high patient and physician approval.

  2. Chondrocyte death in mechanically injured articular cartilage--the influence of extracellular calcium.

    PubMed

    Amin, Anish K; Huntley, James S; Bush, Peter G; Simpson, A Hamish R W; Hall, Andrew C

    2009-06-01

    Calcium is thought to be an important regulator of chondrocyte death associated with articular cartilage injury. Our objective was to determine the influence of extracellular calcium on chondrocyte death following mechanical injury. Using a surgically relevant model of sharp mechanical injury (with a scalpel) and confocal laser scanning microscopy (CLSM), in situ chondrocyte death was quantified within the full thickness of articular cartilage as a function of medium calcium concentration and time (2.5 h and 7 days). Exposure of articular cartilage to calcium-free media (approximately 0 mM) significantly reduced superficial zone chondrocyte death after mechanical injury compared with exposure to calcium-rich media (2-20 mM, ANOVA at 2.5 h, p = 0.002). In calcium-rich media, although the extent of chondrocyte death increased with increasing medium calcium concentration, cell death remained localized to the superficial zone of articular cartilage over 7 days (ANOVA, p < 0.05). However, in calcium-free media, there was an increase in chondrocyte death within deeper zones of articular cartilage over 7 days. The early (within hours) chondroprotective effect in calcium-free media suggests that the use of joint irrigation solutions without added calcium may decrease chondrocyte death from mechanical injury during articular surgery. The delayed (within days) increase in chondrocyte death in calcium-free media supports the use of calcium supplementation in media used during cartilage culture for tissue engineering or transplantation.

  3. The cellular transport of calcium in rat liver.

    PubMed

    Wallach, S; Reizenstein, D L; Bellavia, J V

    1966-03-01

    The bidirectional transport of calcium in rat liver was studied using slices labeled with Ca(47) in a closed two compartment system. Steady-state conditions were observed with influx and efflux transfer coefficients of 0.070 and 0.018 per minute, respectively. The rapidly exchanging cell fraction of calcium existed at a concentration three times higher than the average cell concentration of calcium and occupied cell loci comprising less than 25% of the cell mass, suggesting that calcium associated with the cell membranes, nuclei, and mitochondria participated in the rapidly exchanging fraction. At pH 7.4 and 377deg;C, the influx transfer coefficient was 25% above the steady-state condition and accumulation of calcium by the slices occurred. Studies of the effects of varied physical and chemical conditions revealed that the influx transfer coefficient was increased by elevated pH, strontium, certain metabolic inhibitors, and 2 mM concentrations of cyclic adenosinemonophosphate and adenosinetriphosphate. The influx transfer coefficient was decreased by reduced temperature, decreased pH, magnesium, and 10 mM adenosinetriphosphate. The efflux transfer coefficient was increased by elevated pH, strontium, iodoacetate, and adenosinetriphosphate, and was decreased by reduced temperature and by N-ethylmaleimide. These data support the thesis that cell transport of calcium is accomplished by the attachment of calcium atoms to the cell surface and transport through the plasma membrane bound to either specific carriers or to membrane constituents. Conditions which change the affinities, capacities, and mobilities of plasma membrane ligands that bind calcium or cause extracellular chelation of calcium are capable of altering the rate of calcium transport.

  4. The technology for wireline re-entry of deep ocean boreholes employed for the Dianaut Program

    NASA Astrophysics Data System (ADS)

    Floury, Luc; Gable, Robert

    1992-03-01

    More than 850 holes have been drilled in the world's oceans over the past 24 years, in connection with the Deep Sea Drilling Project (DSDP) and the Ocean Drilling Program (ODP). At least 45 of these holes were fitted with a re-entry cone and many were cased through the sedimentary and unconsolidated layers, allowing hole re-entry with a drill string from a drilling vessel and wireline logging to the drill stem. Re-entry of seafloor drill holes with a wireline logger positioned on the seabed was first successfully accomplished during the FARE program. The DIANAUT program was a scientific application of seafloor wireline re-entry utilizing the logging shuttle ‘Nadia’ in combination with the manned submersible ‘Nautile’. The Nadia re-entry logging system was successfully seated in drill re-entry cones of three boreholes in the Atlantic Ocean (water depths of 1666, 4485, and, 4976 m) and logging operations with different probes (temperature, heat-pulse flowmeter, BHTV, fluid sampler, magnetometer) were performed from the seafloor with full logging control and data acquisition from the Nautile. In the near future the logging shuttle ‘Nadia’ could be developed into a support facility for long-term downhole measurements and later into an unmanned seafloor logging system.

  5. 1994 entry-level athletic training salaries.

    PubMed

    Moss, C L

    1996-01-01

    In this study, I examined salaries for entry-level positions in athletic training during the year 1994. An entry-level position was defined as a position to be filled with an athletic trainer certified by the NATA, with no full-time paid employment experience. According to the "Placement Vacancy Notice" (NATA, Dallas, TX) and "BYLINE" (Athletic Trainer Services, Inc, Mt Pleasant, MI), there were 432 entry-level vacancies in hospital/clinics, college/universities, and high school settings. A total of 271 surveys (63%) were returned. Overall, beginning salaries for entry-level athletic training positions were $23,228 (+/-$3,177) for a bachelor's degree and $25,362 (+/-$3,883) for a master's degree. A stipend ($4,216 +/- $2,039) was included in 86% of the high school positions. The term of contract for high school was usually a 10-month position (10.0 +/- .9 months), hospital/clinic, 12-months (11.7 +/- .7 months), while the college/university varied from 9 to 12 months (10.5 +/- 1.2 months). Also included in the study was fringe benefit information: pension (other than Social Security), life, medical, dental, and vision insurance. Continued studies are recommended to establish salary norms and trends for entry-level positions so that athletic trainers will understand what monetary compensation to expect for their services. PMID:16558367

  6. Skip entry trajectory planning and guidance

    NASA Astrophysics Data System (ADS)

    Brunner, Christopher William

    A numerical predictor-corrector (NPC) method for trajectory planning and closed-loop guidance of low lift-to-drag (L/D) ratio vehicles during the skip entry phase of a lunar-return mission is presented. The strategy calls for controlling the trajectory by modulation of the magnitude of the vehicle's bank angle. The magnitude of the bank angle used in the skip phase is determined by satisfying the downrange requirement to the landing site. The problem is formulated as a nonlinear univariate root-finding problem. Full three degree of freedom (3DOF) nonlinear trajectory dynamics are included to achieve high accuracy of the landing prediction. In addition, the proposed approach automatically yields a direct entry trajectory when the downrange is such that a skip entry is no longer necessary. The same algorithm repeatedly applied on-board in every guidance cycle realizes closed-loop guidance in the skip entry phase. A number of issues are identified and addressed that are critical in closed-loop implementations. Extensive 3DOF dispersion simulations are performed to evaluate the performance of the proposed approach, and the results demonstrate very reliable and robust performance of the algorithm in highly stressful dispersed conditions. Comparison is made between the proposed algorithm and an earlier skip algorithm developed for the Apollo space program. It is shown that the proposed algorithm is superior to the Apollo algorithm especially when used for entries with long downranges.

  7. 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.

  8. 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.

  9. Mechanism for defoaming by oils and calcium soap in aqueous systems.

    PubMed

    Zhang, Hui; Miller, Clarence A; Garrett, Peter R; Raney, Kirk H

    2003-07-15

    The effect of oils, hardness, and calcium soap on foam stability of aqueous solutions of commercial surfactants was investigated. For conditions where negligible calcium soap was formed, stability of foams made with 0.1 wt% solutions of a seven-EO alcohol ethoxylate containing dispersed drops of n-hexadecane, triolein, or mixtures of these oils with small amounts of oleic acid could be understood in terms of entry, spreading, and bridging coefficients, i.e., ESB analysis. However, foams made from solutions containing 0.01 wt% of three-EO alcohol ethoxysulfate sodium salt and the same dispersed oils were frequently more stable than expected based on ESB analysis, reflecting that repulsion due to overlap of electrical double layers in the asymmetric oil-water-air film made oil entry into the air-water interface more difficult than the theory predicts. When calcium soap was formed in situ by the reaction of fatty acids in the oil with calcium, solid soap particles were observed at the surfaces of the oil drops. The combination of oil and calcium soap produced a synergistic effect facilitating the well-known bridging instability of foam films or Plateau borders and producing a substantial defoaming effect. A possible mechanism of instability involving increases in disjoining pressure at locations where small soap particles approach the air-water interface is discussed. For both surfactants with the triolein-oleic acid mixtures, calculated entry and bridging coefficients for conditions when calcium soap formed were positive shortly after foam generation but negative at equilibrium. These results are consistent with the experimental observation that most defoaming action occurred shortly after foam generation rather than at later times.

  10. Calcium Signaling in Taste Cells

    PubMed Central

    Medler, Kathryn F.

    2014-01-01

    The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. PMID:25450977

  11. Indirect activation of neuronal noncapacitative Ca2+ entry is the final step involved in the neurotoxic effect of Tityus serrulatus scorpion beta-toxin.

    PubMed

    Grolleau, Françoise; Stankiewicz, Maria; Kielbasiewicz, Ewa; Martin-Eauclaire, Marie-France; Lavialle, Céline; De Vente, Jan; Lapied, Bruno

    2006-03-01

    Interweaving strategies of electrophysiology, calcium imaging and immunocytochemistry bring new insights into the mode of action of the Brazilian scorpion Tityus serrulatusbeta-toxin VII. Pacemaker dorsal unpaired median neurons isolated from the cockroach central nervous system were used to study the effects of toxin VII. In current-clamp, 50 nm toxin VII produced a membrane depolarization and reduced spiking. At 200 nM, depolarization associated with multiphasic effects was seen. After artificial hyperpolarization, plateau potentials on which spontaneous electrical activity appeared were observed. In voltage clamp, toxin VII induced a negative shift of the voltage dependence of sodium current activation without significant effect on steady-state inactivation. In addition, toxin VII produced a permanent TTX-sensitive holding inward current, indicating that background sodium channels were targeted by beta-toxin. Cell-attached patch recordings indicated that these channels were switched from unclustered single openings to current fluctuating between distinct subconductance levels exhibiting increased open probability and open-time distribution. Toxin VII also produced a TTX-sensitive [Ca2+]i rise. Immunostaining with Cav2.2(alpha1b) antibodies and calcium imaging data obtained with omega-CgTx GVIA indicated that N-type high-voltage-activated calcium channels initiated calcium influx and were an essential intermediate in the pathway linking toxin VII-modified sodium channels to the activation of an additional route for calcium entry. By using inhibitors of (i) noncapacitative calcium entry (inhibitor LOE-908), (ii) NO-sensitive guanylyl cyclase (ODQ) and (iii) phosphodiesterase 2 (EHNA), together with cGMP antibodies, we demonstrated that noncapacitative calcium entry was the final step in a complex combination of events that was initiated by toxin VII-alteration of sodium channels and then involved successive activation of other membrane ion channels. PMID:16553610

  12. Earth Entry Vehicle for Mars Sample Return

    NASA Technical Reports Server (NTRS)

    Mitcheltree, R. A.; Braun, R. D.; Hughes. S. J.; Simonsen, L. C.

    2000-01-01

    The driving requirement for design of a Mars Sample return mission is assuring containment of the returned samples. The impact of this requirement on developmental costs, mass allocation, and design approach of the Earth Entry Vehicle is significant. A simple Earth entry vehicle is described which can meet these requirements and safely transport the Mars Sample Return mission's sample through the Earth's atmosphere to a recoverable location on the surface. Detailed analysis and test are combined with probabilistic risk assessment to design this entirely passive concept that circumvents the potential failure modes of a parachute terminal descent system. The design also possesses features that mitigate other risks during the entry, descent, landing and recovery phases. The results of a full-scale drop test are summarized.

  13. Cubesat Application for Planetary Entry Missions (CAPE)

    NASA Technical Reports Server (NTRS)

    Esper, Jaime; Baumann, Jean-Pierre; Herdrich, Georg

    2013-01-01

    The Cubesat Application for Planetary Entry Missions (CAPE) concept describes a high-performing Cubesat system which includes a propulsion module and miniaturized technologies capable of surviving atmospheric entry heating, while reliably transmitting scientific and engineering data. The Micro Return Capsule 2 (MIRKA2) is CAPE’s first planetary entry probe flight prototype. Within this context, this paper summarizes CAPE’s configuration and typical operational scenario. It also summarizes MIRKA2’s design and basic aerodynamic characteristics, and discusses potential challenges drawn from the experience of missions such as Stardust and MUSES-C. CAPE not only opens the door to new planetary mission capabilities, it also offers relatively low-cost opportunities especially suitable to university participation.

  14. Neuronal Expression of the Human Neuropeptide S Receptor NPSR1 Identifies NPS-Induced Calcium Signaling Pathways

    PubMed Central

    Erdmann, Frank; Kügler, Sebastian; Blaesse, Peter; Lange, Maren D.; Skryabin, Boris V.; Pape, Hans-Christian; Jüngling, Kay

    2015-01-01

    The neuropeptide S (NPS) system was discovered as a novel neurotransmitter system a decade ago and has since been identified as a key player in the modulation of fear and anxiety. Genetic variations of the human NPS receptor (NPSR1) have been associated with pathologies like panic disorders. However, details on the molecular fundamentals of NPSR1 activity in neurons remained elusive. We expressed NPSR1 in primary hippocampal cultures. Using single-cell calcium imaging we found that NPSR1 stimulation induced calcium mobilization from the endoplasmic reticulum via activation of IP3 and ryanodine receptors. Store-operated calcium channels were activated in a downstream process mediating entry of extracellular calcium. We provide the first detailed analysis of NPSR1 activity and the underlying intracellular pathways with respect to calcium mobilization in neurons. PMID:25714705

  15. Predictors of re-entry into the child protection system in Singapore: a cumulative ecological-transactional risk model.

    PubMed

    Li, Dongdong; Chu, Chi Meng; Ng, Wei Chern; Leong, Wai

    2014-11-01

    This study examines the risk factors of re-entry for 1,750 child protection cases in Singapore using a cumulative ecological-transactional risk model. Using administrative data, the present study found that the overall percentage of Child Protection Service (CPS) re-entry in Singapore is 10.5% based on 1,750 cases, with a range from 3.9% (within 1 year) to 16.5% (within 8 years after case closure). One quarter of the re-entry cases were observed to occur within 9 months from case closure. Seventeen risk factors, as identified from the extant literature, were tested for their utility to predict CPS re-entry in this study using a series of Cox regression analyses. A final list of seven risk factors (i.e., children's age at entry, case type, case closure result, duration of case, household income, family size, and mother's employment status) was used to create a cumulative risk score. The results supported the cumulative risk model in that higher risk score is related to higher risk of CPS re-entry. Understanding the prevalence of CPS re-entry and the risk factors associated with re-entry is the key to informing practice and policy in a culturally relevant way. The results from this study could then be used to facilitate critical case management decisions in order to enhance positive outcomes of families and children in Singapore's care system.

  16. Mars Science Laboratory Entry Capsule Aerothermodynamics and Thermal Protection System

    NASA Technical Reports Server (NTRS)

    Edquist, Karl T.; Hollis, Brian R.; Dyakonov, Artem A.; Laub, Bernard; Wright, Michael J.; Rivellini, Tomasso P.; Slimko, Eric M.; Willcockson, William H.

    2007-01-01

    The Mars Science Laboratory (MSL) spacecraft is being designed to carry a large rover (greater than 800 kg) to the surface of Mars using a blunt-body entry capsule as the primary decelerator. The spacecraft is being designed for launch in 2009 and arrival at Mars in 2010. The combination of large mass and diameter with non-zero angle-of-attack for MSL will result in unprecedented convective heating environments caused by turbulence prior to peak heating. Navier-Stokes computations predict a large turbulent heating augmentation for which there are no supporting flight data1 and little ground data for validation. Consequently, an extensive experimental program has been established specifically for MSL to understand the level of turbulent augmentation expected in flight. The experimental data support the prediction of turbulent transition and have also uncovered phenomena that cannot be replicated with available computational methods. The result is that the flight aeroheating environments predictions must include larger uncertainties than are typically used for a Mars entry capsule. Finally, the thermal protection system (TPS) being used for MSL has not been flown at the heat flux, pressure, and shear stress combinations expected in flight, so a test program has been established to obtain conditions relevant to flight. This paper summarizes the aerothermodynamic definition analysis and TPS development, focusing on the challenges that are unique to MSL.

  17. Calcium and bone health--goodbye, calcium supplements?

    PubMed

    Ströhle, A; Hadji, P; Hahn, A

    2015-10-01

    This review assesses (1) the potential role of calcium supplements in the prevention and treatment of osteoporosis and osteoporotic fractures, and (2) the safety of calcium supplements with respect to cardiovascular health as well. With regard to (1), a total calcium intake of < 800 mg/day is associated with increased loss of bone mineral density in peri- and postmenopausal women with an increase in fracture risk. Hereby, the effect of calcium supplements on fracture prevention is dependent primary on baseline calcium intake. The strongest protective effect has been reported in individuals with a calcium intake < 700 mg/day and in high-risk groups. A calcium intake of about 1000-1200 mg/day seems to be sufficient for general fracture prevention. With regard to (2), an analysis of the data based on the Hill criteria does not demonstrate convincing evidence that calcium supplements increase cardiovascular risk. In the long term, total calcium intake of 2500 mg/day (from food and supplements) continues to be classified as safe. This value should not be exceeded for an extended period of time. PMID:25689871

  18. DSMC simulations of OREX entry conditions

    NASA Technical Reports Server (NTRS)

    Moss, James N.; Gupta, Roop N.; Price, Joseph M.

    1996-01-01

    Results of direct simulation Monte Carlo (DSMC) solutions are presented for the Japanese Orbital Reentry Experiment (OREX) vehicle, a 50 deg half-angle spherically blunted cone with a nose radius of 1.35 m and a base diameter of 3.4 m. The flow conditions simulated are those for entry into the Earth's atmosphere at a nominal velocity of about 7.4 km/s and zero incidence. Calculations are made for the higher altitude portion of entry, encompassing the transitional flow regime (altitudes of 200 to 80 km). Comparisons with flight measured values are made for axial acceleration, surface pressure, and stagnation point heating.

  19. [Renal calcium excretion and urolithiasis].

    PubMed

    Aruga, Seiji; Honma, Yukio

    2011-10-01

    Patients with urolithiasis have been increasing in the world, especially morbidity of calcium nephrolithiasis has been increasing in the advanced countries. The changes in the environmental factors including alternation of diet are said to be associated with the increment of morbidity of kidney stone. Idiopathic hypercalciuria is one of the most important risk factor of calcium nephrolithiasis and is classified into absorptive, resorptive, and renal leak. Though the origins of these three types of hypercalciuria are different, increased bone resorption and increased calcium absorption from gut tend to be observed simultaneously. Not only genetic abnormalities in the proteins which are involved in calcium metabolisms but environmental factors such as high sodium intake and chronic acid load caused by increased ingestion of animal protein have been considered to be associated with increased urinary calcium excretion. Renal metabolisms of oxalate and phosphate which are important compositions of calcium containing stone, uric acid as a promoter and citrate as a inhibitor of nephrolithiasis are also described.

  20. Scientific evidence contradicts findings and assumptions of Canadian Safety Panel 6: microwaves act through voltage-gated calcium channel activation to induce biological impacts at non-thermal levels, supporting a paradigm shift for microwave/lower frequency electromagnetic field action.

    PubMed

    Pall, Martin L

    2015-01-01

    This review considers a paradigm shift on microwave electromagnetic field (EMF) action from only thermal effects to action via voltage-gated calcium channel (VGCC) activation. Microwave/lower frequency EMFs were shown in two dozen studies to act via VGCC activation because all effects studied were blocked by calcium channel blockers. This mode of action was further supported by hundreds of studies showing microwave changes in calcium fluxes and intracellular calcium [Ca2+]i signaling. The biophysical properties of VGCCs/similar channels make them particularly sensitive to low intensity, non-thermal EMF exposures. Non-thermal studies have shown that in most cases pulsed fields are more active than are non-pulsed fields and that exposures within certain intensity windows have much large biological effects than do either lower or higher intensity exposures; these are both consistent with a VGCC role but inconsistent with only a heating/thermal role. Downstream effects of VGCC activation include calcium signaling, elevated nitric oxide (NO), NO signaling, peroxynitrite, free radical formation, and oxidative stress. Downstream effects explain repeatedly reported biological responses to non-thermal exposures: oxidative stress; single and double strand breaks in cellular DNA; cancer; male and female infertility; lowered melatonin/sleep disruption; cardiac changes including tachycardia, arrhythmia, and sudden cardiac death; diverse neuropsychiatric effects including depression; and therapeutic effects. Non-VGCC non-thermal mechanisms may occur, but none have been shown to have effects in mammals. Biologically relevant safety standards can be developed through studies of cell lines/cell cultures with high levels of different VGCCs, measuring their responses to different EMF exposures. The 2014 Canadian Report by a panel of experts only recognizes thermal effects regarding safety standards for non-ionizing radiation exposures. Its position is therefore contradicted by each

  1. Scientific evidence contradicts findings and assumptions of Canadian Safety Panel 6: microwaves act through voltage-gated calcium channel activation to induce biological impacts at non-thermal levels, supporting a paradigm shift for microwave/lower frequency electromagnetic field action.

    PubMed

    Pall, Martin L

    2015-01-01

    This review considers a paradigm shift on microwave electromagnetic field (EMF) action from only thermal effects to action via voltage-gated calcium channel (VGCC) activation. Microwave/lower frequency EMFs were shown in two dozen studies to act via VGCC activation because all effects studied were blocked by calcium channel blockers. This mode of action was further supported by hundreds of studies showing microwave changes in calcium fluxes and intracellular calcium [Ca2+]i signaling. The biophysical properties of VGCCs/similar channels make them particularly sensitive to low intensity, non-thermal EMF exposures. Non-thermal studies have shown that in most cases pulsed fields are more active than are non-pulsed fields and that exposures within certain intensity windows have much large biological effects than do either lower or higher intensity exposures; these are both consistent with a VGCC role but inconsistent with only a heating/thermal role. Downstream effects of VGCC activation include calcium signaling, elevated nitric oxide (NO), NO signaling, peroxynitrite, free radical formation, and oxidative stress. Downstream effects explain repeatedly reported biological responses to non-thermal exposures: oxidative stress; single and double strand breaks in cellular DNA; cancer; male and female infertility; lowered melatonin/sleep disruption; cardiac changes including tachycardia, arrhythmia, and sudden cardiac death; diverse neuropsychiatric effects including depression; and therapeutic effects. Non-VGCC non-thermal mechanisms may occur, but none have been shown to have effects in mammals. Biologically relevant safety standards can be developed through studies of cell lines/cell cultures with high levels of different VGCCs, measuring their responses to different EMF exposures. The 2014 Canadian Report by a panel of experts only recognizes thermal effects regarding safety standards for non-ionizing radiation exposures. Its position is therefore contradicted by each

  2. Inhibitory action of oestrogen on calcium-induced mitosis in rat bone marrow and thymus.

    PubMed

    Smith, G R; Gurson, M L; Riddell, A J; Perris, A D

    1975-04-01

    In the male rat injections of CaCl-2 and MgCl-2 stimulated mitosis in bone marrow and thymus tissue. The magnesium salt was also mitogenic in the normal female, but calcium only exerted its mitogenic effect after ovariectomy. Oestradiol, but not progesterone replacement therpy abolished calcium-induced mitosis in the ovariectomized rat. The inability of calcium to stimulate cell division was also apparent in the thyroparathyroidectomized female rat, suggesting the oestradiol blockage did not operate via some indirect action on the calcium homeostatic hormones calcitonin or parathyroid hormone. When thymic lymphocytes derived from male or female rats were isolated and maintained in suspension, increased calcium or magnesium concentrations in the culture medium stimulated the entry of cells into mitosis. Addition of oestradiol to the culture medium abolished the mitogenic effect of increased calcium levels, but had no effect on magnesium-induced proliferation. These experiments suggested that oestradiol might act at the cell surface to prevent the influx of calcium but not magnesium ions into the interior of the cell and thus to block the sequence of biochemical events which led to the initiation of DNA synthesis and culminate in mitosis.

  3. Calcium Kinetics During Space Flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Wastney, Meryl E.; OBrien, Kimberly O.; Lane, Helen W.

    1999-01-01

    Bone loss is one of the most detrimental effects of space flight, threatening to limit the duration of human space missions. The ability to understand and counteract this loss will be critical for crew health and safety during and after extended-duration missions. The hypotheses to be tested in this project are that space flight alters calcium homeostasis and bone mineral metabolism, and that calcium homeostasis and bone mineral metabolism will return to baseline within days to weeks of return to Earth. These hypotheses will be evidenced by elevated rates of bone mineral resorption and decreased bone mineral deposition, decreased absorption of dietary calcium, altered calcitropic endocrine profiles, elevated excretion of calcium in urine and feces, and elevated excretion of markers of bone resorption. The second hypothesis will be evidenced by return of indices of calcium homeostasis and bone metabolism to preflight levels within days to weeks of return to Earth. Studies will be conducted on International Space Station astronauts before, during, and after extended-duration flights. Measurements of calcium kinetics, bone mass, and endocrine/biochemical markers of bone and calcium homeostasis will be conducted. Kinetic studies utilizing dual isotope tracer kinetic studies and mathematical modeling techniques will allow for determination of bone calcium deposition, bone calcium resorption, dietary calcium absorption and calcium excretion (both urinary and endogenous fecal excretion). These studies will build upon preliminary work conducted on the Russian Mir space station. The results from this project will be critical for clarifying how microgravity affects bone and calcium homeostasis, and will provide an important control point for assessment of countermeasure efficacy. These results are expected to aid in developing countermeasures for bone loss, both for space crews and for individuals on Earth who have metabolic bone diseases.

  4. Intracellular calcium puffs in osteoclasts.

    PubMed

    Radding, W; Jordan, S E; Hester, R B; Blair, H C

    1999-12-15

    We studied intracellular calcium ([Ca(2+)](i)) in acid-secreting bone-attached osteoclasts, which produce a high-calcium acidic extracellular compartment. Acid secretion and [Ca(2+)](i) were followed using H(+)-restricted dyes and fura-2 or fluo-3. Whole cell calcium of acid-secreting osteoclasts was approximately 100 nM, similar to cells on inert substrate that do not secrete acid. However, measurements in restricted areas of the cell showed [Ca(2+)](i) transients to 500-1000 nM consistent with calcium puffs, transient (millisecond) localized calcium elevations reported in other cells. Spot measurements at 50-ms intervals indicated that puffs were typically less than 400 ms. Transients did not propagate in waves across the cell in scanning confocal measurements. Calcium puffs occurred mainly over regions of acid secretion as determined using lysotracker red DND99 and occurred at irregular periods averaging 5-15 s in acid secreting cells, but were rare in lysotracker-negative nonsecretory cells. The calmodulin antagonist trifluoperazine, cell-surface calcium transport inhibitors lanthanum or barium, and the endoplasmic reticulum ATPase inhibitor thapsigargin had variable acute effects on the mean [Ca(2+)](i) and puff frequency. However, none of these agents prevented calcium puff activity, suggesting that the mechanism producing the puffs is independent of these processes. We conclude that [Ca(2+)](i) transients in osteoclasts are increased in acid-secreting osteoclasts, and that the puffs occur mainly near the acid-transporting membrane. Cell membrane acid transport requires calcium, suggesting that calcium puffs function to maintain acid secretion. However, membrane H(+)-ATPase activity was insensitive to calcium in the 100 nM-1 microM range. Thus, any effects of calcium puffs on osteoclastic acid transport must be indirect.

  5. SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification.

    PubMed

    Alqadah, Amel; Hsieh, Yi-Wen; Schumacher, Jennifer A; Wang, Xiaohong; Merrill, Sean A; Millington, Grethel; Bayne, Brittany; Jorgensen, Erik M; Chuang, Chiou-Fen

    2016-01-01

    The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons.

  6. Pertussis toxin reduces calcium influx to protect ischemic stroke in a middle cerebral artery occlusion model.

    PubMed

    Tang, Zhiwei; Li, Shiping; Han, Pengcheng; Yin, Junxiang; Gan, Yan; Liu, Qingwei; Wang, Jinkun; Wang, Chongqian; Li, Yu; Shi, Jiong

    2015-12-01

    Increased calcium influx secondary to glutamate induced excitotoxicity initiates and potentiates devastating pathological changes following ischemic stroke. Pertussis toxin (PTx), a G-protein blocker, is known to suppress intracellular calcium accumulation. We hypothesize that PTx can protect against stroke by blocking calcium influx. In a permanent middle cerebral artery occlusion model, PTx (1000 ng) was given intraperitoneally 30 min after inducing stroke. Magnetic Resonance Imaging of perfusion and T2-weighted brain scans were obtained to evaluate cerebral blood flow (CBF) and infarct volume. Primary neuronal culture was used to test glutamate induced excitotoxicity and calcium influx. We established a non-linear exponential curve model to minimize variations in animal cerebrovasculature. A reduction of 40-60% in relative CBF was a critical window where infarct volume started to increase as rCBF reduced. PTx showed maximal effects in reducing infarct volume at this window. In vitro studies further demonstrated PTx increased neuronal cell survival by decreasing glutamate-induced calcium influx into neurons and preventing neurons from apoptosis. PTx salvages the ischemic penumbra by blocking calcium influx. This provides us a new mechanism upon which experimental therapies can be explored to treat ischemic stroke. In ischemic stroke, excessive glutamate binds to AMPA receptor that depolarizes calcium channel and/ or NMDA receptor. Both of them allow calcium to enter the cell. The overload of calcium triggers cellular cascade that includes Caspase activation and release, leading to pre-mature cell death. We have demonstrated that PTx, a G-protein inhibitor, blocks calcium entry which in turn prevents further cellular damage.

  7. SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification

    PubMed Central

    Schumacher, Jennifer A.; Wang, Xiaohong; Merrill, Sean A.; Millington, Grethel; Bayne, Brittany; Jorgensen, Erik M.; Chuang, Chiou-Fen

    2016-01-01

    The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons. PMID:26771544

  8. 78 FR 12132 - 60-Day Notice of Proposed Information Collection: Electronic Diversity Visa Entry Form

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-21

    ... Notice of Proposed Information Collection: Electronic Diversity Visa Entry Form ACTION: Notice of request...: Chief, Legislation and Regulations Division, Visa Services--DSP-0122, 2401 E Street NW., Washington DC... proposed collection instrument and supporting documents, to Sydney Taylor, Visa Services, U.S....

  9. Inclusion of Medical-Legal Issues in Entry-Level Occupational and Physical Therapy Curricula.

    ERIC Educational Resources Information Center

    Ekelman, Beth A.; Goodman, Glenn; Dal Bello-Haas, Vanina

    2000-01-01

    Directors of 47 occupational therapy (OT) and 65 physical therapy (PT) accredited entry-level programs responded to a survey by indicating their support for inclusion of medical-legal issues in the curriculum. Only 40% of OT and 52% of PT directors believed lawyers should deliver instruction; most felt their faculty were qualified to teach these…

  10. Transition, Retraining, and Change for Entry. Final Report from July 1, 1983 - August 31, 1984.

    ERIC Educational Resources Information Center

    VanderLugt, Marilyn J.

    Goals of the "Transition, Retraining, and Change for Entry" project were to provide counseling and/or group support for single heads of households or persons entering nontraditional employment and to provide placement services for the target group. A third goal was to disseminate information about the value of and opportunities in nontraditional…

  11. Administrator Entry Year Programming: A Cross Institutional Pilot Program--Process, Program Descriptions, and Lessons Learned.

    ERIC Educational Resources Information Center

    Trenta, Louis; Beebe, Robert; Cosiano, Patrick; Eastridge, Harry

    This paper reviews processes used to develop a cross institutional, pilot administrator entry year program which provided leadership and learning support for beginning principals, assisted in further development of Ohio's administrative portfolio, provided a collaborative learning community, and created a statewide learning community to help…

  12. 21 CFR 184.1187 - Calcium alginate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium alginate. 184.1187 Section 184.1187 Food... GRAS § 184.1187 Calcium alginate. (a) Calcium alginate (CAS Reg. No. 9005-35-0) is the calcium salt of alginic acid, a natural polyuronide constituent of certain brown algae. Calcium alginate is prepared...

  13. Food Distribution. The Supermarket Entry Occupations.

    ERIC Educational Resources Information Center

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This guide is designed to assist the coordinator of the Marketing and Distributive Education Cooperative Education Program in improving and expanding the instructional activities needed to prepare individuals to function in the food industry's entry-level jobs. The instructional material provides information about what is expected of a student…

  14. TEST CELL STUDIES OF RADON ENTRY

    EPA Science Inventory

    The report gives results of a study to contrast the effectiveness of slab-in-stem wall (SSW) with floating slab (FS) construction practices, to measure radon transport and entry for model testing, to develop protocols relevant to depressurized radon measurements, and to determine...

  15. 32 CFR 770.45 - Entry procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base New London, Groton... consent of the Commanding Officer, Naval Submarine Base New London, or his authorized representative shall, in writing, submit a request to the Commanding Officer, Naval Submarine Base New London, at...

  16. 32 CFR 770.45 - Entry procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base New London, Groton... consent of the Commanding Officer, Naval Submarine Base New London, or his authorized representative shall, in writing, submit a request to the Commanding Officer, Naval Submarine Base New London, at...

  17. 32 CFR 770.45 - Entry procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base New London, Groton... consent of the Commanding Officer, Naval Submarine Base New London, or his authorized representative shall, in writing, submit a request to the Commanding Officer, Naval Submarine Base New London, at...

  18. 32 CFR 770.45 - Entry procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base New London, Groton... consent of the Commanding Officer, Naval Submarine Base New London, or his authorized representative shall, in writing, submit a request to the Commanding Officer, Naval Submarine Base New London, at...

  19. 32 CFR 770.44 - Entry restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base New... upon Naval Submarine Base New London, or remaining thereon by any person for any purpose without the advance consent of the Commanding Officer, Naval Submarine Base New London, or his...

  20. 32 CFR 770.44 - Entry restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Base Entry Regulations for Naval Submarine Base New... upon Naval Submarine Base New London, or remaining thereon by any person for any purpose without the advance consent of the Commanding Officer, Naval Submarine Base New London, or his...