Sample records for calcium increase triggers

  1. Early calcium increase triggers the formation of olfactory long-term memory in honeybees. (United States)

    Perisse, Emmanuel; Raymond-Delpech, Valérie; Néant, Isabelle; Matsumoto, Yukihisa; Leclerc, Catherine; Moreau, Marc; Sandoz, Jean-Christophe


    Synaptic plasticity associated with an important wave of gene transcription and protein synthesis underlies long-term memory processes. Calcium (Ca2+) plays an important role in a variety of neuronal functions and indirect evidence suggests that it may be involved in synaptic plasticity and in the regulation of gene expression correlated to long-term memory formation. The aim of this study was to determine whether Ca2+ is necessary and sufficient for inducing long-term memory formation. A suitable model to address this question is the Pavlovian appetitive conditioning of the proboscis extension reflex in the honeybee Apis mellifera, in which animals learn to associate an odor with a sucrose reward. By modulating the intracellular Ca2+ concentration ([Ca2+]i) in the brain, we show that: (i) blocking [Ca2+]i increase during multiple-trial conditioning selectively impairs long-term memory performance; (ii) conversely, increasing [Ca2+]i during single-trial conditioning triggers long-term memory formation; and finally, (iii) as was the case for long-term memory produced by multiple-trial conditioning, enhancement of long-term memory performance induced by a [Ca2+]i increase depends on de novo protein synthesis. Altogether our data suggest that during olfactory conditioning Ca2+ is both a necessary and a sufficient signal for the formation of protein-dependent long-term memory. Ca2+ therefore appears to act as a switch between short- and long-term storage of learned information.

  2. Inhibitors of arachidonate-regulated calcium channel signaling suppress triggered activity induced by the late sodium current. (United States)

    Wolkowicz, Paul; Umeda, Patrick K; Sharifov, Oleg F; White, C Roger; Huang, Jian; Mahtani, Harry; Urthaler, Ferdinand


    Disturbances in myocyte calcium homeostasis are hypothesized to be one cause for cardiac arrhythmia. The full development of this hypothesis requires (i) the identification of all sources of arrhythmogenic calcium and (ii) an understanding of the mechanism(s) through which calcium initiates arrhythmia. To these ends we superfused rat left atria with the late sodium current activator type II Anemonia sulcata toxin (ATXII). This toxin prolonged atrial action potentials, induced early afterdepolarization, and provoked triggered activity. The calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 (N-[2-[[[3-(4-chlorophenyl)-2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulphon-amide) suppressed ATXII triggered activity but its inactive congener KN-92 (2-[N-(4-methoxy benzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) did not. Neither drug affected normal atrial contractility. Calcium entry via L-type channels or calcium leakage from sarcoplasmic reticulum stores are not critical for this type of ectopy as neither verapamil ((RS)-2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl]-(methyl)amino}-2-prop-2-ylpentanenitrile) nor ryanodine affected ATXII triggered activity. By contrast, inhibitors of the voltage independent arachidonate-regulated calcium (ARC) channel and the store-operated calcium channel specifically suppressed ATXII triggered activity without normalizing action potentials or affecting atrial contractility. Inhibitors of cytosolic calcium-dependent phospholipase A2 also suppressed triggered activity suggesting that this lipase, which generates free arachidonate, plays a key role in ATXII ectopy. Thus, increased left atrial late sodium current appears to activate atrial Orai-linked ARC and store operated calcium channels, and these voltage-independent channels may be unexpected sources for the arrhythmogenic calcium that underlies triggered activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Cellular Mechanisms of Calcium-Mediated Triggered Activity (United States)

    Song, Zhen

    Life-threatening cardiac arrhythmias continue to pose a major health problem. Ventricular fibrillation, which is a complex form of electrical wave turbulence in the lower chambers of the heart, stops the heart from pumping and is the largest cause of natural death in the United States. Atrial fibrillation, a related form of wave turbulence in the upper heart chambers, is in turn the most common arrhythmia diagnosed in clinical practice. Despite extensive research to date, mechanisms of cardiac arrhythmias remain poorly understood. It is well established that both spatial disorder of the refractory period of heart cells and triggered activity (TA) jointly contribute to the initiation and maintenance of arrhythmias. TA broadly refers to the abnormal generation of a single or a sequence of abnormal excitation waves from a small submillimeter region of the heart in the interval of time between two normal waves generated by the heart's natural pacemaker (the sinoatrial node). TA has been widely investigated experimentally and occurs in several pathological conditions where the intracellular concentration of free Ca2+ ions in heart cells becomes elevated. Under such conditions, Ca2+ can be spontaneously released from intracellular stores, thereby driving an electrogenic current that exchanges 3Na+ ions for one Ca2+ ion across the cell membrane. This current in turn depolarizes the membrane of heart cells after a normal excitation. If this calcium-mediated "delayed after depolarization'' (DAD) is sufficiently large, it can generate an action potential. While the arrhythmogenic importance of spontaneous Ca2+ release and DADs is well appreciated, the conditions under which they occur in heart pathologies remain poorly understood. Calcium overload is only one factor among several other factors that can promote DADs, including sympathetic nerve stimulation, different expression levels of membrane ion channels and calcium handling proteins, and different mutations of those

  4. Transgenic plants with increased calcium stores (United States)

    Wyatt, Sarah (Inventor); Tsou, Pei-Lan (Inventor); Robertson, Dominique (Inventor); Boss, Wendy (Inventor)


    The present invention provides transgenic plants over-expressing a transgene encoding a calcium-binding protein or peptide (CaBP). Preferably, the CaBP is a calcium storage protein and over-expression thereof does not have undue adverse effects on calcium homeostasis or biochemical pathways that are regulated by calcium. In preferred embodiments, the CaBP is calreticulin (CRT) or calsequestrin. In more preferred embodiments, the CaBP is the C-domain of CRT, a fragment of the C-domain, or multimers of the foregoing. In other preferred embodiments, the CaBP is localized to the endoplasmic reticulum by operatively associating the transgene encoding the CaBP with an endoplasmic reticulum localization peptide. Alternatively, the CaBP is targeted to any other sub-cellular compartment that permits the calcium to be stored in a form that is biologically available to the plant. Also provided are methods of producing plants with desirable phenotypic traits by transformation of the plant with a transgene encoding a CaBP. Such phenotypic traits include increased calcium storage, enhanced resistance to calcium-limiting conditions, enhanced growth and viability, increased disease and stress resistance, enhanced flower and fruit production, reduced senescence, and a decreased need for fertilizer production. Further provided are plants with enhanced nutritional value as human food or animal feed.

  5. Store-operated calcium entry and increased endothelial cell permeability. (United States)

    Norwood, N; Moore, T M; Dean, D A; Bhattacharjee, R; Li, M; Stevens, T


    We hypothesized that myosin light chain kinase (MLCK) links calcium release to activation of store-operated calcium entry, which is important for control of the endothelial cell barrier. Acute inhibition of MLCK caused calcium release from inositol trisphosphate-sensitive calcium stores and prevented subsequent activation of store-operated calcium entry by thapsigargin, suggesting that MLCK serves as an important mechanism linking store depletion to activation of membrane calcium channels. Moreover, in voltage-clamped single rat pulmonary artery endothelial cells, thapsigargin activated an inward calcium current that was abolished by MLCK inhibition. F-actin disruption activated a calcium current, and F-actin stabilization eliminated the thapsigargin-induced current. Thapsigargin increased endothelial cell permeability in the presence, but not in the absence, of extracellular calcium, indicating the importance of calcium entry in decreasing barrier function. Although MLCK inhibition prevented thapsigargin from stimulating calcium entry, it did not prevent thapsigargin from increasing permeability. Rather, inhibition of MLCK activity increased permeability that was especially prominent in low extracellular calcium. In conclusion, MLCK links store depletion to activation of a store-operated calcium entry channel. However, inhibition of calcium entry by MLCK is not sufficient to prevent thapsigargin from increasing endothelial cell permeability.

  6. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

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    Bading Hilmar


    Full Text Available Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types. Results Using laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border. Conclusion Thus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events.

  7. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients (United States)

    Eder, Anja; Bading, Hilmar


    Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types. Results Using laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border. Conclusion Thus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events. PMID:17663775


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    Wesley Smith


    Level-1 Trigger Hardware and Software New Forward Scintillating Counters (FSC) for rapidity gap measurements have been installed and integrated into the Trigger recently. For the Global Muon Trigger, tuning of quality criteria has led to improvements in muon trigger efficiencies. Several subsystems have started campaigns to increase spares by recovering boards or producing new ones. The barrel muon sector collector test system has been reactivated, new η track finder boards are in production, and φ track finder boards are under revision. In the CSC track finder, an η asymmetry problem has been corrected. New pT look-up tables have also improved efficiency. RPC patterns were changed from four out of six coincident layers to three out of six in the barrel, which led to a significant increase in efficiency. A new PAC firmware to trigger on heavy stable charged particles allows looking for chamber hit coincidences in two consecutive bunch-crossings. The redesign of the L1 Trigger Emulator...


    CERN Document Server

    W. Smith from contributions of C. Leonidopoulos, I. Mikulec, J. Varela and C. Wulz.

    Level-1 Trigger Hardware and Software Over the past few months, the Level-1 trigger has successfully recorded data with cosmic rays over long continuous stretches as well as LHC splash events, beam halo, and collision events. The L1 trigger hardware, firmware, synchronization, performance and readiness for beam operation were reviewed in October. All L1 trigger hardware is now installed at Point 5, and most of it is completely commissioned. While the barrel ECAL Trigger Concentrator Cards are fully operational, the recently delivered endcap ECAL TCC system is still being commissioned. For most systems there is a sufficient number of spares available, but for a few systems additional reserve modules are needed. It was decided to increase the overall L1 latency by three bunch crossings to increase the safety margin for trigger timing adjustments. In order for CMS to continue data taking during LHC frequency ramps, the clock distribution tree needs to be reset. The procedures for this have been tested. A repl...


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    J. Alimena


    Trigger Strategy Group The Strategy for Trigger Evolution And Monitoring (STEAM) group is responsible for the development of future High-Level Trigger menus, as well as of its DQM and validation, in collaboration and with the technical support of the PdmV group. Taking into account the beam energy and luminosity expected in 2015, a rough estimate of the trigger rates indicates a factor four increase with respect to 2012 conditions. Assuming that a factor two can be tolerated thanks to the increase in offline storage and processing capabilities, a toy menu has been developed using the new OpenHLT workflow to estimate the transverse energy/momentum thresholds that would halve the current trigger rates. The CPU time needed to run the HLT has been compared between data taken with 25 ns and 50 ns bunch spacing, for equivalent pile-up: no significant difference was observed on the global time per event distribution at the only available data point, corresponding to a pile-up of about 10 interactions. Using th...

  11. Calcium and caffeine interaction in increased calcium balance in ovariectomized rats

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    Sandra Tavares da Silva


    Full Text Available OBJECTIVE: This study investigated the effects of caffeine intake associated with inadequate or adequate calcium intake in laparotomized or ovariectomized rats by means of the calcium balance. Forty adults Wistar rats were ovariectomized or laparotomized. METHODS: The animals (n=40 were randomly placed in eight groups receiving the AIN-93 diet with 100% or 50% of the recommended calcium intake with or without added caffeine (6mg/kg/day. The animals were kept in individuals metabolic cages at a temperature of 24°±2ºC, light/dark cycles of 12/12 hours, and deionized water available ad libitum. On the 8th week of the experiment, food consumption was measured and 24-hour urine and 4-day feces were collected to determine calcium balance [Balance=Ca intake-(Urinary Ca+Fecal Ca]. RESULTS: Animals with adequate calcium intake presented higher balances and rates of calcium absorption and retention (p<0.05 than those with inadequate calcium intake, regardless of caffeine intake (p<0.05. Caffeine intake did not affect urinary calcium excretion but increased balance (p<0.05 in the groups with adequate calcium intake. CONCLUSION: Adequate calcium intake attenuated the negative effects of estrogen deficiency and improved calcium balance even in the presence of caffeine.

  12. Removal of calcium ions triggers a novel type of intercadherin interaction

    DEFF Research Database (Denmark)

    Troyanovsky, R B; Klingelhöfer, Jörg; Troyanovsky, S


    incorporating the cell-cell adhesive receptors, E-cadherin, desmoglein or desmocollin. Sedimentation and biochemical analysis demonstrated that calcium removal triggers a rapid formation of a novel type of complex formed via direct lateral E-cadherin-desmoglein, E-cadherin-desmocollin and desmoglein......-desmocollin dimerization of the extracellular cadherin regions. Replacement of Trp(156) and Val(157) of E-cadherin, that has been shown to abolish lateral and adhesive E-cadherin homodimerization in standard cultures, did not influence the formation of these 'calcium-sensitive' complexes. Furthermore, experiments...... with this mutant revealed that EGTA induced lateral Trp(156)/Val(157)-independent homodimerization of E-cadherin. Deletion mutagenesis of E-cadherin showed that these complexes are mediated by at least two extracellular cadherin domains, EC3 and EC4. Notably, protein kinase inhibitor H-7 which confers EGTA...

  13. Stochastic initiation and termination of calcium-mediated triggered activity in cardiac myocytes. (United States)

    Song, Zhen; Qu, Zhilin; Karma, Alain


    Cardiac myocytes normally initiate action potentials in response to a current stimulus that depolarizes the membrane above an excitation threshold. Aberrant excitation can also occur due to spontaneous calcium (Ca2+) release (SCR) from intracellular stores after the end of a preceding action potential. SCR drives the Na+/Ca2+ exchange current inducing a "delayed afterdepolarization" that can in turn trigger an action potential if the excitation threshold is reached. This "triggered activity" is known to cause arrhythmias, but how it is initiated and terminated is not understood. Using computer simulations of a ventricular myocyte model, we show that initiation and termination are inherently random events. We determine the probability of those events from statistical measurements of the number of beats before initiation and before termination, respectively, which follow geometric distributions. Moreover, we elucidate the origin of randomness by a statistical analysis of SCR events, which do not follow a Poisson process observed in other eukaryotic cells. Due to synchronization of Ca2+ releases during the action potential upstroke, waiting times of SCR events after the upstroke are narrowly distributed, whereas SCR amplitudes follow a broad normal distribution with a width determined by fluctuations in the number of independent Ca2+ wave foci. This distribution enables us to compute the probabilities of initiation and termination of bursts of triggered activity that are maintained by a positive feedback between the action potential upstroke and SCR. Our results establish a theoretical framework for interpreting complex and varied manifestations of triggered activity relevant to cardiac arrhythmias.

  14. Serum Calcium Increase Correlates With Worsening of Lipid Profile (United States)

    Gallo, Luigia; Faniello, Maria C.; Canino, Giovanni; Tripolino, Cesare; Gnasso, Agostino; Cuda, Giovanni; Costanzo, Francesco S.; Irace, Concetta


    Abstract Despite the well-documented role of calcium in cell metabolism, its role in the development of cardiovascular disease is still under heavy debate. Several studies suggest that calcium supplementation might be associated with an increased risk of coronary heart disease, whereas others underline a significant effect on lowering high blood pressure and hyperlipidemia. The purpose of this study was to investigate, in a large nonselected cohort from South Italy, if serum calcium levels correlate with lipid values and can therefore be linked to higher individual cardiovascular risk. Eight-thousand-six-hundred-ten outpatients addressed to the Laboratory of Clinical Biochemistry, University of Magna Græcia, Catanzaro, Italy from January 2012 to December 2013 for routine blood tests, were enrolled in the study. Total HDL-, LDL- and non-HDL colesterol, triglycerides, and calcium were determined with standard methods. We observed a significant association between total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, triglycerides, and serum calcium in men and postmenopause women. Interestingly, in premenopause women, we only found a direct correlation between serum calcium, total cholesterol, and HDL-cholesterol. Calcium significantly increased while increasing total cholesterol and triglycerides in men and postmenopause women. Our results confirm that progressive increase of serum calcium level correlates with worsening of lipid profile in our study population. Therefore, we suggest that a greater caution should be used in calcium supplement prescription particularly in men and women undergoing menopause, in which an increase of serum lipids is already known to be associated with a higher cardiovascular risk. PMID:26937904

  15. Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium.

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    Vivek Mishra

    Full Text Available Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825 on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated

  16. Alpha hemolysin induces an increase of erythrocytes calcium: a FLIM 2-photon phasor analysis approach.

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    Susana Sanchez

    Full Text Available α-Hemolysin (HlyA from Escherichia coli is considered as the prototype of a family of toxins called RTX (repeat in toxin, a group of proteins that share genetic and structural features. HlyA is an important virulence factor in E. coli extraintestinal infections, such as meningitis, septicemia and urinary infections. High concentrations of the toxin cause the lysis of several cells such as erythrocytes, granulocytes, monocytes, endothelial and renal epithelial cells of different species. At low concentrations it induces the production of cytokines and apoptosis. Since many of the subcytolytic effects in other cells have been reported to be triggered by the increase of intracellular calcium, we followed the calcium concentration inside the erythrocytes while incubating with sublytic concentrations of HlyA. Calcium concentration was monitored using the calcium indicator Green 1, 2-photon excitation, and fluorescence lifetime imaging microscopy (FLIM. Data were analyzed using the phasor representation. In this report, we present evidence that, at sublytic concentrations, HlyA induces an increase of calcium concentration in rabbit erythrocytes in the first 10 s. Results are discussed in relation to the difficulties of measuring calcium concentrations in erythrocytes where hemoglobin is present, the contribution of the background and the heterogeneity of the response observed in individual cells.


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    Wesley Smith

    Level-1 Trigger Hardware and Software The hardware of the trigger components has been mostly finished. The ECAL Endcap Trigger Concentrator Cards (TCC) are in production while Barrel TCC firmware has been upgraded, and the Trigger Primitives can now be stored by the Data Concentrator Card for readout by the DAQ. The Regional Calorimeter Trigger (RCT) system is complete, and the timing is being finalized. All 502 HCAL trigger links to RCT run without error. The HCAL muon trigger timing has been equalized with DT, RPC, CSC and ECAL. The hardware and firmware for the Global Calorimeter Trigger (GCT) jet triggers are being commissioned and data from these triggers is available for readout. The GCT energy sums from rings of trigger towers around the beam pipe beam have been changed to include two rings from both sides. The firmware for Drift Tube Track Finder, Barrel Sorter and Wedge Sorter has been upgraded, and the synchronization of the DT trigger is satisfactory. The CSC local trigger has operated flawlessly u...

  18. Calcium intake increases risk of prostate cancer among Singapore Chinese (United States)

    Butler, Lesley M.; Wong, Alvin S.; Koh, Woon-Puay; Wang, Renwei; Yuan, Jian-Min; Yu, Mimi C.


    Consumption of dairy products, the primary source of calcium in Western diets, has been found to be positively associated with prostate cancer. In an Asian diet, non-dairy foods are the major contributors of calcium. Thus, a study of dietary calcium and prostate cancer in Asians can better inform on whether calcium, as opposed to other dairy components is responsible for the dairy foods-prostate cancer association. We examined calcium intake and prostate cancer risk among 27,293 men of the Singapore Chinese Health Study that was established between 1993 and 1998. As of December 31, 2007, 298 incident prostate cancer cases had been diagnosed among the cohort members. Diet was assessed at baseline with a validated 165-item food frequency questionnaire. It is hypothesized that there is greater net absorption of calcium in smaller individuals. Therefore, the calcium-prostate cancer association was also assessed in stratified analyses by median body mass index (BMI). Vegetables were the largest contributor of daily calcium intake in the study population. Overall, we observed a modest, statistically nonsignificant 25% increase in prostate cancer risk for the 4th (median = 659 mg/day) versus 1st (median=211 mg/day) quartiles of calcium intake after adjustment for potential confounders. The association became considerably stronger and achieved statistical significance (hazard ratio=2.03; 95% confidence interval: 1.23, 3.34; P for trend=0.01) for men with below median (22.9 kg/m2) BMI. Dietary calcium may be a risk factor for prostate cancer even at relatively low intake. PMID:20516117


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    Roberta Arcidiacono


    Trigger Studies Group (TSG) The Trigger Studies Group has just concluded its third 2013 workshop, where all POGs presented the improvements to the physics object reconstruction, and all PAGs have shown their plans for Trigger development aimed at the 2015 High Level Trigger (HLT) menu. The Strategy for Trigger Evolution And Monitoring (STEAM) group is responsible for Trigger menu development, path timing, Trigger performance studies coordination, HLT offline DQM as well as HLT release, menu and conditions validation – this last task in collaboration with PdmV (Physics Data and Monte Carlo Validation group). In the last months the group has delivered several HLT rate estimates and comparisons, using the available data and Monte Carlo samples. The studies were presented at the Trigger workshops in September and December, and STEAM has contacted POGs and PAGs to understand the origin of the discrepancies observed between 8 TeV data and Monte Carlo simulations. The most recent results show what the...

  20. Triggers

    NARCIS (Netherlands)

    Breitbarth, A.; van Riemsdijk, H.C.


    The concept of 'trigger' is a core concept of Chomsky's Minimalist Program. The idea that certain types of movement are triggered by some property of the target position is at least as old as the notion that the movement of noun phrases to the subject position is triggered by their need to receive


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    Wesley Smith

    Level-1 Trigger Hardware and Software The trigger synchronization procedures for running with cosmic muons and operating with the LHC were reviewed during the May electronics week. Firmware maintenance issues were also reviewed. Link tests between the new ECAL endcap trigger concentrator cards (TCC48) and the Regional Calorimeter Trigger have been performed. Firmware for the energy sum triggers and an upgraded tau trigger of the Global Calorimeter Triggers has been developed and is under test. The optical fiber receiver boards for the Track-Finder trigger theta links of the DT chambers are now all installed. The RPC trigger is being made more robust by additional chamber and cable shielding and also by firmware upgrades. For the CSC’s the front-end and trigger motherboard firmware have been updated. New RPC patterns and DT/CSC lookup tables taking into account phi asymmetries in the magnetic field configuration are under study. The motherboard for the new pipeline synchronizer of the Global Trigg...


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    W. Smith


      Level-1 Trigger The Level-1 Trigger group is ready to deploy improvements to the L1 Trigger algorithms for 2012. These include new high-PT patterns for the RPC endcap, an improved CSC PT assignment, a new PT-matching algorithm for the Global Muon Trigger, and new calibrations for ECAL, HCAL, and the Regional Calorimeter Trigger. These should improve the efficiency, rate, and stability of the L1 Trigger. The L1 Trigger group also is migrating the online systems to SLC5. To make the data transfer from the Global Calorimeter Trigger to the Global Trigger more reliable and also to allow checking the data integrity online, a new optical link system has been developed by the GCT and GT groups and successfully tested at the CMS electronics integration facility in building 904. This new system is now undergoing further tests at Point 5 before being deployed for data-taking this year. New L1 trigger menus have recently been studied and proposed by Emmanuelle Perez and the L1 Detector Performance Group...


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    W. Smith

    At the March meeting, the CMS trigger group reported on progress in production, tests in the Electronics Integration Center (EIC) in Prevessin 904, progress on trigger installation in the underground counting room at point 5, USC55, the program of trigger pattern tests and vertical slice tests and planning for the Global Runs starting this summer. The trigger group is engaged in the final stages of production testing, systems integration, and software and firmware development. Most systems are delivering final tested electronics to CERN. The installation in USC55 is underway and integration testing is in full swing. A program of orderly connection and checkout with subsystems and central systems has been developed. This program includes a series of vertical subsystem slice tests providing validation of a portion of each subsystem from front-end electronics through the trigger and DAQ to data captured and stored. After full checkout, trigger subsystems will be then operated in the CMS Global Runs. Continuous...


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    Wesley Smith

    Level-1 Trigger Hardware and Software The production of the trigger hardware is now basically finished, and in time for the turn-on of the LHC. The last boards produced are the Trigger Concentrator Cards for the ECAL Endcaps (TCC-EE). After the recent installation of the four EE Dees, the TCC-EE prototypes were used for their commissioning. Production boards are arriving and are being tested continuously, with the last ones expected in November. The Regional Calorimeter Trigger hardware is fully integrated after installation of the last EE cables. Pattern tests from the HCAL up to the GCT have been performed successfully. The HCAL triggers are fully operational, including the connection of the HCAL-outer and forward-HCAL (HO/HF) technical triggers to the Global Trigger. The HCAL Trigger and Readout (HTR) board firmware has been updated to permit recording of the tower “feature bit” in the data. The Global Calorimeter Trigger hardware is installed, but some firmware developments are still n...


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    by Wesley Smith


    Level-1 Trigger Hardware and Software The overall status of the L1 trigger has been excellent and the running efficiency has been high during physics fills. The timing is good to about 1%. The fine-tuning of the time synchronization of muon triggers is ongoing and will be completed after more than 10 nb-1 of data have been recorded. The CSC trigger primitive and RPC trigger timing have been refined. A new configuration for the CSC Track Finder featured modified beam halo cuts and improved ghost cancellation logic. More direct control was provided for the DT opto-receivers. New RPC Cosmic Trigger (RBC/TTU) trigger algorithms were enabled for collision runs. There is further work planned during the next technical stop to investigate a few of the links from the ECAL to the Regional Calorimeter Trigger (RCT). New firmware and a new configuration to handle trigger rate spikes in the ECAL barrel are also being tested. A board newly developed by the tracker group (ReTRI) has been installed and activated to block re...

  6. Some Factors Trigger Increasing Foodborne Diseases Cases of Livestock Origin

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    Anni Kusumaningsih


    Full Text Available Food is an essential need for various human body activities. Consequently, food must be guaranteed to be free from biological, chemical, and physical contaminants and other hazardous substances that can obstruct health. The presence of various hazardous contaminants in food may result in the appearance of foodborne diseases, i.e. human diseases spread through contaminated food and drinks. Biological contaminants in food can be bacteria, viruses, parasites, moulds, or fungi. The most dangerous biological contaminants that may cause an epidemic disease in human are pathogenic bacteria such as Salmonella spp., Escherichia coli, Bacillus anthracis, Clostridium spp., Listeria monocytogenes, Campylobacter spp., Vibrio cholerae, Enterobacter sakazakii, Shigella, etc. Researchers believe that there are several factors that can be the trigger that increase of foodborne diseases cases such as community demography by increasing the individual groups that are more susceptible to pathogenic foodborne infections, human behaviour related to the changes in the community life style and consumption, the advances in industrial and technological sectors through the increase of large scale food industries concentrated in one location, the global trade or travel, and increasing bacterial resistances against antimicrobials as the result of the increasing the uses of antimicrobials for disease prevention and cure in animals and humans.


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    W. Smith


    Level-1 Trigger Hardware and Software The Level-1 Trigger hardware has performed well during both the recent proton-proton and heavy ion running. Efforts were made to improve the visibility and handling of alarms and warnings. The tracker ReTRI boards that prevent fixed frequencies of Level-1 Triggers are now configured through the Trigger Supervisor. The Global Calorimeter Trigger (GCT) team has introduced a buffer cleanup procedure at stops and a reset of the QPLL during configuring to ensure recalibration in case of a switch from the LHC clock to the local clock. A device to test the cables between the Regional Calorimeter Trigger and the GCT has been manufactured. A wrong charge bit was fixed in the CSC Trigger. The ECAL group is improving crystal masking and spike suppression in the trigger primitives. New firmware for the Drift Tube Track Finder (DTTF) sorters was developed to improve fake track tagging and sorting. Zero suppression was implemented in the DT Sector Collector readout. The track finder b...


    CERN Multimedia

    Wesley Smith

    Trigger Hardware The status of the trigger components was presented during the September CMS Week and Annual Review and at the monthly trigger meetings in October and November. Procedures for cold and warm starts (e.g. refreshing of trigger parameters stored in registers) of the trigger subsystems have been studied. Reviews of parts of the Global Calorimeter Trigger (GCT) and the Global Trigger (GT) have taken place in October and November. The CERN group summarized the status of the Trigger Timing and Control (TTC) system. All TTC crates and boards are installed in the underground counting room, USC55. The central clock system will be upgraded in December (after the Global Run at the end of November GREN) to the new RF2TTC LHC machine interface timing module. Migration of subsystem's TTC PCs to SLC4/ XDAQ 3.12 is being prepared. Work is on going to unify the access to Local Timing Control (LTC) and TTC CMS interface module (TTCci) via SOAP (Simple Object Access Protocol, a lightweight XML-based messaging ...


    CERN Multimedia

    W. Smith from contributions of C. Leonidopoulos


    Level-1 Trigger Hardware and Software Since nearly all of the Level-1 (L1) Trigger hardware at Point 5 has been commissioned, activities during the past months focused on the fine-tuning of synchronization, particularly for the ECAL and the CSC systems, on firmware upgrades and on improving trigger operation and monitoring. Periodic resynchronizations or hard resets and a shortened luminosity section interval of 23 seconds were implemented. For the DT sector collectors, an automatic power-off was installed in case of high temperatures, and the monitoring capabilities of the opto-receivers and the mini-crates were enhanced. The DTTF and the CSCTF now have improved memory lookup tables. The HCAL trigger primitive logic implemented a new algorithm providing better stability of the energy measurement in the presence of any phase misalignment. For the Global Calorimeter Trigger, additional Source Cards have been manufactured and tested. Testing of the new tau, missing ET and missing HT algorithms is underw...


    CERN Multimedia

    Wesley Smith

    Level-1 Trigger Hardware and Software The final parts of the Level-1 trigger hardware are now being put in place. For the ECAL endcaps, more than half of the Trigger Concentrator Cards for the ECAL Endcap (TCC-EE) are now available at CERN, such that one complete endcap can be covered. The Global Trigger now correctly handles ECAL calibration sequences, without being influenced by backpressure. The Regional Calorimeter Trigger (RCT) hardware is complete and working in USC55. Intra-crate tests of all 18 RCT crates and the Global Calorimeter Trigger (GCT) are regularly taking place. Pattern tests have successfully captured data from HCAL through RCT to the GCT Source Cards. HB/HE trigger data are being compared with emulator results to track down the very few remaining hardware problems. The treatment of hot and dead cells, including their recording in the database, has been defined. For the GCT, excellent agreement between the emulator and data has been achieved for jets and HF ET sums. There is still som...


    CERN Multimedia

    W. Smith

    Level-1 Trigger Hardware and Software The trigger system has been constantly in use in cosmic and commissioning data taking periods. During CRAFT running it delivered 300 million muon and calorimeter triggers to CMS. It has performed stably and reliably. During the abort gaps it has also provided laser and other calibration triggers. Timing issues, namely synchronization and latency issues, have been solved. About half of the Trigger Concentrator Cards for the ECAL Endcap (TCC-EE) are installed, and the firmware is being worked on. The production of the other half has started. The HCAL Trigger and Readout (HTR) card firmware has been updated, and new features such as fast parallel zero-suppression have been included. Repairs of drift tube (DT) trigger mini-crates, optical links and receivers of sector collectors are under way and have been completed on YB0. New firmware for the optical receivers of the theta links to the drift tube track finder is being installed. In parallel, tests with new eta track finde...


    CERN Multimedia

    R. Carlin with contributions from D. Acosta


    Level-1 Trigger Data-taking continues at cruising speed, with high availability of all components of the Level-1 trigger. We have operated the trigger up to a luminosity of 7.6E33, where we approached 100 kHz using the 7E33 prescale column.  Recently, the pause without triggers in case of an automatic "RESYNC" signal (the "settle" and "recover" time) was reduced in order to minimise the overall dead-time. This may become very important when the LHC comes back with higher energy and luminosity after LS1. We are also preparing for data-taking in the proton-lead run in early 2013. The CASTOR detector will make its comeback into CMS and triggering capabilities are being prepared for this. Steps to be taken include improved cooperation with the TOTEM trigger system and using the LHC clock during the injection and ramp phases of LHC. Studies are being finalised that will have a bearing on the Trigger Technical Design Report (TDR), which is to be rea...


    CERN Multimedia

    W. Smith

    At the December meeting, the CMS trigger group reported on progress in production, tests in the Electronics Integration Center (EIC) in Prevessin 904, progress on trigger installation in the underground counting room at point 5, USC55, and results from the Magnet Test and Cosmic Challenge (MTCC) phase II. The trigger group is engaged in the final stages of production testing, systems integration, and software and firmware development. Most systems are delivering final tested electronics to CERN. The installation in USC55 is underway and moving towards integration testing. A program of orderly connection and checkout with subsystems and central systems has been developed. This program includes a series of vertical subsystem slice tests providing validation of a portion of each subsystem from front-end electronics through the trigger and DAQ to data captured and stored. This is combined with operations and testing without beam that will continue until startup. The plans for start-up, pilot and early running tri...


    CERN Multimedia

    W. Smith

    Level-1 Trigger Hardware and Software The road map for the final commissioning of the level-1 trigger system has been set. The software for the trigger subsystems is being upgraded to run under CERN Scientific Linux 4 (SLC4). There is also a new release for the Trigger Supervisor (TS 1.4), which implies upgrade work by the subsystems. As reported by the CERN group, a campaign to tidy the Trigger Timing and Control (TTC) racks has begun. The machine interface was upgraded by installing the new RF2TTC module, which receives RF signals from LHC Point 4. Two Beam Synchronous Timing (BST) signals, one for each beam, can now be received in CMS. The machine group will define the exact format of the information content shortly. The margin on the locking range of the CMS QPLL is planned for study for different subsystems in the next Global Runs, using a function generator. The TTC software has been successfully tested on SLC4. Some TTC subsystems have already been upgraded to SLC4. The TTCci Trigger Supervisor ...


    CERN Multimedia

    W. Smith, from contributions of D. Acosta


      The L1 Trigger group deployed several major improvements this year. Compared to 2011, the single-muon trigger rate has been reduced by a factor of 2 and the η coverage has been restored to 2.4, with high efficiency. During the current technical stop, a higher jet seed threshold will be applied in the Global Calorimeter Trigger in order to significantly reduce the strong pile-up dependence of the HT and multi-jet triggers. The currently deployed L1 menu, with the “6E33” prescales, has a total rate of less than 100 kHz and operates with detector readout dead time of less than 3% for luminosities up to 6.5 × 1033 cm–2s–1. Further prescale sets have been created for 7 and 8 × 1033 cm–2s–1 luminosities. The L1 DPG is evaluating the performance of the Trigger for upcoming conferences and publication. Progress on the Trigger upgrade was reviewed during the May Upgrade Week. We are investigating scenarios for stagin...


    CERN Multimedia

    R. Arcidiacono


      In 2013 the Trigger Studies Group (TSG) has been restructured in three sub-groups: STEAM, for the development of new HLT menus and monitoring their performance; STORM, for the development of HLT tools, code and actual configurations; and FOG, responsible for the online operations of the High Level Trigger. The Strategy for Trigger Evolution And Monitoring (STEAM) group is responsible for Trigger Menu development, path timing, trigger performance studies coordination, HLT offline DQM as well as HLT release, menu and conditions validation – in collaboration and with the technical support of the PdmV group. Since the end of proton-proton data taking, the group has started preparing for 2015 data taking, with collisions at 13 TeV and 25 ns bunch spacing. The reliability of the extrapolation to higher energy is being evaluated comparing the trigger rates on 7 and 8 TeV Monte Carlo samples with the data taken in the past two years. The effect of 25 ns bunch spacing is being studied on the d...


    CERN Multimedia

    W. Smith


    Level-1 Trigger Hardware and Software Overall the L1 trigger hardware has been running very smoothly during the last months of proton running. Modifications for the heavy-ion run have been made where necessary. The maximal design rate of 100 kHz can be sustained without problems. All L1 latencies have been rechecked. The recently installed Forward Scintillating Counters (FSC) are being used in the heavy ion run. The ZDC scintillators have been dismantled, but the calorimeter itself remains. We now send the L1 accept signal and other control signals to TOTEM. Trigger cables from TOTEM to CMS will be installed during the Christmas shutdown, so that the TOTEM data can be fully integrated within the CMS readout. New beam gas triggers have been developed, since the BSC-based trigger is no longer usable at high luminosities. In particular, a special BPTX signal is used after a quiet period with no collisions. There is an ongoing campaign to provide enough spare modules for the different subsystems. For example...


    CERN Multimedia

    by Wesley Smith


    Level-1 Trigger Hardware and Software After the winter shutdown minor hardware problems in several subsystems appeared and were corrected. A reassessment of the overall latency has been made. In the TTC system shorter cables between TTCci and TTCex have been installed, which saved one bunch crossing, but which may have required an adjustment of the RPC timing. In order to tackle Pixel out-of-syncs without influencing other subsystems, a special hardware/firmware re-sync protocol has been introduced in the Global Trigger. The link between the Global Calorimeter Trigger and the Global Trigger with the new optical Global Trigger Interface and optical receiver daughterboards has been successfully tested in the Electronics Integration Centre in building 904. New firmware in the GCT now allows a setting to remove the HF towers from energy sums. The HF sleeves have been replaced, which should lead to reduced rates of anomalous signals, which may allow their inclusion after this is validated. For ECAL, improvements i...

  19. Contractions induced by a calcium-triggered release of calcium from the sarcoplasmic reticulum of single skinned cardiac cells. (United States)

    Fabiato, A; Fabiato, F


    1. Fragments of single cardiac cells were obtained by homogenization of ventricular tissue from adult rats. Remaining pieces of sacrolemma were removed by micro-dissection. Tension was recorded from the ends of the skinned (sarcolemma-free) cells with a photodiode force transducer. 2. In the presence of a strong buffering of the free [Ca2+] with 4-0 mM total EGTA, a tonic tension was obtained that increased according to t sigmoid curve when the free ([Ca2+] was increased from 10(-6-75)M to 10(-5-0)M. This curve was not modified by the destruction of the sarcoplasmic reticulum (SR) by the detergent Brij 58. Therefore, the tonic tension corresponded to the direct effect of the free [Ca2+] present in the buffer on the myofilaments. 3. In the presence of a slight buffering of the free [Ca2+] with 0-050 mM total EGTA, cyclic contractions were observed that were attributed to cyclic releases and re-sequestrations of Ca2+ by the SR. The absence of effect of azide and ruthenium red on the cyclic contractions obtained at a free [Ca2+] lower than 10(-6-50)M demonstrated that the mitochondria played no role in the triggering of these contractions. 4. Cyclic contractions were induced by a slight variation of free [Ca2+] in the buffer from 10(-7-65)M to 10(-7-40)M. Their amplitude at 10(-7-40)M free Ca2+ was equal to the tonic tension developed by a free [Ca2+] 20 times higher applied to the myofilaments when the SR was destroyed by detergent or functionally inhibited by high total [EGTA]. It was concluded that these cyclic contractions corresponded to a Ca2+-triggered release of Ca2+ from the SR. 5. The cyclic contractions were induced by the filling of the SR with Ca2+ to a critical level at which it released a fraction of the Ca2+ it contained. Each contraction was followed by a re-sequestration of Ca2+, the kinetics of which conditioned the duration of the cycles. 6. The amplitude of the cyclic contractions increased when the free [Ca2+] that triggered them was increased


    CERN Multimedia

    W. Smith

    Level-1 Trigger Hardware The CERN group is working on the TTC system. Seven out of nine sub-detector TTC VME crates with all fibers cabled are installed in USC55. 17 Local Trigger Controller (LTC) boards have been received from production and are in the process of being tested. The RF2TTC module replacing the TTCmi machine interface has been delivered and will replace the TTCci module used to mimic the LHC clock. 11 out of 12 crates housing the barrel ECAL off-detector electronics have been installed in USC55 after commissioning at the Electronics Integration Centre in building 904. The cabling to the Regional Calorimeter Trigger (RCT) is terminated. The Lisbon group has completed the Synchronization and Link mezzanine board (SLB) production. The Palaiseau group has fully tested and installed 33 out of 40 Trigger Concentrator Cards (TCC). The seven remaining boards are being remade. The barrel TCC boards have been tested at the H4 test beam, and good agreement with emulator predictions were found. The cons...

  1. Increasing of Mechanical Parameters of Clay soil Using Calcium Chloride (United States)

    Beheshty, Seyyed Amir Hossein; Moosa Aniran, Mir; Firoozfar, Alireza; Kiamehr, Ramin


    Research on roads to increase the resistance of weak soils to build structures on it has been increased in recent years. The present article provide the effects of different mixtures containing calcium chloride solution and clay soil on mechanical parameters such as, compressibility, compressive strength, shear strength and durability characteristic. In this study also is investigated evaluation the effect of road subgrade based on proposed material. The used clay soil in this research was obtained from zanjan city where is located in northwestern of Iran. The obtained results show that the calcium chloride solution could play a major role in reducing the cost and required time for building roads and also building foundation on these types of soils.

  2. The increasing of enamel calcium level after casein phosphopeptideamorphous calcium phosphate covering

    Directory of Open Access Journals (Sweden)

    Widyasri Prananingrum


    Full Text Available Background: Caries process is characterized by the presence of demineralization. Demineralization is caused by organic acids as a result of carbohydrate substrate fermentation. Remineralization is a natural repair process for non-cavitated lesions. Remineralization occurs if there are Ca2+ and PO43- ions in sufficient quantities. Casein-amorphous calcium phosphate phosphopeptide (CPP-ACP is a paste material containing milk protein (casein, that actually contains minerals, such as calcium and phosphate. The casein ability to stabilize calcium phosphate and enhance mineral solubility and bioavailability confers upon CPP potential to be biological delivery vehicles for calcium and phosphate. Purpose: The aim of this study was to determine the calcium levels in tooth enamel after being covered with CPP-ACP 2 times a day for 3, 14 and 28 days. Methods: Sample were bovine incisors of 3 year old cows divided into 4 groups, namely group I as control group, group II, III and IV as treatment groups covered with CPP-ACP 2 times a day. All of those teeth were then immersed in artificial saliva. Group II was immersed for 3 days, while group III was immersed for 14 days, and group IV was immersed for 28 days. One drop of CPP-ACP was used to cover the entire labial surface of teeth. The measurement of the calcium levels was then conducted by using titration method. All data were analyzed by One- Way ANOVA test with 5% degree of confidence. Results: The results showed significant difference of the calcium levels in tooth enamel of those groups after covered with CPP-ACP 2 times a day for 3, 14 and 28 days (p = 0.001. There is also significant difference of the calcium levels in tooth enamel of those treatment groups and the control group (p = 0.001. Conclusion: The calcium levels of tooth enamel are increased after covered with CPP-ACP 2 times a day for 3, 14 and 28 days.Latar belakang: Proses terjadinya karies gigi ditandai oleh adanya demineralisasi

  3. Triggered intracellular calcium waves in dog and human left atrial myocytes from normal and failing hearts. (United States)

    Aistrup, Gary L; Arora, Rishi; Grubb, Søren; Yoo, Shin; Toren, Benjamin; Kumar, Manvinder; Kunamalla, Aaron; Marszalec, William; Motiwala, Tej; Tai, Shannon; Yamakawa, Sean; Yerrabolu, Satya; Alvarado, Francisco J; Valdivia, Hector H; Cordeiro, Jonathan M; Shiferaw, Yohannes; Wasserstrom, John Andrew


    Abnormal intracellular Ca2+ cycling contributes to triggered activity and arrhythmias in the heart. We investigated the properties and underlying mechanisms for systolic triggered Ca2+ waves in left atria from normal and failing dog hearts. Intracellular Ca2+ cycling was studied using confocal microscopy during rapid pacing of atrial myocytes (36 °C) isolated from normal and failing canine hearts (ventricular tachypacing model). In normal atrial myocytes (NAMs), Ca2+ waves developed during rapid pacing at rates ≥ 3.3 Hz and immediately disappeared upon cessation of pacing despite high sarcoplasmic reticulum (SR) load. In heart failure atrial myocytes (HFAMs), triggered Ca2+ waves (TCWs) developed at a higher incidence at slower rates. Because of their timing, TCW development relies upon action potential (AP)-evoked Ca2+ entry. The distribution of Ca2+ wave latencies indicated two populations of waves, with early events representing TCWs and late events representing conventional spontaneous Ca2+ waves. Latency analysis also demonstrated that TCWs arise after junctional Ca2+ release has occurred and spread to non-junctional (cell core) SR. TCWs also occurred in intact dog atrium and in myocytes from humans and pigs. β-adrenergic stimulation increased Ca2+ release and abolished TCWs in NAMs but was ineffective in HFAMs making this a potentially effective adaptive mechanism in normals but potentially arrhythmogenic in HF. Block of Ca-calmodulin kinase II also abolished TCWs, suggesting a role in TCW formation. Pharmacological manoeuvres that increased Ca2+ release suppressed TCWs as did interventions that decreased Ca2+ release but these also severely reduced excitation-contraction coupling. TCWs develop during the atrial AP and thus could affect AP duration, producing repolarization gradients and creating a substrate for reentry, particularly in HF where they develop at slower rates and a higher incidence. TCWs may represent a mechanism for the initiation

  4. Remote sensing observations of phytoplankton increases triggered by successive typhoons (United States)

    Huang, Lei; Zhao, Hui; Pan, Jiayi; Devlin, Adam


    Phytoplankton blooms in the Western North Pacific, triggered by two successive typhoons with different intensities and translation speeds under different pre-existing oceanic conditions, were observed and analyzed using remotely sensed chlorophyll-a (Chl-a), sea surface temperature (SST), and sea surface height anomaly (SSHA) data, as well as typhoon parameters and CTD (conductivity, temperature, and depth) profiles. Typhoon Sinlaku, with relatively weaker intensity and slower translation speed, induced a stronger phytoplankton bloom than Jangmi with stronger intensity and faster translation speed (Chl-a>0.18 mg·m‒3 versus Chl-aphytoplankton blooms in the study area. Pre-existing cyclonic circulations provided a relatively unstable thermodynamic structure for Sinlaku, and therefore cold water with rich nutrients could be brought up easily. The mixed-layer deepening caused by Typhoon Sinlaku, which occurred first, could have triggered an unfavorable condition for the phytoplankton bloom induced by Typhoon Jangmi which followed afterwards. The sea surface temperature cooling by Jangmi was suppressed due to the presence of the thick upper-ocean mixed-layer, which prevented the deeper cold water from being entrained into the upper-ocean mixed layer, leading to a weaker phytoplankton augment. The present study suggests that both wind (including typhoon translation speed and intensity) and pre-existing conditions (e.g., mixed-layer depths, eddies, and nutrients) play important roles in the strong phytoplankton bloom, and are responsible for the stronger phytoplankton bloom after Sinlaku's passage than that after Jangmi's passage. A new typhoon-influencing parameter is introduced that combines the effects of the typhoon forcing (including the typhoon intensity and translation speed) and the oceanic pre-condition. This parameter shows that the forcing effect of Sinlaku was stronger than that of Jangmi.

  5. Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins

    DEFF Research Database (Denmark)

    Hsu, Yu-Juei; Dimke, Henrik Anthony; Schoeber, Joost P H


    Although gender differences in the renal handling of calcium have been reported, the overall contribution of androgens to these differences remains uncertain. We determined here whether testosterone affects active renal calcium reabsorption by regulating calcium transport proteins. Male mice had...... higher urinary calcium excretion than female mice and their renal calcium transporters were expressed at a lower level. We also found that orchidectomized mice excreted less calcium in their urine than sham-operated control mice and that the hypocalciuria was normalized after testosterone replacement...... calcium transport. Thus, our study shows that gender differences in renal calcium handling are, in part, mediated by the inhibitory actions of androgens on TRPV5-mediated active renal calcium transport....

  6. Calcium fertilization increases the concentration of calcium in sapwood and calcium oxalate in foliage of red spruce (United States)

    Kevin T. Smith; Walter C. Shortle; Jon H. Connolly; Rakesh Minocha; Jody Jellison


    Calcium cycling plays a key role in the health and productivity of red spruce forests in the northeastern US. A portion of the flowpath of calcium within forests includes translocation as Ca2+ in sapwood and accumulation as crystals of calcium oxalate in foliage. Concentrations of Ca in these tree tissues have been used as markers of...

  7. Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Bosche, Bert, E-mail: [Department of Neurology, University of Duisburg-Essen (Germany); Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Schäfer, Matthias, E-mail: [Institute of Physiology, Justus-Liebig-University Giessen (Germany); Graf, Rudolf, E-mail: [Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Härtel, Frauke V., E-mail: [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany); Schäfer, Ute, E-mail: [Research Unit for Experimental Neurotraumatology, Medical University of Graz (Austria); Noll, Thomas, E-mail: [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany)


    Highlights: •We investigate free calcium as a central signalling element in endothelial cells. •Inhibition of glycolysis with 2-deoxy-D-glucose reduces cellular ATP. •This manoeuvre leads to a biphasic increase and overload of free calcium. •Pre-treatment with lithium for 24 h abolishes both phases of the calcium increase. •This provides a new strategy to protect endothelial calcium homeostasis and barrier function. -- Abstract: Cytosolic free calcium concentration ([Ca{sup 2+}]{sub i}) is a central signalling element for the maintenance of endothelial barrier function. Under physiological conditions, it is controlled within narrow limits. Metabolic inhibition during ischemia/reperfusion, however, induces [Ca{sup 2+}]{sub i} overload, which results in barrier failure. In a model of cultured porcine aortic endothelial monolayers (EC), we addressed the question of whether [Ca{sup 2+}]{sub i} overload can be prevented by lithium treatment. [Ca{sup 2+}]{sub i} and ATP were analysed using Fura-2 and HPLC, respectively. The combined inhibition of glycolytic and mitochondrial ATP synthesis by 2-desoxy-D-glucose (5 mM; 2-DG) plus sodium cyanide (5 mM; NaCN) caused a significant decrease in cellular ATP content (14 ± 1 nmol/mg protein vs. 18 ± 1 nmol/mg protein in the control, n = 6 culture dishes, P < 0.05), an increase in [Ca{sup 2+}]{sub i} (278 ± 24 nM vs. 71 ± 2 nM in the control, n = 60 cells, P < 0.05), and the formation of gaps between adjacent EC. These observations indicate that there is impaired barrier function at an early state of metabolic inhibition. Glycolytic inhibition alone by 10 mM 2-DG led to a similar decrease in ATP content (14 ± 2 nmol/mg vs. 18 ± 1 nmol/mg in the control, P < 0.05) with a delay of 5 min. The [Ca{sup 2+}]{sub i} response of EC was biphasic with a peak after 1 min (183 ± 6 nM vs. 71 ± 1 nM, n = 60 cells, P < 0.05) followed by a sustained increase in [Ca{sup 2+}]{sub i}. A 24-h pre-treatment with 10 mM of lithium

  8. Modulation of intracellular calcium waves and triggered activities by mitochondrial ca flux in mouse cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Zhenghang Zhao

    Full Text Available Recent studies have suggested that mitochondria may play important roles in the Ca(2+ homeostasis of cardiac myocytes. However, it is still unclear if mitochondrial Ca(2+ flux can regulate the generation of Ca(2+ waves (CaWs and triggered activities in cardiac myocytes. In the present study, intracellular/cytosolic Ca(2+ (Cai (2+ was imaged in Fluo-4-AM loaded mouse ventricular myocytes. Spontaneous sarcoplasmic reticulum (SR Ca(2+ release and CaWs were induced in the presence of high (4 mM external Ca(2+ (Cao (2+. The protonophore carbonyl cyanide p-(trifluoromethoxyphenylhydrazone (FCCP reversibly raised basal Cai (2+ levels even after depletion of SR Ca(2+ in the absence of Cao (2+ , suggesting Ca(2+ release from mitochondria. FCCP at 0.01 - 0.1 µM partially depolarized the mitochondrial membrane potential (Δψ m and increased the frequency and amplitude of CaWs in a dose-dependent manner. Simultaneous recording of cell membrane potentials showed the augmentation of delayed afterdepolarization amplitudes and frequencies, and induction of triggered action potentials. The effect of FCCP on CaWs was mimicked by antimycin A (an electron transport chain inhibitor disrupting Δψ m or Ru360 (a mitochondrial Ca(2+ uniporter inhibitor, but not by oligomycin (an ATP synthase inhibitor or iodoacetic acid (a glycolytic inhibitor, excluding the contribution of intracellular ATP levels. The effects of FCCP on CaWs were counteracted by the mitochondrial permeability transition pore blocker cyclosporine A, or the mitochondrial Ca(2+ uniporter activator kaempferol. Our results suggest that mitochondrial Ca(2+ release and uptake exquisitely control the local Ca(2+ level in the micro-domain near SR ryanodine receptors and play an important role in regulation of intracellular CaWs and arrhythmogenesis.

  9. Calcium and vitamin D supplementation increases spinal BMD in healthy, postmenopausal women

    DEFF Research Database (Denmark)

    Baeksgaard, L; Andersen, K P; Hyldstrup, Lars


    We undertook a double-masked, randomized, placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip, spine and forearm. The study was performed in 240 healthy women, 58-67 years of age. Duration....... Together with significant changes in serum calcium and serum parathyroid hormone, this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium (calcium carbonate) and 14 micrograms vitamin D3 increases intestinal calcium absorption. A positive effect on BMD was demonstrated...... of treatment was 2 years. Bone mineral density (BMD) was measured at the lumbar spine, hip and forearm. A dietary questionnaire was administered twice during the study and revealed a fairly good calcium and vitamin D intake (919 mg calcium/day; 3.8 micrograms vitamin D/day). An increase in lumbar spine BMD...

  10. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients


    Eder, Anja; Bading, Hilmar


    Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nuc...

  11. Increasing Water Temperature Triggers Dominance of Small Freshwater Plankton (United States)

    Rasconi, Serena; Gall, Andrea; Winter, Katharina; Kainz, Martin J.


    Climate change scenarios predict that lake water temperatures will increase up to 4°C and rainfall events will become more intense and frequent by the end of this century. Concurrently, supply of humic substances from terrestrial runoff is expected to increase, resulting in darker watercolor (“brownification”) of aquatic ecosystems. Using a multi-seasonal, low trophic state mesocosm experiment, we investigated how higher water temperature and brownification affect plankton community composition, phenology, and functioning. We tested the hypothesis that higher water temperature (+3°C) and brownification will, a) cause plankton community composition to shift toward small sized phytoplankton and cyanobacteria, and, b) extend the length of the growing season entailing higher phytoplankton production later in the season. We demonstrate that the 3°C increase of water temperature favored the growth of heterotrophic bacteria and small sized autotrophic picophytoplankton cells with significantly higher primary production during warmer fall periods. However, 3X darker water (effect of brownification) caused no significant changes in the plankton community composition or functioning relative to control conditions. Our findings reveal that increased temperature change plankton community structure by favoring smaller sized species proliferation (autotrophic phytoplankton and small size cladocerans), and increase primary productivity and community turnover. Finally, results of this multi-seasonal experiment suggest that warming by 3°C in aquatic ecosystems of low trophic state may cause planktonic food web functioning to become more dominated by fast growing, r-trait species (i.e., small sizes and rapid development). PMID:26461029

  12. Intraoperative Autotriggered Pressure Support Ventilation Resistant to Increased Flow Trigger Threshold. (United States)

    Benitez Lopez, Julio; Rao, Sripad P; McNeer, Richard R; Dudaryk, Roman


    Oscillations from cardiac pulsations are normally transmitted to mediastinal structures without any consequence. Autotriggering (AT) of mechanical ventilation occurs when an inspiratory trigger, typically negative inspiratory flow in anesthesia ventilators, is met in the absence of patient effort. AT can lead to respiratory alkalosis, opioid overdose, prolonged mechanical ventilation, and lung hyperinflation. This entity has been reported in both critical care and operating room environments. Increasing the flow trigger usually resolves AT in all cases. We report a case of AT that failed to respond to increasing the flow trigger threshold to its maximal value on the GE Datex-Ohmeda Avance S5® anesthesia station.

  13. Membrane tubulation in lipid vesicles triggered by the local application of calcium ions

    DEFF Research Database (Denmark)

    Ali Doosti, Baharan; Pezeshkian, Weria; Bruhn, Dennis Skjøth


    Experimental and theoretical studies on ion-lipid interactions, predict that binding of calcium ions to cell membranes leads to macroscopic mechanical effects and membrane remodeling. Herein, we provide experimental evidence that a point-source of Ca2+ acting upon a negatively charged membrane, g...

  14. Calcium (United States)

    ... Turn to calcium-fortified (or "calcium-set") tofu, soy milk, tempeh, soy yogurt, and cooked soybeans (edamame). Calcium-fortified foods. Look for calcium-fortified orange juice, soy or rice milk, breads, and cereal. Beans. You can get decent ...

  15. Phosphate decreases urine calcium and increases calcium balance: A meta-analysis of the osteoporosis acid-ash diet hypothesis

    Directory of Open Access Journals (Sweden)

    Eliasziw Michael


    Full Text Available Abstract Background The acid-ash hypothesis posits that increased excretion of "acidic" ions derived from the diet, such as phosphate, contributes to net acidic ion excretion, urine calcium excretion, demineralization of bone, and osteoporosis. The public is advised by various media to follow an alkaline diet to lower their acidic ion intakes. The objectives of this meta-analysis were to quantify the contribution of phosphate to bone loss in healthy adult subjects; specifically, a to assess the effect of supplemental dietary phosphate on urine calcium, calcium balance, and markers of bone metabolism; and to assess whether these affects are altered by the b level of calcium intake, c the degree of protonation of the phosphate. Methods Literature was identified through computerized searches regarding phosphate with surrogate and/or direct markers of bone health, and was assessed for methodological quality. Multiple linear regression analyses, weighted for sample size, were used to combine the study results. Tests of interaction included stratification by calcium intake and degree of protonation of the phosphate supplement. Results Twelve studies including 30 intervention arms manipulated 269 subjects' phosphate intakes. Three studies reported net acid excretion. All of the meta-analyses demonstrated significant decreases in urine calcium excretion in response to phosphate supplements whether the calcium intake was high or low, regardless of the degree of protonation of the phosphate supplement. None of the meta-analyses revealed lower calcium balance in response to increased phosphate intakes, whether the calcium intake was high or low, or the composition of the phosphate supplement. Conclusion All of the findings from this meta-analysis were contrary to the acid ash hypothesis. Higher phosphate intakes were associated with decreased urine calcium and increased calcium retention. This meta-analysis did not find evidence that phosphate intake

  16. Annual Feedback Is an Effective Tool for a Sustained Increase in Calcium Intake among Older Women

    Directory of Open Access Journals (Sweden)

    Geoffrey C. Nicholson


    Full Text Available We aimed to optimize calcium intake among the 2,000+ older women taking part in the Vital D study. Calcium supplementation was not included in the study protocol. Our hypothesis was that annual feedback of calcium intake and informing women of strategies to improve calcium intake can lead to a sustained increase in the proportion of women who consume adequate levels of the mineral. Calcium intake was assessed on an annual basis using a validated short food frequency questionnaire (FFQ. Supplemental calcium intake was added to the dietary estimate. Participants and their nominated doctor were sent a letter that the participant’s estimated daily calcium intake was adequate or inadequate based on a cutoff threshold of 800 mg/day. General brief statements outlining the importance of an adequate calcium intake and bone health were included in all letters. At baseline, the median daily consumption of calcium was 980 mg/day and 67 percent of 1,951 participants had calcium intake of at least 800 mg per day. Of the 644 older women advised of an inadequate calcium intake at baseline (< 800 mg/day, 386 (60% had increased their intake by at least 100 mg/day when re-assessed twelve months later. This desirable change was sustained at 24 months after baseline with almost half of these women (303/644 consuming over 800 mg calcium per day. This study devised an efficient method to provide feedback on calcium intake to over 2,000 older women. The improvements were modest but significant and most apparent in those with a low intake at baseline. The decreased proportion of these women with an inadequate intake of calcium 12- and 24-months later, suggests this might be a practical, low cost strategy to maintain an adequate calcium intake among older women.

  17. Licochalcone A induces T24 bladder cancer cell apoptosis by increasing intracellular calcium levels. (United States)

    Yang, Xinhui; Jiang, Jiangtao; Yang, Xinyan; Han, Jichun; Zheng, Qiusheng


    Licochalcone A (LCA) has been reported to significantly inhibit cell proliferation, increase reactive oxygen species (ROS) levels, and induce apoptosis of T24 human bladder cancer cells via mitochondria and endoplasmic reticulum (ER) stress-triggered signaling pathways. Based on these findings, the present study aimed to investigate the mechanisms by which LCA induces apoptosis of T24 cells. Cultured T24 cells were treated with LCA, and cell viability was measured using the sulforhodamine B assay. Apoptosis was detected by flow cytometry with Annexin V/propidium iodide staining, and by fluorescent microscopy with Hoechst 33258 staining. The levels of intracellular free calcium ions were determined using Fluo-3 AM dye marker. Intracellular ROS levels were assessed using the 2',7'-dichlorodihydrofluorescein diacetate probe assay. The mitochondrial membrane potential was measured using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl benzimidazole carbocyanine iodide. Furthermore, the mRNA expression levels of B‑cell lymphoma (Bcl)‑extra large, Bcl‑2‑associated X protein, Bcl‑2‑interacting mediator of cell death, apoptotic protease activating factor‑1 (Apaf‑1), calpain 2, cysteinyl aspartate specific proteinase (caspase)‑3, caspase‑4 and caspase‑9 were determined using reverse transcription semiquantitative and quantitative polymerase chain reaction analyses. Treatment with LCA inhibited proliferation and induced apoptosis of T24 cells, and increased intracellular Ca2+ levels and ROS production. Furthermore, LCA induced mitochondrial dysfunction, decreased mitochondrial membrane potential, and increased the mRNA expression levels of Apaf‑1, caspase‑9 and caspase‑3. Exposure of T24 cells to LCA also triggered calpain 2 and caspase‑4 activation, resulting in apoptosis. These findings indicated that LCA increased intracellular Ca2+ levels, which may be associated with mitochondrial dysfunction. In addition, the ER stress pathway may be

  18. Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion. (United States)

    Diao, Jiajie; Grob, Patricia; Cipriano, Daniel J; Kyoung, Minjoung; Zhang, Yunxiang; Shah, Sachi; Nguyen, Amie; Padolina, Mark; Srivastava, Ankita; Vrljic, Marija; Shah, Ankita; Nogales, Eva; Chu, Steven; Brunger, Axel T


    The molecular underpinnings of synaptic vesicle fusion for fast neurotransmitter release are still unclear. Here, we used a single vesicle-vesicle system with reconstituted SNARE and synaptotagmin-1 proteoliposomes to decipher the temporal sequence of membrane states upon Ca(2+)-injection at 250-500 μM on a 100-ms timescale. Furthermore, detailed membrane morphologies were imaged with cryo-electron microscopy before and after Ca(2+)-injection. We discovered a heterogeneous network of immediate and delayed fusion pathways. Remarkably, all instances of Ca(2+)-triggered immediate fusion started from a membrane-membrane point-contact and proceeded to complete fusion without discernible hemifusion intermediates. In contrast, pathways that involved a stable hemifusion diaphragm only resulted in fusion after many seconds, if at all. When complexin was included, the Ca(2+)-triggered fusion network shifted towards the immediate pathway, effectively synchronizing fusion, especially at lower Ca(2+)-concentration. Synaptic proteins may have evolved to select this immediate pathway out of a heterogeneous network of possible membrane fusion pathways.DOI:

  19. Codissolution of calcium hydrogenphosphate and sodium hydrogencitrate in water. Spontaneous supersaturation of calcium citrate increasing calcium bioavailability

    DEFF Research Database (Denmark)

    Hedegaard, Martina Vavrusova; Danielsen, Bente Pia; Garcia, André Castilho


    . The supersaturated solutions had a pH around 4.7, and calcium binding to hydrogencitrate as the dominant citrate species during precipitation was found to be exothermic with a determined association constant of 357 L mol-1 at 25 °C for unit ionic strength, and δH° = -22 ± 2 kJ mol-1, δS° = -26 ± 8 J K-1 mol-1...

  20. Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus. (United States)

    Lee, C-T; Lien, Y-H H; Lai, L-W; Chen, J-B; Lin, C-R; Chen, H-C


    Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression of calcium and magnesium transporters in the kidney was determined by real-time polymerase chain reaction, and the abundance of protein was assessed by immunoblotting. Our results showed that diabetic rats had significant increase in the fractional excretion for calcium and magnesium (both P diabetic rats. Sodium chloride cotransporter was also increased (207 +/- 10%). No change was found in paracellin-1 (cortex: 108 +/- 8%; medulla: 110 +/- 10%). Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 +/- 10%) and TRPV5 (211 +/- 10%), but no changes in paracellin-1 in Western blotting (cortex: 110 +/- 7%; medulla: 99 +/- 7%). Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance. In conclusion, our results demonstrated increased renal calcium and magnesium transporter abundance in STZ-induced diabetic rats, which may represent a compensatory adaptation for the increased load of calcium and magnesium to the distal tubule.

  1. Novel role for STIM1 as a trigger for calcium influx factor production. (United States)

    Csutora, Peter; Peter, Krisztina; Kilic, Helena; Park, Kristen M; Zarayskiy, Vladislav; Gwozdz, Tomasz; Bolotina, Victoria M


    STIM1 has been recently identified as a Ca(2+) sensor in endoplasmic reticulum (ER) and an initiator of the store-operated Ca(2+) entry (SOCE) pathway, but the mechanism of SOCE activation remains controversial. Here we focus on the early ER-delimited steps of the SOCE pathway and demonstrate that STIM1 is critically involved in initiating of production of calcium influx factor (CIF), a diffusible messenger that can deliver the signal from the stores to plasma membrane and activate SOCE. We discovered that CIF production is tightly coupled with STIM1 expression and requires functional integrity of its intraluminal sterile alpha-motif (SAM) domain. We demonstrate that 1) molecular knockdown or overexpression of STIM1 results in corresponding impairment or amplification of CIF production and 2) inherent deficiency in the ER-delimited CIF production and SOCE activation in some cell types can be a result of their deficiency in STIM1 protein; expression of a wild-type STIM1 in such cells was sufficient to fully rescue their ability to produce CIF and SOCE. We found that glycosylation sites in the ER-resident SAM domain of STIM1 are essential for initiation of CIF production. We propose that after STIM1 loses Ca(2+) from EF hand, its intraluminal SAM domain may change conformation, and via glycosylation sites it can interact with and activate CIF-producing machinery. Thus, CIF production appears to be one of the earliest STIM1-dependent events in the ER lumen, and impairment of this process results in impaired SOCE response.

  2. Calcium supplementation increases blood creatinine concentration in a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Elizabeth L Barry

    Full Text Available Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied.We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004-2013 at 11 clinical centers in the United States. Healthy participants (N = 1,675 aged 45-75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate, vitamin D3 (1000 IU, both, or placebo for three or five years. Changes in blood creatinine and total calcium concentration were measured after one year of treatment and multiple linear regression was used to estimate effects on creatinine concentrations.After one year of treatment, blood creatinine was 0.013±0.006 mg/dL higher on average among participants randomized to calcium compared to placebo after adjustment for other determinants of creatinine (P = 0.03. However, the effect of calcium treatment appeared to be larger among participants who consumed the most alcohol (2-6 drinks/day or whose estimated glomerular filtration rate (eGFR was less than 60 ml/min/1.73 m2 at baseline. The effect of calcium treatment on creatinine was only partially mediated by a concomitant increase in blood total calcium concentration and was independent of randomized vitamin D treatment. There did not appear to be further increases in creatinine after the first year of calcium treatment.Among healthy adults participating in a randomized clinical trial, daily supplementation with 1200 mg of elemental calcium caused a small increase in blood creatinine. If confirmed, this finding may have implications for clinical and public health recommendations for calcium NCT00153816.

  3. Calcium (United States)

    ... and blood vessels contract and expand, to secrete hormones and enzymes and to send messages through the nervous system. It is important to get plenty of calcium in the foods you eat. Foods rich in calcium include Dairy products such as milk, cheese, and yogurt Leafy, green vegetables Fish with ...

  4. Short term tolvaptan increases water intake and effectively decreases urinary calcium oxalate, calcium phosphate, and uric acid supersaturations (United States)

    Cheungpasitporn, Wisit; Erickson, Stephen B.; Rule, Andrew D.; Enders, Felicity; Lieske, John C.


    Purpose Many patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should reduce urinary supersaturation (SS) of stone forming solutes, but this has never been proven. Materials and Methods We conducted a double blind, randomized, placebo-controlled, crossover study in 21 adult calcium urinary stone formers stratified as majority calcium oxalate(CaOx, n=10) or calcium phosphate(CaP, n=11). Patients received tolvaptan 45 mg/day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24h urines was collected at the end of weeks 1 and 3. Results Tolvaptan vs. placebo decreased urinary osmolality (204±96 vs 529±213 mOsm/kg, P0.05 for all interactions). Conclusions Tolvaptan increases urine volume and decreases urinary SS in calcium stone formers. Further study is needed to determine if long term use of V2 receptor antagonists results in fewer stone events. PMID:26598423

  5. Expression of the high capacity calcium-binding domain of calreticulin increases bioavailable calcium stores in plants (United States)

    Wyatt, Sarah E.; Tsou, Pei-Lan; Robertson, Dominique; Brown, C. S. (Principal Investigator)


    Modulation of cytosolic calcium levels in both plants and animals is achieved by a system of Ca2+-transport and storage pathways that include Ca2+ buffering proteins in the lumen of intracellular compartments. To date, most research has focused on the role of transporters in regulating cytosolic calcium. We used a reverse genetics approach to modulate calcium stores in the lumen of the endoplasmic reticulum. Our goals were two-fold: to use the low affinity, high capacity Ca2+ binding characteristics of the C-domain of calreticulin to selectively increase Ca2+ storage in the endoplasmic reticulum, and to determine if those alterations affected plant physiological responses to stress. The C-domain of calreticulin is a highly acidic region that binds 20-50 moles of Ca2+ per mole of protein and has been shown to be the major site of Ca2+ storage within the endoplasmic reticulum of plant cells. A 377-bp fragment encoding the C-domain and ER retention signal from the maize calreticulin gene was fused to a gene for the green fluorescent protein and expressed in Arabidopsis under the control of a heat shock promoter. Following induction on normal medium, the C-domain transformants showed delayed loss of chlorophyll after transfer to calcium depleted medium when compared to seedlings transformed with green fluorescent protein alone. Total calcium measurements showed a 9-35% increase for induced C-domain transformants compared to controls. The data suggest that ectopic expression of the calreticulin C-domain increases Ca2+ stores, and that this Ca2+ reserve can be used by the plant in times of stress.

  6. Calcium and vitamin D supplementation increases spinal BMD in healthy, postmenopausal women

    DEFF Research Database (Denmark)

    Baeksgaard, L; Andersen, K P; Hyldstrup, Lars


    We undertook a double-masked, randomized, placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip, spine and forearm. The study was performed in 240 healthy women, 58-67 years of age. Duration...... of treatment was 2 years. Bone mineral density (BMD) was measured at the lumbar spine, hip and forearm. A dietary questionnaire was administered twice during the study and revealed a fairly good calcium and vitamin D intake (919 mg calcium/day; 3.8 micrograms vitamin D/day). An increase in lumbar spine BMD...... not significant, the same trend was seen at the hip. No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group. In conclusion, we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group...

  7. Calcium sensing in exocytosis

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Wu, Bingbing; Han, Weiping


    Neurotransmitters, neuropeptides and hormones are released through regulated exocytosis of synaptic vesicles and large dense core vesicles. This complex and highly regulated process is orchestrated by SNAREs and their associated proteins. The triggering signal for regulated exocytosis is usually...... an increase in intracellular calcium levels. Besides the triggering role, calcium signaling modulates the precise amount and kinetics of vesicle release. Thus, it is a central question to understand the molecular machineries responsible for calcium sensing in exocytosis. Here we provide an overview of our...

  8. Calcium (United States)

    ... from dietary supplements are linked to a greater risk of kidney stones, especially among older adults. But calcium from foods does not appear to cause kidney stones. For most people, other factors (such as not drinking enough fluids) probably have ...

  9. A systematic review of behavioural interventions to increase maternal calcium intake. (United States)

    Jung, Mary E; Stork, Matthew J; Stapleton, Jessica; Bourne, Jessica E; Martin Ginis, Kathleen A


    Pregnancy and lactation are a time when adequate calcium consumption is essential for the development of the fetus and to ensure the health of the mother. Over 50% of Canadian women of childbearing and rearing age fail to meet the recommended daily intake of calcium. Identification of effective behavioural intervention strategies for increasing calcium intake is needed within this specific population. This paper brings together all published behavioural interventions designed to increase calcium consumption in pregnant, lactating or post-partum mothers in a systematic review. Relevant studies were obtained through searches of MEDLINE, EMBASE, PsycINFO, CINAHL and the Cochrane Library with no date restrictions. Studies were evaluated using previously published criteria for evaluating calcium behaviour change interventions. This systematic literature review identified five behavioural calcium interventions conducted within this population. Three interventions aimed to improve overall dietary behaviours, the fourth aimed to promote breastfeeding (including increasing calcium consumption) and the fifth aimed to increase daily servings of yoghurt. Only one of the five interventions yielded large effect sizes, with a mean change of 954 mg of calcium per day post-intervention. The number of behavioural change techniques did not appear to be related to intervention efficacy. Only one study used a theoretical framework to guide the intervention. This review highlights the lack of research examining behaviour change interventions aimed at increasing calcium consumption in pregnant, lactating and post-partum women and provides practical suggestions for researchers wishing to intervene with this population in the future. © 2014 John Wiley & Sons Ltd.

  10. Calcium intake is not associated with increased coronary artery calcification: the Framingham Study. (United States)

    Samelson, Elizabeth J; Booth, Sarah L; Fox, Caroline S; Tucker, Katherine L; Wang, Thomas J; Hoffmann, Udo; Cupples, L Adrienne; O'Donnell, Christopher J; Kiel, Douglas P


    Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification, which is a measure of atherosclerosis that predicts risk of ischemic heart disease independent of other risk factors. This was an observational, prospective cohort study. Participants included 690 women and 588 men in the Framingham Offspring Study (mean age: 60 y; range: 36-83 y) who attended clinic visits and completed food-frequency questionnaires in 1998-2001 and underwent computed tomography scans 4 y later in 2002-2005. The mean age-adjusted coronary artery-calcification Agatston score decreased with increasing total calcium intake, and the trend was not significant after adjustment for age, BMI, smoking, alcohol consumption, vitamin D-supplement use, energy intake, and, for women, menopause status and estrogen use. Multivariable-adjusted mean Agatston scores were 2.36, 2.52, 2.16, and 2.39 (P-trend = 0.74) with an increasing quartile of total calcium intake in women and 4.32, 4.39, 4.19, and 4.37 (P-trend = 0.94) in men, respectively. Results were similar for dietary calcium and calcium supplement use. Our study does not support the hypothesis that high calcium intake increases coronary artery calcification, which is an important measure of atherosclerosis burden. The evidence is not sufficient to modify current recommendations for calcium intake to protect skeletal health with respect to vascular calcification risk.

  11. Increasing Calcium Oxide (Cao) to Accelerate Moulting and Survival Rate Vannamei Shrimp (Litopenaeus Vannamei))


    Erlando, Gito; ', Rusliadi; Mulyadi,


    The research about the increasing Calcium Oxide (CaO) to accelerate moulting and survival rate vannamei shrimp (Litopenaeus vannamei) was conducted from Agustus until September 2015 at Balai Perikanan Budidaya Air Payau, Instalasi Pembenihan Udang (IPU) Gelung, Situbondo Provinsi Jawa Timur. The purpose of this research was to investigate optimum doses calcium oxide to accelerate moulting and the survival rate vannamei shrimp (Litopenaeus vannamei). Vannamei shrimp with size PL25 were used in...

  12. Calcium dobesilate increased endothelium-dependent relaxation in isolated rabbit aorta. (United States)

    Ruiz, E; Tejerina, T


    1. The aim of this study was to investigate the effects of calcium dobesilate on relaxant and contractile responses in the isolated rabbit aorta. 2. Calcium dobesilate (10(-6) and 10(-4) M) shifted the concentration-response curve induced by noradrenaline (10(-8)-10(-4) M) downward and to the right, the IC50 being 5.1 +/- 1.1 x 10(-7) M in the control and 7.5 +/- 1.2 x 10(-6) M and 3.1 +/- 1.9 x 10(-6) M in the presence of calcium dobesilate, 10(-6) M and 10(-4) M respectively. 3. Calcium dobesilate, 10(-5) M, increased the endothelium-dependent relaxation induced by acetylcholine (10(-8)-10(-5) M) but had no actions in the absence of endothelium.

  13. Excessive signal transduction of gain-of-function variants of the calcium-sensing receptor (CaSR are associated with increased ER to cytosol calcium gradient.

    Directory of Open Access Journals (Sweden)

    Marianna Ranieri

    Full Text Available In humans, gain-of-function mutations of the calcium-sensing receptor (CASR gene are the cause of autosomal dominant hypocalcemia or type 5 Bartter syndrome characterized by an abnormality of calcium metabolism with low parathyroid hormone levels and excessive renal calcium excretion. Functional characterization of CaSR activating variants has been so far limited at demonstrating an increased sensitivity to external calcium leading to lower Ca-EC50. Here we combine high resolution fluorescence based techniques and provide evidence that for the efficiency of calcium signaling system, cells expressing gain-of-function variants of CaSR monitor cytosolic and ER calcium levels increasing the expression of the Sarco-Endoplasmic Reticulum Calcium-ATPase (SERCA and reducing expression of Plasma Membrane Calcium-ATPase (PMCA. Wild-type CaSR (hCaSR-wt and its gain-of-function (hCaSR-R990G; hCaSR-N124K variants were transiently transfected in HEK-293 cells. Basal intracellular calcium concentration was significantly lower in cells expressing hCaSR-wt and its gain of function variants compared to mock. In line, FRET studies using the D1ER probe, which detects [Ca2+]ER directly, demonstrated significantly higher calcium accumulation in cells expressing the gain of function CaSR variants compared to hCaSR-wt. Consistently, cells expressing activating CaSR variants showed a significant increase in SERCA activity and expression and a reduced PMCA expression. This combined parallel regulation in protein expression increases the ER to cytosol calcium gradient explaining the higher sensitivity of CaSR gain-of-function variants to external calcium. This control principle provides a general explanation of how cells reliably connect (and exacerbate receptor inputs to cell function.

  14. Excessive Signal Transduction of Gain-of-Function Variants of the Calcium-Sensing Receptor (CaSR) Are Associated with Increased ER to Cytosol Calcium Gradient (United States)

    Di Mise, Annarita; Vezzoli, Giuseppe; Soldati, Laura; Svelto, Maria; Valenti, Giovanna


    In humans, gain-of-function mutations of the calcium-sensing receptor (CASR) gene are the cause of autosomal dominant hypocalcemia or type 5 Bartter syndrome characterized by an abnormality of calcium metabolism with low parathyroid hormone levels and excessive renal calcium excretion. Functional characterization of CaSR activating variants has been so far limited at demonstrating an increased sensitivity to external calcium leading to lower Ca-EC50. Here we combine high resolution fluorescence based techniques and provide evidence that for the efficiency of calcium signaling system, cells expressing gain-of-function variants of CaSR monitor cytosolic and ER calcium levels increasing the expression of the Sarco-Endoplasmic Reticulum Calcium-ATPase (SERCA) and reducing expression of Plasma Membrane Calcium-ATPase (PMCA). Wild-type CaSR (hCaSR-wt) and its gain-of-function (hCaSR-R990G; hCaSR-N124K) variants were transiently transfected in HEK-293 cells. Basal intracellular calcium concentration was significantly lower in cells expressing hCaSR-wt and its gain of function variants compared to mock. In line, FRET studies using the D1ER probe, which detects [Ca2+]ER directly, demonstrated significantly higher calcium accumulation in cells expressing the gain of function CaSR variants compared to hCaSR-wt. Consistently, cells expressing activating CaSR variants showed a significant increase in SERCA activity and expression and a reduced PMCA expression. This combined parallel regulation in protein expression increases the ER to cytosol calcium gradient explaining the higher sensitivity of CaSR gain-of-function variants to external calcium. This control principle provides a general explanation of how cells reliably connect (and exacerbate) receptor inputs to cell function. PMID:24244430

  15. Acetate transiently inhibits myocardial contraction by increasing mitochondrial calcium uptake. (United States)

    Schooley, James F; Namboodiri, Aryan M A; Cox, Rachel T; Bünger, Rolf; Flagg, Thomas P


    There is a close relationship between cardiovascular disease and cardiac energy metabolism, and we have previously demonstrated that palmitate inhibits myocyte contraction by increasing Kv channel activity and decreasing the action potential duration. Glucose and long chain fatty acids are the major fuel sources supporting cardiac function; however, cardiac myocytes can utilize a variety of substrates for energy generation, and previous studies demonstrate the acetate is rapidly taken up and oxidized by the heart. In this study, we tested the effects of acetate on contractile function of isolated mouse ventricular myocytes. Acute exposure of myocytes to 10 mM sodium acetate caused a marked, but transient, decrease in systolic sarcomere shortening (1.49 ± 0.20% vs. 5.58 ± 0.49% in control), accompanied by a significant increase in diastolic sarcomere length (1.81 ± 0.01 μm vs. 1.77 ± 0.01 μm in control), with a near linear dose response in the 1-10 mM range. Unlike palmitate, acetate caused no change in action potential duration; however, acetate markedly increased mitochondrial Ca(2+) uptake. Moreover, pretreatment of cells with the mitochondrial Ca(2+) uptake blocker, Ru-360 (10 μM), markedly suppressed the effect of acetate on contraction. Lehninger and others have previously demonstrated that the anions of weak aliphatic acids such as acetate stimulate Ca(2+) uptake in isolated mitochondria. Here we show that this effect of acetate appears to extend to isolated cardiac myocytes where it transiently modulates cell contraction.

  16. The proarrhythmic antihistaminic drug terfenadine increases spontaneous calcium release in human atrial myocytes. (United States)

    Hove-Madsen, Leif; Llach, Anna; Molina, Cristina E; Prat-Vidal, Cristina; Farré, Jordi; Roura, Santiago; Cinca, Juan


    Spontaneous calcium release from the sarcoplasmic reticulum in cardiac myocytes plays a central role in cardiac arrhythmogenesis. Compounds intended for therapeutical use that interfere with intracellular calcium handling may therefore have an undesired proarrhythmic potential. Here we have used isolated human atrial myocytes to compare the effect of the proarrhythmic antihistaminic drug terfenadine with the non-proarrhythmic antihistaminic drugs fexofenadine and rupatadine on intracellular calcium homeostasis. Perforated patch-clamp technique was used to measure ionic currents and to detect spontaneous calcium release from the sarcoplasmic reticulum. Our results show that the compound terfenadine, with known arrhythmogenic effects, inhibits L-type calcium current (I(Ca)) with an IC(50) of 185 nM when cells are stimulated at 1.0 Hz. The inhibitory effect of 0.3 muM terfenadine increased from 19+/-4% at stimulation frequency of 0.2 Hz to 63+/-6% at 2.0 Hz. Moreover, terfenadine also increased spontaneous calcium release from the sarcoplasmic reticulum. At a concentration of 1 muM, terfenadine significantly increased the spontaneous Na-Ca exchange current (I(NCX)) frequency from 0.48+/-0.25 to 1.93+/-0.67 s(-1). In contrast, fexofenadine and rupatadine did not change I(Ca) or the frequency of spontaneous I(NCX). We conclude that the proarrhythmic antihistaminic drug terfenadine alters intracellular calcium handling in isolated human atrial myocytes. This experimental model may be suitable to screen for potential arrhythmogenic side-effects of compounds intended for therapeutical use.

  17. Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons.

    Directory of Open Access Journals (Sweden)

    Gytis Svirskis

    Full Text Available The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum.

  18. Increased calcium absorption from synthetic stable amorphous calcium carbonate: double-blind randomized crossover clinical trial in postmenopausal women. (United States)

    Vaisman, Nachum; Shaltiel, Galit; Daniely, Michal; Meiron, Oren E; Shechter, Assaf; Abrams, Steven A; Niv, Eva; Shapira, Yami; Sagi, Amir


    Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with 44Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl2 labeled with 42Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24-hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC (p calcium supplementation. © 2014 American Society for Bone and Mineral Research.

  19. Genetically modified Medicago truncatula lacking calcium oxalate has increased calcium bioavailability and partially rescues vitamin D receptor knockout mice phenotypes (United States)

    How the distribution and sequestered form of plant macro/micro-nutrients influence their bioavailability, and ultimately impact human health, is poorly understood. The legume Medicago truncatula has a portion of its tissue calcium sequestered in the form of the calcium oxalate crystal, which reduces...

  20. Rhein triggers apoptosis via induction of endoplasmic reticulum stress, caspase-4 and intracellular calcium in primary human hepatic HL-7702 cells

    Energy Technology Data Exchange (ETDEWEB)

    KoraMagazi, Arouna [Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu (China); Wang, Dandan [Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu (China); Yousef, Bashir; Guerram, Mounia [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu (China); Yu, Feng, E-mail: [Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu (China); Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing, Jiangsu (China)


    Rhein is an active component of rhubarb; a traditional Chinese medicine reported to induce apoptosis and cause liver toxicity. However, rhein's apoptotic-inducing effects, as well as its molecular mechanisms of action on hepatic cells need to be further explored. In the present study, rhein was found to trigger apoptosis in primary human hepatic HL-7702 cells as showed by annexin V/PI double staining assay and nuclear morphological changes demonstrated by Hoechst 33258 staining. Moreover, it was observed that the mechanism implicated in rhein-induced apoptosis was caspase-dependent, presumably via ER-stress associated pathways, as illustrated by up-regulation of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), C-Jun N-terminal kinase (JNK) and CCAAT/enhancer-binding protein homologous protein (CHOP). Meanwhile, caspase-4 as a hallmark of ER-stress, was also showed to be activated following by caspase-3 activation. Furthermore, rhein also promoted intracellular elevation of calcium that contributed in apoptosis induction. Interestingly, pre-treatment with calpain inhibitor I reduced the effects of rhein on apoptosis induction and JNK activation. These data suggested that rhein-induced apoptosis through ER-stress and elevated intracellular calcium level in HL-7702 cells. - Highlights: • Rhein triggers apoptotic cell death on primary human hepatic HL-7702 cells. • Rhein leads to caspase-4 activation in HL-7702 cells. • Rhein induces endoplasmic reticulum stress pathways in HL-7702 cells. • Rhein causes elevation of intracellular calcium concentrations in HL-7702 cells.

  1. Heavy rainfall triggers increased nocturnal flight in desert populations of the Pacific black duck (Anas superciliosa). (United States)

    McEvoy, J F; Ribot, R F H; Wingfield, J C; Bennett, A T D


    Understanding of avian nocturnal flight comes mainly from northern hemisphere species in seasonal temperate ecosystems where nocturnal flight is often precisely timed and entrained by annual photoperiod. Here we investigate patterns of nocturnal flight in waterbirds of Australian desert ecosystems that fly considerable distances to find temporary water bodies formed from rainfall which is highly unpredictable seasonally and spatially, and when there is sufficient water, they then breed. How they perform these feats of navigation and physiology remain poorly known. Using GPS tracking of 38 satellite tagged Pacific black ducks (Anas superciliosa) in two contrasting ecosystems, before and after heavy rainfall we revealed a key role for facultative nocturnal flight in the movement ecology of this species. After large rainfall events, birds rapidly increased nocturnal flight activity in the arid aseasonal ecosystem, but not in the mesic seasonal one. Nocturnal flights occurred throughout the night in both ecosystems. Long range flights (>50 km in 2 hours) occurred almost exclusively at night; at night the distance flown was higher than during the day, birds visited more locations, and the locations were more widely dispersed. Our work reveals that heavy rainfall triggers increased nocturnal flight activity in desert populations of waterbirds.

  2. Increase of a Calcium Independent Transglutaminase Activity in the Erythrocyte during the Infection with Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Wasserman Moisés


    Full Text Available We have studied the activity of a calcium dependent transglutaminase (EC during the growth of the parasite Plasmodium falciparum inside the infected human erythrocyte. There is only one detectable transglutaminase in the two-cell-system, and its origin is erythrocytic. No activity was detected in preparations of the parasite devoid of erythrocyte cytoplasm. The Michaelis Menten constants (Km of the enzyme for the substrates N'N'dimethylcaseine and putrescine were undistinguishable whether the cell extracts used in their determination were obtained from normal or from infected red cells. The total activity of transglutaminase in stringently synchronized cultures, measured at 0.5mM Ca2+, decreased with the maturation of the parasite. However, a fraction which became irreversibly activated and independent of calcium concentration was detected. The proportion of this fraction grew with maturation; it represented only 20% of the activity in 20 hr-old-trophozoites while in 48-hr-schizonts it was more than 85% of the total activity. The activation of this fraction of transglutaminase did not depend on an increase in the erythrocyte cytoplasmic calcium, since most of the calcium was shown to be located in the parasite.

  3. Calcium gluconate in phosphate buffered saline increases gene delivery with adenovirus type 5.

    Directory of Open Access Journals (Sweden)

    Marko T Ahonen

    Full Text Available BACKGROUND: Adenoviruses are attractive vectors for gene therapy because of their stability in vivo and the possibility of production at high titers. Despite exciting preclinical data with various approaches, there are only a few examples of clear efficacy in clinical trials. Effective gene delivery to target cells remains the key variable determining efficacy and thus enhanced transduction methods are important. METHODS/RESULTS: We found that heated serum could enhance adenovirus 5 mediated gene delivery up to twentyfold. A new protein-level interaction was found between fiber knob and serum transthyretin, but this was not responsible for the observed effect. Instead, we found that heating caused the calcium and phosphate present in the serum mix to precipitate, and this was responsible for enhanced gene delivery. This finding could have relevance for designing preclinical experiments with adenoviruses, since calcium and phosphate are present in many solutions. To translate this into an approach potentially testable in patients, we used calcium gluconate in phosphate buffered saline, both of which are clinically approved, to increase adenoviral gene transfer up to 300-fold in vitro. Gene transfer was increased with or without heating and in a manner independent from the coxsackie-adenovirus receptor. In vivo, in mouse studies, gene delivery was increased 2-, 110-, 12- and 13-fold to tumors, lungs, heart and liver and did not result in increased pro-inflammatory cytokine induction. Antitumor efficacy of a replication competent virus was also increased significantly. CONCLUSION: In summary, adenoviral gene transfer and antitumor efficacy can be enhanced by calcium gluconate in phosphate buffered saline.

  4. Latent myofascial trigger points are associated with an increased intramuscular electromyographic activity during synergistic muscle activation. (United States)

    Ge, Hong-You; Monterde, Sonia; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars


    The aim of this study was to evaluate intramuscular muscle activity from a latent myofascial trigger point (MTP) in a synergistic muscle during isometric muscle contraction. Intramuscular activity was recorded with an intramuscular electromyographic (EMG) needle inserted into a latent MTP or a non-MTP in the upper trapezius at rest and during isometric shoulder abduction at 90° performed at 25% of maximum voluntary contraction in 15 healthy subjects. Surface EMG activities were recorded from the middle deltoid muscle and the upper, middle, and lower parts of the trapezius muscle. Maximal pain intensity and referred pain induced by EMG needle insertion and maximal pain intensity during contraction were recorded on a visual analog scale. The results showed that higher visual analog scale scores were observed following needle insertion and during muscle contraction for latent MTPs than non-MTPs (P activity in the upper trapezius muscle was significantly higher at rest and during shoulder abduction at latent MTPs compared with non-MTPs (P latent MTPs are associated with increased intramuscular, but not surface, EMG amplitude of synergist activation. The increased amplitude of synergistic muscle activation may result in incoherent muscle activation pattern of synergists inducing spatial development of new MTPs and the progress to active MTPs. This article presents evidence of increased intramuscular, but not surface, muscle activity of latent MTPs during synergistic muscle activation. This incoherent muscle activation pattern may overload muscle fibers in synergists during muscle contraction and may contribute to spatial pain propagation. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Cumulative Stressors Trigger Increased Vulnerability of Diatom Communities to Additional Disturbances. (United States)

    Morin, Soizic; Bonet, Berta; Corcoll, Natàlia; Guasch, Helena; Bottin, Marius; Coste, Michel


    Chronic, non-lethal stressors occurring gradually (in space or time) can result in cumulative impacts that are more dramatic than higher intensities or occasional critical levels of any single one of these stressors. The negative effects of the chronic stressors trigger lasting impacts that may grow in intensity and become problematic over time and/or to higher trophic levels. In rivers, aquatic organisms experience this type of cumulative stress along the up- to downstream gradient in natural and anthropogenic contaminants generally observed in inhabited watersheds. Diatoms are a major component of the periphyton in rivers; their richness and diversity in natural communities are directly related to their varied ecological preferences and sensitivity to disturbance. In this study, we monitored from 2003 to 2008 the changes in the diversity of taxonomic and non-taxonomic features along a small river (Riou-Mort, South West France), at three sites: one site upstream considered as a reference for this watershed, one intermediate site with high nutrient load, and one downstream site exposed to both nutrient and metal pollution. The cumulative impacts of nutrients plus metals led to a gradual decrease in species richness and diversity, and in a potential capacity to cope with additional stresses, e.g., climate change-related ones. This is reflected by a decrease in species richness downstream, more dramatic in the hot summer of 2003 than in cooler summers. With the increasingly protective environmental regulations (e.g., Water Framework Directive in Europe), accumulation of stresses on aquatic resources are recommended to receive increasing attention, in particular considering the expected changes in climate.

  6. Sources of variability in cytosolic calcium transients triggered by stimulation of homogeneous uro-epithelial cell monolayers. (United States)

    Appleby, Peter A; Shabir, Saqib; Southgate, Jennifer; Walker, Dawn


    Epithelial tissue structure is the emergent outcome of the interactions between large numbers of individual cells. Experimental cell biology offers an important tool to unravel these complex interactions, but current methods of analysis tend to be limited to mean field approaches or representation by selected subsets of cells. This may result in bias towards cells that respond in a particular way and/or neglect local, context-specific cell responses. Here, an automated algorithm was applied to examine in detail the individual calcium transients evoked in genetically homogeneous, but asynchronous populations of cultured non-immortalized normal human urothelial cells when subjected to either the global application of an external agonist or a localized scratch wound. The recorded calcium transients were classified automatically according to a set of defined metrics and distinct sub-populations of cells that responded in qualitatively different ways were observed. The nature of this variability in the homogeneous cell population was apportioned to two sources: intrinsic variation in individual cell responses and extrinsic variability due to context-specific factors of the environment, such as spatial heterogeneity. Statistically significant variation in the features of the calcium transients evoked by scratch wounding according to proximity to the wound edge was identified. The manifestation of distinct sub-populations of cells is considered central to the coordination of population-level response resulting in wound closure.

  7. Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Shan-Li [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Sun, Ming-Rui [Department of Pharmacology, Qiqihaer Medical College, Qiqihaer 160001 (China); Li, Ting-Ting; Yin, Xin [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Xu, Chang-Qing [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Sun, Yi-Hua, E-mail: [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)


    Research highlights: {yields} Calcium-sensing receptor (CaR) activation stimulates TRP channels. {yields} CaR promoted transient receptor potential C3 (TRPC3) expression. {yields} Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. {yields} TRPC channels activation induced by CaR activator sustained the increased [Ca{sup 2+}]{sub i} to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca{sup 2+} overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue and promote the apoptosis of cardiomyocytes by Ca{sup 2+} overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca{sup 2+}]{sub i} levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca{sup 2+} stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca{sup 2+}]{sub i} in the absence of [Ca{sup 2+}]{sub o} and the subsequent restoration of [Ca{sup 2+}]{sub o} sustained the increased [Ca{sup 2+}]{sub i} for a few minutes, whereas, the persisting elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl{sub 3}) or spermine also resulted in the same effect and the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of [Ca{sup 2+}]{sub o}. In adult and neonatal rat cardiomyocytes, GdCl{sub 3

  8. GABA(A) Increases Calcium in Subventricular Zone Astrocyte-Like Cells Through L- and T-Type Voltage-Gated Calcium Channels

    DEFF Research Database (Denmark)

    Young, Stephanie Z; Platel, Jean-Claude; Nielsen, Jakob V


    induced Ca(2+) increases in 40-50% of SVZ astrocytes. GABA(A)-induced Ca(2+) increases were prevented with nifedipine and mibefradil, blockers of L- and T-type voltage-gated calcium channels (VGCC). The L-type Ca(2+) channel activator BayK 8644 increased the percentage of GABA(A)-responding astrocyte...

  9. Increasing insolation and greenhouse gas concentration trigger Bølling-Allerød warming (United States)

    Obase, Takashi; Abe-Ouchi, Ayako


    During the last deglaciation, a major global warming was punctuated by several abrupt climate changes, likely related to Atlantic Meridional Overturning Curculation (AMOC) (Clark et al. 2012). Transient deglaciation experiments from the Last Glacial Maximum have been conducted by applying time-dependent insolation, greenhouse gas concentrations, and glacial meltwater forcing (Liu et al. 2009). They have showed that reduction in glacial meltwater discharge rate into North Atlantic induces abrupt recovery of AMOC, warming of Greenland and cooling of Antarctica (bipolar response) during the period of Bølling-Allerød (BA, 14.6 ka). We conduct a transient simulation from the Last Glacial Maximum to BA using an atmosphere-ocean coupled general circulation model (AOGCM) MIROC 4m (an IPCC-class Japanese community model). The model is initialized with the 21ka, and we change insolation, greenhouse gas concentrations and meltwater fluxes following the protocol of PMIP4 (Ivanovic et al. 2016). Glacial meltwater is derived from ice sheet reconstruction (ICE6g, Peltier et al. 2015). We assume the glacial meltwater due to ice sheet loss is uniformly applied to the area of 50-70N North Atlantic Ocean. We conduct additional experiments branched from 16 ka, where 50-80% of ICE6g meltwater fluxes are applied without reducing the meltwater fluxes before the BA. The model results show that abrupt resumption of AMOC and warming of Greenland occurred at around the period of BA even under hosing of 0.06 Sv. Transition from cold stadial mode to warm interstadial mode occurs in about 100 years, which is consistent with reconstructions (Buizert et al. 2014). The result implies that increasing summer insolation and greenhouse gas concentration trigger abrupt AMOC recovery and warming in the Northern Hemisphere, and large fluctuation of meltwater due to ice sheet melting may not be necessary.

  10. A grape-enriched diet increases bone calcium retention and cortical bone properties in ovariectomized rats. (United States)

    Hohman, Emily E; Weaver, Connie M


    Grapes and their associated phytochemicals have been investigated for beneficial effects on cardiovascular health, cancer prevention, and other chronic diseases, but the effect of grape consumption on bone health has not been fully determined. We previously found short-term benefits of grape products on reducing bone turnover in ovariectomized rats. The objective of this study was to determine the long-term benefits of a grape-enriched diet on bone in ovariectomized rats. Rats were ovariectomized at 3 mo of age and were administered a single dose of (45)Ca to prelabel bones at 4 mo of age. After a 1-mo equilibration period, baseline urinary (45)Ca excretion was determined. Rats (n = 22/group) were then randomly assigned to a modified AIN93M diet containing 25% freeze-dried grape powder or to a control diet for 8 wk. Urinary (45)Ca excretion was monitored throughout the study to determine changes in bone (45)Ca retention. Calcium balance was assessed after 1 and 8 wk of consuming the experimental diets, and a calcium kinetic study was performed at 8 wk. After 8 wk, femurs were collected for micro-computed tomographic imaging, 3-point bending, and reference point indentation. Rats fed the grape-enriched diet had 44% greater net bone calcium retention than did rats fed the control diet. There were no differences in calcium balance due to diet at either week 1 or week 8, but there was a significant increase in net calcium absorption (10.6%) and retention (5.7%) from week 1 to week 8 in the grape-enriched diet group only. Grape-enriched diet-fed rats had 3% greater cortical thickness and 11% greater breaking strength. There were no differences in femur bone mineral density, trabecular microarchitecture, or reference point indentation variables due to diet. This study of ovariectomized rats indicates that the consumption of grape products may improve calcium utilization and suppress bone turnover, resulting in improvements in bone quality. © 2015 American Society for

  11. Increased Calcium Supplementation Postpartum Is Associated with Breastfeeding among Chinese Mothers: Finding from Two Prospective Cohort Studies. (United States)

    Zhao, Jian; Zhao, Yun; Binns, Colin W; Lee, Andy H


    The calcium supplementation status during the postpartum period among Chinese lactating women is still unclear. The objective of this study is to utilize data from two population-based prospective cohort studies to examine the calcium supplementation status and to identify whether breastfeeding is associated with increased calcium supplementation among Chinese mothers after child birth. Information from 1540 mothers on breastfeeding and calcium supplementation measured at discharge, 1, 3, and 6 months postpartum were extracted to evaluate the association between breastfeeding and calcium supplementation postpartum. A generalized linear mixed model was applied to each study initially to account for the inherent correlation among repeated measurements, adjusting for socio-demographic, obstetric factors and calcium supplementation during pregnancy. In addition, breastfeeding status measured at different follow-up time points was treated as a time dependent variable in the longitudinal analysis. Furthermore, the effect sizes of the two cohort studies were pooled using fixed effect model. Based on the two cohort studies, the pooled likelihood of taking calcium supplementation postpartum among breastfeeding mothers was 4.02 times (95% confidence interval (2.30, 7.03)) higher than that of their non-breastfeeding counterparts. Dietary supplementation intervention programs targeting different subgroups should be promoted in Chinese women, given currently a wide shortage of dietary calcium intake and calcium supplementation postpartum.


    Directory of Open Access Journals (Sweden)

    Muliani **


    Full Text Available Calcium and moderate intensity swimming exercise can increase bone density. The aim of this research is to see the effect of orally calcium consumption and swimming activity to decrease osteoclast and increase osteoblast in radial perimenopausal mice (Mus musculus bone. Pretest and pos#est control group design was used in this research. Research subject used 15-16 aged mice (Mus musculus which divided into 4 groups (each group consisted of 13 mice, that was control, lactate calcium, swimming and lactate calcium and swimming. Treatment was given 90 days. This study showed a significant difference of the mean of the pos#est osteoblast between control and experimental groups (P<0.05. There was no significant difference between lactate calcium and swimming groups (P>0.05. Enhancement of osteoblast mean in combination group was greater than the other experimental groups. There was a significant difference of the mean of the pos#est  osteoclast between control and experimental groups (P<0.05, without significant difference between lactate calcium,   swimming groups and combination of lactate calcium and swimming group (P>0.05.  Conclusion: either lactate calcium or swimming decreases osteoclast and increases osteoblast of the mice but the osteoblast enhancement will be bigger when they are given together at once

  13. Effect of increased strut porosity of calcium phosphate bone graft substitute biomaterials on osteoinduction. (United States)

    Coathup, Melanie J; Hing, Karin A; Samizadeh, Sorousheh; Chan, Oliver; Fang, Yvette S; Campion, Charlie; Buckland, Thomas; Blunn, Gordon W


    The effect of increasing strut porosity on the osteoinductivity of porous calcium phosphate (CaP) and silicate-substituted calcium phosphate (SiCaP) bone substitute materials was investigated in an ovine ectopic model. One to two millimeter-sized granules or block implants with strut porosities of 10, 20, or 30% were inserted into the left and right paraspinalis muscle. At 12 weeks, histological sections were prepared through the center of each implant and bone contact, bone area and implant area quantified. Backscattered scanning electron microscopy (bSEM) was used to visualize bone within small pores in the struts of the scaffolds. Increased bone formation was measured in the SiCaP with 30% strut porosity (5.482% ± 1.546%) when compared with the nonsilicate CaP with the same morphology (1.160% ± 0.502%, p = 0.02), indicating that silicate substitution may increase osteoinduction. Greater bone formation was seen in scaffolds with increased strut porosity. No bone growth was found in any of the SiCaP scaffold with 10% porosity. There was no significant difference between block and granule specimens. Scanning electron microscopy and EDX in combination with histology demonstrated bone formation within pores <5 μm in size. The use of silicate-substituted CaP material with increased strut porosity may further augment repair and regeneration in bony sites. Copyright © 2012 Wiley Periodicals, Inc.

  14. Triiodothyronine increases calcium loss in a bed rest antigravity model for space flight. (United States)

    Smith, Steven R; Lovejoy, Jennifer C; Bray, George A; Rood, Jennifer; Most, Marlene M; Ryan, Donna H


    Bed rest has been used as a model to simulate the effects of space flight on bone metabolism. Thyroid hormones accelerate bone metabolism. Thus, supraphysiologic doses of this hormone might be used as a model to accelerate bone metabolism during bed rest and potentially simulate space flight. The objective of the study was to quantitate the changes in bone turnover after low doses of triiodothyronine (T(3)) added to short-term bed rest. Nine men and 5 women were restricted to bed rest for 28 days with their heads positioned 6 degrees below their feet. Subjects were randomly assigned to receive either placebo or oral T(3) at doses of 50 to 75 microg/d in a single-blind fashion. Calcium balance was measured over 5-day periods; and T(3), thyroxine, thyroid-stimulating hormone, immunoreactive parathyroid hormone, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline were measured weekly. Triiodothyronine increased 2-fold in the men and 5-fold in the women during treatment, suppressing both thyroxine and thyroid-stimulating hormone. Calcium balance was negative by 300 to 400 mg/d in the T(3)-treated volunteers, primarily because of the increased fecal loss that was not present in the placebo group. Urinary deoxypyridinoline to creatinine ratio, a marker of bone resorption, increased 60% in the placebo group during bed rest, but more than doubled in the T(3)-treated subjects (P < .01), suggesting that bone resorption was enhanced by treatment with T(3). Changes in serum osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, were similar in T(3)- and placebo-treated subjects. Triiodothyronine increases bone resorption and fecal calcium loss in subjects at bed rest.

  15. Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Albertoni, G.; Schor, N. [Divisão de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)


    Resveratrol (Resv) is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells (ihMCs). ihMCs were preincubated with Resv (12.5 µM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h. The intracellular calcium concentration [Ca{sup 2+}]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT) and pre-pro endothelin-1 (ppET-1) mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII) and endothelin-1 (ET-1) were assayed by ELISA. UA significantly increased [Ca{sup 2+}]i. Pre-incubation with Resv significantly reduced the change in [Ca{sup 2+}]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca{sup 2+}]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.

  16. Effect of Heart Rate and Body Mass Index on the Interscan and Interobserver Variability of Coronary Artery Calcium Scoring at Prospective ECG-Triggered 64-Slice CT

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Jun; Kiguchi, Masao; Fujioka, Chikako [Hiroshima University Hospital, Hiroshima (Japan); Matsuura, Noriaki; Yamamoto, Hideya; Kitagawa, Toshiro; Ito, Katsuhide [Hiroshima University, Hiroshima (Japan)


    To test the effects of heart rate, body mass index (BMI) and noise level on interscan and interobserver variability of coronary artery calcium (CAC) scoring on a prospective electrocardiogram (ECG)-triggered 64-slice CT. One hundred and ten patients (76 patients with CAC) were scanned twice on prospective ECG-triggered scans. The scan parameters included 120 kV, 82 mAs, a 2.5 mm thickness, and an acquisition center at 45% of the RR interval. The interscan and interobserver variability on the CAC scores (Agatston, volume, and mass) was calculated. The factors affecting the variability were determined by plotting it against heart rate, BMI, and noise level (defined as the standard deviation: SD). The estimated effective dose was 1.5 {+-} 0.2 mSv. The mean heart rate was 63 {+-} 12 bpm (range, 44-101 bpm). The patient BMIs were 24.5 {+-} 4.5 kg/m{sup 2} (range, 15.5-42.3 kg/m2). The mean and median interscan variabilities were 11% and 6%, respectively by volume, and 11% and 6%, respectively, by mass. Moreover, the mean and median of the algorithms were lower than the Agatston algorithm (16% and 9%, respectively). The mean and median interobserver variability was 10% and 4%, respectively (average of algorithms). The mean noise levels were 15 {+-} 4 Hounsfield unit (HU) (range, 8-25 HU). The interscan and interobserver variability was not correlated with heart rate, BMI, or noise level. The interscan and interobserver variability of CAC on a prospective ECG-triggered 64-slice CT with high image quality and 45% of RR acquisition is not significantly affected by heart rate, BMI, or noise level. The volume or mass algorithms show reduced interscan variability compared to the Agatston scoring (p < 0.05)

  17. Transient Oxygen/Glucose Deprivation Causes a Delayed Loss of Mitochondria and Increases Spontaneous Calcium Signaling in Astrocytic Processes. (United States)

    O'Donnell, John C; Jackson, Joshua G; Robinson, Michael B


    Recently, mitochondria have been localized to astrocytic processes where they shape Ca(2+) signaling; this relationship has not been examined in models of ischemia/reperfusion. We biolistically transfected astrocytes in rat hippocampal slice cultures to facilitate fluorescent confocal microscopy, and subjected these slices to transient oxygen/glucose deprivation (OGD) that causes delayed excitotoxic death of CA1 pyramidal neurons. This insult caused a delayed loss of mitochondria from astrocytic processes and increased colocalization of mitochondria with the autophagosome marker LC3B. The losses of neurons in area CA1 and mitochondria in astrocytic processes were blocked by ionotropic glutamate receptor (iGluR) antagonists, tetrodotoxin, ziconotide (Ca(2+) channel blocker), two inhibitors of reversed Na(+)/Ca(2+) exchange (KB-R7943, YM-244769), or two inhibitors of calcineurin (cyclosporin-A, FK506). The effects of OGD were mimicked by NMDA. The glutamate uptake inhibitor (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-l-aspartate increased neuronal loss after OGD or NMDA, and blocked the loss of astrocytic mitochondria. Exogenous glutamate in the presence of iGluR antagonists caused a loss of mitochondria without a decrease in neurons in area CA1. Using the genetic Ca(2+) indicator Lck-GCaMP-6S, we observed two types of Ca(2+) signals: (1) in the cytoplasm surrounding mitochondria (mitochondrially centered) and (2) traversing the space between mitochondria (extramitochondrial). The spatial spread, kinetics, and frequency of these events were different. The amplitude of both types was doubled and the spread of both types changed by ∼2-fold 24 h after OGD. Together, these data suggest that pathologic activation of glutamate transport and increased astrocytic Ca(2+) through reversed Na(+)/Ca(2+) exchange triggers mitochondrial loss and dramatic increases in Ca(2+) signaling in astrocytic processes. Astrocytes, the most abundant cell type in the brain

  18. Serum Calcium Increase Correlates With Worsening of Lipid Profile: An Observational Study on a Large Cohort From South Italy. (United States)

    Gallo, Luigia; Faniello, Maria C; Canino, Giovanni; Tripolino, Cesare; Gnasso, Agostino; Cuda, Giovanni; Costanzo, Francesco S; Irace, Concetta


    Despite the well-documented role of calcium in cell metabolism, its role in the development of cardiovascular disease is still under heavy debate. Several studies suggest that calcium supplementation might be associated with an increased risk of coronary heart disease, whereas others underline a significant effect on lowering high blood pressure and hyperlipidemia. The purpose of this study was to investigate, in a large nonselected cohort from South Italy, if serum calcium levels correlate with lipid values and can therefore be linked to higher individual cardiovascular risk.Eight-thousand-six-hundred-ten outpatients addressed to the Laboratory of Clinical Biochemistry, University of Magna Græcia, Catanzaro, Italy from January 2012 to December 2013 for routine blood tests, were enrolled in the study. Total HDL-, LDL- and non-HDL colesterol, triglycerides, and calcium were determined with standard methods.We observed a significant association between total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, triglycerides, and serum calcium in men and postmenopause women. Interestingly, in premenopause women, we only found a direct correlation between serum calcium, total cholesterol, and HDL-cholesterol. Calcium significantly increased while increasing total cholesterol and triglycerides in men and postmenopause women.Our results confirm that progressive increase of serum calcium level correlates with worsening of lipid profile in our study population. Therefore, we suggest that a greater caution should be used in calcium supplement prescription particularly in men and women undergoing menopause, in which an increase of serum lipids is already known to be associated with a higher cardiovascular risk.

  19. Increased urinary calcium excretion caused by ceftriaxone: possible association with urolithiasis. (United States)

    Kimata, Takahisa; Kaneko, Kazunari; Takahashi, Masaya; Hirabayashi, Masato; Shimo, Tomohiko; Kino, Minoru


    The administration of ceftriaxone is known to be associated with biliary pseudolithiasis, although the development of urolithiasis has only rarely been reported. We treated a young male with bacterial meningitis complicated by urinary precipitates composed of ceftriaxone-calcium salt, which prompted us to study whether ceftriaxone administration predisposes children to the formation of urinary precipitates. The case-control study reported here included 83 children with bacterial pneumonia aged from 3 months to 8.9 years. The children were divided into one group of 43 children who received ceftriaxone (group A) and a second group of 40 children who received amoxicillin (group B). Paired samples of serum and urine before and after treatment were obtained from the patients in each group. There were no significant differences in demographic characteristics and blood biochemistry between the groups. However, the mean urinary calcium to creatinine ratio (uCa/Cr; mg/mg) was significantly higher in group A patients than in group B patients after treatment (0.19 vs. 0.09, respectively; p ceftriaxone and the uCa/Cr in group A (p = 0.10, r = 0.24). Our results are the first to demonstrate that ceftriaxone has the potential to significantly increase urinary excretion of calcium, which may be linked to ceftriaxone-related urolithiasis or sludge. We therefore suggest that it is worthwhile monitoring the uCa/Cr levels in patients on ceftriaxone as they may be at greater risk for developing large stones and renal damage.

  20. Activation of a P2Y4-like purinoceptor triggers an increase in cytosolic [Ca2+] in the red blood cells of the lizard Ameiva ameiva (Squamata, Teiidae

    Directory of Open Access Journals (Sweden)

    Sartorello R.


    Full Text Available An increasing number of pathophysiological roles for purinoceptors are emerging, some of which have therapeutic potential. Erythrocytes are an important source of purines, which can be released under physiological and physiopathological conditions, acting on purinergic receptors associated with the same cell or with neighboring cells. Few studies have been conducted on lizards, and have been limited to ATP agonist itself. We have previously shown that the red blood cells (RBCs of the lizard Ameiva ameiva store Ca2+ in the endoplasmic reticulum (ER and that the purinergic agonist ATP triggers a rapid and transient increase of [Ca2+]c by mobilization of the cation from internal stores. We also reported the ability of the second messenger IP3 to discharge the ER calcium pool of the ER. Here we characterize the purinoceptor present in the cytoplasmic membrane of the RBCs of the lizard Ameiva ameiva by the selective use of ATP analogues and pyrimidine nucleotides. The nucleotides UTP, UDP, GTP, and ATPgammaS triggered a dose-dependent response, while interestingly 2MeSATP, 2ClATP, alpha, ß-ATP, and ADP failed to do so in a 1- to 200-µm con- centration. The EC50 obtained for the compounds tested was 41.77 µM for UTP, 48.11 µM for GTP, 53.11 µM for UDP, and 30.78 µM for ATPgammaS. The present data indicate that the receptor within the RBCs of Ameiva ameiva is a P2Y4-like receptor due to its pharmacological similarity to the mammalian P2Y4 receptor.

  1. Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells

    DEFF Research Database (Denmark)

    Bjerregaard, Henning F.

    peroxide (H2O2) has traditionally been regarded as toxic by-products of aerobic metabolism. However, recent findings indicate that H2O2 act as a signalling molecule. The aim of the present study was to monitor, in real time, the rates of ROS generation in order to directly determine their production......Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells. Henning F. Bjerregaard, Roskilde University, Department of Science, Systems and Models , 4000 Roskilde, Denmark. HFB@ RUC.DK Reactive oxygen species (ROS) like, hydrogen...... to G-protein stimulation of phospholipase C and release of inositol -3 phosphate. Cd (0.4 mM) treatment of A6 cells enhanced the ROS production after one minutes incubation. The production rate was constant for at least 10 to 20 min. Experiments showed that the Cd induced increase in ROS production...

  2. Extremely Low Frequency Electromagnetic Fields Facilitate Vesicle Endocytosis by Increasing Presynaptic Calcium Channel Expression at a Central Synapse. (United States)

    Sun, Zhi-cheng; Ge, Jian-long; Guo, Bin; Guo, Jun; Hao, Mei; Wu, Yi-chen; Lin, Yi-an; La, Ting; Yao, Pan-tong; Mei, Yan-ai; Feng, Yi; Xue, Lei


    Accumulating evidence suggests significant biological effects caused by extremely low frequency electromagnetic fields (ELF-EMF). Although exo-endocytosis plays crucial physical and biological roles in neuronal communication, studies on how ELF-EMF regulates this process are scarce. By directly measuring calcium currents and membrane capacitance at a large mammalian central nervous synapse, the calyx of Held, we report for the first time that ELF-EMF critically affects synaptic transmission and plasticity. Exposure to ELF-EMF for 8 to 10 days dramatically increases the calcium influx upon stimulation and facilitates all forms of vesicle endocytosis, including slow and rapid endocytosis, endocytosis overshoot and bulk endocytosis, but does not affect the RRP size and exocytosis. Exposure to ELF-EMF also potentiates PTP, a form of short-term plasticity, increasing its peak amplitude without impacting its time course. We further investigated the underlying mechanisms and found that calcium channel expression, including the P/Q, N, and R subtypes, at the presynaptic nerve terminal was enhanced, accounting for the increased calcium influx upon stimulation. Thus, we conclude that exposure to ELF-EMF facilitates vesicle endocytosis and synaptic plasticity in a calcium-dependent manner by increasing calcium channel expression at the nerve terminal.

  3. Vitamin D deficiency and calcium intake in reference to increased body mass index in children and adolescents. (United States)

    Al-Musharaf, Sara; Al-Othman, Abdulaziz; Al-Daghri, Nasser M; Krishnaswamy, Soundararajan; Yusuf, Deqa S; Alkharfy, Khalid M; Al-Saleh, Yousef; Al-Attas, Omar S; Alokail, Majed S; Moharram, Osama; Yakout, Sobhy; Sabico, Shaun; Chrousos, George P


    Vitamin D deficiency has been linked to several chronic diseases in adults. Studies focusing on children and adolescents, however, are limited. In this randomized cross-sectional study, we aimed to determine the prevalence of vitamin D deficiency and its relationship with childhood obesity and dietary calcium intake among a population of healthy urban Saudi children and adolescents. To achieve this, 331 randomly selected Saudi children (53.8% females and 46.2% males) aged 6-17 years were included. Demographic, medical, and dietary information were collected; anthropometrics were measured. Levels of serum fasting glucose, lipid profile, 25(OH) D, and for albumin corrected calcium were analyzed. Vitamin D deficiency was noted in all subjects, with girls having significantly lower vitamin D levels than boys. Mean calcium intake was found to be 60% of the required dietary allowance (RDA), while the mean vitamin D intake was 23% of RDA. Vitamin D status and calcium intake were comparable in both normal and overweight/obese children and adolescents. Vitamin D status was highest among children who had calcium intake >800 mg/day. In adolescents there was insignificant but decreasing trend in BMI, which was observed to be highest among those whose calcium intake was 800 mg/day. results from this study suggest the importance of vitamin D fortification and increased dietary calcium in the Saudi diet to meet RDA requirements and avoid onset of vitamin D deficiency-related diseases in Saudi children and adolescents.

  4. Does adding an appended oncology module to the Global Trigger Tool increase its value?

    DEFF Research Database (Denmark)

    Mattsson, Thea Otto; Knudsen, Janne Lehmann; Brixen, Kim


    OBJECTIVE: To determine any additional value in the evaluation of safety levels by adding an appended oncology module to the Institute for Healthcare Improvement's Global Trigger Tool (GTT). DESIGN: Comparison of two independent retrospective chart reviews: one review team using the general GTT...... method and one using the general GTT method plus the appended oncology module on the same inpatient charts. SETTING: The Department of Clinical Oncology at a Danish University Hospital (1000 beds). PARTICIPANTS: All inpatients admitted to the hospital in 2010, n = 3692, biweekly sample of 10 admission...... per 1000 admission days. RESULTS: No significant (95% confidence interval) difference was found between review teams using the general GTT versus the general GTT plus the appended oncology module on the total number of identified AEs, AEs per 100 admissions, AEs per 1000 admission days...

  5. Evidence that increased calcium intake does not prevent early postmenopausal bone loss

    DEFF Research Database (Denmark)

    Hosking, D J; Ross, P D; Thompson, D E


    Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium...... intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose...... were not significantly associated with changes in BMD or bone turnover. Even women whose total calcium intake was >1333 mg/d (the highest tertile of total calcium intake) showed a decline in BMD of almost 2%, similar to declines in the lower two tertiles of total calcium intake (

  6. Calcium in milk and fermentation by yoghurt bacteria increase the resistance of rats to Salmonella infection.


    Bovee-Oudenhoven, I; Termont, D; Dekker, R. (Rudolf); Van der Meer, R


    Calcium in milk products stimulates gastric acid secretion and inhibits the cytolytic activity of intestinal contents. Based on these effects, it was hypothesised that calcium might lessen the severity of food borne intestinal infections. The possible differential effects of a low calcium milk and normal milk products (milk, acidified milk, and pasteurised yoghurt) on the resistance of rats to a salmonella infection was therefore studied. Rats were infected orally with Salmonella enteritidis ...

  7. Increasing serum calcium levels and recent return from transplantation as clues to the tuberculous nature of refractory peritoneal dialysis peritonitis

    Directory of Open Access Journals (Sweden)

    L Rodriguez-Osorio


    Full Text Available Peritoneal tuberculosis is an uncommon complication of peritoneal dialysis in Europe. It is more common in Asian immigrants. A delayed diagnosis is frequent and impairs patient outcomes. We present two cases of peritoneal tuberculosis with common features that may help suspect the disease early countries with a low incidence. Both patients were females (of Spanish origin who had recently restarted peritoneal dialysis following kidney transplantation. Both developed bacterial peritonitis clinically that was refractory to conventional antibiotics, despite clearance of bacteria. Both stopped calcium-containing phosphate binders because of increasing serum calcium that in one case led to frank hypercalcemia that persisted despite low calcium dialysate. Peritoneal biopsy was the first positive test in both cases. This report emphasizes the recent return from transplantation and rising serum calcium levels as features that should alert the physician of a potential underlying tuberculous peritonitis.

  8. Latent myofascial trigger points are associated with an increased antagonistic muscle activity during agonist muscle contraction. (United States)

    Ibarra, José Miota; Ge, Hong-You; Wang, Chao; Martínez Vizcaíno, Vicente; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars


    The aim of this study was to evaluate motor unit activity from a latent myofascial trigger point (MTP) in an antagonist muscle during isometric agonist muscle contraction. Intramuscular activity was recorded with an intramuscular electromyographic (EMG) needle inserted into a latent MTP or a non-MTP in the posterior deltoid muscle at rest and during isometric shoulder flexion performed at 25% of maximum voluntary contraction in 14 healthy subjects. Surface EMGs were recorded from the anterior and posterior deltoid muscles. Maximal pain intensity and referred pain induced by EMG needle insertion were recorded on a visual analogue scale. The results showed that higher local pain was observed following needle insertion into latent MTPs (4.64 ± .48 cm) than non-MTPs (2.35 ± .43 cm, P muscle was significantly higher at rest and during shoulder flexion at latent MTPs than non-MTPs (P muscle relaxation following exercise, disordered fine movement control, and unbalanced muscle activation. Elimination of latent MTPs and/or prevention of latent MTPs from becoming active may improve motor functions. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  9. Calcium-phosphate complex increased during subchondral bone remodeling affects earlystage osteoarthritis. (United States)

    Jung, Youn-Kwan; Han, Min-Su; Park, Hye-Ri; Lee, Eun-Ju; Jang, Ji-Ae; Kim, Gun-Woo; Lee, Sun-Young; Moon, DaeWon; Han, Seungwoo


    An activation of osteoclasts and subchondral bone remodeling is a major histologic feature of early-stage osteoarthritis (OA), which can be accompanied by an increase of calcium (Ca) and phosphate (Pi) level in the subchondral milieu. Considering articular cartilage gets most of nutrition from subchondral bone by diffusion, these micro-environmental changes in subchondral bone can affect the physiology of articular chondrocytes. Here, we have shown that Ca is increased and co-localized with Pi in articular cartilage of early-stage OA. The Ca-Pi complex increased the production of MMP-3 and MMP-13 in the hypertrophic chondrocytes, which was dependent on nuclear factor-kappa B (NF-kB), p38 and extracellular signal-regulated kinase (Erk) 1/2 mitogen-activated protein (MAP) kinase and Signal transducer and activator of transcription 3 (STAT3) signaling. The Ca-Pi complexes increased the expression of endocytosis markers, and the inhibition of the formation of the Ca-Pi complex ameliorated the Ca-Pi complex-mediated increases of MMPs expression in hypertrophic chondrocytes. Our data provide insight regarding the Ca-Pi complex as a potential catabolic mediator in the subchondral milieu and support the pathogenic role of subchondral bone in the early stages of cartilage degeneration.

  10. Impact of a nutrition education program to increase intake of calcium-rich foods by Chinese-American women. (United States)

    Lv, Nan; Brown, J Lynne


    Chinese-American women have a high risk of osteoporosis. However, their calcium intake has been reported previously as considerably below the Dietary Reference Intake. Increasing consumption of calcium-rich foods, many of which are also fortified with vitamin D, is a safe way to increase their calcium and vitamin D intake. This study's objective was to pilot-test an intervention to help Chinese-American women incorporate calcium-rich foods into their diet. This intervention was evaluated using a quasi-experimental study with a nested design and pre-, immediate post-, and 3-month follow-up assessments. Calcium and vitamin D intake, Theory of Planned Behavior constructs, and knowledge were measured at three time points. First-generation Chinese-American mothers between 35 and 55 years old (n=141) were recruited from six weekend Chinese schools. Three Chinese schools each were randomly assigned to the experimental (n=71) or control group (n=70). The experimental group received a free heel scan and six weekly interactive lessons designed based on the Theory of Planned Behavior. The control group received six weekly nonrelated financial lessons by mail. Changes for each measure were assessed by linear mixed model with repeated measures adjusted for confounding variables. Compared to the control group, the experimental group improved all measures considerably, except two subjective norm constructs (normative belief and motivation to comply) at post-assessments. The experimental group significantly increased its baseline calcium (t=7.898, P<0.001) and vitamin D intake (t=6.609; P<0.001) at posttest and this increase was retained at follow-up. Results suggest that this theory-based intervention is effective for increasing the dietary calcium and vitamin D intake of Chinese-American women. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

  11. Fatty Liver, Insulin Resistance, and Obesity: Relationships With Increase in Coronary Artery Calcium Over Time. (United States)

    Sung, Ki-Chul; Ryu, Seungho; Lee, Jong-Young; Lee, Sung Ho; Cheong, Eun Sun; Wild, Sarah H; Byrne, Christopher D


    Nonalcoholic fatty liver disease, insulin resistance (IR), and obesity frequently coexist with type 2 diabetes mellitus (DM), but it is uncertain whether these risk factors for vascular disease contribute to a change in atherosclerosis over time, independently of DM status. We hypothesized that the combination of fatty liver, IR, and obesity would be associated with an increase in coronary artery calcium (CAC) score over time, independently of DM status, other cardiovascular risk factors, and medications. Data were analyzed from a South Korean occupational cohort of 2175 people. The outcome was increase in cardiac computed tomography CAC score between baseline and follow-up. Insulin resistance was defined by homeostatic model assessment of insulin resistance (HOMA-IR) ≥75th percentile and fatty liver by ultrasound. In 592 (27.2%) participants, CAC score increased from baseline (mean ± SD; mean age at baseline, 44.8 ± 5.5 years); and in 1583 subjects, CAC did not change or improved during follow-up (mean age, 41.6 ± 5.6 years). Diabetes mellitus, HOMA-IR, fatty liver, and obesity prevalence were all higher (all P obesity, and fatty liver was independently associated with increase in CAC score over time (hazard ratio: 2.46, 95% confidence interval: 1.50-4.03). The combination of fatty liver, IR, and obesity is associated with progression of atherosclerosis over time independently of DM, cardiovascular risk factors, and all medications for cardiovascular disease and DM. © 2016 Wiley Periodicals, Inc.

  12. Can calcium ionophore "use" in patients with diminished ovarian reserve increase fertilization and pregnancy rates? A randomized, controlled study. (United States)

    Caglar Aytac, Pinar; Kilicdag, Esra Bulgan; Haydardedeoglu, Bulent; Simsek, Erhan; Cok, Tayfun; Parlakgumus, Huriye Ayse


    To determine whether calcium ionophore solution can improve the fertilization rate in patients with diminished ovarian reserve whose partners have normal sperm parameters. Between January 2014 and August 2014, patients with diminished ovarian reserve were randomized to make artificial oocyte activation with calcium ionophore solution. University hospital. A total of 296 patients who had diminished ovarian reserve and partners with normal sperm parameters were included in the study. Metaphase 2 oocytes were treated with calcium ionophore solution (GM508 Cult-Active) for 15 minutes just after intracytoplasmic sperm injection. Fertilization rate, implantation rate, clinical pregnancy rate, ongoing pregnancy rate. Fertilization, implantation, pregnancy, and ongoing pregnancy rates for the calcium ionophore and control groups were 60.7% and 55.4%, 12.8% and 10.7%, 21% and 12.8%, and 10.9% and 6.1%, respectively. This is the first prospective, randomized, controlled study to analyze the effect of calcium ionophore solution on fertilization rate in patients with diminished ovarian reserve. We did not observe any differences in fertilization, clinical pregnancy, or ongoing pregnancy rates between the groups. We propose that fertilization ratios could not be increased by artificial oocyte activation via application of calcium ionophore solution in patients with diminished ovarian reserve. NCT02045914. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Mitochondrial reactive oxygen species generation and calcium increase induced by visible light in astrocytes. (United States)

    Jou, Mei-Jie; Jou, Shuo-Bin; Guo, Mei-Jin; Wu, Hong-Yueh; Peng, Tsung-I


    Mitochondria contain photosensitive chromophores that can be activated or inhibited by light in the visible range. Rather than utilizing light energy, however, mitochondrial electron transport oxidation-reduction reaction and energy coupling could be stimulated or damaged by visible light. Our previous work demonstrated that reactive oxygen species (ROS) were generated in cultured astrocytes after visible laser irradiation. With confocal fluorescence microscopy, we found that ROS were generated mostly from mitochondria. This mitochondrial ROS (mROS) formation plays a critical role in photoirradiation-induced phototoxicity and apoptosis. In this study, we measured changes of mitochondrial calcium level ([Ca(2+)](m)) in cultured astrocytes (RBA-1 cell line) irradiated with blue light and examined the association between mROS formation and [Ca(2+)](m) level changes. Changes of intracellular ROS and [Ca(2+)](m) were visualized using fluorescent probes 2',7'-dichlorodihydrofluorescein (DCF), and rhod-2. After exposure to visible light irradiation, RBA-1 astrocytes showed a rapid increase in ROS accumulation particularly in the mitochondrial area. Increase in [Ca(2+)](m) was also induced by photoirradiation. The levels of increase in DCF fluorescence intensity varied among different astrocytes. Some of the cells generated much higher levels of ROS than others. For those cells that had high ROS levels, mitochondrial Ca(2+) levels were also high. In cells that had mild ROS levels, mitochondrial Ca(2+) levels were only slightly increased. The rate of increase in DCF fluorescence seemed to be close to the rate of rhod-2 fluorescence increase. There is a positive and close correlation between mitochondrial ROS levels and mitochondrial Ca(2+) levels in astrocytes irradiated by visible light.

  14. Secular decline of seawater calcium increases seawater buffering and pH (United States)

    Hain, M.; Sigman, D. M.; Higgins, J. A.; Haug, G. H.


    Reconstructed changes in seawater calcium and magnesium concentration ([Ca2+], [Mg2+]) predictably affect the ocean's acid/base and carbon chemistry. Yet inaccurate formulations of chemical equilibrium "constants" are currently in use to account for these changes. Here we develop an efficient implementation of the MIAMI Ionic Interaction Model (Millero and Pierrot, 1998) to predict all chemical equilibrium constants required for carbon chemistry calculations under variable [Ca2+] and [Mg2+] (Hain et al., 2015). We investigate the impact of [Ca2+] and [Mg2+] on the relationships among the ocean's pH, CO2, dissolved inorganic carbon (DIC), saturation state of CaCO3 (Ω), and buffer capacity. Increasing [Ca2+] and/or [Mg2+] enhances "ion pairing," which increases seawater buffering by increasing the concentration ratio of total to "free" (uncomplexed) carbonate ion. An increase in [Ca2+], however, also causes a decline in carbonate ion to maintain a given Ω, thereby overwhelming the ion pairing effect and decreasing seawater buffering. Given the reconstructions of Eocene [Ca2+] and [Mg2+] ([Ca2+]~20mM; [Mg2+]~30 mM), Eocene seawater would have required essentially the same DIC as today to simultaneously explain a similar-to-modern Ω and the estimated Eocene atmospheric CO2 of ~1000 ppm. During the Cretaceous, at ~4 times modern [Ca2+], ocean buffering would have been at a minimum. Overall, during times of high seawater [Ca2+], CaCO3 saturation, pH, and atmospheric CO2 were more susceptible to perturbations of the global carbon cycle. For example, given both Eocene and Cretaceous seawater [Ca2+] and [Mg2+], a doubling of atmospheric CO2 would require less carbon addition to the ocean/atmosphere system than under modern seawater composition. Moreover, increase in seawater buffering since the Cretaceous may have been a driver of evolution by raising energetic demands of biologically controlled calcification and CO2 concentration mechanisms that aid photosynthesis.

  15. Hunting Increases Phosphorylation of Calcium/Calmodulin-Dependent Protein Kinase Type II in Adult Barn Owls

    Directory of Open Access Journals (Sweden)

    Grant S. Nichols


    Full Text Available Juvenile barn owls readily adapt to prismatic spectacles, whereas adult owls living under standard aviary conditions do not. We previously demonstrated that phosphorylation of the cyclic-AMP response element-binding protein (CREB provides a readout of the instructive signals that guide plasticity in juveniles. Here we investigated phosphorylation of calcium/calmodulin-dependent protein kinase II (pCaMKII in both juveniles and adults. In contrast to CREB, we found no differences in pCaMKII expression between prism-wearing and control juveniles within the external nucleus of the inferior colliculus (ICX, the major site of plasticity. For prism-wearing adults that hunted live mice and are capable of adaptation, expression of pCaMKII was increased relative to prism-wearing adults that fed passively on dead mice and are not capable of adaptation. This effect did not bear the hallmarks of instructive information: it was not localized to rostral ICX and did not exhibit a patchy distribution reflecting discrete bimodal stimuli. These data are consistent with a role for CaMKII as a permissive rather than an instructive factor. In addition, the paucity of pCaMKII expression in passively fed adults suggests that the permissive default setting is “off” in adults.

  16. Increases in myocardial workload induced by rapid atrial pacing trigger alterations in global metabolism.

    Directory of Open Access Journals (Sweden)

    Aslan T Turer

    Full Text Available To determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis.Nineteen patients referred for cardiac catheterization were enrolled. Peripheral and selective coronary sinus (CS blood sampling was performed at serial timepoints following the initiation of pacing, and metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS.Pacing-stress resulted in a 225% increase in the median rate·pressure product from baseline. Increased myocardial work induced significant changes in the peripheral concentration of 43 of 125 metabolites assayed, including large changes in purine [adenosine (+99%, p = 0.006, ADP (+42%, p = 0.01, AMP (+79%, p = 0.004, GDP (+69%, p = 0.003, GMP (+58%, p = 0.01, IMP (+50%, p = 0.03, xanthine (+61%, p = 0.0006], and several bile acid metabolites. The CS changes in metabolites qualitatively mirrored those in the peripheral blood in both timing and magnitude, suggesting the heart was not the major source of the metabolite release.Isolated increases in myocardial work can induce changes in the plasma metabolome, but these changes do not appear to be directly cardiac in origin. A number of these dynamic metabolites have known signaling functions. Our study provides additional evidence to a growing body of literature on metabolic 'cross-talk' between the heart and other organs.

  17. Increased osteoblast density in the presence of novel calcium phosphate coated magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Pareta, Rajesh A; Webster, Thomas J [Division of Engineering and Department of Orthopedics, Brown University, Providence, RI 02912 (United States); Taylor, Erik [Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712 (United States)], E-mail:


    Bone diseases (including osteoporosis, osteoarthritis and bone cancer) are of great concern to the medical world. Drugs are available to treat such diseases, but often these drugs are not specifically targeted to the site of the disease and, thus, lack an immediate directed therapeutic effect. The optimal drug delivery system should enhance healthy bone growth with high specificity to the site of bone disease. It has been previously shown that magnetic nanoparticles can be directed in the presence of a magnetic field to any part of the body, allowing for site-specific drug delivery and possibly an immediate increase in bone density. The objective of the present study was to build off of this evidence and determine the density of osteoblasts (bone forming cells) in the presence of various uncoated and coated magnetic nanoparticles that could eventually be used in drug delivery applications. Results showed that some magnetic nanoparticles (specifically, {gamma}-Fe{sub 2}O{sub 3}) significantly promoted osteoblast density (that is, cells per well) after 5 and 8 days of culture compared to controls (no particles). These magnetic nanoparticles were further coated with calcium phosphate (CaP; the main inorganic component of bone) to tailor them for treating various bone diseases. The coatings were conducted in the presence of either bovine serum albumin (BSA) or citric acid (CA) to reduce magnetic nanoparticle agglomeration, a common problem resulting from the use of nanoparticles which decreases their effectiveness. Results with these coatings showed that magnetic nanoparticles, specifically ({gamma}-Fe{sub 2}O{sub 3}), coated in the presence of BSA significantly increased osteoblast density compared to controls after 1 day. In this manner, this study provided unexpected evidence that CaP-coated {gamma}-Fe{sub 2}O{sub 3} magnetic nanoparticles increased osteoblast density (compared to no particles) and, thus, should be further studied to treat numerous bone diseases.

  18. Increased magma production and volcanism triggered by the Messinian Salinity Crisis (United States)

    Sternai, Pietro; Caricchi, Luca; Garcia-Castellanos, Daniel; Castelltort, Sebastien


    For more than four decades, large controversies about the causes, effects and timing of the Mediterranean Messinian Salinity Crisis (MSC) have evolved in the light of a continuously growing body of evidences. The igneous response to such extreme event, however, has remained largely unexplored despite known relationships between surface load variations and the production of magma. Here, we compile published geochemical and isotopic data and recognize a two-fold increase of volcanic eruptions from pan-Mediterranean magmatic provinces coinciding with the proposed "shallow-water phase" of the MSC between 5.70-5.33 Ma. Estimates of surface load variations due to the desiccation event corrected for water density change and deposition of salt deposits suggest a net mean lithospheric unloading of up to 15 MPa during the shallow-water phase of the MSC. Because the timescale of interest is too short for changes of the Mediterranean tectonics to significantly affect the bulk of the magma production, we propose that such net surface unloading enhanced the mantle decompression melting and dike formation, in turn causing the observed increase of volcanic events. If correct, the Mediterranean magmatic record provides an independent validation of the "shallow-water" model for the formation of salt deposits and testifies the high sensitivity of the melting of the Earth's interior to the surface forcing.

  19. Fitness attenuates the prevalence of increased coronary artery calcium in individuals with metabolic syndrome. (United States)

    Ekblom-Bak, Elin; Ekblom, Örjan; Fagman, Erika; Angerås, Oskar; Schmidt, Caroline; Rosengren, Annika; Börjesson, Mats; Bergström, Göran


    Background The association between cardiorespiratory fitness, physical activity and coronary artery calcium (CAC) is unclear, and whether higher levels of fitness attenuate CAC prevalence in subjects with metabolic syndrome is not fully elucidated. The present study aims to: a) investigate the independent association of fitness on the prevalence of CAC, after adjustment for moderate-to-vigorous physical activity and sedentary time, and b) study the possible attenuation of increased CAC by higher fitness, in participants with metabolic syndrome. Design Cross-sectional. Methods In total 678 participants (52% women), 50-65 years old, from the SCAPIS pilot study were included. Fitness (VO 2 max) was estimated by submaximal cycle ergometer test and moderate-to-vigorous physical activity and sedentary time were assessed using hip-worn accelerometers. CAC score (CACS) was quantified using the Agatston score. Results The odds of having a significant CACS (≥100) was half in participants with moderate/high fitness compared with their low fitness counterparts. Further consideration of moderate-to-vigorous physical activity, sedentary time and number of components of the metabolic syndrome did only slightly alter the effect size. Those with metabolic syndrome had 47% higher odds for significant CAC compared with those without metabolic syndrome. However, moderate/high fitness seems to partially attenuate this risk, as further joint analysis indicated an increased odds for having significant CAC only in the unfit metabolic syndrome participants. Conclusions Being fit is associated with a reduced risk of having significant CAC in individuals with metabolic syndrome. While still very much underutilized, fitness should be taken into consideration in everyday clinical risk prediction in addition to the traditional risk factors of the metabolic syndrome.

  20. The Yin and Yang of Calcium Effects on Synaptic Vesicle Endocytosis (United States)

    Wu, Xin-Sheng


    A large number of studies suggest that calcium triggers and accelerates vesicle endocytosis at many synapses and non-neuronal secretory cells. However, many studies show that prolonging the duration of the stimulation train, which induces more calcium influx, slows down endocytosis; and several studies suggest that instead of triggering endocytosis, calcium actually inhibits endocytosis. Here we addressed this apparent conflict at a large nerve terminal, the calyx of Held in rat brainstem, in which recent studies suggest that transient calcium increase up to tens of micromolar concentration at the micro/nano domain triggers endocytosis. By dialyzing 0–1 μm calcium into the calyx via a whole-cell pipette, we found that slow endocytosis was inhibited by calcium dialysis in a concentration-dependent manner. Thus, prolonged, small, and global calcium increase inhibits endocytosis, whereas transient and large calcium increase at the micro/nano domain triggers endocytosis and facilitates endocytosis. This yin and yang effect of calcium may reconcile apparent conflicts regarding whether calcium accelerates or inhibits endocytosis. Whether endocytosis is fast or slow depends on the net outcome between the yin and yang effect of calcium. PMID:24523554

  1. Price transparency for MRIs increased use of less costly providers and triggered provider competition. (United States)

    Wu, Sze-jung; Sylwestrzak, Gosia; Shah, Christiane; DeVries, Andrea


    To encourage patients to select high-value providers, an insurer-initiated price transparency program that focused on elective advanced imaging procedures was implemented. Patients having at least one outpatient magnetic resonance imaging (MRI) scan in 2010 or 2012 were divided according to their membership in commercial health plans participating in the program (the intervention group) or in nonparticipating commercial health plans (the reference group) in similar US geographic regions. Patients in the intervention group were informed of price differences among available MRI facilities and given the option of selecting different providers. For those patients, the program resulted in a $220 cost reduction (18.7 percent) per test and a decrease in use of hospital-based facilities from 53 percent in 2010 to 45 percent in 2012. Price variation between hospital and nonhospital facilities for the intervention group was reduced by 30 percent after implementation. Nonparticipating members residing in intervention areas also observed price reductions, which indicates increased price competition among providers. The program significantly reduced imaging costs. This suggests that patients select lower-price facilities when informed about available alternatives. Project HOPE—The People-to-People Health Foundation, Inc.

  2. Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

    Directory of Open Access Journals (Sweden)

    Schulkin Jay


    Full Text Available Abstract Background Corticotropin-releasing factor (CRF is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior. Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 μl or amphetamine (20 μg/0.2 μl. Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results Microinjections of the highest dose of CRF (500 ng or amphetamine (20 μg selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress

  3. Increasing Calcium Carbonate (Caco3) To Growt And Survival Rate Vannamei Shrimp (Litopenaeus Vannamei))


    Heriadi, Unggul Fitrah; ', Mulyadi; Putra, Iskandar


    This research was conducted in March 2016 - April 2016 for 21 days at the NationalBroodstock Center For Shrimp and Mollusk Karangasem Bali. The purpose of this study todetermine the effect of calcium carbonate (CaCO3) on the growth and survival rate vanameishrimp (Litopeneaus vannamei). Vanamei shrimp size PL25 were used in the research. Thecontainer used fiber tub with capacity 250 liters and the volume of water used is 100 liters.The treatment is giving of calcium carbonate 20 mg, 35mg, 50m...

  4. Calcium Increases Xylella fastidiosa Surface Attachment, Biofilm Formation, and Twitching Motility (United States)

    Cruz, Luisa F.; Cobine, Paul A.


    Xylella fastidiosa is a plant-pathogenic bacterium that forms biofilms inside xylem vessels, a process thought to be influenced by the chemical composition of xylem sap. In this work, the effect of calcium on the production of X. fastidiosa biofilm and movement was analyzed under in vitro conditions. After a dose-response study with 96-well plates using eight metals, the strongest increase of biofilm formation was observed when medium was supplemented with at least 1.0 mM CaCl2. The removal of Ca by extracellular (EGTA, 1.5 mM) and intracellular [1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA/AM), 75 μM] chelators reduced biofilm formation without compromising planktonic growth. The concentration of Ca influenced the force of adhesion to the substrate, biofilm thickness, cell-to-cell aggregation, and twitching motility, as shown by assays with microfluidic chambers and other assays. The effect of Ca on attachment was lost when cells were treated with tetracycline, suggesting that Ca has a metabolic or regulatory role in cell adhesion. A double mutant (fimA pilO) lacking type I and type IV pili did not improve biofilm formation or attachment when Ca was added to the medium, while single mutants of type I (fimA) or type IV (pilB) pili formed more biofilm under conditions of higher Ca concentrations. The concentration of Ca in the medium did not significantly influence the levels of exopolysaccharide produced. Our findings indicate that the role of Ca in biofilm formation may be related to the initial surface and cell-to-cell attachment and colonization stages of biofilm establishment, which rely on critical functions by fimbrial structures. PMID:22194297

  5. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to lactose and increase in calcium absorption leading to an increase in calcium retention (ID 668) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to lactose and increase in calcium absorption leading to an increase in calcium retention. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member...... States or directly from stakeholders. The food constituent that is the subject of the health claim is lactose. The Panel considers that lactose is sufficiently characterised. The claimed effect is “calcium absorption”. The target population is assumed to be the general population. The Panel notes...... between the consumption of lactose and an increase in calcium absorption leading to an increase in calcium retention....

  6. Icariin, a Novel Blocker of Sodium and Calcium Channels, Eliminates Early and Delayed Afterdepolarizations, As Well As Triggered Activity, in Rabbit Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Wanzhen Jiang


    Full Text Available Icariin, a flavonoid monomer from Herba Epimedii, has confirmed pharmacological and biological effects. However, its effects on arrhythmias and cardiac electrophysiology remain unclear. Here we investigate the effects of icariin on ion currents and action potentials (APs in the rabbit myocardium. Furthermore, the effects of icariin on aconitine-induced arrhythmias were assessed in whole rabbits. Ion currents and APs were recorded in voltage-clamp and current-clamp mode in rabbit left ventricular myocytes (LVMs and left atrial myocytes (LAMs, respectively. Icariin significantly shortened action potential durations (APDs at 50 and 90% repolarization (APD50 and APD90 and reduced AP amplitude (APA and the maximum upstroke velocity (Vmax of APs in LAMs and LVMs; however, icariin had no effect on resting membrane potential (RMP in these cells. Icariin decreased the rate-dependence of the APD and completely abolished anemonia toxin II (ATX-II-induced early afterdepolarizations (EADs. Moreover, icariin significantly suppressed delayed afterdepolarizations (DADs and triggered activities (TAs elicited by isoproterenol (ISO, 1 μM and high extracellular calcium concentrations ([Ca2+]o, 3.6 mM in LVMs. Icariin also decreased INaT in a concentration-dependent manner in LAMs and LVMs, with IC50 values of 12.28 ± 0.29 μM (n = 8 cells/4 rabbits and 11.83 ± 0.92 μM (n = 10 cells/6 rabbits; p > 0.05 vs. LAMs, respectively, and reversed ATX-II-induced INaL in a concentration-dependent manner in LVMs. Furthermore, icariin attenuated ICaL in a dose-dependent manner in LVMs. The corresponding IC50 value was 4.78 ± 0.89 μM (n = 8 cells/4 rabbits, indicating that the aforementioned current in LVMs was 2.8-fold more sensitive to icariin than ICaL in LAMs (13.43 ± 2.73 μM; n = 9 cells/5 rabbits. Icariin induced leftward shifts in the steady-state inactivation curves of INaT and ICaL in LAMs and LVMs but did not have a significant effect on their activation

  7. Calcium addition to increase the production of phosphate granules in anaerobic treatment of black water

    NARCIS (Netherlands)

    Cunha, Jorge Ricardo; Schott, Chris; Weijden, van der Renata D.; Leal, Lucía Hernández; Zeeman, Grietje; Buisman, Cees


    Simultaneous recovery of calcium phosphate granules (CaP granules) and methane from vacuum collected black water (BW), using an upflow anaerobic sludge blanket (UASB) reactor was previously investigated. It was calculated that only 2% of the total phosphorus (P) fed was present as CaP granules

  8. Channelrhodopsin-2-expressed dorsal root ganglion neurons activates calcium channel currents and increases action potential in spinal cord. (United States)

    Zhang, Yi; Yue, Jing; Ai, Midan; Ji, Zhigang; Liu, Zhiguo; Cao, Xuehong; Li, Li


    We used optogenetic techniques in spinal cord and dorsal root ganglion (DRG) neuron studies. This study investigated changes in channelrhodopsin-2 (ChR2) expression in the spinal cord and DRG neurons using optogenetic techniques. The results show the possibility of using optogenetics to treat neuropathic pain. Previous studies have shown that activated ChR2 induces an increase in DRG neuron action potential. Western blot analysis was used to measure ChR2 protein levels in the spinal cord and DRG neurons or rats intrathecally injected with ChR2 lentivirus. Electrophysiology recording was used to detect differences in action potential levels in the spinal cord and calcium channel currents in the DRG neurons. Our studies showed that ChR2 expression increased the action potential in the spinal cord and increased calcium channel currents in DRG neurons. We successfully expressed the ChR2 protein in the spinal cord and DRG neurons. We also found that ChR2 increased the action potential in the spinal cord and activated the calcium channel in DRG neurons. These findings support the research possibilities of using optogenetic studies to improve treatment for neuropathic pain. N/A.

  9. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Bjerrum, Poul J; Jessen, Torben E


    motility and acrosome reaction. All men delivered samples for routine semen analysis and blood for measurements of follicle stimulating hormone, Inhibin B, 25-hydroxy-VD, albumin, alkaline phosphatase, calcium and parathyroid hormone (PTH). RESULTS In the association study, 44% were VD insufficient (75 n...... concentration, sperm motility and induced the acrosome reaction in mature spermatozoa, and VD serum levels were positively associated with sperm motility, suggesting a role for VD in human sperm function....

  10. Innate immune recognition of double-stranded RNA triggers increased expression of NKG2D ligands after virus infection. (United States)

    Esteso, Gloria; Guerra, Susana; Valés-Gómez, Mar; Reyburn, Hugh T


    Self/non-self-discrimination by the innate immune system relies on germline-encoded, non-rearranging receptors expressed by innate immune cells recognizing conserved pathogen-associated molecular patterns. The natural killer group 2D (NKG2D) receptor is a potent immune-activating receptor that binds human genome-encoded ligands, whose expression is negligible in normal tissues, but increased in stress and disease conditions for reasons that are incompletely understood. Here it is not clear how the immune system reconciles receptor binding of self-proteins with self/non-self-discrimination to avoid autoreactivity. We now report that increased expression of NKG2D ligands after virus infection depends on interferon response factors activated by the detection of viral double-stranded RNA by pattern-recognition receptors (RIG-I/MDA-5) and that NKG2D ligand up-regulation can be blocked by the expression of viral dsRNA-binding proteins. Thus, innate immunity-mediated recognition of viral nucleic acids triggers the infected cell to release interferon for NK cell recruitment and to express NKG2D ligands to become more visible to the immune system. Finally, the observation that NKG2D-ligand induction is a consequence of signaling by pattern-recognition receptors that have been selected over evolutionary time to be highly pathogen-specific explains how the risks of autoreactivity in this system are minimized. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.; Meer, Berend van; Ward-van Oostwaard, Dorien [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); Passier, Robert [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); MIRA, University of Twente (Netherlands); Tertoolen, Leon G.J.; Mummery, Christine L. [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); Casini, Simona, E-mail: [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands)


    One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation. - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.

  12. Evaluation of fermentation conditions triggering increased antibacterial activity from a near-shore marine intertidal environment-associated Streptomyces species

    Directory of Open Access Journals (Sweden)

    A.L. English


    Full Text Available A near-shore marine intertidal environment-associated Streptomyces isolate (USC-633 from the Sunshine Coast Region of Queensland, Australia, cultivated under a range of chemically defined and complex media to determine optimal parameters resulting in the secretion of diverse array of secondary metabolites with antimicrobial properties against various antibiotic resistant bacteria. Following extraction, fractioning and re-testing of active metabolites resulted in persistent antibacterial activity against Escherichia coli (Migula (ATCC 13706 and subsequent Nuclear Magnetic Resonance (NMR analysis of the active fractions confirmed the induction of metabolites different than the ones in fractions which did not display activity against the same bacterial species. Overall findings again confirmed the value of One Strain–Many Compounds (OSMAC approach that tests a wide range of growth parameters to trigger bioactive compound secretion increasing the likelihood of finding novel therapeutic agents. The isolate was found to be adaptable to both marine and terrestrial conditions corresponding to its original near-shore marine intertidal environment. Wide variations in its morphology, sporulation and diffusible pigment production were observed when different growth media were used.

  13. Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton. (United States)

    Haffner-Luntzer, Melanie; Heilmann, Aline; Heidler, Verena; Liedert, Astrid; Schinke, Thorsten; Amling, Michael; Yorgan, Timur Alexander; Vom Scheidt, Annika; Ignatius, Anita


    Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J

  14. IgG from Amyotrophic Lateral Sclerosis Patients Increases Current Through P-Type Calcium Channels in Mammalian Cerebellar Purkinje Cells and in Isolated Channel Protein in Lipid Bilayer (United States)

    Llinas, R.; Sugimori, M.; Cherksey, B. D.; Smith, R. Glenn; Delbono, O.; Stefani, E.; Appel, S.


    The effect of the IgG from amyotrophic lateral sclerosis (ALS) patients was tested on the voltage-dependent barium currents (IBa) in mammalian dissociated Purkinje cells and in isolated P-type calcium channels in lipid bilayers. Whole cell clamp of Purkinje cells demonstrates that ALS IgG increases the amplitude of IBa without modifying their voltage kinetics. This increased IBa could be blocked by a purified nonpeptide toxin from Agelenopsis aperta venom (purified funnel-web spider toxin) or by a synthetic polyamine analog (synthetic funnel-web spider toxin) and by a peptide toxin from the same spider venom, ω-Aga-IVA. Similar results were obtained on single-channel recordings from purified P channel protein. The addition of ALS IgG increased single-channel IBa open time without affecting slope conductance. The results described above were not seen with normal human IgG nor with boiled ALS IgG. It is concluded that ALS IgG enhances inward current through P-type calcium channels. Since P-type Ca2+ channels are present in motoneuron axon terminals, we propose that the enhanced calcium current triggered by ALS IgG may contribute to neuronal damage in ALS.

  15. Higher serum 25-hydroxyvitamin D levels in school-age children are inconsistently associated with increased calcium absorption. (United States)

    Abrams, Steven A; Hicks, Penni D; Hawthorne, Keli M


    Increasing serum 25-hydroxyvitamin D (25-OHD) in adults may enhance calcium absorption (Ca-abs). There are few similar pediatric data leading to uncertainty about the optimal target for 25-OHD to maximize Ca-abs. Our objective was to evaluate the relationship between 25-OHD and Ca-abs in a large cohort of school-age children and adolescents. We evaluated data from 439 Ca-abs measurements performed using dual-tracer stable isotope techniques conducted at our center over a 15-yr period in 251 healthy children, 4.9-16.7 yr of age. Serum 25-OHD ranged from 28 to 197 nmol/liter (mean 85 +/- 2 nmol/liter) (sem). Total Ca-abs (intake times fractional absorption) were significantly correlated to 25-OHD in the whole population (r = 0.16, P = 0.001). This relationship was closer in the 197 studies in early puberty (Tanner 2 or 3, r = 0.35, P < 0.001) and not significant in pre- or late pubertal subjects. For the whole population, fractional Ca-abs adjusted for calcium intake were slightly but significantly higher at 25-OHD of 28-50 nmol/liter (0.344 +/- 0.019) compared with 25-OHD of 50-80 nmol/liter (0.280 +/- 0.014) or 25-OHD greater than 80 nmol/liter (0.297 +/- 0.015, P < 0.01 for each), suggesting adaptation to moderately low 25-OHD values. There is no consistent pattern of relationship between 25-OHD and either fractional or total calcium absorption in school-age children. However, there appears to be a modest calcium absorptive response to higher 25-OHD during early puberty.

  16. Can nontriggered thoracic CT be used for coronary artery calcium scoring? A phantom study

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Xueqian [Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen, The Netherlands and Center for Medical Imaging – North East Netherlands, Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen (Netherlands); Greuter, Marcel J. W. [Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen (Netherlands); Groen, Jaap M. [Department of Radiology, Zaans Medical Center, 1500EE Zaandam (Netherlands); Bock, Geertruida H. de [Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen (Netherlands); Oudkerk, Matthijs [Center for Medical Imaging – North East Netherlands, Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen (Netherlands); Jong, Pim A. de [Department of Radiology, University Medical Center Utrecht, University of Utrecht, 3584CX Utrecht (Netherlands); Vliegenthart, Rozemarijn [Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen, The Netherlands and Center for Medical Imaging – North East Netherlands, Department of Radiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700RB Groningen (Netherlands)


    Purpose: Coronary artery calcium score, traditionally based on electrocardiography (ECG)-triggered computed tomography (CT), predicts cardiovascular risk. However, nontriggered CT is extensively utilized. The study-purpose is to evaluate the in vitro agreement in coronary calcium score between nontriggered thoracic CT and ECG-triggered cardiac CT.Methods: Three artificial coronary arteries containing calcifications of different densities (high, medium, and low), and sizes (large, medium, and small), were studied in a moving cardiac phantom. Two 64-detector CT systems were used. The phantom moved at 0–90 mm/s in nontriggered low-dose CT as index test, and at 0–30 mm/s in ECG-triggered CT as reference. Differences in calcium scores between nontriggered and ECG-triggered CT were analyzed by t-test and 95% confidence interval. The sensitivity to detect calcification was calculated as the percentage of positive calcium scores.Results: Overall, calcium scores in nontriggered CT were not significantly different to those in ECG-triggered CT (p > 0.05). Calcium scores in nontriggered CT were within the 95% confidence interval of calcium scores in ECG-triggered CT, except predominantly at higher velocities (≥50 mm/s) for the high-density and large-size calcifications. The sensitivity for a nonzero calcium score was 100% for large calcifications, but 46%± 11% for small calcifications in nontriggered CT.Conclusions: When performing multiple measurements, good agreement in positive calcium scores is found between nontriggered thoracic and ECG-triggered cardiac CT. Agreement decreases with increasing coronary velocity. From this phantom study, it can be concluded that a high calcium score can be detected by nontriggered CT, and thus, that nontriggered CT likely can identify individuals at high risk of cardiovascular disease. On the other hand, a zero calcium score in nontriggered CT does not reliably exclude coronary calcification.

  17. Endothelial NO synthase phosphorylated at SER635 produces NO without requiring intracellular calcium increase. (United States)

    Boo, Yong Chool; Sorescu, George P; Bauer, Philip M; Fulton, David; Kemp, Bruce E; Harrison, David G; Sessa, William C; Jo, Hanjoong


    Shear stress stimulates NO production involving the Ca2+-independent mechanisms in endothelial cells. We have shown that exposure of bovine aortic endothelial cells (BAEC) to shear stress stimulates phosphorylation of eNOS at S635 and S1179 by the protein kinase A- (PKA-) dependent mechanisms. We examined whether phosphorylation of S635 of eNOS induced by PKA stimulates NO production in a calcium-independent manner. Expression of a constitutively active catalytic subunit of PKA (Cqr) in BAEC induced phosphorylation of S635 and S1179 residues and dephosphorylation of T497. Additionally, Cqr expression stimulated NO production, which could not be prevented by treating cells with the intracellular calcium chelator BAPTA-AM. To determine the role of each eNOS phosphorylation site in NO production, HEK-293 cells transfected with eNOS point mutants whereby S116, T497, S635, and S1179 were mutated to either A or D. Maximum NO production from S635D-expressing cells was significantly higher than that of either wild type or S635A in both basal and elevated [Ca2+]i conditions. More interestingly, S635D cells produced NO even when [Ca2+]i was nearly depleted by BAPTA-AM. We confirmed these results obtained in HEK-293 cells in BAEC transfected with S635D, S635A, or wild-type eNOS vector. These findings suggest that, once phosphorylated at S635 residue, eNOS produces NO without requiring any changes in [Ca2+]i. PKA-dependent phosphorylation of eNOS S635 and subsequent basal NO production in a Ca2+-independent manner may play an important role in regulating vascular biology and pathophysiology.

  18. Increase of nerve growth factor levels in the human herniated intervertebral disc: can annular rupture trigger discogenic back pain? (United States)

    Aoki, Yasuchika; Nakajima, Arata; Ohtori, Seiji; Takahashi, Hiroshi; Watanabe, Fusako; Sonobe, Masato; Terajima, Fumiaki; Saito, Masahiko; Takahashi, Kazuhisa; Toyone, Tomoaki; Watanabe, Atsuya; Nakajima, Takayuki; Takazawa, Makoto; Nakagawa, Koichi


    Nerve growth factor (NGF) has an important role in the generation of discogenic pain. We hypothesized that annular rupture is a trigger for discogenic pain through the action of NGF. In this study, the protein levels of NGF in discs from patients with disc herniation were examined and compared with those from discs of patients with other lumbar degenerative disc diseases. Patients (n = 55) with lumbar degenerative disc disease treated by surgery were included. Nucleus pulposus tissue (or herniated disc tissue) was surgically removed and homogenized; protein levels were quantified using an enzyme-linked immunosorbent assay (ELISA) for NGF. Levels of NGF in the discs were compared between 1) patients with herniated discs (herniated group) and those with other lumbar degenerative disc diseases (non-herniated group), and 2) low-grade and high-grade degenerated discs. Patient's symptoms were assessed using a visual analog scale (VAS) and the Oswestry disability index (ODI); the influence of NGF levels on pre- and post-operative symptoms was examined. Mean levels of NGF in discs of patients were significantly higher in herniated discs (83.4 pg/mg total protein) than those in non-herniated discs (68.4 pg/mg). This study reports that NGF increased in herniated discs, and may play an important role in the generation of discogenic pain. Analysis of patient symptoms revealed that pre-operative NGF levels were related to post-operative residual lower extremity pain and LBP in motion. The results suggest that NGF in the disc is related to pain generation, however, the impact of NGF on generation of LBP varies in individual patients.

  19. Hypochlorhydria‐induced calcium malabsorption does not affect fracture healing but increases post‐traumatic bone loss in the intact skeleton (United States)

    Haffner‐Luntzer, Melanie; Heilmann, Aline; Heidler, Verena; Liedert, Astrid; Schinke, Thorsten; Amling, Michael; Yorgan, Timur Alexander; vom Scheidt, Annika


    ABSTRACT Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post‐traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr−/− mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr−/− and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium‐enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro‐computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme‐linked immunosorbent assay. Fracture healing was unaffected in Cckbr−/− mice. However, Cckbr−/− mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr−/− mice. Therefore, under conditions of hypochlorhydria‐induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society

  20. Gonadotropin-releasing hormone agonist trigger increases the number of oocytes and embryos available for cryopreservation in cancer patients undergoing ovarian stimulation for fertility preservation. (United States)

    Pereira, Nigel; Kelly, Amelia G; Stone, Logan D; Witzke, Justine D; Lekovich, Jovana P; Elias, Rony T; Schattman, Glenn L; Rosenwaks, Zev


    To compare the oocyte and embryo yield associated with GnRH-agonist triggers vs. hCG triggers in cancer patients undergoing controlled ovarian stimulation (COS) for fertilization preservation. Retrospective cohort study. Academic center. Cancer patients undergoing COS with letrozole and gonadotropins or gonadotropin-only protocols for oocyte or embryo cryopreservation. Gonadotropin-releasing hormone agonist or hCG trigger. Number of metaphase II (MII) oocytes or two-pronuclei (2PN) embryos available for cryopreservation were primary outcomes. Separate multivariate linear regression models were used to assess the effect of trigger type on the primary outcomes, after controlling for confounders of interest. A total of 341 patients were included, 99 (29.0%) in the GnRH-agonist group and 242 (71%) in the hCG group. There was no difference in the baseline demographics of patients receiving GnRH-agonist or hCG triggers. Within the letrozole and gonadotropins group (n = 269), the number (mean ± SD, 11.8 ± 5.8 vs. 9.9 ± 6.0) and percentage of MII oocytes (89.6% vs. 73.0%) available for cryopreservation was higher with GnRH-agonist triggers compared with hCG triggers. Similar results were noted with GnRH-agonist triggers in the gonadotropin-only group (n = 72) (i.e., a higher number [13.3 ± 7.9 vs. 9.3 ± 6.0] and percentage of MII oocytes [85.7% vs. 72.8%] available for cryopreservation). Multivariate linear regression demonstrated approximately three more MII oocytes and 2PN embryos available for cryopreservation in the GnRH-agonist trigger group, irrespective of cancer and COS protocol type. Utilization of a GnRH-agonist trigger increases the number of MII oocytes and 2PN embryos available for cryopreservation in cancer patients undergoing COS for fertility preservation. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  1. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis (United States)

    Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.; hide


    Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

  2. Ciliary neurotrophic factor-treated astrocyte-conditioned medium increases the intracellular free calcium concentration in rat cortical neurons. (United States)

    Sun, Meiqun; Liu, Hongli; Min, Shengping; Wang, Hongtao; Wang, Xiaojing


    Ciliary neurotrophic factor (CNTF) is involved in the activation of astrocytes. A previous study showed that CNTF-treated astrocyte-conditioned medium (CNTF-ACM) contributed to the increase of the calcium current and the elevation of corresponding ion channels in cortical neurons. On this basis, it is reasonable to assume that CNTF-ACM may increase the intracellular free calcium concentration ([Ca 2+ ] i ) in neurons. In the present study, the effects of CNTF-ACM on [Ca 2+ ] i in rat cortical neurons were determined, and on this basis, the aim was to investigate the potential active ingredients in ACM that are responsible for this biological process. As expected, the data indicated that CNTF-ACM resulted in a clear elevation of [Ca 2+ ] i in neurons. Additionally, the fibroblast growth factor-2 (FGF-2) contained in the CNTF-ACM was found to participate in the upregulation of [Ca 2+ ] i . Taken together, CNTF induces the production of active factors (at least including FGF-2) released from astrocytes, which finally potentiate the increase of [Ca 2+ ] i in cortical neurons.

  3. Does Increased Expression of the Plasma Membrane Calcium-ATPase Isoform 2 Confer Resistance to Apoptosis on Breast Cancer Cells?

    National Research Council Canada - National Science Library

    VanHouten, Joshua N


    The plasma membrane calcium ATPase isoform 2 (PMCA2) is highly expressed on the apical membrane of mammary epithelial cells during lactation, and is the predominant pump responsible for calcium transport into milk...

  4. Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

    National Research Council Canada - National Science Library

    Bridget M. Stroup; Emily A. Sawin; Sangita G. Murali; Neil Binkley; Karen E. Hansen; Denise M. Ney


    .... We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design...

  5. Specific inhibition of stretch‐induced increase in L‐type calcium channel currents by herbimycin A in canine basilar arterial myocytes

    National Research Council Canada - National Science Library

    Kimura, Makoto; Obara, Kazuo; Sasase, Tomohiko; Ishikawa, Tomohisa; Tanabe, Yoshiyuki; Nakayama, Koichi


    ...‐activated barium currents (I Ba ) through L‐type calcium channels increased by hypotonic solution were investigated in canine basilar arterial myocytes by the whole‐cell patch‐clamp technique...

  6. Addition of Wollastonite Fibers to Calcium Phosphate Cement Increases Cell Viability and Stimulates Differentiation of Osteoblast-Like Cells

    Directory of Open Access Journals (Sweden)

    Juliana Almeida Domingues


    Full Text Available Calcium phosphate cement (CPC that is based on α-tricalcium phosphate (α-TCP is considered desirable for bone tissue engineering because of its relatively rapid degradation properties. However, such cement is relatively weak, restricting its use to areas of low mechanical stress. Wollastonite fibers (WF have been used to improve the mechanical strength of biomaterials. However, the biological properties of WF remain poorly understood. Here, we tested the response of osteoblast-like cells to being cultured on CPC reinforced with 5% of WF (CPC-WF. We found that both types of cement studied achieved an ion balance for calcium and phosphate after 3 days of immersion in culture medium and this allowed subsequent long-term cell culture. CPC-WF increased cell viability and stimulated cell differentiation, compared to nonreinforced CPC. We hypothesize that late silicon release by CPC-WF induces increased cell proliferation and differentiation. Based on our findings, we propose that CPC-WF is a promising material for bone tissue engineering applications.

  7. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Tada, Hiroyuki [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Nemoto, Eiji, E-mail: [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Kanaya, Sousuke; Hamaji, Nozomu; Sato, Hisae; Shimauchi, Hidetoshi [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)


    Dental pulp cells, which have been shown to share phenotypical features with osteoblasts, are capable of differentiating into odontoblast-like cells and generating a dentin-like mineral structure. Elevated extracellular Ca{sup 2+}Ca{sub o}{sup 2+} has been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of Ca{sub o}{sup 2+} signaling in odontogenesis remains unclear. We found that elevated Ca{sub o}{sup 2+} increases bone morphogenetic protein (BMP)-2 gene expression in human dental pulp cells. The increase was modulated not only at a transcriptional level but also at a post-transcriptional level, because treatment with Ca{sup 2+} increased the stability of BMP-2 mRNA in the presence of actinomycin D, an inhibitor of transcription. A similar increase in BMP-2 mRNA level was observed in other human mesenchymal cells from oral tissue; periodontal ligament cells and gingival fibroblasts. However, the latter cells exhibited considerably lower expression of BMP-2 mRNA compared with dental pulp cells and periodontal ligament cells. The BMP-2 increase was markedly inhibited by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and partially inhibited by the L-type Ca{sup 2+} channels inhibitor, nifedipine. However, pretreatment with nifedipine had no effect on ERK1/2 phosphorylation triggered by Ca{sup 2+}, suggesting that the Ca{sup 2+} influx from Ca{sup 2+} channels may operate independently of ERK signaling. Dental pulp cells do not express the transcript of Ca{sup 2+}-sensing receptors (CaSR) and only respond slightly to other cations such as Sr{sup 2+} and spermine, suggesting that dental pulp cells respond to Ca{sub o}{sup 2+} to increase BMP-2 mRNA expression in a manner different from CaSR and rather specific for Ca{sub o}{sup 2+} among cations.

  8. Sodium-dependent action potentials induced by brevetoxin-3 trigger both IP3 increase and intracellular Ca2+ release in rat skeletal myotubes. (United States)

    Liberona, José Luis; Cárdenas, J César; Reyes, Roberto; Hidalgo, Jorge; Molgó, Jordi; Jaimovich, Enrique


    Brevetoxin-3 (PbTx-3), described to increase the open probability of voltage-dependent sodium channels, caused trains of action potentials and fast oscillatory changes in fluorescence intensity of fluo-3-loaded rat skeletal muscle cells in primary culture, indicating that the toxin increased intracellular Ca2+ levels. PbTx-3 did not elicit calcium transients in dysgenic myotubes (GLT cell line), lacking the alpha1 subunit of the dihydropyridine receptor (DHPR), but after transfection of the alpha1DHPR cDNA to GLT cells, PbTx-3 induced slow calcium transients that were similar to those of normal cells. Ca2+ signals evoked by PbTx-3 were inhibited by blocking either IP3 receptors, with 2-aminoethoxydiphenyl borate, or phospholipase C with U73122. PbTx-3 caused a tetrodotoxin-sensitive increase in intracellular IP3 mass levels, dependent on extra-cellular Na+. A similar increase in IP3 mass was induced by high K+ depolarization but no action potential trains (nor calcium signals) were elicited by prolonged depolarization under current clamp conditions. The increase in IP3 mass induced by either PbTx-3 or K+ was also detected in Ca2+-free medium. These results establish that the effect of the toxin on both intracellular Ca2+ and IP3 levels occurs via a membrane potential sensor instead of directly by Na+ flux and supports the notion of a train of action potentials being more efficient as a stimulus than sustained depolarization, suggesting that tetanus is the physiological stimulus for the IP3-dependent calcium signal involved in regulation of gene expression.

  9. Increase of calcium and reduction of lactose concentration in milk by treatment with kefir grains and eggshell. (United States)

    Fina, Brenda L; Brun, Lucas R; Rigalli, Alfredo


    Dairy products are the main source of calcium (Ca), but the loss of the consumption habit contributes to low consumption in adulthood, which leads to osteoporosis and increased fracture risk. Domestic use of kefir is straightforward and the eggshell is a natural discarded source of Ca. This paper proposes the development of an enriched Ca reduced lactose milk using eggshell and kefir. During the in vitro preparation, the pH, Ca and lactose contents were measured. Ca intestinal absorption of untreated milk and milk with kefir was compared. Finally, human volunteers consumed this dairy product and 24-h urine Ca was measured. Results showed that the beverage has lower lactose and higher Ca than untreated milk and milk with kefir. Intestinal Ca absorption was not different between both milks and an increase in urinary Ca excretion was observed in humans. This study provides a methodology to prepare at home a dairy product that could contribute to improve the Ca intake in adults.

  10. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine


    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibi...

  11. Young adolescents who respond to an inulin-type fructan substantially increase total absorbed calcium and daily calcium accretion to the skeleton (United States)

    Calcium absorption and whole-body bone mineral content are greater in young adolescents who receive 8 g/d of Synergy, a mixture of inulin-type fructans (ITF), compared with those who received a maltodextrin control. Not all adolescents responded to this intervention, however. We evaluated 32 respond...

  12. Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting.

    Directory of Open Access Journals (Sweden)

    Manoocher Soleimani

    Full Text Available Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2 and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2 in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of

  13. PR3 and elastase alter PAR1 signaling and trigger vWF release via a calcium-independent mechanism from glomerular endothelial cells. (United States)

    Tull, Samantha P; Bevins, Anne; Kuravi, Sahithi Jyothsna; Satchell, Simon C; Al-Ani, Bahjat; Young, Stephen P; Harper, Lorraine; Williams, Julie M; Rainger, George Ed; Savage, Caroline O S


    Neutrophil proteases, proteinase-3 (PR3) and elastase play key roles in glomerular endothelial cell (GEC) injury during glomerulonephritis. Endothelial protease-activated receptors (PARs) are potential serine protease targets in glomerulonephritis. We investigated whether PAR1/2 are required for alterations in GEC phenotype that are mediated by PR3 or elastase during active glomerulonephritis. Endothelial PARs were assessed by flow cytometry. Thrombin, trypsin and agonist peptides for PAR1 and PAR2, TFLLR-NH(2) and SLIGKV-NH(2,) respectively, were used to assess alterations in PAR activation induced by PR3 or elastase. Endothelial von Willebrand Factor (vWF)release and calcium signaling were used as PAR activation markers. Both PR3 and elastase induced endothelial vWF release, with elastase inducing the highest response. PAR1 peptide induced GEC vWF release to the same extent as PR3. However, knockdown of PARs by small interfering RNA showed that neither PAR1 nor PAR2 activation caused PR3 or elastase-mediated vWF release. Both proteases interacted with and disarmed surface GEC PAR1, but there was no detectable interaction with cellular PAR2. Neither protease induced a calcium response in GEC. Therefore, PAR signaling and serine protease-induced alterations in endothelial function modulate glomerular inflammation via parallel but independent pathways.

  14. PR3 and elastase alter PAR1 signaling and trigger vWF release via a calcium-independent mechanism from glomerular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Samantha P Tull

    Full Text Available Neutrophil proteases, proteinase-3 (PR3 and elastase play key roles in glomerular endothelial cell (GEC injury during glomerulonephritis. Endothelial protease-activated receptors (PARs are potential serine protease targets in glomerulonephritis. We investigated whether PAR1/2 are required for alterations in GEC phenotype that are mediated by PR3 or elastase during active glomerulonephritis. Endothelial PARs were assessed by flow cytometry. Thrombin, trypsin and agonist peptides for PAR1 and PAR2, TFLLR-NH(2 and SLIGKV-NH(2, respectively, were used to assess alterations in PAR activation induced by PR3 or elastase. Endothelial von Willebrand Factor (vWFrelease and calcium signaling were used as PAR activation markers. Both PR3 and elastase induced endothelial vWF release, with elastase inducing the highest response. PAR1 peptide induced GEC vWF release to the same extent as PR3. However, knockdown of PARs by small interfering RNA showed that neither PAR1 nor PAR2 activation caused PR3 or elastase-mediated vWF release. Both proteases interacted with and disarmed surface GEC PAR1, but there was no detectable interaction with cellular PAR2. Neither protease induced a calcium response in GEC. Therefore, PAR signaling and serine protease-induced alterations in endothelial function modulate glomerular inflammation via parallel but independent pathways.

  15. Dynamic triggering (United States)

    Hill, David P.; Prejean, Stephanie; Schubert, Gerald


    Dynamic stresses propagating as seismic waves from large earthquakes trigger a spectrum of responses at global distances. In addition to locally triggered earthquakes in a variety of tectonic environments, dynamic stresses trigger tectonic (nonvolcanic) tremor in the brittle–plastic transition zone along major plate-boundary faults, activity changes in hydrothermal and volcanic systems, and, in hydrologic domains, changes in spring discharge, water well levels, soil liquefaction, and the eruption of mud volcanoes. Surface waves with periods of 15–200 s are the most effective triggering agents; body-wave trigger is less frequent. Triggering dynamic stresses can be < 1 kPa.

  16. Normal and Malignant Cells Exhibit Differential Responses to Calcium Electroporation. (United States)

    Frandsen, Stine K; Krüger, Mie B; Mangalanathan, Uma M; Tramm, Trine; Mahmood, Faisal; Novak, Ivana; Gehl, Julie


    Calcium electroporation may offer a simple general tool for anticancer therapy. Transient permeabilization of cancer cell membranes created by applying short, high-voltage pulses in tumors enables high calcium influxes that trigger cell death. In this study, we compared the relative sensitivity of different human tumor models and normal tissues to calcium electroporation. Plasma membrane Ca(2+)-ATPase (PMCA) protein expression was confirmed in vitro in all cancer cell lines and normal primary dermal fibroblasts studied. In all tumor types tested in vivo, calcium electroporation effectively induced necrosis, with a range of sensitivities observed (36%-88%) 2 days after treatment. Necrosis was induced using calcium concentrations of 100-500 mmol/L and injection volumes 20%-80% of tumor volume. Notably, only limited effects were seen in normal tissue. Calcium content increased >7-fold in tumor and skin tissue after calcium electroporation but decreased in skin tissue 4 hours after treatment to levels comparable with untreated controls, whereas calcium content endured at high levels in tumor tissue. Mechanistic experiments in vitro indicated that calcium influx was similar in fibroblasts and cancer cells. However, we observed decreased PMCA expression in cancer cells compared with fibroblasts, offering a potential explanation for the different calcium content in tumor cells versus normal tissues. Overall, our results suggest that calcium electroporation can elicit a rapid and selective necrosis of solid tumors, with limited deleterious effects on surrounding normal tissues. Cancer Res; 77(16); 4389-401. ©2017 AACR. ©2017 American Association for Cancer Research.

  17. Reduction of exchangeable calcium and magnesium in soil with increasing pH

    Directory of Open Access Journals (Sweden)

    Miyazawa Mário


    Full Text Available A laboratory study was conducted with soil samples and synthetic solutions to investigate possible mechanisms related with reduction in KCl exchangeable Ca and Mg with increasing pH. Increasing soil pH over 5.3 with CaCO3 added to the soil and with NaOH solution added to soil/KCl suspension increased adsorptions of Ca and Mg. The reduction of Mg was greater than Ca and was related to the concentration of soil exchangeable Al. The decreases of soluble Ca and Mg following addition of Al in synthetic solution were at pH > 7.5. The isomorphic coprecipitation reaction with Al compounds may be the most possible mechanism responsible for the decrease of exchangeable Ca and Mg with increasing pH. Possible chemical reactions are presented.

  18. Carbon Tetrachloride Increases Intracellular Calcium in Rat Liver and Hepatocyte Cultures (United States)


    small increase in cAMP can synergize with the effect of Ca++ has not been excluded. Halogenated Analogs of Carbon Tetrachloride...SKF-525A, chloramphenicol , cimetidine, piperonyl butoxide, and carbon monoxide. Preliminary results indicated that effective concentrations of

  19. Increased calcium content and inhomogeneity of mineralization render bone toughness in osteoporosis: mineralization, morphology and biomechanics of human single trabeculae. (United States)

    Busse, Björn; Hahn, Michael; Soltau, Markus; Zustin, Jozef; Püschel, Klaus; Duda, Georg N; Amling, Michael


    The differentiation and degree of the effects of mineral content and/or morphology on bone quality remain, to a large extent, unanswered due to several microarchitectural particularities in spatial measuring fields (e.g., force transfer, trajectories, microcalli). Therefore, as the smallest basic component of cancellous bone, we focused on single trabeculae to investigate the effects of mineralization and structure, both independently and in superposition. Transiliac Bordier bone cores and T12 vertebrae were obtained from 20 females at autopsy for specimen preparation, enabling radiographical analyses, histomorphometry, Bone Mineral Density Distribution (BMDD) analyses, and trabecular singularization to be performed. Evaluated contact X-rays and histomorphometric limits from cases with osteoporotic vertebral fractures generated two subdivisions, osteoporotic (n=12, Ø 78 years) and non-osteoporotic (n=8, Ø 49 years) cases, based on fracture appearance and bone volume (BV/TV). Measurements of trabecular number (Tb.N.), trabecular separation (Tb.Sp.), trabecular thickness (Tb.Th.), trabecular bone pattern factor (TBPf) and eroded surface (ES/BS) were carried out to provide detailed structural properties of the investigated groups. The mechanical properties of 400 rod-like single vertebral trabeculae, assessed by three-point bending, were matched with mineral properties as quantified by BMDD analyses of cross-sectioned rod-like and plate-like trabeculae, both in superposition and independently. Non-osteoporotic iliac crests and vertebrae displayed linear dependency on structure parameters, whereas osteoporotic compartments proved to be non-correlated with bone structure. Independent of trabecular thickness, osteoporotic rod-like trabeculae showed decreases in Young's modulus, fracture load, yield strength, ultimate stress, work to failure and bending stiffness, along with significantly increased mean calcium content and calcium width. Non-osteoporotic trabeculae

  20. Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen

    DEFF Research Database (Denmark)

    Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten Joan


    loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased...... on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O(2) tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca(2+) activity in PCs. The increased wave...... activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology....

  1. Pre-harvest calcium application increases biomass and delays senescence of broccoli microgreens (United States)

    Microgreen consumption has been steadily increasing in recent years due to consumer awareness of their unique color, rich flavor, and concentrated bioactive compounds such as vitamins, minerals and antioxidants. However, industrial production and marketing is limited by their short shelf-life assoc...

  2. New random trigger-feature for ultrashort-pulsed laser increases throughput, accuracy and quality in micromachining applications (United States)

    Oehler, Andreas; Ammann, Hubert; Benetti, Marco; Wassermann, Dominique; Jaeggi, Beat; Remund, Stefan; Neuenschwander, Beat


    For most micromachining applications, the laser focus has to be moved across the workpiece, either by steering the beam or by moving the workpiece. To maximize throughput, this movement should be as fast as possible. However, the required positioning accuracy often limits the obtainable speed. Especially the machining of small and complex features with high precision is constrained by the motion-system's maximum acceleration, limiting the obtainable moving spot velocity to very low values. In general, processing speed can vary widely within the same processing job. To obtain optimum quality at maximum throughput, ideally the pulse energy and the pulse-to-pulse pitch on the workpiece are kept constant. This is only possible if laser-pulses can be randomly triggered, synchronized to the current spot velocity. For ultrafast lasers this is not easily possible, as by design they are usually operated at a fixed pulse repetition rate. The pulse frequency can only be changed by dividing down with integer numbers which leads to a rather coarse frequency grid, especially when applied close to the maximum used operating frequency. This work reports on a new technique allowing random triggering of an ultrafast laser. The resulting timing uncertainty is less than ±25ns, which is negligible for real-world applications, energy stability is <2% rms. The technique allows using acceleration-ramps of the implemented motion system instead of applying additional override moves or skywriting techniques. This can reduce the processing time by up to 40%. Results of applying this technique to different processing geometries and strategies will be presented.

  3. Dietary mannitol increased the absorption of calcium and magnesium in rats. (United States)

    Xiao, J; Sakaguchi, E; Min, X; Kawasaki, K


    The effect of mannitol on bone-related mineral absorption and retention and the mechanism was investigated in this study. Fourteen 8-week-old male Wistar rats in experiment 1 and same number and age cecectomized Wistar male rats in experiment 2 were divided into two subgroups of seven animals, respectively, fed diets containing 0 or 4% mannitol for 28 days. Mineral balance tests were determined twice during days 8-12 and days 22-26, and the rats were slaughtered on day 28 both in experiment 1 and experiment 2. The whole caecum and colon were collected with the content to analyse tissue weight, content weight, content's pH and moisture, organic acids' concentration and mineral levels. In experiment 1, Ca absorption and retention and Mg absorption were significantly increased by mannitol feeding during days 8-12. Caecal total weight, tissue weight and content weight were increased, the pH of caecum and colon was reduced, and the concentrations of caecal short-chain fatty acids (SCFAs) were modified by mannitol feeding. In experiment 2, during days 8-12 and days 22-26, Ca absorption and retention were significantly lowered by mannitol feeding in cecectomized rats; however, mannitol feeding decreased Mg absorption during days 8-12, but did not impact Mg retention. Colonic total weight, tissue weight and content weight were significantly increased, and colonic pH was reduced by mannitol feeding. In conclusion, dietary mannitol increased the absorption of Ca and Mg and the caecum markedly contributed to this promoting effect of mannitol. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  4. Inhibitory effect of donepezil on bradykinin-induced increase in the intracellular calcium concentration in cultured cortical astrocytes. (United States)

    Makitani, Kouki; Nakagawa, Shota; Izumi, Yasuhiko; Akaike, Akinori; Kume, Toshiaki


    Donepezil is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, we investigated the responses of astrocytes to bradykinin, an inflammatory mediator, and the effect of donepezil on these responses using cultured cortical astrocytes. Bradykinin induced a transient increase of intracellular calcium concentration ([Ca(2+)]i) in cultured astrocytes. Bradykinin-induced [Ca(2+)]i increase was inhibited by the exposure to thapsigargin, which depletes Ca(2+) stores on endoplasmic reticulum, but not by the exclusion of extracellular Ca(2+). Twenty four hours pretreatment of donepezil reduced the bradykinin-induced [Ca(2+)]i increase. This reduction was inhibited not only by mecamylamine, a nAChR antagonist, but also by PI3K and Akt inhibitors. In addition, donepezil inhibited bradykinin-induced increase of the intracellular reactive oxygen species level in astrocytes. These results suggest that donepezil inhibits the inflammatory response induced by bradykinin via nAChR and PI3K-Akt pathway in astrocytes. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  5. Inhibitory effect of donepezil on bradykinin-induced increase in the intracellular calcium concentration in cultured cortical astrocytes

    Directory of Open Access Journals (Sweden)

    Kouki Makitani


    Full Text Available Donepezil is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, we investigated the responses of astrocytes to bradykinin, an inflammatory mediator, and the effect of donepezil on these responses using cultured cortical astrocytes. Bradykinin induced a transient increase of intracellular calcium concentration ([Ca2+]i in cultured astrocytes. Bradykinin-induced [Ca2+]i increase was inhibited by the exposure to thapsigargin, which depletes Ca2+ stores on endoplasmic reticulum, but not by the exclusion of extracellular Ca2+. Twenty four hours pretreatment of donepezil reduced the bradykinin-induced [Ca2+]i increase. This reduction was inhibited not only by mecamylamine, a nAChR antagonist, but also by PI3K and Akt inhibitors. In addition, donepezil inhibited bradykinin-induced increase of the intracellular reactive oxygen species level in astrocytes. These results suggest that donepezil inhibits the inflammatory response induced by bradykinin via nAChR and PI3K-Akt pathway in astrocytes.

  6. Important role of PLC-γ1 in hypoxic increase in intracellular calcium in pulmonary arterial smooth muscle cells. (United States)

    Yadav, Vishal R; Song, Tengyao; Joseph, Leroy; Mei, Lin; Zheng, Yun-Min; Wang, Yong-Xiao


    An increase in intracellular calcium concentration ([Ca(2+)](i)) in pulmonary arterial smooth muscle cells (PASMCs) induces hypoxic cellular responses in the lungs; however, the underlying molecular mechanisms remain incompletely understood. We report, for the first time, that acute hypoxia significantly enhances phospholipase C (PLC) activity in mouse resistance pulmonary arteries (PAs), but not in mesenteric arteries. Western blot analysis and immunofluorescence staining reveal the expression of PLC-γ1 protein in PAs and PASMCs, respectively. The activity of PLC-γ1 is also augmented in PASMCs following hypoxia. Lentiviral shRNA-mediated gene knockdown of mitochondrial complex III Rieske iron-sulfur protein (RISP) to inhibit reactive oxygen species (ROS) production prevents hypoxia from increasing PLC-γ1 activity in PASMCs. Myxothiazol, a mitochondrial complex III inhibitor, reduces the hypoxic response as well. The PLC inhibitor U73122, but not its inactive analog U73433, attenuates the hypoxic vasoconstriction in PAs and hypoxic increase in [Ca(2+)](i) in PASMCs. PLC-γ1 knockdown suppresses its protein expression and the hypoxic increase in [Ca(2+)](i). Hypoxia remarkably increases inositol 1,4,5-trisphosphate (IP(3)) production, which is blocked by U73122. The IP(3) receptor (IP(3)R) antagonist 2-aminoethoxydiphenyl borate (2-APB) or xestospongin-C inhibits the hypoxic increase in [Ca(2+)](i). PLC-γ1 knockdown or U73122 reduces H(2)O(2)-induced increase in [Ca(2+)](i) in PASMCs and contraction in PAs. 2-APB and xestospongin-C produce similar inhibitory effects. In conclusion, our findings provide novel evidence that hypoxia activates PLC-γ1 by increasing RISP-dependent mitochondrial ROS production in the complex III, which causes IP(3) production, IP(3)R opening, and Ca(2+) release, playing an important role in hypoxic Ca(2+) and contractile responses in PASMCs.

  7. Infrasound increases intracellular calcium concentration and induces apoptosis in hippocampi of adult rats. (United States)

    Liu, Zhaohui; Gong, Li; Li, Xiaofang; Ye, Lin; Wang, Bin; Liu, Jing; Qiu, Jianyong; Jiao, Huiduo; Zhang, Wendong; Chen, Jingzao; Wang, Jiuping


    In the present study, we determined the effect of infrasonic exposure on apoptosis and intracellular free Ca²⁺ ([Ca²⁺]i) levels in the hippocampus of adult rats. Adult rats were randomly divided into the control and infrasound exposure groups. For infrasound treatment, animals received infrasonic exposure at 90 (8 Hz) or 130 dB (8 Hz) for 2 h per day. Hippocampi were dissected, and isolated hippocampal neurons were cultured. The [Ca²⁺]i levels in hippocampal neurons from adult rat brains were determined by Fluo-3/AM staining with a confocal microscope system on days 1, 7, 14, 21 and 28 following infrasonic exposure. Apoptosis was evaluated by Annexin V-FITC and propidium iodide double staining. Positive cells were sorted and analyzed by flow cytometry. Elevated [Ca²⁺]i levels were observed on days 14 and 21 after rats received daily treatment with 90 or 130 dB sound pressure level (SPL) infrasonic exposure (p<0.01 vs. control). The highest levels of [Ca²⁺]i were detected in the 130 dB SPL infrasonic exposure group. Meanwhile, apoptosis in hippocampal neurons was found to increase on day 7 following 90 dB SPL infrasound exposure, and significantly increased on day 14. Upon 130 dB infrasound treatment, apoptosis was first observed on day 14, whereas the number of apoptotic cells gradually decreased thereafter. Additionally, a marked correlation between cell apoptosis and [Ca²⁺]i levels was found on day 14 and 21 following daily treatment with 90 and 130 dB SPL, respectively. These results demonstrate that a period of infrasonic exposure induced apoptosis and upregulated [Ca²⁺]i levels in hippocampal neurons, suggesting that infrasound may cause damage to the central nervous system (CNS) through the Ca²⁺‑mediated apoptotic pathway in hippocampal neurons.

  8. Cytoskeleton rotation relocates mitochondria to the immunological synapse and increases calcium signals. (United States)

    Maccari, Ilaria; Zhao, Renping; Peglow, Martin; Schwarz, Karsten; Hornak, Ivan; Pasche, Mathias; Quintana, Ariel; Hoth, Markus; Qu, Bin; Rieger, Heiko


    Ca2+ microdomains and spatially resolved Ca2+ signals are highly relevant for cell function. In T cells, local Ca2+ signaling at the immunological synapse (IS) is required for downstream effector functions. We present experimental evidence that the relocation of the MTOC towards the IS during polarization drags mitochondria along with the microtubule network. From time-lapse fluorescence microscopy we conclude that mitochondria rotate together with the cytoskeleton towards the IS. We hypothesize that this movement of mitochondria towards the IS together with their functionality of absorption and spatial redistribution of Ca2+ is sufficient to significantly increase the cytosolic Ca2+ concentration. To test this hypothesis we developed a whole cell model for Ca2+ homoeostasis involving specific geometries for mitochondria and use the model to calculate the spatial distribution of Ca2+ concentrations within the cell body as a function of the rotation angle and the distance from the IS. We find that an inhomogeneous distribution of PMCA pumps on the cell membrane, in particular an accumulation of PMCA at the IS, increases the global Ca2+ concentration and decreases the local Ca2+ concentration at the IS with decreasing distance of the MTOC from the IS. Unexpectedly, a change of CRAC/Orai activity is not required to explain the observed Ca2+ changes. We conclude that rotation-driven relocation of the MTOC towards the IS together with an accumulation of PMCA pumps at the IS are sufficient to control the observed Ca2+ dynamics in T-cells during polarization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Japanese citrus fruit (sudachi) juice is associated with increased bioavailability of calcium from whole small fish and suppressed bone resorption in rats. (United States)

    Nii, Yoshitaka; Fukuta, Kazuhiro; Sakai, Kentaro; Yamamoto, Shigeru


    Shirasuboshi (boiled and semi-dried whitebait) is a processed fish food that contains abundant calcium. It is eaten whole and commonly consumed in Japan. In this study, the effect of sudachi (Citrus sudachi) juice on calcium, magnesium and phosphorus bioavailability, and bone metabolism in rats was examined. After 14 d of diets low in calcium and phosphorus, male Sprague-Dawley rats were fed shirasuboshi diets containing dried shirasuboshi powder treated with 20% (S20) or 40% (S40) sudachi juice, or distilled water (C) (0.5% Ca; 0.3% P) for 14 d. The apparent absorptions and retentions of calcium, magnesium and phosphorus from shirasuboshi were determined. Bone formation was calculated by measuring serum osteocalcin, and bone resorption by measuring urinary pyridinoline and deoxypyridinoline. The apparent absorption and retention of calcium and magnesium in the S20 group were significantly higher than in the C and S40 groups. Although serum osteocalcin was not affected by the addition of sudachi juice, the urinary pyridinoline and deoxypyridinoline concentrations in the S40 group were significantly lower than in the C and S20 groups. Our results indicate that sudachi juice added to shirasuboshi was associated with increased calcium bioavailability and suppressed bone resorption in rats.

  10. Increased sodium/calcium exchanger activity enhances beta-adrenergic-mediated increase in heart rate: Whole-heart study in a homozygous sodium/calcium exchanger overexpressor mouse model. (United States)

    Kaese, Sven; Bögeholz, Nils; Pauls, Paul; Dechering, Dirk; Olligs, Jan; Kölker, Katharina; Badawi, Sascha; Frommeyer, Gerrit; Pott, Christian; Eckardt, Lars


    The cardiac sodium/calcium (Na(+)/Ca(2+)) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown. The purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function. Langendorff-perfused, beating whole hearts of NCX-OE and the corresponding wild-type (WT) were studied ± isoproterenol (ISO; 0.2 μM). Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN-WCL were obtained. At baseline, basal heart rate was unaltered between NCX-OE and WT (WT: cycle length [CL] 177.6 ± 40.0 ms, no. of hearts [n] = 20; NCX-OE: CL 185.9 ± 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 ± 13.4 ms, n = 20; NCX-OE: CL 117.7 ± 14.2 ms, n = 18; P heart rate. Mechanistically, increased NCX inward mode activity may promote acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus enhancing chronotropy in NCX-OE. These findings suggest a novel potential therapeutic target for heart rate control in the presence of increased NCX activity, such as heart failure. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  11. Aluminum-induced dreierketten chain cross-links increase the mechanical properties of nanocrystalline calcium aluminosilicate hydrate (United States)

    Geng, Guoqing; Myers, Rupert J.; Li, Jiaqi; Maboudian, Roya; Carraro, Carlo; Shapiro, David A.; Monteiro, Paulo J. M.


    The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that the ab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. The c-axis of non-cross-linked C-(A-)S-H is more deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca2+ of the interlayer. Dreierketten chain cross-links act as ‘columns’ to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a ‘bottom-up’ approach.

  12. Chronic fluoxetine treatment increases NO bioavailability and calcium-sensitive potassium channels activation in rat mesenteric resistance arteries. (United States)

    Pereira, Camila A; Ferreira, Nathanne S; Mestriner, Fabiola L; Antunes-Rodrigues, José; Evora, Paulo R B; Resstel, Leonardo B M; Carneiro, Fernando S; Tostes, Rita C


    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has effects beyond its antidepressant properties, altering, e.g., mechanisms involved in blood pressure and vasomotor tone control. Although many studies have addressed the acute impact of fluoxetine on the cardiovascular system, there is a paucity of information on the chronic vascular effects of this SSRI. We tested the hypothesis that chronic fluoxetine treatment enhances the vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling and activation of potassium (K+) channels. Wistar rats were divided into two groups: (I) vehicle (water for 21 days) or (II) chronic fluoxetine (10 mg/kg/day in the drinking water for 21 days). Fluoxetine treatment increased endothelium-dependent and independent vasorelaxation (analyzed by mesenteric resistance arteries reactivity) as well as constitutive NO synthase (NOS) activity, phosphorylation of eNOS at Serine1177 and NO production, determined by western blot and fluorescence. On the other hand, fluoxetine treatment did not alter vascular expression of neuronal and inducible NOS or guanylyl cyclase (GC). Arteries from fluoxetine-treated rats exhibited increased relaxation to pinacidil. Increased acetylcholine vasorelaxation was abolished by a calcium-activated K+ channel (KCa) blocker, but not by an inhibitor of KATP channels. On the other hand, vascular responses to Bay 41-2272 and 8-bromo-cGMP were similar between the groups. In conclusion, chronic fluoxetine treatment increases endothelium-dependent and independent relaxation of mesenteric resistance arteries by mechanisms that involve increased eNOS activity, NO generation, and KCa channels activation. These effects may contribute to the cardiovascular effects associated with chronic fluoxetine treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Increased acellular and cellular surface mineralization induced by nanogrooves in combination with a calcium-phosphate coating. (United States)

    Klymov, Alexey; Song, Jiankang; Cai, Xinjie; Te Riet, Joost; Leeuwenburgh, Sander; Jansen, John A; Walboomers, X Frank


    The current work evaluated the influence of nanoscale surface-topographies in combination with a calcium phosphate (CaP) coating on acellular and cellular surface mineralization. Four groups of substrates were produced, including smooth, grooved (940nm pitch, 430nm groove width, 185nm depth), smooth coated, and grooved coated. The substrates were characterized by scanning/transmission electron microscopy and atomic force microscopy. Osteoblast-like MC3T3 cells were cultured on the substrates for a period up to 35days under osteogenic conditions. Differentiation was observed by alkaline phosphatase assay and PCR of collagen I (COLI), osteopontin (OPN), osteocalcin (OC), bone-morphogenic protein 2 (BMP2), and bone sialoprotein (BSP). Mineralization was quantified by a calcium assay and Alizarin Red staining. In addition, acellular mineralization was determined after incubation of substrates in just cell culture medium without cells. Results showed that a reproducible nano-metric (∼50nm) CaP-layer could be applied on the substrates, without losing the integrity of the topographical features. While no relevant differences were found for cell viability, cells on smooth surfaces proliferated for a longer period than cells on grooved substrates. In addition, differentiation was affected by topographies, as indicated by an increased expression of OC, OPN and ALP activity. Deposition of a CaP coating significantly increased the acellular mineralization of smooth as well grooved substrate-surfaces. However, this mineralizing effect was strongly reduced in the presence of cells. In the cell seeded situation, mineralization was significantly increased by the substrate topography, while only a minor additive effect of the coating was observed. In conclusion, the model presented herein can be exploited for experimental evaluation of cell-surface interaction processes and optimization of bone-anchoring capability of implants. The model showed that substrates modified with Ca

  14. Increase in the dosage amount of vitamin D3 preparations by switching from calcium carbonate to lanthanum carbonate. (United States)

    Hyodo, Toru; Kawakami, Junko; Mikami, Noriko; Wakai, Haruki; Ishii, Daisuke; Yoshida, Kazunari; Iwamura, Masatsugu; Hida, Miho; Kurata, Yasuhisa


    It is widely known that dialysis patients who are administered vitamin D preparations have a better prognosis than patients who are not. In this study, of 22 patients on maintenance dialysis who had been administered calcium (Ca) carbonate in our hospital, we investigated the dosage amount of vitamin D3 preparations after the phosphorus (P) binder was switched from Ca carbonate to the newly developed lanthanum carbonate (LC). After completely switching to LC, the dosage amount of oral vitamin D3 preparation (alfacalcidol equivalent) was significantly increased from 0.094 μg/day to 0.375 μg/day (P = 0.0090). No significant changes were observed in the values of serum corrected Ca, alkaline phosphatase, intact parathyroid hormone and P after switching. The administration of LC enabled complete cessation of the administration of Ca carbonate preparations, and increased the dosage amount of vitamin D3 preparations. Therefore, LC may be a useful P binder to improve patient prognosis. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

  15. High vitamin D and calcium intakes increase bone mineral (Ca and P) content in high-fat diet-induced obese mice. (United States)

    Song, Qingming; Sergeev, Igor N


    Vitamin D and calcium are essential for bone formation, mineralization, and remodeling. Recent studies demonstrated that an increased body mass can be detrimental to bone health. However, whether an increase in dietary vitamin D and calcium intakes in obesity is beneficial to bone health has not been established. The aim of this study was to examine the effects of increased vitamin D and calcium intakes, alone or in combination, on bone status in a high-fat diet-induced obesity (DIO) mouse model. We hypothesized that DIO in growing mice affects bone mineral status and that high vitamin D and calcium intakes will promote mineralization of the growing bone in obesity via Ca(2+) regulatory hormones, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and parathyroid hormone (PTH). Male mice were fed high vitamin D3 (10 000 IU/kg), high calcium (1.2%), or high vitamin D3 plus high-calcium diets containing 60% energy as fat for 10 weeks. Bone weight, specific gravity, mineral (Ca and P), and collagen (hydroxyproline) content were measured in the femur and the tibia. Regulators of Ca(2+) metabolism and markers of bone status (PTH, 25-hydroxyvitamin D [25(OH)D], 1,25(OH)2D3, and osteocalcin) were measured in blood plasma. Diet-induced obese mice exhibited lower bone Ca and P content and relative bone weight compared with the normal-fat control mice, whereas collagen (hydroxyproline) content was not different between the two groups. High vitamin D3 and calcium intakes significantly increased bone Ca and P content and relative bone weight in DIO mice, which was accompanied by an increase in 1,25(OH)2D3 and a decrease in PTH and osteocalcin concentrations in blood. The findings obtained indicate that increased vitamin D and calcium intakes are effective in increasing mineral (Ca and P) content in the growing bone of obese mice and that the hormonal mechanism of this effect may involve the vitamin D-PTH axis. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The calcium-sensing receptor R990G polymorphism is associated with increased risk of hypertriglyceridemia in obese Chinese. (United States)

    He, Yong-Han; Kong, Wei-Lan; Wang, Guan; Zhao, Yue; Bi, Ming-Xin; Na, Li-Xin; Wang, Mao-Qing; Perry, Ben; Li, Ying


    We have demonstrated that the calcium-sensing receptor (CaSR) is involved in lipid metabolism; however, whether CaSR polymorphisms affect lipid metabolism in obesity is still unclear. The present study aimed to determine the effects of CaSR polymorphisms on HTG risk in obese Chinese. A total of 972 subjects with HTG and 1197 with normal triglyceride (NTG) were stratified by body mass index (BMI) into normal weight, overweight or obesity subgroups. After 12-h fasting, CaSR polymorphisms in exon 7 were determined in the blood. Serum lipids and glucose, as well as height, body weight and waist circumference were measured. The anthropometric and metabolic characteristics of the NTG subjects were re-evaluated 3 years later. There were no genotypic or allelic distribution differences for the A986S or Q1011E polymorphisms between the NTG and HTG groups. However, the G/G genotypic and G allelic distributions of the CaSR R990G polymorphism in the HTG group were higher than the NTG group (pHTG group was significantly higher than in the NTG group (p=0.001), and showed an increased risk of HTG at baseline [OR=2.55, 95% CI=1.65-3.92, pHTG (β=0.927, pHTG, especially in obese Chinese, and may be a potential genetic predictor of diseases related to HTG. © 2013.

  17. Sucralose, an activator of the glucose-sensing receptor, increases ATP by calcium-dependent and -independent mechanisms. (United States)

    Li, Longfei; Ohtsu, Yoshiaki; Nakagawa, Yuko; Masuda, Katsuyoshi; Kojima, Itaru


    Sucralose is an artificial sweetener and activates the glucose-sensing receptor expressed in pancreatic β-cells. Although sucralose does not enter β-cells nor acts as a substrate for glucokinase, it induces a marked elevation of intracellular ATP ([ATP]c). The present study was conducted to identify the signaling pathway responsible for the elevation of [ATP]c induced by sucralose. Previous studies have shown that sucralose elevates cyclic AMP (cAMP), activates phospholipase C (PLC) and stimulates Ca(2+) entry by a Na(+)-dependent mechanism in MIN6 cells. The addition of forskolin induced a marked elevation of cAMP, whereas it did not affect [ATP]c. Carbachol, an activator of PLC, did not increase [ATP]c. In addition, activation of protein kinase C by dioctanoylglycerol did not affect [ATP]c. In contrast, nifedipine, an inhibitor of the voltage-dependent Ca(2+) channel, significantly reduced [ATP]c response to sucralose. Removal of extracellular Na(+) nearly completely blocked sucralose-induced elevation of [ATP]c. Stimulation of Na(+) entry by adding a Na(+) ionophore monensin elevated [ATP]c. The monensin-induced elevation of [ATP]c was only partially inhibited by nifedipine and loading of BAPTA, both of which completely abolished elevation of [Ca(2+)]c. These results suggest that Na(+) entry is critical for the sucralose-induced elevation of [ATP]c. Both calcium-dependent and -independent mechanisms are involved in the action of sucralose.

  18. Conservation of body calcium by increased dietary intake of potassium: A potential measure to reduce the osteoporosis process during prolonged exposure to microgravity (United States)

    Nechay, Bohdan R.


    During the 1988 NASA Summer Faculty Fellowship Program, it was proposed that the loss of skeletal calcium upon prolonged exposure to microgravity could be explained, in part, by a renal maladjustment characterized by an increased urinary excretion of calcium. It was theorized that because the conservation of body fluids and electrolytes depends upon the energy of adenosine triphosphate and enzymes that control the use of its energy for renal ion transport, an induction of renal sodium and potassium-dependent adenosine triphosphatase (Na + K ATPase) by oral loading with potassium would increase the reabsorption of sodium directly and that of calcium indirectly, leading to improved hydration and to reduced calcium loss. Preliminary studies showed the following. Rats drinking water containing 0.2 M potassium chloride for six to 13 days excreted in urine 22 muEq of calcium and 135 muEq of sodium per 100 grams of body weight per day. The corresponding values for control rats drinking tap water were 43 muEq and 269 muEq respectively. Renal Na + K ATPase activity in potassium loaded rats was higher than in controls. Thus, oral potassium loading resulted in increased Na + K ATPase activity and diminished urinary excretion of calcium and of sodium as predicted by the hypothesis. An extension of these studies to humans has the potential of resulting in development of harmless, non-invasive, drug-free, convenient measures to reduce bone loss and other electrolyte and fluid problems in space travelers exposed to prolonged periods of microgravity.

  19. Calcium - urine (United States)

    Urinary Ca+2; Kidney stones - calcium in urine; Renal calculi - calcium in your urine; Parathyroid - calcium in urine ... Urine calcium level can help your provider: Decide on the best treatment for the most common type of kidney ...

  20. Jellyfish Stings Trigger Gill Disorders and Increased Mortality in Farmed Sparus aurata (Linnaeus, 1758) in the Mediterranean Sea. (United States)

    Bosch-Belmar, Mar; M'Rabet, Charaf; Dhaouadi, Raouf; Chalghaf, Mohamed; Daly Yahia, Mohamed Néjib; Fuentes, Verónica; Piraino, Stefano; Kéfi-Daly Yahia, Ons


    Jellyfish are of particular concern for marine finfish aquaculture. In recent years repeated mass mortality episodes of farmed fish were caused by blooms of gelatinous cnidarian stingers, as a consequence of a wide range of hemolytic, cytotoxic, and neurotoxic properties of associated cnidocytes venoms. The mauve stinger jellyfish Pelagia noctiluca (Scyphozoa) has been identified as direct causative agent for several documented fish mortality events both in Northern Europe and the Mediterranean Sea aquaculture farms. We investigated the effects of P. noctiluca envenomations on the gilthead sea bream Sparus aurata by in vivo laboratory assays. Fish were incubated for 8 hours with jellyfish at 3 different densities in 300 l experimental tanks. Gill disorders were assessed by histological analyses and histopathological scoring of samples collected at time intervals from 3 hours to 4 weeks after initial exposure. Fish gills showed different extent and severity of gill lesions according to jellyfish density and incubation time, and long after the removal of jellyfish from tanks. Jellyfish envenomation elicits local and systemic inflammation reactions, histopathology and gill cell toxicity, with severe impacts on fish health. Altogether, these results shows P. noctiluca swarms may represent a high risk for Mediterranean finfish aquaculture farms, generating significant gill damage after only a few hours of contact with farmed S. aurata. Due to the growth of the aquaculture sector and the increased frequency of jellyfish blooms in the coastal waters, negative interactions between stinging jellyfish and farmed fish are likely to increase with the potential for significant economic losses.

  1. Pulling the Trigger: How Threats to the Nation Increase Support for Military Action via the Generation of Hubris

    Directory of Open Access Journals (Sweden)

    Yuval Feinstein


    Full Text Available Previous studies of public opinion in the United States have reported positive associations between national hubris and support for military actions. This article argues that in addition to its stable aspect, national hubris has a contextual aspect: under perceived symbolic threats to the nation, national hubris increases and boosts support for military action. To test this argument, which is grounded in a sociological and social psychological understanding of individuals as members of collectivities who pursue a symbolic politics of status achievement and maintenance, a survey-experiment was conducted with a nationally representative sample. In the experiment, participants who were exposed to rhetoric that highlighted symbolic threats to the nation to justify an impending military action against Iran’s nuclear facilities reported higher levels of national hubris and were more likely to support the military action than either participants who were exposed to internationalist rhetoric or those in the control group.

  2. Greater Volume but not Higher Density of Abdominal Aortic Calcium Is Associated With Increased Cardiovascular Disease Risk: MESA (Multi-Ethnic Study of Atherosclerosis). (United States)

    Forbang, Nketi I; Michos, Erin D; McClelland, Robyn L; Remigio-Baker, Rosemay A; Allison, Matthew A; Sandfort, Veit; Ix, Joachim H; Thomas, Isac; Rifkin, Dena E; Criqui, Michael H


    Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard. Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66±9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08-1.33; P<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04-1.59; P=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05-1.36; P<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events. The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries. © 2016 American Heart Association, Inc.

  3. The pain-induced decrease in low-threshold motor unit discharge rate is not associated with the amount of increase in spike-triggered average torque. (United States)

    Farina, Dario; Arendt-Nielsen, Lars; Roatta, Silvestro; Graven-Nielsen, Thomas


    Activation of nociceptive afferents decreases motor unit discharge rates in static contractions. There is also evidence that during experimental muscle pain the motor unit twitch force increases, which has been hypothesized to compensate for the decrease in discharge rate to maintain constant force. This study examined whether there is an association between the magnitude of change in motor unit discharge rate and the amount of increase in the spike-triggered average torque during experimental muscle pain. Sixteen subjects performed three constant-torque isometric ankle dorsi-flexions at 10% of the maximal force (MVC) alternated with two contractions at constant discharge rate of a target motor unit, before and following injection of 0.5 ml of hypertonic (painful) or isotonic (control) saline into the tibialis anterior muscle. The discharge rate of the target unit at 10% MVC decreased following injection of hypertonic saline (P<0.05; mean+/-SD, before: 9.9+/-1.3 pulses per second, pps; after injection: 8.9+/-1.0 pps). The peak of the spike-triggered average torque increased with pain (P<0.05; before: 0.56+/-0.55 mNm; during pain: 0.95+/-1.02 mNm) but the increase was not correlated with the decrease in discharge rate (R=0.08). Propagation velocity and action potential peak-to-peak amplitude did not change with pain. The pain-induced modifications in the estimated motor unit twitch torque (1) were not caused by changes in muscle fiber action potential, and (2) were not associated with the decrease in discharge rate. Maintenance of constant force during static painful contractions is not explained by a matching between changes in contractile and control motor unit properties.

  4. Modularized study of human calcium signalling pathway

    Indian Academy of Sciences (India)


    When there is an extracellular change, cells get the message either by introduction of calcium ions into ... as it precipitates phosphate, the established energy currency of cells. Prolonged high intracellular calcium ... trigger proteins upon binding with free calcium ion(s) change their confirmation to modulate enzymes and ion ...

  5. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Activation of receptors coupled to the phospholipase C/IP3 signalling pathway results in a rapid release of calcium from its intracellular stores, eventually leading to depletion of these stores. Calcium store depletion triggers an influx of extracellular calcium across the plasma membrane, a mechanism known as the ...

  6. Microdamage induced calcium efflux from bone matrix activates intracellular calcium signaling in osteoblasts via L-type and T-type voltage-gated calcium channels. (United States)

    Jung, Hyungjin; Best, Makenzie; Akkus, Ozan


    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Calcium metabolism and cardiovascular function after spaceflight (United States)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; hide


    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P platelet free calcium (intracellular calcium concentration) were also reduced (P metabolism (P metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  8. Triggering Klystrons

    Energy Technology Data Exchange (ETDEWEB)

    Stefan, Kelton D.; /Purdue U. /SLAC


    To determine if klystrons will perform to the specifications of the LCLS (Linac Coherent Light Source) project, a new digital trigger controller is needed for the Klystron/Microwave Department Test Laboratory. The controller needed to be programmed and Windows based user interface software needed to be written to interface with the device over a USB (Universal Serial Bus). Programming the device consisted of writing logic in VHDL (VHSIC (Very High Speed Integrated Circuits) hardware description language), and the Windows interface software was written in C++. Xilinx ISE (Integrated Software Environment) was used to compile the VHDL code and program the device, and Microsoft Visual Studio 2005 was used to compile the C++ based Windows software. The device was programmed in such a way as to easily allow read/write operations to it using a simple addressing model, and Windows software was developed to interface with the device over a USB connection. A method of setting configuration registers in the trigger device is absolutely necessary to the development of a new triggering system, and the method developed will fulfill this need adequately. More work is needed before the new trigger system is ready for use. The configuration registers in the device need to be fully integrated with the logic that will generate the RF signals, and this system will need to be tested extensively to determine if it meets the requirements for low noise trigger outputs.

  9. Calcium and Vitamin D increase mRNA levels for the growth control hIK1 channel in human epidermal keratinocytes but functional channels are not observed

    Directory of Open Access Journals (Sweden)

    Rossie Sandra


    Full Text Available Abstract Background Intermediate-conductance, calcium-activated potassium channels (IKs modulate proliferation and differentiation in mesodermal cells by enhancing calcium influx, and they contribute to the physiology of fluid movement in certain epithelia. Previous reports suggest that IK channels stimulate proliferative growth in a keratinocyte cell line; however, because these channels indirectly promote calcium influx, a critically unique component of the keratinocyte differentiation program, an alternative hypothesis is that they would be anti-proliferative and pro-differentiating. This study addresses these hypotheses. Methods Real-time PCR, patch clamp electrophysiology, and proliferation assays were used to determine if human IK1 (hIK1 expression and function are correlated with either proliferation or differentiation in cultured human skin epidermal keratinocytes, and skin biopsies grown in explant culture. Results hIK1 mRNA expression in human keratinocytes and skin was increased in response to anti-proliferative/pro-differentiating stimuli (elevated calcium and Vitamin D. Correspondingly, the hIK1 agonist 1-EBIO inhibited keratinocyte proliferation suggesting that the channel could be anti-proliferative and pro-differentiating. However, this proliferative inhibition by 1-EBIO was not reversed by a panel of hIK1 blockers, calling into question the mechanism of 1-EBIO action. Subsequent patch clamp electrophysiological analysis failed to detect hIK1 channel currents in keratinocytes, even those expressing substantial hIK1 mRNA in response to calcium and Vitamin D induced differentiation. Identical electrophysiological recording conditions were then used to observe robust IK1 currents in fibroblasts which express IK1 mRNA levels comparable to those of keratinocytes. Thus, the absence of observable hIK1 currents in keratinocytes was not a function of the electrophysiological techniques. Conclusion Human keratinocyte differentiation is

  10. Calcium supplementation and inflammation increase mortality in rheumatoid arthritis: A 15-year cohort study in 609 patients from the Oslo Rheumatoid Arthritis Register. (United States)

    Provan, Sella A; Olsen, Inge C; Austad, Cathrine; Haugeberg, Glenn; Kvien, Tore K; Uhlig, Till


    To investigate whether osteoporosis or use of calcium supplementations predict all-cause mortality, or death from CVD, in a longitudinal cohort of patients with rheumatoid arthritis (RA). Patients in the Oslo RA register (ORAR) were examined, and bone mineral density was measured in 1996. The cohort was linked to the Norwegian Cause of Death registry on December 31, 2010. Death from CVD was defined in 3 following different outcomes: (1) primary atherosclerotic death, (2) atherosclerotic death as one of the 5 listed causes of death, and (3) CVD according to World Health Organization (WHO) definition as primary cause of death. Baseline predictors of all-cause mortality and death from CVD were identified in separate Cox regression models, using backwards selection. Sensitivity analyses were performed including analyses of interactions and competing risk. A total of 609 patients were examined in 1996/1997. By December 31, 2010, 162 patients (27%) had died, resulting in 7439 observed patient-years. Of the deceased, 40 (24.7%) had primary atherosclerotic death. In the final model of all-cause mortality increased baseline ESR [hazard ratio (HR) 1.02 per mm/h, 95% CI: 1.01-1.03], calcium supplementation (1.74, 1.07-2.84), and osteoporosis, defined as a T score ≤2.5 SD at any location, (1.58, 1.07-2.32) predicted higher mortality rates, in models adjusted for age, gender, and a propensity score. In the final model of primary atherosclerotic death, increased ESR (1.03 per mm/h, 1.01-1.05) and calcium supplementation (3.39, 1.41-8.08), predicted higher mortality. Increased baseline ESR and use of calcium supplementation were predictors of increased all-cause mortality and risk of death from CVD in this longitudinal study of patients with RA. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Dietary polydextrose increases calcium absorption in normal rats Polidextrose aumenta a absorção de cálcio em ratos

    Directory of Open Access Journals (Sweden)

    Elisvânia Freitas dos Santos


    Full Text Available BACKGROUND: Gastric surgery is known to cause bone disorders, possibly related to an impaired capacity for the absorption of dietary calcium. AIM: To verify if polydextrose (PDX could stimulate calcium absorption in partially gastrectomized and sham operated rats. METHODS: The rats were laparotomized (sham-operated control or partially gastrectomized (Billroth II, in groups of 20 each. Half in each operated group were fed a control diet (AIN-93M without PDX or the same diet containing (PDX 50g/Kg of diet for eight weeks. The rats were divided into four subgroups: sham-operated and gastrectomized without PDX; sham-operated and gastrectomized with PDX. On the final day of the study, total blood was collected for determination of serum calcium concentration. RESULTS: In the diet with PDX, excretion of calcium in the feces was significantly lower than in the groups not receiving PDX, irrespective of the operation. Apparent calcium absorption and serum calcium was higher in the sham operated PDX fed group than in the control group. In sham operated rats, the calcium concentration in bone was higher in the PDX fed group. CONCLUSION: The polydextrose feeding increased calcium absorption and bone calcium concentration in normal rats, which may be relevant for decreasing the risk of osteoporosis. Partially gastrectomy did not affect the bone calcium concentration in 56 days of experimental period.RACIONAL: A cirurgia gástrica é conhecida por causar desordens ósseas, possivelmente relacionado com a absorção do cálcio na dieta. OBJETIVO: verificar se polidextrose (PDX poderia estimular a absorção de cálcio em ratos parcialmente gastrectomizados e ratos sham operados. MÉTODOS: Os ratos foram laparotomizadas (sham-operados de controle ou parcialmente gastrectomizados (Billroth II, em grupos de 20 animais cada. Metade de cada grupo operado foi alimentada com uma dieta controle (AIN-93M sem PDX ou a mesma dieta contendo (PDX 50g/kg de ração durante

  12. Calcium pathway machinery at fertilization in echinoderms. (United States)

    Ramos, Isabela; Wessel, Gary M


    Calcium signaling in cells directs diverse physiological processes. The calcium waves triggered by fertilization is a highly conserved calcium signaling event essential for egg activation, and has been documented in every egg tested. This activity is one of the few highly conserved events of egg activation through the course of evolution. Echinoderm eggs, as well as many other cell types, have three main intracellular Ca(2+) mobilizing messengers - IP3, cADPR and NAADP. Both cADPR and NAADP were identified as Ca(2+) mobilizing messengers using the sea urchin egg homogenate, and this experimental system, along with the intact urchin and starfish oocyte/egg, continues to be a vital tool for investigating the mechanism of action of calcium signals. While many of the major regulatory steps of the IP3 pathway are well resolved, both cADPR and NAADP remain understudied in terms of our understanding of the fundamental process of egg activation at fertilization. Recently, NAADP has been shown to trigger Ca(2+) release from acidic vesicles, separately from the ER, and a new class of calcium channels, the two-pore channels (TPCs), was identified as the likely targets for this messenger. Moreover, it was found that both cADPR and NAADP can be synthesized by the same family of enzymes, the ADP-rybosyl cyclases (ARCs). In this context of increasing amount of information, the potential coupling and functional roles of different messengers, intracellular stores and channels in the formation of the fertilization calcium wave in echinoderms will be critically evaluated. Copyright © 2012. Published by Elsevier India Pvt Ltd.

  13. A low dietary cation-anion difference precalving and calcium supplementation postcalving increase plasma calcium but not milk production in a pasture-based system. (United States)

    Roche, J R; Dalley, D; Moate, P; Grainger, C; Rath, M; O'Mara, F


    It was hypothesized that a reduction in the dietary cation-anion difference (DCAD) before calving, combined with an increase in Ca intake after calving, would reduce the incidence of periparturient hypocalcaemia and increase milk production in pasture-based dairy cows. Cows (n = 40) were assigned to one of two DCAD levels before calving (i.e., +7 and +50 mEq/100 g). Each group was then assigned to one of two dietary Ca concentrations after calving (i.e., 1.0 and 0.7%) in a 2 x 2 factorial design. The lower DCAD resulted in a nonrespiratory reduction in systemic pH as indicated by a lower urine pH. This acidosis resulted in an increased concentration of Ca in urine before calving. The lower precalving DCAD helped prevent the decline in blood Ca caused by the onset of lactation, even though blood Ca concentration was lower before calving compared with cows receiving a high DCAD. Supplementation of cows with Ca after calving increased plasma Ca concentration on the day of calving and during the subsequent 14 d. Milk production was not affected by pre- or postcalving treatments.

  14. Calmodulin activation by calcium transients in the postsynaptic density of dendritic spines.

    Directory of Open Access Journals (Sweden)

    Daniel X Keller


    Full Text Available The entry of calcium into dendritic spines can trigger a sequence of biochemical reactions that begins with the activation of calmodulin (CaM and ends with long-term changes to synaptic strengths. The degree of activation of CaM can depend on highly local elevations in the concentration of calcium and the duration of transient increases in calcium concentration. Accurate measurement of these local changes in calcium is difficult because the spaces are so small and the numbers of molecules are so low. We have therefore developed a Monte Carlo model of intracellular calcium dynamics within the spine that included calcium binding proteins, calcium transporters and ion channels activated by voltage and glutamate binding. The model reproduced optical recordings using calcium indicator dyes and showed that without the dye the free intracellular calcium concentration transient was much higher than predicted from the fluorescent signal. Excitatory postsynaptic potentials induced large, long-lasting calcium gradients across the postsynaptic density, which activated CaM. When glutamate was released at the synapse 10 ms before an action potential occurred, simulating activity patterns that strengthen hippocampal synapses, the calcium gradient and activation of CaM in the postsynaptic density were much greater than when the order was reversed, a condition that decreases synaptic strengths, suggesting a possible mechanism underlying the induction of long-term changes in synaptic strength. The spatial and temporal mechanisms for selectivity in CaM activation demonstrated here could be used in other signaling pathways.

  15. Environmentally triggered genomic plasticity and capsular polysaccharide formation are involved in increased ethanol and acetic acid tolerance in Kozakia baliensis NBRC 16680. (United States)

    Brandt, Julia U; Born, Friederike-Leonie; Jakob, Frank; Vogel, Rudi F


    Kozakia baliensis NBRC 16680 secretes a gum-cluster derived heteropolysaccharide and forms a surface pellicle composed of polysaccharides during static cultivation. Furthermore, this strain exhibits two colony types on agar plates; smooth wild-type (S) and rough mutant colonies (R). This switch is caused by a spontaneous transposon insertion into the gumD gene of the gum-cluster, resulting in a heteropolysaccharide secretion deficient, rough phenotype. To elucidate, whether this is a directed switch triggered by environmental factors, we checked the number of R and S colonies under different growth conditions including ethanol and acetic acid supplementation. Furthermore, we investigated the tolerance of R and S strains against ethanol and acetic acid in shaking and static growth experiments. To get new insights into the composition and function of the pellicle polysaccharide, the polE gene of the R strain was additionally deleted, as it was reported to be involved in pellicle formation in other acetic acid bacteria. The number of R colonies was significantly increased upon growth on acetic acid and especially ethanol. The morphological change from K. baliensis NBRC 16680 S to R strain was accompanied by changes in the sugar contents of the produced pellicle EPS. The R:ΔpolE mutant strain was not able to form a regular pellicle anymore, but secreted an EPS into the medium, which exhibited a similar sugar monomer composition as the pellicle polysaccharide isolated from the R strain. The R strain had a markedly increased tolerance towards acetic acid and ethanol compared to the other NBRC 16680 strains (S, R:ΔpolE). A relatively high intrinsic acetic acid tolerance was also observable for K. baliensis DSM 14400 T , which might indicate diverse adaptation mechanisms of different K. baliensis strains in altering natural habitats. The results suggest that the genetically triggered R phenotype formation is directly related to increased acetic acid and ethanol

  16. Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism. (United States)

    Shimohata, Atsushi; Ishihara, Keiichi; Hattori, Satoko; Miyamoto, Hiroyuki; Morishita, Hiromasa; Ornthanalai, Guy; Raveau, Matthieu; Ebrahim, Abdul Shukkur; Amano, Kenji; Yamada, Kazuyuki; Sago, Haruhiko; Akiba, Satoshi; Mataga, Nobuko; Murphy, Niall P; Miyakawa, Tsuyoshi; Yamakawa, Kazuhiro


    Ts1Cje mice have a segmental trisomy of chromosome 16 that is orthologous to human chromosome 21 and display Down syndrome-like cognitive impairments. Despite the occurrence of affective and emotional impairments in patients with Down syndrome, these parameters are poorly documented in Down syndrome mouse models, including Ts1Cje mice. Here, we conducted comprehensive behavioral analyses, including anxiety-, sociability-, and depression-related tasks, and biochemical analyses of monoamines and their metabolites in Ts1Cje mice. Ts1Cje mice showed enhanced locomotor activity in novel environments and increased social contact with unfamiliar partners when compared with wild-type littermates, but a significantly lower activity in familiar environments. Ts1Cje mice also exhibited some signs of decreased depression like-behavior. Furthermore, Ts1Cje mice showed monoamine abnormalities, including increased extracellular dopamine and serotonin, and enhanced catabolism in the striatum and ventral forebrain. This study constitutes the first report of deviated monoamine metabolism that may help explain the basis for abnormal behaviors, including the environmental stimuli-triggered hyperactivity, increased sociability and decreased depression-like behavior in Ts1Cje mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Calcium Carbonate (United States)

    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 ...

  18. Calcium supplements (United States)

    ... this page: // Calcium supplements To use the sharing features on this page, please enable JavaScript. WHO SHOULD TAKE CALCIUM SUPPLEMENTS? Calcium is an important mineral for the ...

  19. ATLAS Trigger System

    CERN Document Server

    Petersen, B A; The ATLAS collaboration


    During the data taking period from 2009 until 2011, the ATLAS trigger has been very successfully used to collect proton-proton data at LHC centre-of-mass energies between 900 GeV and 7 TeV. The three-level trigger system reduces the event rate from the design bunch-crossing rate of 40 MHz to an average recording rate of about 300 Hz. Using custom electronics with input from the calorimeter and muon detectors, the first level rejects most background collisions in less than 2.5 microseconds. Then follow two levels of software-based triggers. The trigger system is designed to select events by identifying muons, electrons, photons, taus, jets and B hadron candidates, as well as using global event signatures, such as missing transverse energy. We give an overview of the strategy and performance of the different trigger selections based mainly on the experience during the 2011 LHC run, where the trigger menu needed quick adaptations to the continuous increase of luminosity throughout the year. Examples of trigger e...

  20. Basic FGF enhances calcium permeable channel openings in adult rat cardiac myocytes: implication in the bFGF-induced increase of free Ca2+ content. (United States)

    Merle, P L; Usson, Y; Robert-Nicoud, M; Verdetti, J


    Basic fibroblast growth factor (bFGF) has been implicated in the changes in gene expression that, under pathological conditions such as ischemia or volume overload, lead to adult cardiomyocyte hypertrophy. In many tissues, one of the first events following cell activation by growth factors is an enhancement of the intracellular free calcium concentration, generated by fluxes from internal storage compartments and through channels of the plasma membrane. The present study was undertaken to determine whether cardiac myocytes isolated from adult rat ventricles express Ca2+-permeable channels activated by bFGF. Using the cell-attached mode of the patch-clamp technique, we observed that bFGF (from 0.1-10 nM) induced an increase of fast burst openings, mediated by Ca2+-permeable channels with low conductance (15 pS) and voltage-independence. Inside-out patch-clamp experiments revealed that inositol 1,4,5-trisphosphate (5 microM) enhanced the opening of Ca2+-permeable channels with similar properties as the bFGF-induced channels, indicating that IP3 may be a second messenger of this process. Confocal fluorescence imaging of intracellular free calcium provided direct evidence that bFGF induced an increase of cytoplasmic and nucleoplasmic free Ca2+ concentrations which were generated, in part, by Ca2+ influx through the plasma membrane. In conclusion, this study supports the presence, in the plasma membrane of adult cardiac myocytes, of messenger-activated calcium channels which could play key roles in the calcium-dependent pathways that are activated in response to growth factors. Copyright 1997 Academic Press Limited.

  1. Induction of peritoneal sepsis increases the susceptibility of isolated hearts to a calcium paradox-mediated injury. (United States)

    Omachi, Akira; Sharma, Avadhesh C; Alden, Kris J; Sam, Albert D; Ferguson, James L


    The present study was designed to test the hypothesis that induction of chronic peritoneal sepsis in rats would produce a more severe calcium paradox-mediated myocardial injury in isolated heart preparation than is seen in normal hearts, and that this would be inhibited by sucrose as in normal hearts. Male Sprague-Dawley rats were made septic using 200 mg of cecal material (obtained from a donor rat) suspended in 5 mL of 5% dextrose in sterile water D5 W/kg. In septic animals, the cecal material was injected in the peritoneum, while sham-septic animals received only D5 W/kg (5 mL/kg). A third group consisting of normal rats (no surgery) group was also included. Hearts were harvested from all three groups and were subjected to a calcium paradox-mediated injury in an isolated heart preparation. Hearts were perfused with Krebs-Henseleit (KH) medium and were allowed to stabilize, followed by a perfusion with Ca2+-free KH for 10 min. After this 10-min Ca2+-free KH perfusion, rats were reperfused with KH medium for 60 min. Ca2+-free KH medium was used in control experiments, while sucrose experiments were conducted with the same medium except that 150 mM sucrose replaced 75 mM NaCl. A marked decrease in ATP and phosphocreatine occurred during Ca2+ reperfusion in all hearts in absence of sucrose. In the presence of the disaccharide, no change in high-energy phosphate (HEP) levels was observed in normal hearts, while lower ATP concentrations were seen in sham and septic hearts. Thus, sucrose did not inhibit cellular injury in sham and septic hearts as it did in normal hearts, and this might be due to a smaller HEP availability. Control studies with normal, sham, and septic hearts exhibited cessation of contractions in the absence of Ca2+, and appearance of large amounts of cytosolic protein in the effluent perfusate during Ca2+ reperfusion. With normal hearts, perfusion with sucrose caused a 96% inhibition of the total creatine kinase (CK) release observed in control

  2. Is there an acute exercise-induced physiological/biochemical threshold which triggers increased speed of cognitive functioning? A meta-analytic investigation

    National Research Council Canada - National Science Library

    Terry McMorris Beverley J. Hale


    Purpose: The purpose of this study was to examine, using meta-analytic measures, the evidence regarding the optimal exercise intensity at which improvements in speed of cognitive function are triggered...

  3. C2-domain containing calcium sensors in neuroendocrine secretion

    DEFF Research Database (Denmark)

    Pinheiro, Paulo S; Houy, Sébastien; Sørensen, Jakob B


    to calcium, trigger the merger of cargo-filled vesicles with the plasma membrane. Low-affinity, fast-kinetics calcium sensors of the synaptotagmin family - especially synaptotagmin-1 and synaptotagmin-2 - are the main calcium sensors for fast exocytosis triggering in many cell types. Their functions extend...... the properties and possible interplay of (some of) the major C2-domain containing calcium sensors in calcium-triggered exocytosis. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases"....

  4. Calcitriol (1,25-dihydroxyvitamin D3) increases L-type calcium current via protein kinase A signaling and modulates calcium cycling and contractility in isolated mouse ventricular myocytes. (United States)

    Tamayo, María; Manzanares, Esmeralda; Bas, Manuel; Martín-Nunes, Laura; Val-Blasco, Almudena; Jesús Larriba, María; Fernández-Velasco, María; Delgado, Carmen


    Calcitriol, the bioactive metabolite of vitamin D, exerts its effects through interaction with the nuclear vitamin D receptor (VDR) to induce genomic responses. Calcitriol may also induce rapid responses via plasma membrane-associated VDR, involving the activation of second messengers and modulation of voltage-dependent channels. VDR is expressed in cardiomyocytes, but the molecular and cellular mechanisms involved in the rapid responses of calcitriol in the heart are poorly understood. The aim of the present study was to analyze the rapid nongenomic effect of calcitriol on L-type calcium channels, intracellular Ca(2+) ([Ca(2+)]i) transients, and cell contractility in ventricular myocytes. We used the whole-cell patch-clamp technique to record L-type calcium current (ICaL) and confocal microscopy to study global [Ca(2+)]i transients evoked by electrical stimulation and cell shortening in adult mouse ventricular myocytes treated with vehicle or with calcitriol. In some experiments, ICaL was recorded using the perforated patch-clamp technique. Calcitriol treatment of cardiomyocytes induced a concentration-dependent increase in ICaL density (Half maximal effective concentration (EC50) = 0.23 nM) and a significant increase in peak [Ca(2+)]i transients and cell contraction. The effect of calcitriol on ICaL was prevented by pretreatment of cardiomyocytes with the protein kinase A (PKA) inhibitor KT-5720 but not with the β-adrenergic blocker propranolol. The effect of calcitriol on ICaL was absent in myocytes isolated from VDR knockout mice. Calcitriol induces a rapid response in mouse ventricular myocytes that involves a VDR-PKA-dependent increase in ICaL density, enhancing [Ca(2+)]i transients and contraction. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  5. Triggering Artefacts

    DEFF Research Database (Denmark)

    Mogensen, Preben Holst; Robinson, Mike


    The paper presents a general critique of the use of conceptual frameworks in design, illustrated by the well known synchronous/asynchronous, co-located/non-co-located framework. It argues that while frameworks are a necessary and inevitable starting point for design, the business of tailoring...... and adapting them to specific situations need not be ad hoc.Triggering artefacts are a way of systematically challenging both designers' preunderstandings and the conservatism of work practice. Experiences from the Great Belt tunnel and bridge project are used to illustrate howtriggering artefacts change...

  6. Impact of calcium signaling during infection of Neisseria meningitidis to human brain microvascular endothelial cells. (United States)

    Asmat, Tauseef M; Tenenbaum, Tobias; Jonsson, Ann-Beth; Schwerk, Christian; Schroten, Horst


    The pili and outer membrane proteins of Neisseria meningitidis (meningococci) facilitate bacterial adhesion and invasion into host cells. In this context expression of meningococcal PilC1 protein has been reported to play a crucial role. Intracellular calcium mobilization has been implicated as an important signaling event during internalization of several bacterial pathogens. Here we employed time lapse calcium-imaging and demonstrated that PilC1 of meningococci triggered a significant increase in cytoplasmic calcium in human brain microvascular endothelial cells, whereas PilC1-deficient meningococci could not initiate this signaling process. The increase in cytosolic calcium in response to PilC1-expressing meningococci was due to efflux of calcium from host intracellular stores as demonstrated by using 2-APB, which inhibits the release of calcium from the endoplasmic reticulum. Moreover, pre-treatment of host cells with U73122 (phospholipase C inhibitor) abolished the cytosolic calcium increase caused by PilC1-expressing meningococci demonstrating that active phospholipase C (PLC) is required to induce calcium transients in host cells. Furthermore, the role of cytosolic calcium on meningococcal adherence and internalization was documented by gentamicin protection assay and double immunofluorescence (DIF) staining. Results indicated that chelation of intracellular calcium by using BAPTA-AM significantly impaired PilC1-mediated meningococcal adherence to and invasion into host endothelial cells. However, buffering of extracellular calcium by BAPTA or EGTA demonstrated no significant effect on meningococcal adherence to and invasion into host cells. Taken together, these results indicate that meningococci induce calcium release from intracellular stores of host endothelial cells via PilC1 and cytoplasmic calcium concentrations play a critical role during PilC1 mediated meningococcal adherence to and subsequent invasion into host endothelial cells.

  7. Impact of calcium signaling during infection of Neisseria meningitidis to human brain microvascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Tauseef M Asmat

    Full Text Available The pili and outer membrane proteins of Neisseria meningitidis (meningococci facilitate bacterial adhesion and invasion into host cells. In this context expression of meningococcal PilC1 protein has been reported to play a crucial role. Intracellular calcium mobilization has been implicated as an important signaling event during internalization of several bacterial pathogens. Here we employed time lapse calcium-imaging and demonstrated that PilC1 of meningococci triggered a significant increase in cytoplasmic calcium in human brain microvascular endothelial cells, whereas PilC1-deficient meningococci could not initiate this signaling process. The increase in cytosolic calcium in response to PilC1-expressing meningococci was due to efflux of calcium from host intracellular stores as demonstrated by using 2-APB, which inhibits the release of calcium from the endoplasmic reticulum. Moreover, pre-treatment of host cells with U73122 (phospholipase C inhibitor abolished the cytosolic calcium increase caused by PilC1-expressing meningococci demonstrating that active phospholipase C (PLC is required to induce calcium transients in host cells. Furthermore, the role of cytosolic calcium on meningococcal adherence and internalization was documented by gentamicin protection assay and double immunofluorescence (DIF staining. Results indicated that chelation of intracellular calcium by using BAPTA-AM significantly impaired PilC1-mediated meningococcal adherence to and invasion into host endothelial cells. However, buffering of extracellular calcium by BAPTA or EGTA demonstrated no significant effect on meningococcal adherence to and invasion into host cells. Taken together, these results indicate that meningococci induce calcium release from intracellular stores of host endothelial cells via PilC1 and cytoplasmic calcium concentrations play a critical role during PilC1 mediated meningococcal adherence to and subsequent invasion into host endothelial cells.

  8. Saponarin activates AMPK in a calcium-dependent manner and suppresses gluconeogenesis and increases glucose uptake via phosphorylation of CRTC2 and HDAC5. (United States)

    Seo, Woo-Duck; Lee, Ji Hae; Jia, Yaoyao; Wu, Chunyan; Lee, Sung-Joon


    This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did not directly interact with the AMPK protein. Instead, saponarin increased intracellular calcium levels and induced AMPK phosphorylation, which was diminished by co-stimulation with STO-609, an inhibitor of CAMKKβ. Transcription of hepatic gluconeogenesis genes was upregulated by nuclear translocation of CRTC2 and HDAC5, coactivators of CREB and FoxO1 transcription factors, respectively. This nuclear translocation was inhibited by increased phosphorylation of CRTC2 and HDAC5 by saponarin-induced AMPK in HepG2 cells and suppression of CREB and FoxO1 transactivation activities in cells stimulated by saponarin. The results from a chromatin immunoprecipitation assay confirmed the reduced binding of CRTC2 on the PEPCK and G6Pase promoters. In TE671 cells, AMPK phosphorylated HDAC5, which suppressed nuclear penetration and upregulated GLUT4 transcription, leading to enhanced glucose uptake. Collectively, these results suggest that saponarin activates AMPK in a calcium-dependent manner, thus regulating gluconeogenesis and glucose uptake. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. People with the major alleles of ATP2B1 rs17249754 increases the risk of hypertension in high ratio of sodium and potassium, and low calcium intakes. (United States)

    Daily, J W; Kim, B C; Liu, M; Park, S


    It is important to understand what genetic risk factors lead to hypertension and how genotype-specific dietary and lifestyle modification can mitigate the risk of developing hypertension. The ATP2B1 rs17249754 gene, which encodes a calcium pump expressed in vascular smooth muscle was identified as having variants that conferred higher or lower risk of hypertension-with the major allele carriers being increased at risk. However, the effects of dietary intakes on risk of hypertension among carriers of the different alleles have not been fully elucidated. Therefore, we evaluated ATP2B1 rs17249754 and its interaction with dietary intakes of sodium (Na), potassium (K) and calcium (Ca) on the risk of developing hypertension using the Ansan/Ansung (n=8842) and City-Rural (n=5512) cohorts from the Korean Genome and Epidemiology Study. Carriers of the major allele of ATP2B1 rs17249754 were at greater risk of developing hypertension and high Na intake and low Ca increased the risk more in major allele than among minor allele carriers. High potassium intake was more protective against hypertension in the subjects expressing minor alleles and a low Na/K intake ratio was the most consistently beneficial to the subjects expressing the minor allele. When controlling for Na and K, low Ca intake was associated with a substantially higher risk for high systolic blood pressure in the major allele carriers compared with minor allele, suggesting good calcium status is especially important for the major allele carriers. In conclusion, people with the major allele of ATP2B1 rs17249754 are susceptible to hypertension especially in low intake of Ca and high ratio of Na and K.

  10. Prohexadione calcium reduces vegetative growth and increases fruit set of ‘Smith’ pear trees, in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Bruno Carra

    Full Text Available ABSTRACT Prohexadione calcium (P-Ca has been reported to effectively control shoot growth in several pear cultivars, but with a few reports about its efficiency under the climatic conditions of southern Brazil. Therefore, the objective of this study was to evaluate vegetative growth, production, and fruit quality of ‘Smith’ pear trees in response to the use of different rates of P-Ca in the climatic conditions of southern Brazil. The experiment was conducted during the 2013/2014 and 2014/2015 seasons, in a 6-year-old ‘Smith’ pear orchard, trained to a central-leader system, with spacing of 1.5 × 4.8 m, grafted onto Pyrus calleryana Decne. Different P-Ca rates were applied (100, 200, 300, and 400 mg∙L–1 in different stages: first, in early spring for all treatments, and the others when shoot growth resumed (GR, but only for some treatments. Variables for vegetative growth, yield components and fruit quality at harvest and post-harvest were evaluated. The use of P-Ca was effective to control vegetative growth in both seasons, at different rates. Yield components were not affected by P-Ca applications in 2013/2014, except return bloom and return yield. In 2014/2015 season, P-Ca applications positively affected yield components, except average fruit weight and return bloom. P-Ca applications did not alter the qualitative attributes of the fruits of ‘Smith’ pear trees at harvest and after a period of cold storage. These results implicate P-Ca as a potential tool to manage vigor of ‘Smith’ pear trees in climatic conditions of southern Brazil.

  11. Sigma-1 receptor agonist increases axon outgrowth of hippocampal neurons via voltage-gated calcium ions channels. (United States)

    Li, Dong; Zhang, Shu-Zhuo; Yao, Yu-Hong; Xiang, Yun; Ma, Xiao-Yun; Wei, Xiao-Li; Yan, Hai-Tao; Liu, Xiao-Yan


    Sigma-1 receptors (Sig-1Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig-1R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig-1R-mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig-1R on axon outgrowth are not fully understood. To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured naïve hippocampal neurons before and after the application of the Sig-1R agonist, SA4503. Then, electrophysiology and immunofluorescence were used to examine voltage-gated calcium ion channel (VGCCs) currents in the cell membranes and growth cones. We found that Sig-1R activation dramatically enhanced the axonal length of the naïve hippocampal neurons. Application of the Sig-1R antagonist NE100 and gene knockdown techniques both demonstrated the effects of Sig-1R. The growth-promoting effect of SA4503 was accompanied by the inhibition of voltage-gated Ca2+ influx and was recapitulated by incubating the neurons with the L-type, N-type, and P/Q-type VGCC blockers, nimodipine, MVIIA and ω-agatoxin IVA, respectively. This effect was unrelated to glial cells. The application of SA4503 transformed the growth cone morphologies from complicated to simple, which favored axon outgrowth. Sig-1R activation can enhance axon outgrowth and may have a substantial influence on neurogenesis and neurodegenerative diseases. © 2017 John Wiley & Sons Ltd.

  12. Acute Sleep Deprivation Increases Serum Levels of Neuron-Specific Enolase (NSE) and S100 Calcium Binding Protein B (S-100B) in Healthy Young Men (United States)

    Benedict, Christian; Cedernaes, Jonathan; Giedraitis, Vilmantas; Nilsson, Emil K.; Hogenkamp, Pleunie S.; Vågesjö, Evelina; Massena, Sara; Pettersson, Ulrika; Christoffersson, Gustaf; Phillipson, Mia; Broman, Jan-Erik; Lannfelt, Lars; Zetterberg, Henrik; Schiöth, Helgi B.


    Study Objectives: To investigate whether total sleep deprivation (TSD) affects circulating concentrations of neuron-specific enolase (NSE) and S100 calcium binding protein B (S-100B) in humans. These factors are usually found in the cytoplasm of neurons and glia cells. Increasing concentrations of these factors in blood may be therefore indicative for either neuronal damage, impaired blood brain barrier function, or both. In addition, amyloid β (Aβ) peptides 1-42 and 1-40 were measured in plasma to calculate their ratio. A reduced plasma ratio of Aβ peptides 1-42 to 1-40 is considered an indirect measure of increased deposition of Aβ 1-42 peptide in the brain. Design: Subjects participated in two conditions (including either 8-h of nocturnal sleep [22:30-06:30] or TSD). Fasting blood samples were drawn before and after sleep interventions (19:30 and 07:30, respectively). Setting: Sleep laboratory. Participants: 15 healthy young men. Results: TSD increased morning serum levels of NSE (P = 0.002) and S-100B (P = 0.02) by approximately 20%, compared with values obtained after a night of sleep. In contrast, the ratio of Aβ peptides 1-42 to 1-40 did not differ between the sleep interventions. Conclusions: Future studies in which both serum and cerebrospinal fluid are sampled after sleep loss should elucidate whether the increase in serum neuron-specific enolase and S100 calcium binding protein B is primarily caused by neuronal damage, impaired blood brain barrier function, or is just a consequence of increased gene expression in non-neuronal cells, such as leukocytes. Citation: Benedict C; Cedernaes J; Giedraitis V; Nilsson EK; Hogenkamp PS; Vågesjö E; Massena S; Pettersson U; Christoffersson G; Phillipson M; Broman JE; Lannfelt L; Zetterberg H; Schiöth HB. Acute Sleep Deprivation Increases Serum Levels of Neuron-Specific Enolase (NSE) and S100 Calcium Binding Protein B (S-100B) in Healthy Young Men. SLEEP 2014;37(1):195-198. PMID:24470708

  13. Firearm trigger assembly (United States)

    Crandall, David L.; Watson, Richard W.


    A firearm trigger assembly for use with a firearm includes a trigger mounted to a forestock of the firearm so that the trigger is movable between a rest position and a triggering position by a forwardly placed support hand of a user. An elongated trigger member operatively associated with the trigger operates a sear assembly of the firearm when the trigger is moved to the triggering position. An action release assembly operatively associated with the firearm trigger assembly and a movable assembly of the firearm prevents the trigger from being moved to the triggering position when the movable assembly is not in the locked position.

  14. Synthesized mesoporous silica and calcium aluminate cement fillers increased the fluoride recharge and lactic acid neutralizing ability of a resin-based pit and fissure sealant. (United States)

    Surintanasarn, Atikom; Siralertmukul, Krisana; Thamrongananskul, Niyom


    This study evaluated the effect of different types of filler in a resin-based pit and fissure sealant on fluoride release, recharge, and lactic acid neutralization. Resin-based sealant was incorporated with 5% w/w of the following fillers: calcium aluminate cement (CAC), synthesized mesoporous silica (SI), a CAC and SI mixture (CAC+SI), glass-ionomer powder (GIC), and acetic acid-treated GIC (GICA). Sealant without filler served as control. The samples were immersed in deionized water or a lactic acid solution and the concentration of fluoride in the water, before and after fluoride recharge, and the lactic acid pH change, respectively, were determined. The CAC+SI group demonstrated the highest fluoride release after being recharged with fluoride gel. The CAC+SI group also demonstrated increased lactic acid pH. These findings suggest that a resin-based sealant containing synthesized mesoporous silica and calcium aluminate cement may enhance remineralization due to fluoride release and higher pH.

  15. Neurosteroids block the increase in intracellular calcium level induced by Alzheimer’s β-amyloid protein in long-term cultured rat hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Midori Kato-Negishi


    Full Text Available Midori Kato-Negishi1, Masahiro Kawahara21Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-shi, Tokyo 183- 8526, Japan; 2Department of Analytical Chemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino-cho, Nobeoka-shi, Miyazaki 882-8508, JapanAbstract: The neurotoxicity of β-amyloid protein (AβP is implicated in the etiology of Alzheimer’s disease. We previously have demonstrated that AβP forms Ca2+-permeable pores on neuronal membranes, causes a marked increase in intracellular calcium level, and leads to neuronal death. Here, we investigated in detail the features of AβP-induced changes in intracellular Ca2+ level in primary cultured rat hippocampal neurons using a multisite Ca2+- imaging system with fura-2 as a fluorescent probe. Only a small fraction of short-term cultured hippocampal neurons (ca 1 week in vitro exhibited changes in intracellular Ca2+ level after AβP exposure. However, AβP caused an acute increase in intracellular Ca2+ level in long-term cultured neurons (ca 1 month in vitro. The responses to AβP were highly heterogeneous, and immunohistochemical analysis using an antibody to AβP revealed that AβP is deposited on some but not all neurons. Considering that the disruption of Ca2+ homeostasis is the primary event in AβP neurotoxicity, substances that protect neurons from an AβP-induced intracellular Ca2+ level increase may be candidates as therapeutic drugs for Alzheimer’s disease. In line with the search for such protective substances, we found that the preadministration of neurosteroids including dehydroepiandrosterone, dehydroepiandrosterone sulfate, and pregnenolone significantly inhibits the increase in intracellular calcium level induced by AβP. Our results suggest the possible significance of neurosteroids, whose levels are reduced in the elderly, in preventing AβP neurotoxicity

  16. The CMS High Level Trigger

    CERN Document Server

    Gori, Valentina


    The CMS experiment has been designed with a 2-level trigger system: the Level 1 Trigger, implemented on custom-designed electronics, and the High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a tradeoff between the complexity of the algorithms running on the available computing power, the sustainable output rate, and the selection efficiency. Here we will present the performance of the main triggers used during the 2012 data taking, ranging from simpler single-object selections to more complex algorithms combining different objects, and applying analysis-level reconstruction and selection. We will discuss the optimisation of the triggers and the specific techniques to cope with the increasing LHC pile-up, reducing its impact on the physics performance.

  17. The CMS High Level Trigger

    CERN Document Server

    Trocino, Daniele


    The CMS experiment has been designed with a 2-level trigger system: the Level 1 Trigger, implemented in custom-designed electronics, and the High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a tradeoff between the complexity of the algorithms running with the available computing power, the sustainable output rate, and the selection efficiency. We present the performance of the main triggers used during the 2012 data taking, ranging from simple single-object selections to more complex algorithms combining different objects, and applying analysis-level reconstruction and selection. We discuss the optimisation of the trigger and the specific techniques to cope with the increasing LHC pile-up, reducing its impact on the physics performance.

  18. Bone repair in calcium-deficient rats: comparison of xylitol+calcium carbonate with calcium carbonate, calcium lactate and calcium citrate on the repletion of calcium. (United States)

    Hämäläinen, M M


    The potential value of xylitol in calcium therapy was evaluated by comparing the effect of dietary xylitol (50 g/kg diet) + calcium carbonate with the effects of calcium carbonate, calcium lactate and calcium citrate on bone repair of young male rats after the rats consumed for 3 wk a calcium-deficient diet (0.2 g Ca/kg diet). After this calcium-depletion period, the rats were fed for 2 wk one of four diets, each containing 5 g Ca/kg diet as one of the four dietary calcium sources. The diet of the control animals was supplemented with CaCO3 (5 g Ca/kg diet) throughout the study. The Ca-deficient rats showed low bone mass, low serum calcium and high serum 1,25-dihydroxycholecalciferol, parathyroid hormone (1-34 fraction) and osteocalcin concentrations. They also excreted magnesium, phosphate and hydroxyproline in the urine in high concentrations, and had high bone alkaline phosphatase and tartrate-resistant acid phosphatase activities. Most of these changes were reversed by the administered of the calcium salts. The highest recoveries of femoral dry weight, calcium, magnesium and phosphate were observed in the groups receiving xylitol+CaCO3 and calcium lactate. Calcium lactate and calcium citrate caused low serum phosphate concentration compared with rats receiving CaCO3 and with the age-matched Ca-replete controls. Xylitol-treated rats excreted more calcium and magnesium in urine than did the other rats, probably due to increased absorption of these minerals from the gut. These results suggest that dietary xylitol improves the bioavailability of calcium salts.

  19. AMP-activated Protein Kinase Phosphorylates Cardiac Troponin I at Ser-150 to Increase Myofilament Calcium Sensitivity and Blunt PKA-dependent Function* (United States)

    Nixon, Benjamin R.; Thawornkaiwong, Ariyoporn; Jin, Janel; Brundage, Elizabeth A.; Little, Sean C.; Davis, Jonathan P.; Solaro, R. John; Biesiadecki, Brandon J.


    AMP-activated protein kinase (AMPK) is an energy-sensing enzyme central to the regulation of metabolic homeostasis. In the heart AMPK is activated during cardiac stress-induced ATP depletion and functions to stimulate metabolic pathways that restore the AMP/ATP balance. Recently it was demonstrated that AMPK phosphorylates cardiac troponin I (cTnI) at Ser-150 in vitro. We sought to determine if the metabolic regulatory kinase AMPK phosphorylates cTnI at Ser-150 in vivo to alter cardiac contractile function directly at the level of the myofilament. Rabbit cardiac myofibrils separated by two-dimensional isoelectric focusing subjected to a Western blot with a cTnI phosphorylation-specific antibody demonstrates that cTnI is endogenously phosphorylated at Ser-150 in the heart. Treatment of myofibrils with the AMPK holoenzyme increased cTnI Ser-150 phosphorylation within the constraints of the muscle lattice. Compared with controls, cardiac fiber bundles exchanged with troponin containing cTnI pseudo-phosphorylated at Ser-150 demonstrate increased sensitivity of calcium-dependent force development, blunting of both PKA-dependent calcium desensitization, and PKA-dependent increases in length dependent activation. Thus, in addition to the defined role of AMPK as a cardiac metabolic energy gauge, these data demonstrate AMPK Ser-150 phosphorylation of cTnI directly links the regulation of cardiac metabolic demand to myofilament contractile energetics. Furthermore, the blunting effect of cTnI Ser-150 phosphorylation cross-talk can uncouple the effects of myofilament PKA-dependent phosphorylation from β-adrenergic signaling as a novel thin filament contractile regulatory signaling mechanism. PMID:22493448

  20. AMP-activated protein kinase phosphorylates cardiac troponin I at Ser-150 to increase myofilament calcium sensitivity and blunt PKA-dependent function. (United States)

    Nixon, Benjamin R; Thawornkaiwong, Ariyoporn; Jin, Janel; Brundage, Elizabeth A; Little, Sean C; Davis, Jonathan P; Solaro, R John; Biesiadecki, Brandon J


    AMP-activated protein kinase (AMPK) is an energy-sensing enzyme central to the regulation of metabolic homeostasis. In the heart AMPK is activated during cardiac stress-induced ATP depletion and functions to stimulate metabolic pathways that restore the AMP/ATP balance. Recently it was demonstrated that AMPK phosphorylates cardiac troponin I (cTnI) at Ser-150 in vitro. We sought to determine if the metabolic regulatory kinase AMPK phosphorylates cTnI at Ser-150 in vivo to alter cardiac contractile function directly at the level of the myofilament. Rabbit cardiac myofibrils separated by two-dimensional isoelectric focusing subjected to a Western blot with a cTnI phosphorylation-specific antibody demonstrates that cTnI is endogenously phosphorylated at Ser-150 in the heart. Treatment of myofibrils with the AMPK holoenzyme increased cTnI Ser-150 phosphorylation within the constraints of the muscle lattice. Compared with controls, cardiac fiber bundles exchanged with troponin containing cTnI pseudo-phosphorylated at Ser-150 demonstrate increased sensitivity of calcium-dependent force development, blunting of both PKA-dependent calcium desensitization, and PKA-dependent increases in length dependent activation. Thus, in addition to the defined role of AMPK as a cardiac metabolic energy gauge, these data demonstrate AMPK Ser-150 phosphorylation of cTnI directly links the regulation of cardiac metabolic demand to myofilament contractile energetics. Furthermore, the blunting effect of cTnI Ser-150 phosphorylation cross-talk can uncouple the effects of myofilament PKA-dependent phosphorylation from β-adrenergic signaling as a novel thin filament contractile regulatory signaling mechanism.

  1. Urinary calcium and oxalate excretion in healthy adult cats are not affected by increasing dietary levels of bone meal in a canned diet.

    Directory of Open Access Journals (Sweden)

    Nadine Passlack

    Full Text Available This study aimed to investigate the impact of dietary calcium (Ca and phosphorus (P, derived from bone meal, on the feline urine composition and the urinary pH, allowing a risk assessment for the formation of calcium oxalate (CaOx uroliths in cats. Eight healthy adult cats received 3 canned diets, containing 12.2 (A, 18.5 (B and 27.0 g Ca/kg dry matter (C and 16.1 (A, 17.6 (B and 21.1 g P/kg dry matter (C. Each diet was fed over 17 days. After a 7 dayś adaptation period, urine and faeces were collected over 2×4 days (with a two-day rest between, and blood samples were taken. Urinary and faecal minerals, urinary oxalate (Ox, the urinary pH and the concentrations of serum Ca, phosphate and parathyroid hormone (PTH were analyzed. Moreover, the urine was microscopically examined for CaOx uroliths. The results demonstrated that increasing levels of dietary Ca led to decreased serum PTH and Ca and increased faecal Ca and P concentrations, but did not affect the urinary Ca or Ox concentrations or the urinary fasting pH. The urinary postprandial pH slightly increased when the diet C was compared to the diet B. No CaOx crystals were detected in the urine of the cats. In conclusion, urinary Ca excretion in cats seems to be widely independent of the dietary Ca levels when Ca is added as bone meal to a typical canned diet, implicating that raw materials with higher contents of bones are of subordinate importance as risk factors for the formation of urinary CaOx crystals.

  2. [Calcium and bone metabolism across women's life stages. Exercise and sport to increase bone strength in accordance with female lifecycle. (United States)

    Iwamoto, Jun

    Among females who require the strategies for preventing osteoporosis, appropriate exercise and sport through all their life are important to increase or maintain bone mass. However, the type of exercise and sport applied to females is different in accordance with the lifecycle. Jumping exercise increases bone mineral content(BMC)in prepubescent children(premenarcheal girls). Bone mineral density(BMD)is higher in adolescent athletes who are engaged in weight-bearing activities. Jumping exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises increase BMD in young adults and premenopausal women. Walking, aerobic weight-bearing exercise, muscle strengthening exercise, and weight-bearing plus muscle strengthening exercises maintain or increase BMD in postmenopausal women. Thus, appropriate exercise and sport in accordance with the lifecycle are important strategies for preventing osteoporosis in females.

  3. The effect of GlycoPEGylation on the physical stability of human rFVIIa with increasing calcium chloride concentration

    DEFF Research Database (Denmark)

    Plesner, Bitten; Westh, Peter; Hvidt, Søren


    FVIIa, whereas the concentration of CaCl(2) has to be raised to 100mM in order to see the same effect on the GlycoPEGylated rFVIIa compounds. The temperature of aggregation of rFVIIa, T(agg), increased as the CaCl(2) concentration increased from 35 mM to 100 mM, while T(agg) for the GlycoPEGylated r...

  4. Impregnating Coal With Calcium Carbonate (United States)

    Sharma, Pramod K.; Voecks, Gerald E.; Gavalas, George R.


    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.

  5. Calcium D-saccharate

    DEFF Research Database (Denmark)

    Garcia, André Castilho; Hedegaard, Martina Vavrusova; Skibsted, Leif Horsfelt


    Molar conductivity of saturated aqueous solutions of calcium d-saccharate, used as a stabilizer of beverages fortified with calcium d-gluconate, increases strongly upon dilution, indicating complex formation between calcium and d-saccharate ions, for which, at 25 °C, Kassoc = 1032 ± 80, ΔHassoc......° = -34 ± 6 kJ mol-1, and ΔSassoc° = -55 ± 9 J mol-1 K-1, were determined electrochemically. Calcium d-saccharate is sparingly soluble, with a solubility product, Ksp, of (6.17 ± 0.32) × 10-7 at 25 °C, only moderately increasing with the temperature: ΔHsol° = 48 ± 2 kJ mol-1, and ΔSassoc° = 42 ± 7 J mol-1...... K-1. Equilibria in supersaturated solutions of calcium d-saccharate seem only to adjust slowly, as seen from calcium activity measurements in calcium d-saccharate solutions made supersaturated by cooling. Solutions formed by isothermal dissolution of calcium d-gluconate in aqueous potassium d...

  6. Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice.

    Directory of Open Access Journals (Sweden)

    Ravi S Akundi


    Full Text Available PTEN-induced kinase 1 (PINK1 is linked to recessive Parkinsonism (EOPD. Pink1 deletion results in impaired dopamine (DA release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice.Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS, and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i are upregulated in animals with experimentally induced dopaminergic lesions, (ii regulate innate immune responses and/or apoptosis and (iii promote axonal regeneration and sprouting.Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate

  7. Is Increased Intracellular Calcium in Red Blood Cells a Common Component in the Molecular Mechanism Causing Anemia?

    Directory of Open Access Journals (Sweden)

    Laura Hertz


    Full Text Available For many hereditary disorders, although the underlying genetic mutation may be known, the molecular mechanism leading to hemolytic anemia is still unclear and needs further investigation. Previous studies revealed an increased intracellular Ca2+ in red blood cells (RBCs from patients with sickle cell disease, thalassemia, or Gardos channelopathy. Therefore we analyzed RBCs' Ca2+ content from 35 patients with different types of anemia (16 patients with hereditary spherocytosis, 11 patients with hereditary xerocytosis, 5 patients with enzymopathies, and 3 patients with hemolytic anemia of unknown cause. Intracellular Ca2+ in RBCs was measured by fluorescence microscopy using the fluorescent Ca2+ indicator Fluo-4 and subsequent single cell analysis. We found that in RBCs from patients with hereditary spherocytosis and hereditary xerocytosis the intracellular Ca2+ levels were significantly increased compared to healthy control samples. For enzymopathies and hemolytic anemia of unknown cause the intracellular Ca2+ levels in RBCs were not significantly different. These results lead us to the hypothesis that increased Ca2+ levels in RBCs are a shared component in the mechanism causing an accelerated clearance of RBCs from the blood stream in channelopathies such as hereditary xerocytosis and in diseases involving defects of cytoskeletal components like hereditary spherocytosis. Future drug developments should benefit from targeting Ca2+ entry mediating molecular players leading to better therapies for patients.

  8. The Bcl-2 gene polymorphism rs956572AA increases inositol 1,4,5-trisphosphate receptor-mediated endoplasmic reticulum calcium release in subjects with bipolar disorder. (United States)

    Machado-Vieira, Rodrigo; Pivovarova, Natalia B; Stanika, Ruslan I; Yuan, Peixiong; Wang, Yun; Zhou, Rulun; Zarate, Carlos A; Drevets, Wayne C; Brantner, Christine A; Baum, Amber; Laje, Gonzalo; McMahon, Francis J; Chen, Guang; Du, Jing; Manji, Husseini K; Andrews, S Brian


    Bipolar disorder (BPD) is characterized by altered intracellular calcium (Ca(2+)) homeostasis. Underlying mechanisms involve dysfunctions in endoplasmic reticulum (ER) and mitochondrial Ca(2+) handling, potentially mediated by B-cell lymphoma 2 (Bcl-2), a key protein that regulates Ca(2+) signaling by interacting directly with these organelles, and which has been implicated in the pathophysiology of BPD. Here, we examined the effects of the Bcl-2 gene single nucleotide polymorphism (SNP) rs956572 on intracellular Ca(2+) dynamics in patients with BPD. Live cell fluorescence imaging and electron probe microanalysis were used to measure intracellular and intra-organelle free and total calcium in lymphoblasts from 18 subjects with BPD carrying the AA, AG, or GG variants of the rs956572 SNP. Analyses were carried out under basal conditions and in the presence of agents that affect Ca(2+) dynamics. Compared with GG homozygotes, variant AA-which expresses significantly reduced Bcl-2 messenger RNA and protein-exhibited elevated basal cytosolic Ca(2+) and larger increases in inositol 1,4,5-trisphosphate receptor-mediated cytosolic Ca(2+) elevations, the latter in parallel with enhanced depletion of the ER Ca(2+) pool. The aberrant behavior of AA cells was reversed by chronic lithium treatment and mimicked in variant GG by a Bcl-2 inhibitor. In contrast, no differences between SNP variants were found in ER or mitochondrial total Ca(2+) content or in basal store-operated Ca(2+) entry. These results demonstrate that, in patients with BPD, abnormal Bcl-2 gene expression in the AA variant contributes to dysfunctional Ca(2+) homeostasis through a specific ER inositol 1,4,5-trisphosphate receptor-dependent mechanism. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Calcium addition at the Hubbard Brook Experimental Forest increases sugar storage, antioxidant activity and cold tolerance in native red spruce (Picea rubens). (United States)

    Halman, Joshua M; Schaberg, Paul G; Hawley, Gary J; Eagar, Christopher


    In fall (November 2005) and winter (February 2006), we collected current-year foliage of native red spruce (Picea rubens Sarg.) growing in a reference watershed and in a watershed treated in 1999 with wollastonite (CaSiO(3), a slow-release calcium source) to simulate preindustrial soil calcium concentrations (Ca-addition watershed) at the Hubbard Brook Experimental Forest (Thornton, NH). We analyzed nutrition, soluble sugar concentrations, ascorbate peroxidase (APX) activity and cold tolerance, to evaluate the basis of recent (2003) differences between watersheds in red spruce foliar winter injury. Foliar Ca and total sugar concentrations were significantly higher in trees in the Ca-addition watershed than in trees in the reference watershed during both fall (P=0.037 and 0.035, respectively) and winter (P=0.055 and 0.036, respectively). The Ca-addition treatment significantly increased foliar fructose and glucose concentrations in November (P=0.013 and 0.007, respectively) and foliar sucrose concentrations in winter (P=0.040). Foliar APX activity was similar in trees in both watersheds during fall (P=0.28), but higher in trees in the Ca-addition watershed during winter (P=0.063). Cold tolerance of foliage was significantly greater in trees in the Ca-addition watershed than in trees in the reference watershed (P<0.001). Our results suggest that low foliar sugar concentrations and APX activity, and reduced cold tolerance in trees in the reference watershed contributed to their high vulnerability to winter injury in 2003. Because the reference watershed reflects forest conditions in the region, the consequences of impaired physiological function caused by soil Ca depletion may have widespread implications for forest health.

  10. Increasing the calcium content of mealworms (Tenebrio molitor) to improve their nutritional value for bone mineralization of growing chicks. (United States)

    Klasing, K C; Thacker, P; Lopez, M A; Calvert, C C


    The purpose of these studies was to determine the husbandry variables that optimize the Ca content of mealworms (Tenebrio molitor) and to determine the bioavailability of this Ca for bone mineralization in chicks that consume the mealworms. To determine the optimal level of Ca in the substrates used in short-term (mealworms and to determine the length of time that mealworms should be exposed to high-Ca substrates, mealworms were placed in either a wheat bran or a chicken starter substrate supplemented with 0, 4, 8, or 12% Ca from CaCO3. The mealworms were harvested after 0.5, 1, 2, 3, 4, 7, or 14 days. The Ca content of the mealworms was greatest with the use of chicken starter and increased linearly with the Ca content of the substrate. In general, the Ca content of the mealworms increased during the first 24 hr and decreased after > or = 1 wk, especially at the higher levels of Ca supplementation. The chicken starter also resulted in higher levels of vitamin D in mealworms. Mealworms held in wheat bran with 8% Ca were fed to growing chicks. Ca bioavailability was calculated from the chicks' bone ash. The Ca in these mealworms was 76% as bioavailable as the Ca in oyster shell.

  11. Calcium addition at the Hubbard Brook Experimental Forest increases sugar storage, antioxidant activity and cold tolerance in native red spruce (Picea rubens) (United States)

    Joshua M. Halman; Paul G. Schaberg; Gary J. Hawley; Christopher Eagar


    In fall (November 2005) and winter (February 2006), we collected current-year foliage of native red spruce (Picea rubens Sarg.) growing in a reference watershed and in a watershed treated in 1999 with wollastonite (CaSiO3, a slow-release calcium source) to simulate preindustrial soil calcium concentrations (Ca-addition...

  12. MARCKS Protein Is Phosphorylated and Regulates Calcium Mobilization during Human Acrosomal Exocytosis (United States)

    Rodriguez Peña, Marcelo J.; Castillo Bennett, Jimena V.; Soler, Osvaldo M.; Mayorga, Luis S.; Michaut, Marcela A.


    Acrosomal exocytosis is a calcium-regulated exocytosis that can be triggered by PKC activators. The involvement of PKC in acrosomal exocytosis has not been fully elucidated, and it is unknown if MARCKS, the major substrate for PKC, participates in this exocytosis. Here, we report that MARCKS is expressed in human spermatozoa and localizes to the sperm head and the tail. Calcium- and phorbol ester-triggered acrosomal exocytosis in permeabilized sperm was abrogated by different anti-MARCKS antibodies raised against two different domains, indicating that the protein participates in acrosomal exocytosis. Interestingly, an anti-phosphorylated MARCKS antibody was not able to inhibit secretion. Similar results were obtained using recombinant proteins and phospho-mutants of MARCKS effector domain (ED), indicating that phosphorylation regulates MARCKS function in acrosomal exocytosis. It is known that unphosphorylated MARCKS sequesters PIP2. This phospholipid is the precursor for IP3, which in turn triggers release of calcium from the acrosome during acrosomal exocytosis. We found that PIP2 and adenophostin, a potent IP3-receptor agonist, rescued MARCKS inhibition in permeabilized sperm, suggesting that MARCKS inhibits acrosomal exocytosis by sequestering PIP2 and, indirectly, MARCKS regulates the intracellular calcium mobilization. In non-permeabilized sperm, a permeable peptide of MARCKS ED also inhibited acrosomal exocytosis when stimulated by a natural agonist such as progesterone, and pharmacological inducers such as calcium ionophore and phorbol ester. The preincubation of human sperm with the permeable MARCKS ED abolished the increase in calcium levels caused by progesterone, demonstrating that MARCKS regulates calcium mobilization. In addition, the phosphorylation of MARCKS increased during acrosomal exocytosis stimulated by the same activators. Altogether, these results show that MARCKS is a negative modulator of the acrosomal exocytosis, probably by sequestering

  13. PEG and ABA trigger methyl jasmonate accumulation to induce the MEP pathway and increase tanshinone production in Salvia miltiorrhiza hairy roots. (United States)

    Yang, Dongfeng; Ma, Pengda; Liang, Xiao; Wei, Zheng; Liang, Zongsuo; Liu, Yan; Liu, Fenghua


    Tanshinones, a group of active ingredients in Salvia miltiorrhiza, are derived from at least two biosynthetic pathways, which are the mevalonate (MVA) pathway in the cytosol and the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway in the plastids. Abscisic acid (ABA) and methyl jasmonate (MJ) are two well-known plant hormones induced by water stress. In this study, effects of polyethylene glycol (PEG), ABA and MJ on tanshinone production in S. miltiorrhiza hairy roots were investigated, and the role of MJ in PEG- and ABA-induced tanshinone production was further elucidated. The results showed that tanshinone production was significantly enhanced by treatments with PEG, ABA and MJ. The mRNA levels of 3-hydroxy-3-methylglutaryl co-enzyme A reductase (HMGR), 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) and 1-deoxy-d-xylulose 5-phosphate synthase (DXS), as well as the enzyme activities of HMGR and DXS were stimulated by all three treatments. PEG and ABA triggered MJ accumulation. Effects of PEG and ABA on tanshinone production were completely abolished by the ABA biosynthesis inhibitor [tungstate (TUN)] and the MJ biosynthesis inhibitor [ibuprofen (IBU)], while effects of MJ were almost unaffected by TUN. In addition, MJ-induced tanshinone production was completely abolished by the MEP pathway inhibitor [fosmidomycin (FOS)], but was just partially arrested by the MVA pathway inhibitor [mevinolin (MEV)]. In conclusion, a signal transduction model was proposed that exogenous applications of PEG and ABA triggered endogenous MJ accumulation by activating ABA signaling pathway to stimulate tanshinone production, while exogenous MJ could directly induce tanshinone production mainly via the MEP pathway in S. miltiorrhiza hairy roots. Copyright © Physiologia Plantarum 2012.

  14. Filamin and phospholipase C-ε are required for calcium signaling in the Caenorhabditis elegans spermatheca.

    Directory of Open Access Journals (Sweden)

    Ismar Kovacevic


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

  15. Genetically heterogeneous mice show age-related vision deficits not related to increased rod cell L-type calcium channel function in vivo. (United States)

    Berkowitz, Bruce A; Miller, Richard A; Roberts, Robin


    Visual performance declines over time in humans and 2-18 months outbred Long-Evans (LE) rats; vision is maintained in inbred 2-18 months C57BL/6 (B6) mice. Increased rod L-type calcium channel (LTCC) function predicts visual decline in LE rats but does not occur in B6 mice. Genetic diversity may contribute to rod LTCC function escalation time. To test this hypothesis, 4 and 18 months genetically heterogeneous UM-HET3 mice were studied. Rod LTCC function (manganese-enhanced magnetic resonance imaging [MRI]) and ocular anatomy (MRI, optical coherence tomography) were measured in vivo. Light-evoked subretinal space and choroid thickness changes were measured (diffusion-weighted MRI). Visual performance declined over time in the absence of (1) increased rod LTCC function; (2) changes in light-dependent expansion of the subretinal space and choroidal thickness; and (3) retinal thinning. Aging changed anterior and vitreous chambers' axial length and decreased light-stimulated choroidal expansion. Species differences appear to contribute to the LTCC function differences. Aging-related declines in vision in the UM-HET3 mice deserve more attention than they have received so far. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Less increase of CT-based calcium scores of the coronary arteries. Effect three years after breast-conserving radiotherapy using breath-hold

    Energy Technology Data Exchange (ETDEWEB)

    Mast, M.E.; Kempen-Harteveld, M.L. van; Petoukhova, A.L. [Centre West, Radiotherapy, The Hague (Netherlands); Heijenbrok, M.W. [Medical Center Haaglanden, Department of Radiology, The Hague (Netherlands); Scholten, A.N. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiation Oncology, Amsterdam (Netherlands); Wolterbeek, R. [Leiden University Medical Centre, Department of Medical Statistics and Bioinformatics, Leiden (Netherlands); Schreur, J.H.M. [Medical Center Haaglanden, Department of Cardiology, The Hague (Netherlands); Struikmans, H. [Centre West, Radiotherapy, The Hague (Netherlands); Leiden University Medical Centre, Department of Clinical Oncology, Leiden (Netherlands)


    The aim of this prospective longitudinal study was to compare coronary artery calcium (CAC) scores determined before the start of whole breast irradiation with those determined 3 years afterwards. Changes in CAC scores were analysed in 99 breast cancer patients. Three groups were compared: patients receiving left- and right-sided radiotherapy, and those receiving left-sided radiotherapy with breath-hold. We analysed overall CAC scores and left anterior descending (LAD) and right coronary artery (RCA) CAC scores. Between the three groups, changes of the value of the LAD minus the RCA CAC scores of each individual patient were also compared. Three years after breath-hold-based whole breast irradiation, a less pronounced increase of CAC scores was noted. Furthermore, LAD minus RCA scores in patients treated for left-sided breast cancer without breath-hold were higher when compared to LAD minus RCA scores of patients with right-sided breast cancers and those with left-sided breast cancer treated with breath-hold. Breath-hold in breast-conserving radiotherapy leads to a less pronounced increase of CT-based CAC scores. Therefore, breath-hold probably prevents the development of radiation-induced coronary artery disease. However, the sample size of this study is limited and the follow-up period relatively short. (orig.) [German] Das Ziel dieser prospektiven Langzeitstudie war der Vergleich der Coronary-Artery-Calcium-(CAC-)Werte vor Beginn der Brustbestrahlung mit den Werten nach 3 Jahren. Aenderungen der CAC-Werte wurden bei 99 Brustkrebspatienten analysiert. Drei Gruppen wurden untersucht: Patienten nach links- und rechtsseitiger Strahlentherapie sowie mit Bestrahlung unter Atemanhalt. Wir analysierten die Gesamt-CAC-Werte sowie die CAC-Werte der vorderen linken absteigenden (''left anterior descending'', LAD) und der rechten Koronararterie (''right coronary artery'', RCA). Zwischen den drei Gruppen wurden auch die Veraenderungen

  17. Neocortical GABA release at high intracellular sodium and low extracellular calcium: an anti-seizure mechanism. (United States)

    Rassner, Michael P; Moser, Andreas; Follo, Marie; Joseph, Kevin; van Velthoven-Wurster, Vera; Feuerstein, Thomas J


    In epilepsy, the GABA and glutamate balance may be disrupted and a transient decrease in extracellular calcium occurs before and during a seizure. Flow Cytometry based fluorescence activated particle sorting experiments quantified synaptosomes from human neocortical tissue, from both epileptic and non-epileptic patients (27.7% vs. 36.9% GABAergic synaptosomes, respectively). Transporter-mediated release of GABA in human and rat neocortical synaptosomes was measured using the superfusion technique for the measurement of endogenous GABA. GABA release was evoked by either a sodium channel activator or a sodium/potassium-ATPase inhibitor when exocytosis was possible or prevented, and when the sodium/calcium exchanger was active or inhibited. The transporter-mediated release of GABA is because of elevated intracellular sodium. A reduction in the extracellular calcium increased this release (in both non-epileptic and epileptic, except Rasmussen encephalitis, synaptosomes). The inverse was seen during calcium doubling. In humans, GABA release was not affected by exocytosis inhibition, that is, it was solely transporter-mediated. However, in rat synaptosomes, an increase in GABA release at zero calcium was only exhibited when the exocytosis was prevented. The absence of calcium amplified the sodium/calcium exchanger activity, leading to elevated intracellular sodium, which, together with the stimulation-evoked intracellular sodium increment, enhanced GABA transporter reversal. Sodium/calcium exchange inhibitors diminished GABA release. Thus, an important seizure-induced extracellular calcium reduction might trigger a transporter- and sodium/calcium exchanger-related anti-seizure mechanism by augmenting transporter-mediated GABA release, a mechanism absent in rats. Uniquely, the additional increase in GABA release because of calcium-withdrawal dwindled during the course of illness in Rasmussen encephalitis. Seizures cause high Na(+) influx through action potentials. A

  18. Activation of endogenous c-Src or a related tyrosine kinase by intracellular (pY)EEI peptide increases voltage-operated calcium channel currents in rabbit ear artery cells. (United States)

    Wijetunge, S; Hughes, A D


    The effect of activation of endogenous c-Src tyrosine kinase by (pY)EEI peptide was examined on voltage-operated calcium channel (VOC) currents in arterial smooth muscle cells. In single rabbit ear artery cells intracellular application of (pY)EEI peptide increased calcium channel currents. Inactive, non-phosphorylated YEEI peptide had no effect on currents. Peptide-A, a 21 amino acid inhibitor of c-Src inhibited currents and prevented the effect of (pY)EEI peptide on calcium channel currents. These results indicate that activation of intrinsic c-Src increases VOC and support a role for c-Src in the regulation of VOC in vascular smooth muscle cells.

  19. Calcium-sensing beyond neurotransmitters

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Han, Weiping


    Neurotransmitters, neuropeptides and hormones are released through the regulated exocytosis of SVs (synaptic vesicles) and LDCVs (large dense-core vesicles), a process that is controlled by calcium. Synaptotagmins are a family of type 1 membrane proteins that share a common domain structure. Most....... Also, we discuss potential roles of synaptotagmins in non-traditional endocrine systems....... synaptotagmins are located in brain and endocrine cells, and some of these synaptotagmins bind to phospholipids and calcium at levels that trigger regulated exocytosis of SVs and LDCVs. This led to the proposed synaptotagmin-calcium-sensor paradigm, that is, members of the synaptotagmin family function...... as calcium sensors for the regulated exocytosis of neurotransmitters, neuropeptides and hormones. Here, we provide an overview of the synaptotagmin family, and review the recent mouse genetic studies aimed at understanding the functions of synaptotagmins in neurotransmission and endocrine-hormone secretion...

  20. Supplemental calcium attenuates the colitis-related increase in diarrhea, intestinal permeability, and extracellular matrix breakdown in HLA-B27 transgenic rats.

    NARCIS (Netherlands)

    Schepens, M.A.; Schonewille, A.J.; Vink, C.; Schothorst, E.M. van; Kramer, E.; Hendriks, T.; Brummer, R.J.; Keijer, J.; Meer, R. van der; Bovee-Oudenhoven, I.M.


    We have shown in several controlled rat and human infection studies that dietary calcium improves intestinal resistance and strengthens the mucosal barrier. Reinforcement of gut barrier function may alleviate inflammatory bowel disease (IBD). Therefore, we investigated the effect of supplemental

  1. Supplemental calcium attenuates the Colitis-Related increase in Diarrhea, intestinal Permeability, and Extracellular Matrix Breakdown in HLA-B27 Transgenic Rats

    NARCIS (Netherlands)

    Schepens, M.A.A.; Schonewille, A.J.; Vink, C.; Schothorst, van E.M.; Kramer, E.H.M.; Hendriks, T.; Brummer, R.J.; Keijer, J.; Meer, van der R.; Bovee - Oudenhoven, I.M.J.


    We have shown in several controlled rat and human infection studies that dietary calcium improves intestinal resistance and strengthens the mucosal barrier. Reinforcement of gut barrier function may alleviate inflammatory bowel disease (IBD). Therefore, we investigated the effect of supplemental

  2. The discrimination filters to increase the reliability of EEW association on the location using geometric distribution of triggered stations with upgrading a travel time model. (United States)

    Chi, H. C.; Park, J. H.; Lim, I. S.; Seong, Y. J.


    In operation of Earthquake Early Warning System (EEWS), the alerting criteria are one of the most important parameters in optimizing acceptable warning system. During early stage of testing EEW systems from 2011 to 2013, we adapted ElarmS by UC Berkeley BSL to Korean seismic network and applied very simple criteria for event alerting with the combination of the numbers of station and magnitude. As a result of the testing we found out that the real-time test result of Earthquake Early Warning (EEW) system in Korea showed that all events located within seismic network with bigger than magnitude 3.0 were well detected. However, two events located at sea between land and island gave false results with magnitude over 4.0 related to the teleseismic waves and one event located in land gave false results with magnitude over 3.0 related to the teleseismic waves. These teleseismic-relevant false events were caused by logical co-relation during association procedure and the corresponding geometric distribution of associated stations is crescent-shaped. Seismic stations are not deployed uniformly, so the expected bias ratio varies with evaluated epicentral location. This ratio is calculated in advance and stored into database, called as TrigDB, for the discrimination of teleseismic-origin false alarm. We developed a method, so called 'TrigDB back filling', updating location with supplementary association of stations comparing triggered times between sandwiched stations which was not associated previously based on predefined criteria such as travel-time. Because EEW program assume that all events are local, teleseismic-relevant events can give more triggered stations by using back filling of the unassociated stations than the normal association. And we also developed a travel time curve (K-SEIS-1DTT2015) to reduce split event for EEWS. After applying the K-SEIS-1DTT2015 model, these teleseismic-relevant false events are reduced. As a result of these methods we could get more

  3. Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent. (United States)

    Davis, F M; Azimi, I; Faville, R A; Peters, A A; Jalink, K; Putney, J W; Goodhill, G J; Thompson, E W; Roberts-Thomson, S J; Monteith, G R


    Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)- and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin-like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of

  4. The Trigger System of the CMS Experiment

    CERN Document Server

    Felcini, Marta


    We give an overview of the main features of the CMS trigger and data acquisition (DAQ) system. Then, we illustrate the strategies and trigger configurations (trigger tables) developed for the detector calibration and physics program of the CMS experiment, at start-up of LHC operations, as well as their possible evolution with increasing luminosity. Finally, we discuss the expected CPU time performance of the trigger algorithms and the CPU requirements for the event filter farm at start-up.

  5. High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice. (United States)

    Wang, Yang; Dellatore, Peter; Douard, Veronique; Qin, Ling; Watford, Malcolm; Ferraris, Ronaldo P; Lin, Tiao; Shapses, Sue A


    Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (Pdiet (P<.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia.

    LENUS (Irish Health Repository)


    Cystic Fibrosis (CF) is a genetic disease characterised by a deficit in epithelial Cl(-) secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA(4) is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA(4) are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA(4) produced a rapid and transient increase in intracellular Ca(2+). We have investigated, the effect of LXA(4) on Cl(-) secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA(4) stimulated a rapid intracellular Ca(2+) increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA(4) stimulated whole-cell Cl(-) currents which were inhibited by NPPB (calcium-activated Cl(-) channel inhibitor), BAPTA-AM (chelator of intracellular Ca(2+)) but not by CFTRinh-172 (CFTR inhibitor). We found, using confocal imaging, that LXA(4) increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA(4) effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl(-) secretion. The LXA(4) stimulation of intracellular Ca(2+), whole-cell Cl(-) currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX\\/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA(4) in the stimulation of intracellular Ca(2+) signalling leading to Ca(2+)-activated Cl(-) secretion and enhanced ASL height in non-CF and CF bronchial epithelia.

  7. Oxaliplatin administration increases expression of the voltage-dependent calcium channel α2δ-1 subunit in the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Ken Yamamoto


    Full Text Available Oxaliplatin is a chemotherapeutic agent that is effective against various types of cancer including colorectal cancer. Acute cold hyperalgesia is a serious side effect of oxaliplatin treatment. Although the therapeutic drug pregabalin is beneficial for preventing peripheral neuropathic pain by targeting the voltage-dependent calcium channel α2δ-1 (Cavα2δ-1 subunit, the effect of oxaliplatin-induced acute cold hypersensitivity is uncertain. To analyze the contribution of the Cavα2δ-1 subunit to the development of oxaliplatin-induced acute cold hypersensitivity, Cavα2δ-1 subunit expression in the rat spinal cord was analyzed after oxaliplatin treatment. Behavioral assessment using the acetone spray test showed that 6 mg/kg oxaliplatin-induced cold hypersensitivity 2 and 4 days later. Oxaliplatin-induced acute cold hypersensitivity 4 days after treatment was significantly inhibited by pregabalin (50 mg/kg, p.o.. Oxaliplatin (6 mg/kg, i.p. treatment increased the expression level of Cavα2δ-1 subunit mRNA and protein in the spinal cord 2 and 4 days after treatment. Immunohistochemistry showed that oxaliplatin increased Cavα2δ-1 subunit protein expression in superficial layers of the spinal dorsal horn 2 and 4 days after treatment. These results suggest that oxaliplatin treatment increases Cavα2δ-1 subunit expression in the superficial layers of the spinal cord and may contribute to functional peripheral acute cold hypersensitivity.

  8. Osteoporosis, calcium and physical activity.


    Martin, A. D.; Houston, C S


    Sales of calcium supplements have increased dramatically since 1983, as middle-aged women seek to prevent or treat bone loss due to osteoporosis. However, epidemiologic studies have failed to support the hypothesis that larger amounts of calcium are associated with increased bone density or a decreased incidence of fractures. The authors examine the evidence from controlled trials on the effects of calcium supplementation and physical activity on bone loss and find that weight-bearing activit...

  9. Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry. (United States)

    Jackson, Maria D; Tulloch-Reid, Marshall K; Lindsay, Carole M; Smith, Garrett; Bennett, Franklyn I; McFarlane-Anderson, Norma; Aiken, William; Coard, Kathleen C M


    Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case-control study of men 40-80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00-1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01-1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04-4.43 and OR, 2.47 CI, 1.20-4.90 for tertile 3 (P(trend) = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.


    NARCIS (Netherlands)



    It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free

  11. The effect of supplementation of calcium, vitamin D, boron, and increased fluoride intake on bone mechanical properties and metabolic hormones in rat. (United States)

    Ghanizadeh, G; Babaei, M; Naghii, Mohammad Reza; Mofid, M; Torkaman, G; Hedayati, M


    Evidence indicates that optimal nutrition plays a role in bone formation and maintenance. Besides major components of mineralization such as calcium, phosphorus, and vitamin D, other nutrients like boron and fluoride have beneficial role, too. In this study, 34 male Wistar rats were divided into five groups: control diet, fluoride, fluoride + boron, fluoride + calcium + vitamin D, and fluoride + boron + calcium + vitamin D. Boron equal to 1.23 mg, calcium and vitamin D equal to 210 mg + 55 IU and fluoride equal to 0.7 mg/rat/day was added to their drinking water for 8 weeks. Plasma blood samples and bones were collected. Findings are evidence that fluoride + boron intake revealed significant positive effects on bone mechanical properties and bone metabolic hormones. These findings suggest that combined intake of these two elements has beneficial effects on bone stiffness and breaking strength comparing to even calcium + vitamin D supplementation. This evidence dealing with health problems related to bone and skeletal system in humans should justify further investigation of the role of boron and fluoride with other elements in relation to bone.

  12. Calcium Electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha


    BACKGROUND: Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill...... efficacy-and normal cell sensitivity. METHODS: Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29), a bladder transitional cell carcinoma (SW780......), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). RESULTS: The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p

  13. Effect of calcium, magnesium and sodium ions on in vitro nucleation of human gall bladder bile.


    Neithercut, W D


    The effect of increasing the calcium, magnesium and sodium concentration in gall bladder bile samples from 21 patients with gall stones and nine controls on the in vitro rate of formation of cholesterol microcrystals and numbers of cholesterol microcrystals formed was examined. Addition of these cations to raise the mean maximum concentration of calcium ions to 19.8 mmol/l, of magnesium ions to 20 mmol/l and sodium ions to 998 mmol/l did not trigger nucleation in control bile samples or sampl...

  14. Extracellular and Intracellular Regulation of Calcium Homeostasis

    Directory of Open Access Journals (Sweden)

    Felix Bronner


    Full Text Available An organism with an internal skeleton must accumulate calcium while maintaining body fluids at a well-regulated, constant calcium concentration. Neither calcium absorption nor excretion plays a significant regulatory role. Instead, isoionic calcium uptake and release by bone surfaces causes plasma calcium to be well regulated. Very rapid shape changes of osteoblasts and osteoclasts, in response to hormonal signals, modulate the available bone surfaces so that plasma calcium can increase when more low-affinity bone calcium binding sites are made available and can decrease when more high-affinity binding sites are exposed. The intracellular free calcium concentration of body cells is also regulated, but because cells are bathed by fluids with vastly higher calcium concentration, their major regulatory mechanism is severe entry restriction. All cells have a calcium-sensing receptor that modulates cell function via its response to extracellular calcium. In duodenal cells, the apical calcium entry structure functions as both transporter and a vitamin D–responsive channel. The channel upregulates calcium entry, with intracellular transport mediated by the mobile, vitamin D–dependent buffer, calbindin D9K, which binds and transports more than 90% of the transcellular calcium flux. Fixed intracellular calcium binding sites can, like the body's skeleton, take up and release calcium that has entered the cell, but the principal regulatory tool of the cell is restricted entry.

  15. The Central Trigger Processor (CTP)

    CERN Multimedia

    Franchini, Matteo


    The Central Trigger Processor (CTP) receives trigger information from the calorimeter and muon trigger processors, as well as from other sources of trigger. It makes the Level-1 decision (L1A) based on a trigger menu.

  16. The AMP-Dependent Protein Kinase (AMPK Activator A-769662 Causes Arterial Relaxation by Reducing Cytosolic Free Calcium Independently of an Increase in AMPK Phosphorylation

    Directory of Open Access Journals (Sweden)

    Yi Huang


    Full Text Available Although recent studies reveal that activation of the metabolic and Ca2+ sensor AMPK strongly inhibits smooth muscle contraction, there is a paucity of information about the potential linkage between pharmacological AMPK activation and vascular smooth muscle (VSM contraction regulation. Our aim was to test the general hypothesis that the allosteric AMPK activator A-769662 causes VSM relaxation via inhibition of contractile protein activation, and to specifically determine which activation mechanism(s is(are affected. The ability of A-769662 to cause endothelium-independent relaxation of contractions induced by several contractile stimuli was examined in large and small musculocutaneous and visceral rabbit arteries. For comparison, the structurally dissimilar AMPK activators MET, SIM, and BBR were assessed. A-769662 displayed artery- and agonist-dependent differential inhibitory activities that depended on artery size and location. A-769662 did not increase AMPK-pT172 levels, but did increase phosphorylation of the downstream AMPK substrate, acetyl-CoA carboxylase (ACC. A-769662 did not inhibit basal phosphorylation levels of several contractile protein regulatory proteins, and did not alter the activation state of rhoA. A-769662 did not inhibit Ca2+- and GTPγS-induced contractions in β-escin-permeabilized muscle, suggesting that A-769662 must act by inhibiting Ca2+ signaling. In intact artery, A-769662 immediately reduced basal intracellular free calcium ([Ca2+]i, inhibited a stimulus-induced increase in [Ca2+]i, and inhibited a cyclopiazonic acid (CPA-induced contraction. MET increased AMPK-pT172, and caused neither inhibition of contraction nor inhibition of [Ca2+]i. Together, these data support the hypothesis that the differential inhibition of stimulus-induced arterial contractions by A-769662 was due to selective inhibition of a Ca2+ mobilization pathway, possibly involving CPA-dependent Ca2+ entry via an AMPK-independent pathway. That

  17. Cardiovascular Effects of Calcium Supplements

    Directory of Open Access Journals (Sweden)

    Ian R. Reid


    Full Text Available Calcium supplements reduce bone turnover and slow the rate of bone loss. However, few studies have demonstrated reduced fracture incidence with calcium supplements, and meta-analyses show only a 10% decrease in fractures, which is of borderline statistical and clinical significance. Trials in normal older women and in patients with renal impairment suggest that calcium supplements increase the risk of cardiovascular disease. To further assess their safety, we recently conducted a meta-analysis of trials of calcium supplements, and found a 27%–31% increase in risk of myocardial infarction, and a 12%–20% increase in risk of stroke. These findings are robust because they are based on pre-specified analyses of randomized, placebo-controlled trials and are consistent across the trials. Co-administration of vitamin D with calcium does not lessen these adverse effects. The increased cardiovascular risk with calcium supplements is consistent with epidemiological data relating higher circulating calcium concentrations to cardiovascular disease in normal populations. There are several possible pathophysiological mechanisms for these effects, including effects on vascular calcification, vascular cells, blood coagulation and calcium-sensing receptors. Thus, the non-skeletal risks of calcium supplements appear to outweigh any skeletal benefits, and are they appear to be unnecessary for the efficacy of other osteoporosis treatments.

  18. Calcium metabolism and cardiovascular function after spaceflight (United States)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; hide


    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P parathyroid hormone levels (P animals (P = 0.057). However, mean arterial pressure was elevated (P animals fed low- compared with high-calcium diets (P parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  19. Calcium addition at the Hubbard Brook Experimental Forest increases the capacity for stress tolerance and carbon capture in red spruce (Picea rubens) trees during the cold season (United States)

    Paul G. Schaberg; Rakesh Minocha; Stephanie Long; Joshua M. Halman; Gary J. Hawley; Christopher. Eagar


    Red spruce (Picea rubens Sarg.) trees are uniquely vulnerable to foliar freezing injury during the cold season (fall and winter), but are also capable of photosynthetic activity if temperatures moderate. To evaluate the influence of calcium (Ca) addition on the physiology of red spruce during the cold season, we measured concentrations of foliar...

  20. Body fat loss induced by calcium in co-supplementation with conjugated linoleic acid is associated with increased expression of bone formation genes in adult mice. (United States)

    Chaplin, Alice; Palou, Andreu; Serra, Francisca


    The potential of conjugated linoleic acids (CLA) and calcium in weight management in animal models and human studies has been outlined, as well as their use to prevent bone loss at critical stages. In addition, it has been suggested that bone remodeling and energy metabolism are regulated by shared pathways and involve common hormones such as leptin. We have previously shown that supplementation with CLA and calcium in adult obese mice decreases body weight and body fat. The aim of the present study was to assess the effects of these two compounds on bone and energy metabolism markers on bone. Mice (C57BL/6J) were divided into five groups according to diet and treatment (up to 56 days): control (C), high-fat diet (HF), HF+CLA (CLA), HF+calcium (Ca) and HF with both compounds (CLA+Ca). At the end of treatment, bone formation markers were determined in plasma and expression of selected bone and energy markers was determined in tibia by quantitative polymerase chain reaction. Results show that CLA was associated with decreased tibia weight and minor impact on bone markers, whereas calcium, either alone or co-supplemented with CLA, maintained bone weight and promoted the expression of bone formation genes such as bone gamma-carboxyglutamate protein 2 (Bglap2) and collagen Iα1 (Col1a1). Furthermore, it had a significant effect on key players in energy metabolism, in particular leptin and adiponectin tibia receptors. Overall, in addition to the weight loss promoting properties of calcium, on its own or co-supplemented with CLA, our results support beneficial effects on bone metabolism in mice. Copyright © 2015. Published by Elsevier Inc.

  1. Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension


    Tang, Haiyang; Yamamura, Aya; Yamamura, Hisao; Song, Shanshan; Dustin R Fraidenburg; Chen, Jiwang; Gu, Yali; Pohl, Nicole M.; Zhou, Tong; Jiménez-Pérez, Laura; Ayon, Ramon J.; Desai, Ankit A.; Goltzman, David; Rischard, Franz; Khalpey, Zain


    An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and a critical stimulation for PASMC proliferation and migration. Previously, we demonstrated that expression and function of calcium sensing receptors (CaSR) in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH) and animals with experimental pulmonary hypertension (PH) were greater than in PASMC from normal su...

  2. Familial hypocalciuric hypercalcemia and calcium sensing receptor

    DEFF Research Database (Denmark)

    Mrgan, Monija; Nielsen, Sanne; Brixen, Kim


    Familial hypocalciuric hypercalcemia (FHH) is a lifelong, benign autosomal dominant disease characterized by hypercalcemia, normal to increased parathyroid hormone level, and a relatively low renal calcium excretion. Inactivation of the calcium-sensing receptor in heterozygous patients results in...

  3. Calcium signaling and cell proliferation. (United States)

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


    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Inflammation and lymphopenia trigger autoimmunity by suppression of IL-2-controlled regulatory T cell and increase of IL-21-mediated effector T cell expansion. (United States)

    Chevalier, Nina; Thorburn, Alison N; Macia, Laurence; Tan, Jian; Juglair, Laurent; Yagita, Hideo; Yu, Di; Hansbro, Philip M; Mackay, Charles R


    The dynamic interplay between regulatory T cells (T(regs)) and effector T cells (T(effs)) governs the balance between tolerance and effector immune responses. Perturbations of T(reg) frequency and function or imbalances in T(reg)/T(eff) levels are associated with the development of autoimmunity. The factors that mediate these changes remain poorly understood and were investigated in this study in murine autoimmune arthritis. T(regs) displayed a stable phenotype in arthritic mice and were fully functional in in vitro suppression assays. However, their expansion was delayed relative to T(effs) (T follicular helper cells and Th17 cells) during the early stages of autoimmune reactivity. This imbalance is likely to have led to insufficient T(reg) control of T(effs) and induced autoimmunity. Moreover, a counterregulatory and probably IL-7-driven increase in thymic T(reg) production and recruitment to inflamed tissues was too slow for disease prevention. Increased T(eff) over T(reg) expansion was further aggravated by inflammation and lymphopenia. Both these conditions contribute to autoimmune pathogenesis and were accompanied by decreases in the availability of IL-2 and increases in levels of IL-21. IL-2 neutralization or supplementation was used to show that T(reg) expansion mainly depended on this cytokine. IL-21R(-/-) cells were used to demonstrate that IL-21 promoted the maintenance of T(effs). Thus, at inflammatory sites in experimental arthritis, a deficit in IL-2 hampers T(reg) proliferation, whereas exaggerated IL-21 levels overwhelm T(reg) control by supporting T(eff) expansion. This identifies IL-2 and IL-21 as targets for manipulation in therapies for autoimmunity. Copyright © 2014 by The American Association of Immunologists, Inc.

  5. The ALICE trigger electronics

    CERN Document Server

    Krivda, M; Evans, D; Jones, G T; Jovanovic, P; Jusko, A; Králik, I; Lazzeroni, C; Lietava, R; Scott, H; Sándor, L; Tapia Takaki, D; Urbán, J; Villalobos Baillie, O


    The ALICE trigger system (TRG) consists of a Central Trigger Processor (CTP) and up to 24 Local Trigger Units (LTU) for each sub-detector. The CTP receives and processes trigger signals from trigger detectors and the outputs from the CTP are 3 levels of hardware triggers: L0, L1 and L2. The 24 sub-detectors are dynamically partitioned in up to 6 independent clusters. The trigger information is propagated through the LTUs to the Front-end electronics (FEE) of each sub-detector via LVDS cables and optical fibres. The trigger information sent from LTU to FEE can be monitored online for possible errors using the newly developed TTCit board. After testing and commissioning of the trigger system itself on the surface, the ALICE trigger electronics has been installed and tested in the experimental cavern with appropriate ALICE experimental software. Testing the Alice trigger system with detectors on the surface and in the experimental cavern in parallel is progressing very well. Currently one setup is used for testi...

  6. Triggering trigeminal neuralgia

    DEFF Research Database (Denmark)

    Di Stefano, Giulia; Maarbjerg, Stine; Nurmikko, Turo


    Introduction Although it is widely accepted that facial pain paroxysms triggered by innocuous stimuli constitute a hallmark sign of trigeminal neuralgia, very few studies to date have systematically investigated the role of the triggers involved. In the recently published diagnostic classification...... and where cutaneous and mucosal trigger zones are located. Methods Clinical characteristics focusing on trigger factors were collected from 140 patients with trigeminal neuralgia, in a cross-sectional study design. Results Provocation of paroxysmal pain by various trigger manoeuvres was reported by 136...... of the 140 patients. The most frequent manoeuvres were gentle touching of the face (79%) and talking (54%). Trigger zones were predominantly reported in the perioral and nasal region. Conclusion This study confirms that in trigeminal neuralgia, paroxysmal pain is associated with triggers in virtually all...

  7. Downregulation of TIGAR sensitizes the antitumor effect of physapubenolide through increasing intracellular ROS levels to trigger apoptosis and autophagosome formation in human breast carcinoma cells. (United States)

    Ma, Ting; Zhang, Yi; Zhang, Chao; Luo, Jian-Guang; Kong, Ling-Yi


    Physapubenolide (PB) is a cytotoxic withanolide isolated from Physalis angulata that was used as a traditional Chinese medicine. In this study, we investigated the role of TIGAR and ROS in PB-induced apoptosis and autophagosome formation in human breast carcinoma MDA-MB-231 and MCF-7 cells. PB induced apoptosis by decreasing mitochondrial membrane potential and elevating the Bax/Bcl-2 protein expression ratio in MDA-MB-231 and MCF-7 cells. Caspase inhibitor Z-VAD-FMK treatment partly blocked PB induced cytotoxicity, suggesting that apoptosis serves as an important role in the anti-proliferative effect of PB. Meanwhile, PB induced autophagosome formation, as characterized by increased acridine orange-stained positive cells, accumulation of punctate LC3B fluorescence and a greater number of autophagic vacuoles under electron microscopy. Furthermore, PB inhibited autophagic flux as reflected by the overlapping of mCherry and GFP fluorescence when MDA-MB-231 cells were transfected with GFP-mCherry-LC3 plasmid. Depletion of LC3B, ATG5 or ATG7 reduced PB-induced cytotoxicity, indicating that autophagosome associated cell death participated in the anti-cancer effect of PB. Moreover, PB-induced apoptosis and autophagosome formation were linked to the generation of intracellular ROS, and pre-treatment with the antioxidant NAC obviously mitigated the effects. Interestingly, PB treatment slightly increased TIGAR expression at low concentrations but decreased TIGAR expression drastically at high concentrations. Downregulation of TIGAR by small interfering RNA augmented low concentrations of PB-induced apoptosis and autophagosome formation, which contributed to the observed anti-cancer effect of PB and were reversed by NAC pre-treatment. Consistently, in MDA-MB-231 or MCF-7 xenograft mouse model, PB suppressed tumor growth through ROS induced apoptosis and autophagosome associated cell death accompanied with the downregulation of TIGAR. Taken together, these results indicate

  8. Chronic exposure to chlorpyrifos triggered body weight increase and memory impairment depending on human apoE polymorphisms in a targeted replacement mouse model. (United States)

    Peris-Sampedro, Fiona; Basaure, Pia; Reverte, Ingrid; Cabré, Maria; Domingo, José L; Colomina, Maria Teresa


    Despite restrictions on their use, humans are still constantly exposed to organophosphates (OPs). A huge number of studies have ratified the neurotoxic effects of chlorpyrifos (CPF) and suggested its association with neurodegenerative diseases, but data are still scarce. Human apolipoprotein E (apoE) plays an important role in lipid transport and distribution. In humans, the apoE4 isoform has been linked to an increased risk of Alzheimer's disease (AD). ApoE3 is the most prevalent isoform worldwide, and has been often established as the healthful one. The current study, performed in targeted replacement (TR) adult male mice, aimed to inquire whether genetic variations of the human apoE respond differently to a chronic dietary challenge with CPF. At four/five months of age, mice carrying apoE2, apoE3 or apoE4 were pair-fed a diet supplemented with CPF at 0 or 2mg/kg body weight/day for 13weeks. Cholinergic signs were monitored daily and body weight changes weekly. In the last week of treatment, learning and memory were assessed in a Barnes maze task. Dietary CPF challenge increased body weight only in apoE3 mice. Differences in the acquisition and retention of the Barnes maze were attributed to apoE genetic differences. Our results showed that apoE4 mice performed worse than apoE2 and apoE3 carriers in the acquisition period of the spatial task, and that apoE2 mice had poorer retention than the other two genotypes. On the other hand, CPF increased the search velocity of apoE2 subjects during the acquisition period. Retention was impaired only in CPF-exposed apoE3 mice. These results underline that gene×environment interactions need to be taken into account in epidemiological studies. Given that apoE3, the most common polymorphism in humans, has proved to be the most sensitive to CPF, the potential implications for human health merit serious thought. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Sodium orthovanadate associated with pharmacological doses of ascorbate causes an increased generation of ROS in tumor cells that inhibits proliferation and triggers apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Günther, T-hat nia Mara Fischer; Kviecinski, Maicon Roberto; Baron, Carla Cristine; Felipe, Karina Bettega; Farias, Mirelle Sifroni; Ourique da Silva, Fabiana; Bücker, Nádia Cristina Falcão [Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil); Pich, Claus Tröger [Campus de Araranguá, Universidade Federal de Santa Catarina, Araranguá (Brazil); Ferreira, Eduardo Antonio [Universidade de Brasília, Faculdade de Ceilândia, DF (Brazil); Filho, Danilo Wilhelm [Departamento de Ecologia e Zoologia, Universidade Federal de Santa Catarina, Florianópolis (Brazil); Verrax, Julien; Calderon, Pedro Buc [Toxicology and Cancer Biology Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels (Belgium); Pedrosa, Rozangela Curi, E-mail: [Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil)


    Graphical abstract: -- Abstract: Pharmacological doses of ascorbate were evaluated for its ability to potentiate the toxicity of sodium orthovanadate (Na{sub 3}VO{sub 4}) in tumor cells. Cytotoxicity, inhibition of cell proliferation, generation of ROS and DNA fragmentation were assessed in T24 cells. Na{sub 3}VO{sub 4} was cytotoxic against T24 cells (EC{sub 50} = 5.8 μM at 24 h), but in the presence of ascorbate (100 μM) the EC{sub 50} fell to 3.3 μM. Na{sub 3}VO{sub 4} plus ascorbate caused a strong inhibition of cell proliferation (up to 20%) and increased the generation of ROS (4-fold). Na{sub 3}VO{sub 4} did not directly cleave plasmid DNA, at this aspect no synergism was found occurring between Na{sub 3}VO{sub 4} and ascorbate once the resulting action of the combination was no greater than that of both substances administered separately. Cells from Ehrlich ascites carcinoma-bearing mice were used to determine the activity of antioxidant enzymes, the extent of the oxidative damage and the type of cell death. Na{sub 3}VO{sub 4} alone, or combined with ascorbate, increased catalase activity, but only Na{sub 3}VO{sub 4} plus ascorbate increased superoxide dismutase activity (up to 4-fold). Oxidative damage on proteins and lipids was higher due to the treatment done with Na{sub 3}VO{sub 4} plus ascorbate (2–3-fold). Ascorbate potentiated apoptosis in tumor cells from mice treated with Na{sub 3}VO{sub 4}. The results indicate that pharmacological doses of ascorbate enhance the generation of ROS induced by Na{sub 3}VO{sub 4} in tumor cells causing inhibition of proliferation and apoptosis. Apoptosis induced by orthovanadate and ascorbate is closer related to inhibition on Bcl-xL and activation of Bax. Our data apparently rule out a mechanism of cell demise p53-dependent or related to Cdk2 impairment.

  10. ATLAS Tau Trigger

    CERN Document Server

    Belanger-Champagne, C; Bosman, M; Brenner, R; Casado, MP; Czyczula, Z; Dam, M; Demers, S; Farrington, S; Igonkina, O; Kalinowski, A; Kanaya, N; Osuna, C; Pérez, E; Ptacek, E; Reinsch, A; Saavedra, A; Sopczak, A; Strom, D; Torrence, E; Tsuno, S; Vorwerk, V; Watson, A; Xella, S


    Moving to the high energy scale of the LHC, the identification of tau leptons will become a necessary and very powerful tool, allowing a discovery of physics beyond Standard Model. Many models, among them light SM Higgs and various SUSY models, predict an abundant production of taus with respect to other leptons. The reconstruction of hadronic tau decays, although a very challenging task in hadronic enviroments, allows to increase a signal efficiency by at least of factor 2, and provides an independent control sample to disantangle lepton tau decays from prompt electrons and muons. Thanks to the advanced calorimetry and tracking, the ATLAS experiment has developed tools to efficiently identify hadronic taus at the trigger level. In this presentation we will review the characteristics of taus and the methods to suppress low-multiplicity, low-energy jets contributions as well as we will address the tau trigger chain which provide a rejection rate of 10^5. We will further present plans for commissioning the ATLA...

  11. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to beta-palmitate and increased calcium absorption pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    , the Panel took into account the biological plausibility of the mechanism by which beta-palmitate could exert the claimed effect and that three small human intervention studies in preterm and term infants provided some evidence that a higher degree of palmitic acid in the sn-2 position of formula...... (middle or beta) position of the glycerol backbone. Beta-palmitate is considered to be sufficiently characterised. The claimed effect is “beta palmitate enrichment contributes to increase calcium absorption”. The target population proposed by the applicant is infants from birth to 12 months of age......, including healthy infants consuming follow-on formula, preterm infants and infants needing foods for particular nutritional uses including foods for special medical purposes. The Panel considers that an increase in calcium absorption might be a beneficial physiological effect. In weighing the evidence...

  12. Get Enough Calcium (United States)

    ... Calcium Print This Topic En español Get Enough Calcium Browse Sections The Basics Overview Foods and Vitamins ... women, don't get enough calcium. How much calcium do I need every day? Women: If you ...

  13. Calcium carbonate overdose (United States)

    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 ...

  14. Rate Predictions and Trigger/DAQ Resource Monitoring in ATLAS

    CERN Document Server

    Schaefer, D M; The ATLAS collaboration


    Since starting in 2010, the Large Hadron Collider (LHC) has pro- duced collisions at an ever increasing rate. The ATLAS experiment successfully records the collision data with high eciency and excel- lent data quality. Events are selected using a three-level trigger system, where each level makes a more re ned selection. The level-1 trigger (L1) consists of a custom-designed hardware trigger which seeds two higher software based trigger levels. Over 300 triggers compose a trig- ger menu which selects physics signatures such as electrons, muons, particle jets, etc. Each trigger consumes computing resources of the ATLAS trigger system and oine storage. The LHC instantaneous luminosity conditions, desired physics goals of the collaboration, and the limits of the trigger infrastructure determine the composition of the ATLAS trigger menu. We describe a trigger monitoring frame- work for computing the costs of individual trigger algorithms such as data request rates and CPU consumption. This framework has been used...

  15. Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

    Energy Technology Data Exchange (ETDEWEB)

    Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty; Lin, Yu-Hui; Amani, Mehrnaz; Allali-Hassani, Abdellah; Senisterra, Guillermo; Vedadi, Masoud; Tempel, Wolfram; Mackenzie, Farrell; Chau, Irene; Lourido, Sebastian; Sibley, L. David; Hui, Raymond (Toronto); (WU-MED)


    Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.

  16. Calcium dependent current recordings in Xenopus laevis oocytes in microgravity (United States)

    Wuest, Simon L.; Roesch, Christian; Ille, Fabian; Egli, Marcel


    Mechanical unloading by microgravity (or weightlessness) conditions triggers profound adaptation processes at the cellular and organ levels. Among other mechanisms, mechanosensitive ion channels are thought to play a key role in allowing cells to transduce mechanical forces. Previous experiments performed under microgravity have shown that gravity affects the gating properties of ion channels. Here, a method is described to record a calcium-dependent current in native Xenopus laevis oocytes under microgravity conditions during a parabolic flight. A 3-voltage-step protocol was applied to provoke a calcium-dependent current. This current increased with extracellular calcium concentration and could be reduced by applying extracellular gadolinium. The custom-made ;OoClamp; hardware was validated by comparing the results of the 3-voltage-step protocol to results obtained with a well-established two-electrode voltage clamp (TEVC). In the context of the 2nd Swiss Parabolic Flight Campaign, we tested the OoClamp and the method. The setup and experiment protocol worked well in parabolic flight. A tendency that the calcium-dependent current was smaller under microgravity than under 1 g condition could be observed. However, a conclusive statement was not possible due to the small size of the data base that could be gathered.

  17. Calcium in plant cells

    Directory of Open Access Journals (Sweden)

    V. V. Schwartau


    connect ion conformationally rearranged, thus passing the signal through the chain of intermediaries. The most important function of calcium is its participation in many cell signaling pathways. Channels, pumps, gene expression, synthesis of alkaloids, protective molecules, NO etc. respond to changes in [Ca2+]cyt, while transductors are represented by a number of proteins. The universality of calcium is evident in the study in connection with other signaling systems, such as NO, which is involved in the immune response and is able to control the feedback activity of protein activators channels, producing nitric oxide. Simulation of calcium responses can determine the impact of key level and their regulation, and also depends on the type of stimulus and the effector protein that specifically causes certain changes. Using spatiotemporal modeling, scientists showed that the key components for the formation of Ca2+ bursts are the internal and external surfaces of the nucleus membrane. The research was aimed at understanding of the mechanisms of influence of Ca2+-binding components on Ca2+ oscillations. The simulation suggests the existence of a calcium depot EPR with conjugated lumen of the nucleus which releases its contents to nucleoplasm. With these assumptions, the mathematical model was created and confirmed experimentally. It describes the oscillation of nuclear calcium in root hairs of Medicago truncatula at symbiotic relationship of plants and fungi (rhizobia. Calcium oscillations are present in symbiotic relationships of the cortical layer of plant root cells. Before penetration of bacteria into the cells, slow oscillations of Ca2+ are observed, but with their penetration into the cells the oscillation frequency increases. These processes take place by changing buffer characteristics of the cytoplasm caused by signals from microbes, such as Nod-factor available after penetration of bacteria through the cell wall. Thus, the basic known molecular mechanisms for

  18. Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells

    Directory of Open Access Journals (Sweden)

    János Brunner


    Full Text Available Backpropagating action potentials (bAPs and local calcium signals that they trigger are fundamental for dendritic functions. Here we addressed the question what extent the changes of local dendritic membrane properties can contribute to the shaping of the coupling between dendritic action potentials and the local calcium responses. Using a combination of in vitro electrophysiological and confocal imaging techniques we found that activation of dendritic GIRK channels via mGlu2 or GABAB receptors enhanced the bAP¬-triggered calcium signals in the dendrites of dentate gyrus granule cells (GCs. The enhancement of calcium signals was significant only in those dendritic regions, where these receptors are predominantly expressed. Similarly to GIRK channel activation, somatic hyperpolarization by DC current injection (from -64 mV to -77 mV, significantly increased bAP-associated calcium signals in the proximal dendrites. The hyperpolarization was associated with a decrease in the input resistance due to the rectification of the membrane potential of GCs. The effect of hyperpolarization on the calcium signals was maintained when T-type calcium currents were blocked but it decreased when GIRK channels were inhibited. Simultaneous dual somato-dendritic recordings from GCs showed that somatic hyperpolarization accelerated the repolarization phase of dendritic bAP in the proximal region whereas the rising phase and peak amplitude was not affected. We hypothesize that the larger driving force for calcium ions during the faster repolarization can contribute to the increasing in calcium signals. Employment of previously recorded dendritic bAP waveforms from hyperpolarized membrane potential as voltage command evoked larger calcium currents in nucleated patches compared to bAP waveform from the same recording at depolarized membrane potential. Furthermore, addition of native, high-voltage activated, inactivating potassium conductance by somatic dynamic clamp

  19. Calcium-Induced calcium release during action potential firing in developing inner hair cells. (United States)

    Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J


    In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

  20. Impaired IKs channel activation by Ca(2+)-dependent PKC shows correlation with emotion/arousal-triggered events in LQT1. (United States)

    O-Uchi, Jin; Rice, J Jeremy; Ruwald, Martin H; Parks, Xiaorong Xu; Ronzier, Elsa; Moss, Arthur J; Zareba, Wojciech; Lopes, Coeli M


    The most common inherited cardiac arrhythmia, LQT1, is due to IKs potassium channel mutations and is linked to high risk of adrenergic-triggered cardiac events. We recently showed that although exercise-triggered events are very well treated by ß-blockers for these patients, acute arousal-triggered event rate were not significantly reduced after beta-blocker treatment, suggesting that the mechanisms underlying arousal-triggered arrhythmias may be different from those during exercise. IKs is strongly regulated by β-adrenergic receptor (β-AR) signaling, but little is known about the role of α1-AR-mediated regulation. Here we show, using a combination of cellular electrophysiology and computational modeling, that IKs phosphorylation and α1-AR regulation via activation of calcium-dependent PKC isoforms (cPKC) may be a key mechanism to control channel voltage-dependent activation and consequently action potential duration (APD) in response to adrenergic-stimulus. We show that simulated mutation-specific combined adrenergic effects (β+α) on APD were strongly correlated to acute stress-triggered cardiac event rate for patients while β-AR effects alone were not. We were able to show that calcium-dependent PKC signaling is key to normal QT shortening during acute arousal and when impaired, correlates with increased rate of sudden arousal-triggered cardiac events. Our study suggests that the acute α1-AR-cPKC regulation of IKs is important for QT shortening in "fight-or-flight" response and is linked to decreased risk of sudden emotion/arousal-triggered cardiac events in LQT1 patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Trigger Monitoring at ATLAS

    CERN Document Server

    Sidoti, A; The ATLAS collaboration


    Monitoring the trigger behavior through all the trigger level is of fundamental importance to assess the quality of the data taken, to give fast feedback for the trigger configuration design and to monitor the stability of the HLT farm components. In this paper we will present the online monitoring framework and the various tools available in the ATLAS trigger system going from the ones that build the basic monitoring infrastructure and test the basic functionalities of the system to the more elaborated ones that checks the quality of the data taking looking at physics variables reconstructed online. The early experience in the 2009 cosmics data taking period will also be shown.

  2. Modulation of elementary calcium release mediates a transition from puffs to waves in an IP3R cluster model.

    Directory of Open Access Journals (Sweden)

    Martin Rückl


    Full Text Available The oscillating concentration of intracellular calcium is one of the most important examples for collective dynamics in cell biology. Localized releases of calcium through clusters of inositol 1,4,5-trisphosphate receptor channels constitute elementary signals called calcium puffs. Coupling by diffusing calcium leads to global releases and waves, but the exact mechanism of inter-cluster coupling and triggering of waves is unknown. To elucidate the relation of puffs and waves, we here model a cluster of IP3R channels using a gating scheme with variable non-equilibrium IP3 binding. Hybrid stochastic and deterministic simulations show that puffs are not stereotyped events of constant duration but are sensitive to stimulation strength and residual calcium. For increasing IP3 concentration, the release events become modulated at a timescale of minutes, with repetitive wave-like releases interspersed with several puffs. This modulation is consistent with experimental observations we present, including refractoriness and increase of puff frequency during the inter-wave interval. Our results suggest that waves are established by a random but time-modulated appearance of sustained release events, which have a high potential to trigger and synchronize activity throughout the cell.

  3. Calcium paradox and calcium entry blockers

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Slade, A.M.; Nayler, W.G.; Meijler, F.L.


    Reperfusion of isolated hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). This phenomenon is characterized by an excessive influx of calcium into the cells, the rapid onset of myocardial contracture,

  4. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual (United States)

    Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward


    To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate PTHrP secretion and milk calcium transport with calcium availability. To test this idea genetically, we bred BLG-Cre mice with CaSR-floxed mice to ablate the CaSR specifically from mammary epithelial cells only at the onset of lactation (CaSR-cKO mice). Loss of the CaSR in the lactating mammary gland did not disrupt alveolar differentiation or milk production. However, it did increase the secretion of PTHrP into milk and decreased the transport of calcium from the circulation into milk. CaSR-cKO mice did not show accelerated bone resorption, but they did have a decrease in bone formation. Loss of the mammary gland CaSR resulted in hypercalcemia, decreased PTH secretion, and increased renal calcium excretion in lactating mothers. Finally, loss of the mammary gland CaSR resulted in decreased calcium accrual by suckling neonates, likely due to the combination of increased milk PTHrP and decreased milk calcium. These results demonstrate that the mammary gland CaSR coordinates maternal bone and calcium metabolism, calcium transport into milk, and neonatal calcium accrual during lactation. PMID:23782944

  5. Lessons from (triggered) tremor (United States)

    Gomberg, Joan


    I test a “clock-advance” model that implies triggered tremor is ambient tremor that occurs at a sped-up rate as a result of loading from passing seismic waves. This proposed model predicts that triggering probability is proportional to the product of the ambient tremor rate and a function describing the efficacy of the triggering wave to initiate a tremor event. Using data mostly from Cascadia, I have compared qualitatively a suite of teleseismic waves that did and did not trigger tremor with ambient tremor rates. Many of the observations are consistent with the model if the efficacy of the triggering wave depends on wave amplitude. One triggered tremor observation clearly violates the clock-advance model. The model prediction that larger triggering waves result in larger triggered tremor signals also appears inconsistent with the measurements. I conclude that the tremor source process is a more complex system than that described by the clock-advance model predictions tested. Results of this and previous studies also demonstrate that (1) conditions suitable for tremor generation exist in many tectonic environments, but, within each, only occur at particular spots whose locations change with time; (2) any fluid flow must be restricted to less than a meter; (3) the degree to which delayed failure and secondary triggering occurs is likely insignificant; and 4) both shear and dilatational deformations may trigger tremor. Triggered and ambient tremor rates correlate more strongly with stress than stressing rate, suggesting tremor sources result from time-dependent weakening processes rather than simple Coulomb failure.

  6. Data analysis at Level-1 Trigger level

    CERN Document Server

    Wittmann, Johannes; Aradi, Gregor; Bergauer, Herbert; Jeitler, Manfred; Wulz, Claudia; Apanasevich, Leonard; Winer, Brian; Puigh, Darren Michael


    With ever increasing luminosity at the LHC, optimum online data selection is getting more and more important. While in the case of some experiments (LHCb and ALICE) this task is being completely transferred to computer farms, the others - ATLAS and CMS - will not be able to do this in the medium-term future for technological, detector-related reasons. Therefore, these experiments pursue the complementary approach of migrating more and more of the offline and High-Level Trigger intelligence into the trigger electronics. This paper illustrates how the Level-1 Trigger of the CMS experiment and in particular its concluding stage, the Global Trigger, take up this challenge.

  7. Calcium Balance in Chronic Kidney Disease. (United States)

    Hill Gallant, Kathleen M; Spiegel, David M


    The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

  8. AMY trigger system

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Yoshihide [National Laboratory for High Energy Physics, Tsukuba, Ibaraki (Japan)


    A trigger system of the AMY detector at TRISTAN e{sup +}e{sup -} collider is described briefly. The system uses simple track segment and shower cluster counting scheme to classify events to be triggered. It has been operating successfully since 1987.

  9. Development and Online Opertation of Minimum Bias Triggers in ATLAS

    CERN Document Server

    Martin, T; The ATLAS collaboration


    The design of minimum bias triggers should allow for a highly efficient selection on pp-collisions, while minimising any possible bias in the event selection. In ATLAS two main minimum bias triggers have been developed using complementary technologies. A hardware based first level trigger, consisting of 32 plastic scintillators, has proven to efficienctly select pp-interactions. In particular during the start-up phase this trigger played a crucial role for the commissioning of the central trigger processor and detector sub-systems. A complementary selection is achieved by a multi-level minimum bias trigger, seeded off a random trigger on filled bunches. For the event selection at higher trigger levels a dedicated algorithm was developed, able to cope with around 86 millions of detector signals per bunch-crossing. We will present these trigger systems and their deployment online, highlighting their performance and trigger efficiencies. We outline as well the operation with increasing beam intensities and lumin...

  10. Local calcium elevation and cell elongation initiate guided motility in electrically stimulated osteoblast-like cells.

    Directory of Open Access Journals (Sweden)

    Nurdan Ozkucur

    Full Text Available BACKGROUND: Investigation of the mechanisms of guided cell migration can contribute to our understanding of many crucial biological processes, such as development and regeneration. Endogenous and exogenous direct current electric fields (dcEF are known to induce directional cell migration, however the initial cellular responses to electrical stimulation are poorly understood. Ion fluxes, besides regulating intracellular homeostasis, have been implicated in many biological events, including regeneration. Therefore understanding intracellular ion kinetics during EF-directed cell migration can provide useful information for development and regeneration. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the initial events during migration of two osteogenic cell types, rat calvarial and human SaOS-2 cells, exposed to strong (10-15 V/cm and weak (< or = 5 V/cm dcEFs. Cell elongation and perpendicular orientation to the EF vector occurred in a time- and voltage-dependent manner. Calvarial osteoblasts migrated to the cathode as they formed new filopodia or lamellipodia and reorganized their cytoskeleton on the cathodal side. SaOS-2 cells showed similar responses except towards the anode. Strong dcEFs triggered a rapid increase in intracellular calcium levels, whereas a steady state level of intracellular calcium was observed in weaker fields. Interestingly, we found that dcEF-induced intracellular calcium elevation was initiated with a local rise on opposite sides in calvarial and SaOS-2 cells, which may explain their preferred directionality. In calcium-free conditions, dcEFs induced neither intracellular calcium elevation nor directed migration, indicating an important role for calcium ions. Blocking studies using cadmium chloride revealed that voltage-gated calcium channels (VGCCs are involved in dcEF-induced intracellular calcium elevation. CONCLUSION/SIGNIFICANCE: Taken together, these data form a time scale of the morphological and physiological

  11. Combination of low calcium with Y-27632 rock inhibitor increases the proliferative capacity, expansion potential and lifespan of primary human keratinocytes while retaining their capacity to differentiate into stratified epidermis in a 3D skin model.

    Directory of Open Access Journals (Sweden)

    Xanthe L Strudwick

    Full Text Available Human keratinocytes are difficult to isolate and have a limited lifespan. Traditionally, immortalised keratinocyte cell lines are used in vitro due to their ability to bypass senescence and survive indefinitely. However these cells do not fully retain their ability to differentiate in vitro and they are unable to form a normal stratum corneum in organotypic culture. Here we aimed to generate a pool of phenotypically similar keratinocytes from human donors that could be used in monolayer culture, without a fibroblast feeder layer, and in 3D human skin equivalent models. Primary human neonatal epidermal keratinocytes (HEKn were cultured in low calcium, (0.07 mM media, +/-10 μM Y-27632 ROCK inhibitor (HEKn-CaY. mRNA and protein was extracted and expression of differentiation markers Keratin 14 (K14, Keratin 10 (K10 and Involucrin (Inv assessed by qRT-PCR and Western blotting. The differentiation potential of the HEKn-CaY cultures was assessed by increasing calcium levels and removing the Y-27632 for 72 hrs prior to assessment of K14, K10 and Inv. The ability of the HEKn-CaY, to form a stratified epithelium was assessed using a human skin equivalent (HSE model in the absence of Y-27632. Increased proliferative capacity, expansion potential and lifespan of HEKn was observed with the combination of low calcium and 10 μM ROCK inhibitor Y-27632. The removal of Y-27632 and the addition of high calcium to induce differentiation allowed the cells to behave as primary keratinocytes even after extended serial passaging. Prolonged lifespan HEK-CaYs were capable of forming an organised stratified epidermis in 3D HSE cultures, demonstrating their ability to fully stratify and retain their original, primary characteristics. In conclusion, the use of 0.07 mM Calcium and 10 μM Y-27632 in HEKn monocultures provides the opportunity to culture primary human keratinocytes without a cell feeder layer for extended periods of culture whilst retaining their ability to

  12. Promotion of osteogenic differentiation of stem cells and increase of bone-bonding ability in vivo using urease-treated titanium coated with calcium phosphate and gelatin (United States)

    Huang, Zhong-Ming; Qi, Yi-Ying; Du, Shao-Hua; Feng, Gang; Unuma, Hidero; Yan, Wei-Qi


    Because of its excellent biocompatibility and low allergenicity, titanium has been widely used for bone replacement and tissue engineering. To produce a desirable composite with enhanced bone response and mechanical strength, in this study bioactive calcium phosphate (CaP) and gelatin composites were coated onto titanium (Ti) via a novel urease technique. The cellular responses to the CaP/gelatin/Ti (CaP/gel/Ti) and bone bonding ability were evaluated with proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) on CaP/gel/Ti and CaP/Ti in vitro. The results showed that the optical density values, alkaline phosphatase expression and genes expression of MSCs on CaP/gel/Ti were similar to those on CaP/Ti, yet significantly higher than those on pure Ti (p dental implants.

  13. Application of a ready-to-use calcium ionophore increases rates of fertilization and pregnancy in severe male factor infertility. (United States)

    Ebner, Thomas; Köster, Maria; Shebl, Omar; Moser, Marianne; Van der Ven, Hans; Tews, Gernot; Montag, Markus


    To analyze whether a ready-to-use calcium ionophore improves outcomes, from fertilization to live birth, in patients with severe male factor infertility. Artificial oocyte activation offered to applicable patients over a 20-month period. Specialized in vitro fertilization (IVF) centers in Austria and Germany. Twenty-nine azoospermic and 37 cryptozoospermic men. Mature oocytes treated with a ready-to-use Ca(2+)-ionophore (GM508 Cult-Active) immediately after intracytoplasmic sperm injection (ICSI). Rates of fertilization, implantation, clinical pregnancy, and live birth. Patients had had 88 previous cycles without artificial activation that resulted in a fertilization rate of 34.7%, 79 transfers (89.8%), and 5 pregnancies, which all spontaneously aborted except one. After artificial oocyte activation, the fertilization rate was 56.9%. In terms of fertilization rate, both azoospermic (64.4%) and cryptozoospermic (48.4%) men statistically significantly benefited from use of the ionophore. In 73 transfer cycles, positive β-human chorionic gonadotropin levels were observed in 34 cases (46.6%) and 29 cycles (39.7%) that ended with a clinical pregnancy. The corresponding implantation rate was 33.3%. Four spontaneous abortions occurred (11.8%), and 32 healthy children were born. This is the first prospective multicenter study on artificial oocyte activation in severe male factor infertility. Present data indicate that a ready-to-use calcium ionophore can yield high fertilization and pregnancy rates for this particular subgroup. In addition to fertilization failure after ICSI, severe male factor infertility is an additional area for application of artificial oocyte activation. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism. (United States)

    Ardeshirpour, Laleh; Dumitru, Cristina; Dann, Pamela; Sterpka, John; VanHouten, Joshua; Kim, Wonnam; Kostenuik, Paul; Wysolmerski, John


    Lactation is associated with increased bone turnover and rapid bone loss, which liberates skeletal calcium used for milk production. Previous studies suggested that an increase in the skeletal expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL) coupled with a decrease in osteoprotegerin (OPG) levels likely triggered bone loss during lactation. In this study, we treated lactating mice with recombinant OPG to determine whether bone loss during lactation was dependent on RANKL signaling and whether resorption of the maternal skeleton was required to support milk production. OPG treatment lowered bone resorption rates and completely prevented bone loss during lactation but, surprisingly, did not decrease osteoclast numbers. In contrast, OPG was quite effective at lowering osteoblast numbers and inhibiting bone formation in lactating mice. Furthermore, treatment with OPG during lactation prevented the usual anabolic response associated with reversal of lactational bone loss after weaning. Preventing bone loss had no appreciable effect on milk production, milk calcium levels, or maternal calcium homeostasis when mice were on a standard diet. However, when dietary calcium was restricted, treatment with OPG caused maternal hypocalcemia, maternal death, and decreased milk production. These studies demonstrate that RANKL signaling is a requirement for bone loss during lactation, and suggest that osteoclast activity may be required to increase osteoblast numbers during lactation in preparation for the recovery of bone mass after weaning. These data also demonstrate that maternal bone loss is not absolutely required to supply calcium for milk production unless dietary calcium intake is inadequate.

  15. Coronary Calcium Scan (United States)

    ... Back To Health Topics / Coronary Calcium Scan Coronary Calcium Scan Also known as Calcium Scan Test A coronary calcium scan is a CT scan of your heart that detects and measures the amount of calcium in the walls of your coronary arteries. Overview ...

  16. The ATLAS Muon and Tau Trigger

    CERN Document Server

    Dell'Asta, L; The ATLAS collaboration


    [Muon] The ATLAS experiment at CERN's Large Hadron Collider (LHC) deploys a three-levels processing scheme for the trigger system. The level-1 muon trigger system gets its input from fast muon trigger detectors. Fast sector logic boards select muon candidates, which are passed via an interface board to the central trigger processor and then to the High Level Trigger (HLT). The muon HLT is purely software based and encompasses a level-2 (L2) trigger followed by an event filter (EF) for a staged trigger approach. It has access to the data of the precision muon detectors and other detector elements to refine the muon hypothesis. Trigger-specific algorithms were developed and are used for the L2 to increase processing speed for instance by making use of look-up tables and simpler algorithms, while the EF muon triggers mostly benefit from offline reconstruction software to obtain most precise determination of the track parameters. There are two algorithms with different approaches, namely inside-out and outside-in...

  17. Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy. (United States)

    Krause, M; Keller, J; Beil, B; van Driel, I; Zustin, J; Barvencik, F; Schinke, T; Amling, M


    We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution

  18. Normal and malignant cells exhibit differential responses to calcium electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Krüger, Mie Barthold; Mangalanathan, Uma M.


    Calcium electroporation may offer a simple general tool for anticancer therapy. Transient permeabilization of cancer cell membranes created by applying short, high-voltage pulses in tumors enables high calcium influxes that trigger cell death. In this study, we compared the relative sensitivity...... of different human tumor models and normal tissues to calcium electroporation. Plasma membrane Ca(2+)-ATPase (PMCA) protein expression was confirmed in vitro in all cancer cell lines and normal primary dermal fibroblasts studied. In all tumor types tested in vivo, calcium electroporation effectively induced...... tissue after calcium electroporation but decreased in skin tissue 4 hours after treatment to levels comparable with untreated controls, whereas calcium content endured at high levels in tumor tissue. Mechanistic experiments in vitro indicated that calcium influx was similar in fibroblasts and cancer...

  19. PKA controls calcium influx into motor neurons during a rhythmic behavior.

    Directory of Open Access Journals (Sweden)

    Han Wang

    Full Text Available Cyclic adenosine monophosphate (cAMP has been implicated in the execution of diverse rhythmic behaviors, but how cAMP functions in neurons to generate behavioral outputs remains unclear. During the defecation motor program in C. elegans, a peptide released from the pacemaker (the intestine rhythmically excites the GABAergic neurons that control enteric muscle contractions by activating a G protein-coupled receptor (GPCR signaling pathway that is dependent on cAMP. Here, we show that the C. elegans PKA catalytic subunit, KIN-1, is the sole cAMP target in this pathway and that PKA is essential for enteric muscle contractions. Genetic analysis using cell-specific expression of dominant negative or constitutively active PKA transgenes reveals that knockdown of PKA activity in the GABAergic neurons blocks enteric muscle contractions, whereas constitutive PKA activation restores enteric muscle contractions to mutants defective in the peptidergic signaling pathway. Using real-time, in vivo calcium imaging, we find that PKA activity in the GABAergic neurons is essential for the generation of synaptic calcium transients that drive GABA release. In addition, constitutively active PKA increases the duration of calcium transients and causes ectopic calcium transients that can trigger out-of-phase enteric muscle contractions. Finally, we show that the voltage-gated calcium channels UNC-2 and EGL-19, but not CCA-1 function downstream of PKA to promote enteric muscle contractions and rhythmic calcium influx in the GABAergic neurons. Thus, our results suggest that PKA activates neurons during a rhythmic behavior by promoting presynaptic calcium influx through specific voltage-gated calcium channels.

  20. Osteogenic Differentiation of MSC through Calcium Signaling Activation: Transcriptomics and Functional Analysis.

    Directory of Open Access Journals (Sweden)

    Federica Viti

    Full Text Available The culture of progenitor mesenchymal stem cells (MSC onto osteoconductive materials to induce a proper osteogenic differentiation and mineralized matrix regeneration represents a promising and widely diffused experimental approach for tissue-engineering (TE applications in orthopaedics. Among modern biomaterials, calcium phosphates represent the best bone substitutes, due to their chemical features emulating the mineral phase of bone tissue. Although many studies on stem cells differentiation mechanisms have been performed involving calcium-based scaffolds, results often focus on highlighting production of in vitro bone matrix markers and in vivo tissue ingrowth, while information related to the biomolecular mechanisms involved in the early cellular calcium-mediated differentiation is not well elucidated yet. Genetic programs for osteogenesis have been just partially deciphered, and the description of the different molecules and pathways operative in these differentiations is far from complete, as well as the activity of calcium in this process. The present work aims to shed light on the involvement of extracellular calcium in MSC differentiation: a better understanding of the early stage osteogenic differentiation program of MSC seeded on calcium-based biomaterials is required in order to develop optimal strategies to promote osteogenesis through the use of new generation osteoconductive scaffolds. A wide spectrum of analysis has been performed on time-dependent series: gene expression profiles are obtained from samples (MSC seeded on calcium-based scaffolds, together with related microRNAs expression and in vivo functional validation. On this basis, and relying on literature knowledge, hypotheses are made on the biomolecular players activated by the biomaterial calcium-phosphate component. Interestingly, a key role of miR-138 was highlighted, whose inhibition markedly increases osteogenic differentiation in vitro and enhance ectopic bone

  1. A Closer look at calcium absorption and the benefits and risks of dietary versus supplemental calcium. (United States)

    Booth, Anna; Camacho, Pauline


    To perform a thorough search of the literature on calcium research and specifically address the topic of calcium absorption. PubMed and Ovid were the main engines used for primary literature searches; textbooks, review articles, and book chapters are examples of the other sources used for supplemental information. Regarding calcium absorption, it seems apparent that the absorption efficiency of all calcium salts, regardless of solubility, is fairly equivalent and not significantly less than the absorption efficiency of dietary calcium. However, dietary calcium has been shown to have greater impact in bone building than supplemental calcium. This is likely due to improved absorption with meals and the tendency of people to intake smaller amounts more frequently, which is more ideal for the body's method of absorption. In addition, the cardiovascular risks of excessive calcium intake appear to be more closely related to calcium supplements than dietary calcium; this relationship continues to be controversial in the literature. We conclude that further studies are needed for direct comparison of supplemental and dietary calcium to fully establish if one is superior to the other with regard to improving bone density. We also propose further studies on the cardiovascular risk of long-term increased calcium intake and on physician estimates of patients' daily calcium intake to better pinpoint those patients who require calcium supplementation.

  2. Calcium regulation of muscle contraction. (United States)

    Szent-Györgyi, A G


    Calcium triggers contraction by reaction with regulatory proteins that in the absence of calcium prevent interaction of actin and myosin. Two different regulatory systems are found in different muscles. In actin-linked regulation troponin and tropomyosin regulate actin by blocking sites on actin required for complex formation with myosin; in myosin-linked regulation sites on myosin are blocked in the absence of calcium. The major features of actin control are as follows: there is a requirement for tropomyosin and for a troponin complex having three different subunits with different functions; the actin displays a cooperative behavior; and a movement of tropomyosin occurs controlled by the calcium binding on troponin. Myosin regulation is controlled by a regulatory subunit that can be dissociated in scallop myosin reversibly by removing divalent cations with EDTA. Myosin control can function with pure actin in the absence of tropomyosin. Calcium binding and regulation of molluscan myosins depend on the presence of regulatory light chains. It is proposed that the light chains function by sterically blocking myosin sites in the absence of calcium, and that the "off" state of myosin requires cooperation between the two myosin heads. Both myosin control and actin control are widely distributed in different organisms. Many invertebrates have muscles with both types of regulation. Actin control is absent in the muscles of molluscs and in several minor phyla that lack troponin. Myosin control is not found in striated vertebrate muscles and in the fast muscles of crustacean decapods, although regulatory light chains are present. While in vivo myosin control may not be excluded from vertebrate striated muscles, myosin control may be absent as a result of mutations of the myosin heavy chain.

  3. Anti-Gal IgG potentiates natural killer cell migration across porcine endothelium via endothelial cell activation and increased natural killer cell motility triggered by CD16 cross-linking. (United States)

    Hauzenberger, Elenor; Klominek, Julius; Holgersson, Jan


    Xenoreactive antibodies (Ab) are important for the development of acute vascular rejection (AVR) of xenografts characterized by monocytes, natural killer (NK) cells and neutrophils infiltrating the graft. The mechanisms by which anti-galactose alpha 1,3galactose (alpha-Gal) IgG influence NK cell migration across porcine aortic endothelium (PAEC) were investigated. NK cell migration across PAEC increased in the presence of anti-alpha-Gal IgG. Anti-alpha-Gal IgG exposure activated PAEC as shown by an increased expression of CD62E and CD106. NK cells adhered, spread and showed motile forms on plastic surfaces coated with human IgG, IgG Fc and on mAb against CD16, but not on mouse IgG or BSA, suggesting that CD16 cross-linking can mediate increased adhesiveness. Increased NK cell motility was observed on Boyden filters coated with human IgG, IgG Fc, and mAb against CD16 and the alpha 4, alpha 5, alpha L, beta 1 and beta 2 integrin chains. No motile response was seen on mouse IgGor CD7, CD56 and alpha 6 integrin mAb. NK cell migration on human IgG and anti-CD16 Ab was blocked by anti-CD16 or anti-beta 2, but not anti-beta 1 Ab, implying that the motile response triggered by CD16 cross-linking is mediated via beta 2 integrins. Preformed or induced anti-alpha-Gal IgG may therefore contribute to AVR by stimulating innate immune cell infiltration of the graft.

  4. Calcium source (image) (United States)

    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 ...

  5. Calcium and bones (image) (United States)

    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 ...

  6. Calcium hydroxide poisoning (United States)

    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 ...

  7. Calcium Pyrophosphate Deposition (CPPD) (United States)

    ... Patient / Caregiver Diseases & Conditions Calcium Pyrophosphate Deposition (CPPD) Calcium Pyrophosphate Deposition (CPPD) Fast Facts The risk of ... young people, too. Proper diagnosis depends on detecting calcium pyrophosphate crystals in the fluid of an affected ...

  8. Calcium blood test (United States)

    ... page: // Calcium blood test To use the sharing features on this page, please enable JavaScript. The calcium blood test measures the level of calcium in the blood. ...

  9. The ATLAS Trigger System

    CERN Document Server

    Hauser, R


    ATLAS is one of two general-purpose detectors at the next generation proton-proton collider, the LHC. The high rate of interactions and the large number of read-out channels make the trigger system for ATLAS a challenging task. The initial bunch crossing rate of 40~MHz has to be reduced to about 200 Hz while preserving the physics signals against a large background. ATLAS uses a three-level trigger system, with the first level implemented in custom hardware, while the high level trigger systems are implemented in software on commodity hardware. This note describes the physics motivation, the various selection strategies for different channels as well as the physical implementation of the trigger system.

  10. Trigger Finger (Stenosing Tenosynovitis) (United States)

    ... the fingers glide easily with the help of pulleys. These pulleys hold the tendons close to the bone. This ... rod (Figure 1). Trigger finger occurs when the pulley becomes too thick, so the tendon cannot glide ...

  11. Calo trigger acquisition system

    CERN Multimedia

    Franchini, Matteo


    Calo trigger acquisition system - Evolution of the acquisition system from a multiple boards system (upper, orange cables) to a single board one (below, light blue cables) where all the channels are collected in a single board.

  12. Asthma Triggers: Gain Control (United States)

    ... asthma. Dogs, cats, rodents (including hamsters and guinea pigs) and other warm-blooded mammals can trigger asthma ... Page Contact Us to ask a question, provide feedback, or report a problem. Asthma Indoor Air Quality ...

  13. 2017 Tau Trigger Efficiencies

    CERN Document Server

    CMS Collaboration


    Triggers selecting events with hadronically decaying $\\tau$ leptons ($\\tau_h$) are used in a wide variety of CMS analyses, in particular those targeting processes with a $H \\rightarrow \\tau\\tau$ decay. The performance of the $\\tau_h$ triggers is presented for data collected in 2017, corresponding to an integrated luminosity of 41.5\\,fb$^{-1}$ at 13 TeV, and compared with simulation.

  14. The ATLAS Trigger System

    CERN Document Server

    Owen, Rhys Edward; The ATLAS collaboration


    The ATLAS experiment employs a complex trigger system to enable the collaborations physics program. The LHC is now well in to its second running period delivering proton proton collisions at $\\sqrt{s}=13$ TeV with high instantaneous luminosity. This talk will describe the two level hardware and software trigger used to select events in this environment including recent improvements and the latest performance results.

  15. LHCb Topological Trigger Reoptimization

    CERN Document Server

    INSPIRE-00400931; Ilten, Philip; Khairullin, Egor; Rogozhnikov, Alex; Ustyuzhanin, Andrey; Williams, Michael


    The main b-physics trigger algorithm used by the LHCb experiment is the so-called topological trigger. The topological trigger selects vertices which are a) detached from the primary proton-proton collision and b) compatible with coming from the decay of a b-hadron. In the LHC Run 1, this trigger, which utilized a custom boosted decision tree algorithm, selected a nearly 100% pure sample of b-hadrons with a typical efficiency of 60-70%; its output was used in about 60% of LHCb papers. This talk presents studies carried out to optimize the topological trigger for LHC Run 2. In particular, we have carried out a detailed comparison of various machine learning classifier algorithms, e.g., AdaBoost, MatrixNet and neural networks. The topological trigger algorithm is designed to select all "interesting" decays of b-hadrons, but cannot be trained on every such decay. Studies have therefore been performed to determine how to optimize the performance of the classification algorithm on decays not used in the training. ...

  16. Topological Trigger Developments

    CERN Multimedia

    Likhomanenko, Tatiana


    The main b-physics trigger algorithm used by the LHCb experiment is the so-called topological trigger. The topological trigger selects vertices which are a) detached from the primary proton-proton collision and b) compatible with coming from the decay of a b-hadron. In the LHC Run 1, this trigger utilized a custom boosted decision tree algorithm, selected an almost 100% pure sample of b-hadrons with a typical efficiency of 60-70%, and its output was used in about 60% of LHCb papers. This talk presents studies carried out to optimize the topological trigger for LHC Run 2. In particular, we have carried out a detailed comparison of various machine learning classifier algorithms, e.g., AdaBoost, MatrixNet and uBoost. The topological trigger algorithm is designed to select all "interesting" decays of b-hadrons, but cannot be trained on every such decay. Studies have therefore been performed to determine how to optimize the performance of the classification algorithm on decays not used in the training. These inclu...

  17. Short communication: Urinary oxalate and calcium excretion by dogs and cats diagnosed with calcium oxalate urolithiasis

    NARCIS (Netherlands)

    Dijcker, J.C.; Kummeling, A.; Hagen-Plantinga, E.A.; Hendriks, W.H.


    Introduction Urine concentrations of oxalate and calcium play an important role in calcium oxalate (CaOx) urolith formation in dogs and cats, with high excretions of both substances increasing the chance of CaOx urolithiasis. In 17 CaOx-forming dogs, urine calcium:creatinine ratio (Ca:Cr) was found

  18. Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2, with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed. (United States)

    Tomalin, Lewis Elwood; Day, Alison Michelle; Underwood, Zoe Elizabeth; Smith, Graham Robert; Dalle Pezze, Piero; Rallis, Charalampos; Patel, Waseema; Dickinson, Bryan Craig; Bähler, Jürg; Brewer, Thomas Francis; Chang, Christopher Joh-Leung; Shanley, Daryl Pierson; Veal, Elizabeth Ann


    Reactive oxygen species, such as H2O2, can damage cells but also promote fundamental processes, including growth, differentiation and migration. The mechanisms allowing cells to differentially respond to toxic or signaling H2O2 levels are poorly defined. Here we reveal that increasing external H2O2 produces a bi-phasic response in intracellular H2O2. Peroxiredoxins (Prx) are abundant peroxidases which protect against genome instability, ageing and cancer. We have developed a dynamic model simulating in vivo changes in Prx oxidation. Remarkably, we show that the thioredoxin peroxidase activity of Prx does not provide any significant protection against external rises in H2O2. Instead, our model and experimental data are consistent with low levels of extracellular H2O2 being efficiently buffered by other thioredoxin-dependent activities, including H2O2-reactive cysteines in the thiol-proteome. We show that when extracellular H2O2 levels overwhelm this buffering capacity, the consequent rise in intracellular H2O2 triggers hyperoxidation of Prx to thioredoxin-resistant, peroxidase-inactive form/s. Accordingly, Prx hyperoxidation signals that H2O2 defenses are breached, diverting thioredoxin to repair damage. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input. (United States)

    Kalil, Bruna; Ribeiro, Aline B; Leite, Cristiane M; Uchôa, Ernane T; Carolino, Ruither O; Cardoso, Thais S R; Elias, Lucila L K; Rodrigues, José A; Plant, Tony M; Poletini, Maristela O; Anselmo-Franci, Janete A


    In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

  20. Effect of Tetrodotoxin from Crude Puffer Fish (Tetraodon fluviatilis Liver Extract on Intracellular Calcium Level and Apoptosis of HeLa Cell Culture

    Directory of Open Access Journals (Sweden)

    Natanael Untario


    Full Text Available Cervical cancer is the third most commonly diagnosed cancer and fourth leading cause of women death with 8% of total death caused by cancer in women in 2008. Tetrodotoxin (TTX is a potent neurotoxin found in inner organs puffer fish, with the specific mechanism of sodium channel blocking, and widely used for research purposes. Previous reports claimed that TTX has the capability of inhibiting the metastatic process of cancer and apoptotic effect. Studies also show that apoptosis is a process involving the increase of intracellular calcium level, yet the connection between TTX and increase of intracellular calcium level, therefore triggering apoptosis, has not been established. This is an experimental study with post test only control group design, carried out by exposing HeLa cell culture to a crude liver extract of a puffer fish species, Tetraodon fluviatilis. Crude puffer fish liver extract is administered into HeLa cell culture well in different concentrations 10-4, 10-2, and 10-1. Intracellular calcium level and apoptosis were then measured after 18 hours of incubation. Measurements of intracellular calcium level were done by using CLSM with Fura-2AM staining, and apoptosis by using flowcytometry with Annexin V/PI.  The result shows that there is a significant difference between samples both in intracellular calcium (p < 0.05 and apoptosis (p < 0,05. Both intracellular calcium and apoptosis levels are proportional to liver fish extract concentration. Pearson’s correlation test shows correlation between treatment and intracellular calcium levels (p = 0.000, between treatment and apoptosis (p = 0.002, but not between intracellular calcium and apoptosis (p = 0.05. These results suggest that TTX induces an increase in intracellular calcium level and apoptosis, but calcium pathway is not the sole cause of the apoptosis.

  1. The LHCb trigger in Run II

    CERN Document Server

    Michielin, Emanuele


    The LHCb trigger system has been upgraded to allow alignment, calibration and physics analysis to be performed in real time. An increased CPU capacity and improvements in the software have allowed lifetime unbiased selections of beauty and charm decays in the high level trigger. Thanks to offline quality event reconstruction already available online, physics analyses can be performed directly on this information and for the majority of charm physics selections a reduced event format can be written out. Beauty hadron decays are more efficiently triggered by re-optimised inclusive selections, and the HLT2 output event rate is increased by a factor of three.

  2. ATLAS FTK: Fast Track Trigger

    CERN Document Server

    Volpi, Guido; The ATLAS collaboration


    An overview of the ATLAS Fast Tracker processor is presented, reporting the design of the system, its expected performance, and the integration status. The next LHC runs, with a significant increase in instantaneous luminosity, will provide a big challenge to the trigger and data acquisition systems of all the experiments. An intensive use of the tracking information at the trigger level will be important to keep high efficiency in interesting events, despite the increase in multiple p-p collisions per bunch crossing (pile-up). In order to increase the use of tracks within the High Level Trigger (HLT), the ATLAS experiment planned the installation of an hardware processor dedicated to tracking: the Fast TracKer (FTK) processor. The FTK is designed to perform full scan track reconstruction at every Level-1 accept. To achieve this goal, the FTK uses a fully parallel architecture, with algorithms designed to exploit the computing power of custom VLSI chips, the Associative Memory, as well as modern FPGAs. The FT...

  3. Nonlinear dynamical triggering of slow slip

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Paul A [Los Alamos National Laboratory; Knuth, Matthew W [WISCONSIN; Kaproth, Bryan M [PENN STATE; Carpenter, Brett [PENN STATE; Guyer, Robert A [Los Alamos National Laboratory; Le Bas, Pierre - Yves [Los Alamos National Laboratory; Daub, Eric G [Los Alamos National Laboratory; Marone, Chris [PENN STATE


    Among the most fascinating, recent discoveries in seismology have been the phenomena of triggered slip, including triggered earthquakes and triggered-tremor, as well as triggered slow, silent-slip during which no seismic energy is radiated. Because fault nucleation depths cannot be probed directly, the physical regimes in which these phenomena occur are poorly understood. Thus determining physical properties that control diverse types of triggered fault sliding and what frictional constitutive laws govern triggered faulting variability is challenging. We are characterizing the physical controls of triggered faulting with the goal of developing constitutive relations by conducting laboratory and numerical modeling experiments in sheared granular media at varying load conditions. In order to simulate granular fault zone gouge in the laboratory, glass beads are sheared in a double-direct configuration under constant normal stress, while subject to transient perturbation by acoustic waves. We find that triggered, slow, silent-slip occurs at very small confining loads ({approx}1-3 MPa) that are smaller than those where dynamic earthquake triggering takes place (4-7 MPa), and that triggered slow-slip is associated with bursts of LFE-like acoustic emission. Experimental evidence suggests that the nonlinear dynamical response of the gouge material induced by dynamic waves may be responsible for the triggered slip behavior: the slip-duration, stress-drop and along-strike slip displacement are proportional to the triggering wave amplitude. Further, we observe a shear-modulus decrease corresponding to dynamic-wave triggering relative to the shear modulus of stick-slips. Modulus decrease in response to dynamical wave amplitudes of roughly a microstrain and above is a hallmark of elastic nonlinear behavior. We believe that the dynamical waves increase the material non-affine elastic deformation during shearing, simultaneously leading to instability and slow-slip. The inferred

  4. The ATLAS Level-1 Topological Trigger Performance

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00371751; The ATLAS collaboration


    The LHC will collide protons in the ATLAS detector with increasing luminosity through 2016, placing stringent operational and physical requirements to the ATLAS trigger system in order to reduce the 40 MHz collision rate to a manageable event storage rate of 1 kHz, while not rejecting interesting physics events. The Level-1 trigger is the first rate-reducing step in the ATLAS trigger system with an output rate of 100 kHz and decision latency smaller than 2.5 μs. It consists of a calorimeter trigger, muon trigger and a central trigger processor. During the LHC shutdown after the Run 1 finished in 2013, the Level-1 trigger system was upgraded including hardware, firmware and software updates. In particular, new electronics modules were introduced in the real-time data processing path: the Topological Processor System (L1Topo). It consists of a single AdvancedCTA shelf equipped with two Level-1 topological processor blades. They receive real-time information from the Level-1 calorimeter and muon triggers, which...

  5. The Run-2 ATLAS Trigger System

    CERN Document Server

    Shaw, Savanna Marie; The ATLAS collaboration


    The ATLAS trigger has been successfully collecting collision data during the first run of the LHC between 2009-2013 at a centre-of-mass energy between 900 GeV and 8 TeV. The trigger system consists of a hardware Level-1 (L1) and a software based high-level trigger (HLT) that reduces the event rate from the design bunch-crossing rate of 40 MHz to an average recording rate of a few hundred Hz. In Run-2, the LHC will operate at centre-of-mass energies of 13 and 14 TeV resulting in roughly five times higher trigger rates. We will briefly review the ATLAS trigger system upgrades that were implemented during the shutdown, allowing us to cope with the increased trigger rates while maintaining or even improving our efficiency to select relevant physics processes. This includes changes to the L1 calorimeter and muon trigger systems, the introduction of a new L1 topological trigger module and the merging of the previously two-level HLT system into a single event filter farm. At hand of a few examples, we will show the ...

  6. Duodenal active calcium transport in female rats increases with serum calcitriol concentrations, but reaches a plateau far below maximal calcitriol levels. (United States)

    Boass, A; Toverud, S U


    To determine the relationship between serum calcitriol concentration and duodenal active calcium (Ca) transport, a wide range of circulating calcitriol concentrations (18-950 pg/ml) was obtained by feeding nonmated, lactating, and weaned rats vitamin D-sufficient diets containing 0.04, 0.06, 0.1, or 0.4% Ca. Ca transport was measured in vitro with the everted gut sac technique using both the proximal (D-1) and distal (D-2) duodenal halves. The ratio of serosal [Ca]/mucosal [Ca] (S/M) as well as the amount of Ca transported was calculated. The S/M ratio correlated with the serum calcitriol concentration over the range 18-90 pg/ml with slopes for the regression lines of 0.066 +/- 0.010 (R2 = 0.64, n = 27) for D-1 and of 0.036 +/- 0.005 (R2 = 0.73, n = 24) for D-2. The regression lines are significantly different from zero (p transported per 10 cm per hour revealed a pattern similar to that of the S/M ratio. When net Ca absorption was determined from balance studies over 4 days for rats on a 0.04% Ca diet, maximal absorption (mg/day) was already observed at a serum calcitriol concentration of 60-70 pg/ml (n = 14). We conclude that active Ca transport correlates with serum calcitriol concentrations, but that the transport capacity quickly reaches a maximal value, which is maintained over a 10-fold higher range of serum calcitriol concentrations.

  7. Calcium dobesilate: pharmacology and future approaches. (United States)

    Tejerina, T; Ruiz, E


    1. Calcium dobesilate (2,5-dihydroxybenzene sulfonate) is a drug commonly used in the treatment of diabetic retinopathy and chronic venous insufficiency. 2. The pharmacology of calcium dobesilate reveals its ability to decrease capillary permeability, as well as platelet aggregation and blood viscosity. 3. Furthermore, recent data show that calcium dobesilate increases endothelium-dependent relaxation owing to an increase in nitric oxide synthesis.

  8. Calcium signaling in synapse-to-nucleus communication. (United States)

    Hagenston, Anna M; Bading, Hilmar


    Changes in the intracellular concentration of calcium ions in neurons are involved in neurite growth, development, and remodeling, regulation of neuronal excitability, increases and decreases in the strength of synaptic connections, and the activation of survival and programmed cell death pathways. An important aspect of the signals that trigger these processes is that they are frequently initiated in the form of glutamatergic neurotransmission within dendritic trees, while their completion involves specific changes in the patterns of genes expressed within neuronal nuclei. Accordingly, two prominent aims of research concerned with calcium signaling in neurons are determination of the mechanisms governing information conveyance between synapse and nucleus, and discovery of the rules dictating translation of specific patterns of inputs into appropriate and specific transcriptional responses. In this article, we present an overview of the avenues by which glutamatergic excitation of dendrites may be communicated to the neuronal nucleus and the primary calcium-dependent signaling pathways by which synaptic activity can invoke changes in neuronal gene expression programs.

  9. Hardware, firmware and software developments for the upgrade of the ATLAS Level-1 Central Trigger Processor

    CERN Document Server

    Ghibaudi, M; The ATLAS collaboration; Spiwoks, R; Anders, G; Bertelsen, H; Boisen, A; Childers, T; Dam, M; Ellis, N; Farthouat, P; Gabaldon Ruiz, C; Gorini, B; Kaneda, M; Ohm, C; Silva Oliveira, M; Pauly, T; Pottgen, R; Schmieden, K; Xella, S


    The Central Trigger Processor (CTP) is the final stage of the ATLAS first level trigger system which reduces the collision rate of 40 MHz to a Level-1 event rate of 100 kHz. An upgrade of the CTP is currently underway to significantly increase the number of trigger inputs and trigger combinations, allowing additional flexibility for the trigger menu.\

  10. Calcium Supplements: A Risk Factor for Heart Attack? (United States)

    ... factor for heart attack? I've read that calcium supplements may increase the risk of heart attack. ... D. Some doctors think it's possible that taking calcium supplements may increase your risk of a heart ...

  11. CMS Trigger Performance

    CERN Document Server

    Donato, Silvio


    During its second run of operation (Run 2) which started in 2015, the LHC will deliver a peak instantaneous luminosity that may reach $2 \\cdot 10^{34}$ cm$^{-2}$s$^{-1}$ with an average pile-up of about 55, far larger than the design value. Under these conditions, the online event selection is a very challenging task. In CMS, it is realized by a two-level trigger system the Level-1 (L1) Trigger, implemented in custom-designed electronics, and the High Level Trigger (HLT), a streamlined version of the offline reconstruction software running on a computer farm. In order to face this challenge, the L1 trigger has been through a major upgrade compared to Run 1, whereby all electronic boards of the system have been replaced, allowing more sophisticated algorithms to be run online. Its last stage, the global trigger, is now able to perform complex selections and to compute high-level quantities, like invariant masses. Likewise, the algorithms that run in the HLT go through big improvements; in particular, new appr...

  12. The CMS trigger system (United States)

    Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Knünz, V.; König, A.; Krammer, M.; Krätschmer, I.; Liko, D.; Matsushita, T.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Strauss, J.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Knutsson, A.; Lauwers, J.; Luyckx, S.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; Daci, N.; De Bruyn, I.; Deroover, K.; Heracleous, N.; Keaveney, J.; Lowette, S.; Moreels, L.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Van Parijs, I.; Barria, P.; Brun, H.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Fasanella, G.; Favart, L.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Léonard, A.; Maerschalk, T.; Marinov, A.; Perniè, L.; Randle-conde, A.; Reis, T.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Yonamine, R.; Zenoni, F.; Zhang, F.; Beernaert, K.; Benucci, L.; Cimmino, A.; Crucy, S.; Dobur, D.; Fagot, A.; Garcia, G.; Gul, M.; Mccartin, J.; Ocampo Rios, A. A.; Poyraz, D.; Ryckbosch, D.; Salva, S.; Sigamani, M.; Strobbe, N.; Tytgat, M.; Van Driessche, W.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Beluffi, C.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; Ceard, L.; Da Silveira, G. G.; Delaere, C.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Jafari, A.; Jez, P.; Komm, M.; Lemaitre, V.; Mertens, A.; Musich, M.; Nuttens, C.; Perrini, L.; Pin, A.; Piotrzkowski, K.; Popov, A.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Beliy, N.; Hammad, G. H.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hamer, M.; Hensel, C.; Mora Herrera, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Damiao, D. De Jesus; De Oliveira Martins, C.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; De Souza Santos, A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Moon, C. S.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Cheng, T.; Du, R.; Jiang, C. H.; Plestina, R.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Zhang, H.; Asawatangtrakuldee, C.; Ban, Y.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Micanovic, S.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Bodlak, M.; Finger, M.; Finger, M., Jr.; Assran, Y.; El Sawy, M.; Elgammal, S.; Ellithi Kamel, A.; Mahmoud, M. A.; Calpas, B.; Kadastik, M.; Murumaa, M.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Peltola, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Machet, M.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Zghiche, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Chapon, E.; Charlot, C.; Dahms, T.; Davignon, O.; Filipovic, N.; Florent, A.; Granier de Cassagnac, R.; Lisniak, S.; Mastrolorenzo, L.; Miné, P.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Le Bihan, A.-C.; Merlin, J. A.; Skovpen, K.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Bouvier, E.; Carrillo Montoya, C. A.; Chierici, R.; Contardo, D.; Courbon, B.; Depasse, P.; El Mamouni, H.; Fan, J.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Ruiz Alvarez, J. D.; Sabes, D.; Sgandurra, L.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Toriashvili, T.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Edelhoff, M.; Feld, L.; Heister, A.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Ostapchuk, A.; Preuten, M.; Raupach, F.; Schael, S.; Schulte, J. F.; Verlage, T.; Weber, H.; Wittmer, B.; Zhukov, V.; Ata, M.; Brodski, M.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Klingebiel, D.; Knutzen, S.; Kreuzer, P.; Merschmeyer, M.; Meyer, A.; Millet, P.; Olschewski, M.; Padeken, K.; Papacz, P.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Hoehle, F.; Kargoll, B.; Kress, T.; Kuessel, Y.; Künsken, A.; Lingemann, J.; Nehrkorn, A.; Nowack, A.; Nugent, I. M.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Asin, I.; Bartosik, N.; Behnke, O.; Behrens, U.; Bell, A. J.; Borras, K.; Burgmeier, A.; Campbell, A.; Choudhury, S.; Costanza, F.; Diez Pardos, C.; Dolinska, G.; Dooling, S.; Dorland, T.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Flucke, G.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Gunnellini, P.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Karacheban, O.; Kasemann, M.; Katsas, P.; Kieseler, J.; Kleinwort, C.; Korol, I.; Lange, W.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Mankel, R.; Marfin, I.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Naumann-Emme, S.; Nayak, A.; Ntomari, E.; Perrey, H.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Roland, B.; Sahin, M. Ö.; Saxena, P.; Schoerner-Sadenius, T.; Schröder, M.; Seitz, C.; Spannagel, S.; Trippkewitz, K. D.; Walsh, R.; Wissing, C.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Erfle, J.; Garutti, E.; Goebel, K.; Gonzalez, D.; Görner, M.; Haller, J.; Hoffmann, M.; Höing, R. S.; Junkes, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Lapsien, T.; Lenz, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Nowatschin, D.; Ott, J.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Pietsch, N.; Poehlsen, J.; Rathjens, D.; Sander, C.; Scharf, C.; Schettler, H.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Schwandt, J.; Sola, V.; Stadie, H.; Steinbrück, G.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baus, C.; Berger, J.; Böser, C.; Butz, E.; Chwalek, T.; Colombo, F.; De Boer, W.; Descroix, A.; Dierlamm, A.; Fink, S.; Frensch, F.; Friese, R.; Giffels, M.; Gilbert, A.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Katkov, I.; Kornmayer, A.; Lobelle Pardo, P.; Maier, B.; Mildner, H.; Mozer, M. U.; Müller, T.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Röcker, S.; Roscher, F.; Sieber, G.; Simonis, H. J.; Stober, F. M.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weber, M.; Weiler, T.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Psallidas, A.; Topsis-Giotis, I.; Agapitos, A.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Tziaferi, E.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Loukas, N.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Bencze, G.; Hajdu, C.; Hazi, A.; Hidas, P.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Molnar, J.; Szillasi, Z.; Bartók, M.; Makovec, A.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Mal, P.; Mandal, K.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chawla, R.; Gupta, R.; Bhawandeep, U.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Mehta, A.; Mittal, M.; Singh, J. B.; Walia, G.; Kumar, Ashok; Bhardwaj, A.; Choudhary, B. C.; Garg, R. 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    This paper describes the CMS trigger system and its performance during Run 1 of the LHC. The trigger system consists of two levels designed to select events of potential physics interest from a GHz (MHz) interaction rate of proton-proton (heavy ion) collisions. The first level of the trigger is implemented in hardware, and selects events containing detector signals consistent with an electron, photon, muon, τ lepton, jet, or missing transverse energy. A programmable menu of up to 128 object-based algorithms is used to select events for subsequent processing. The trigger thresholds are adjusted to the LHC instantaneous luminosity during data taking in order to restrict the output rate to 100 kHz, the upper limit imposed by the CMS readout electronics. The second level, implemented in software, further refines the purity of the output stream, selecting an average rate of 400 Hz for offline event storage. The objectives, strategy and performance of the trigger system during the LHC Run 1 are described.

  13. The CMS trigger system

    CERN Document Server

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Blobel, Volker; Centis Vignali, Matteo; Draeger, Arne-Rasmus; Erfle, Joachim; Garutti, Erika; Goebel, Kristin; Gonzalez, Daniel; Görner, Martin; Haller, Johannes; Hoffmann, Malte; Höing, Rebekka Sophie; Junkes, Alexandra; Klanner, Robert; Kogler, Roman; Kovalchuk, Nataliia; Lapsien, Tobias; Lenz, Teresa; Marchesini, Ivan; Marconi, Daniele; Meyer, Mareike; Nowatschin, Dominik; Ott, Jochen; Pantaleo, Felice; Peiffer, Thomas; Perieanu, Adrian; Pietsch, Niklas; Poehlsen, Jennifer; Rathjens, Denis; Sander, Christian; Scharf, Christian; Schettler, Hannes; Schleper, Peter; Schlieckau, Eike; Schmidt, Alexander; Schwandt, Joern; Sola, Valentina; Stadie, Hartmut; Steinbrück, Georg; Tholen, Heiner; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Vanhoefer, Annika; Vormwald, Benedikt; Akbiyik, Melike; Barth, Christian; Baus, Colin; Berger, Joram; Böser, Christian; Butz, Erik; Chwalek, Thorsten; Colombo, Fabio; De Boer, Wim; Descroix, Alexis; Dierlamm, Alexander; Fink, Simon; Frensch, Felix; Friese, Raphael; Giffels, Manuel; Gilbert, Andrew; Haitz, Dominik; Hartmann, Frank; Heindl, Stefan Michael; Husemann, Ulrich; Katkov, Igor; Kornmayer, Andreas; Lobelle Pardo, Patricia; Maier, Benedikt; Mildner, Hannes; Mozer, Matthias Ulrich; Müller, Thomas; Müller, Thomas; Plagge, Michael; Quast, Gunter; Rabbertz, Klaus; Röcker, Steffen; Roscher, Frank; Sieber, Georg; Simonis, Hans-Jürgen; Stober, Fred-Markus Helmut; Ulrich, Ralf; Wagner-Kuhr, Jeannine; Wayand, Stefan; Weber, Marc; Weiler, Thomas; Wöhrmann, Clemens; Wolf, Roger; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Giakoumopoulou, Viktoria Athina; Kyriakis, Aristotelis; Loukas, Demetrios; Psallidas, Andreas; Topsis-Giotis, Iasonas; Agapitos, Antonis; Kesisoglou, Stilianos; Panagiotou, Apostolos; Saoulidou, Niki; Tziaferi, Eirini; Evangelou, Ioannis; Flouris, Giannis; Foudas, Costas; Kokkas, Panagiotis; Loukas, Nikitas; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Strologas, John; Bencze, Gyorgy; Hajdu, Csaba; Hazi, Andras; Hidas, Pàl; Horvath, Dezso; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Karancsi, János; Molnar, Jozsef; Szillasi, Zoltan; Bartók, Márton; Makovec, Alajos; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Mal, Prolay; Mandal, Koushik; Sahoo, Deepak Kumar; Sahoo, Niladribihari; Swain, Sanjay Kumar; Bansal, Sunil; Beri, Suman Bala; Bhatnagar, Vipin; Chawla, Ridhi; Gupta, Ruchi; Bhawandeep, Bhawandeep; Kalsi, Amandeep Kaur; Kaur, Anterpreet; Kaur, Manjit; Kumar, Ramandeep; Mehta, Ankita; Mittal, Monika; Singh, Jasbir; Walia, Genius; Kumar, Ashok; Bhardwaj, Ashutosh; Choudhary, Brajesh C; Garg, Rocky Bala; Kumar, Ajay; Malhotra, Shivali; Naimuddin, Md; Nishu, Nishu; Ranjan, Kirti; Sharma, Ramkrishna; Sharma, Varun; Bhattacharya, Satyaki; Chatterjee, Kalyanmoy; Dey, Sourav; Dutta, Suchandra; Jain, Sandhya; Majumdar, Nayana; Modak, Atanu; Mondal, Kuntal; Mukherjee, Swagata; Mukhopadhyay, Supratik; Roy, Ashim; Roy, Debarati; Roy Chowdhury, Suvankar; Sarkar, Subir; Sharan, Manoj; Abdulsalam, Abdulla; Chudasama, Ruchi; Dutta, Dipanwita; Jha, Vishwajeet; Kumar, Vineet; Mohanty, Ajit Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Banerjee, Sudeshna; Bhowmik, Sandeep; Chatterjee, Rajdeep Mohan; Dewanjee, Ram Krishna; Dugad, Shashikant; Ganguly, Sanmay; Ghosh, Saranya; Guchait, Monoranjan; Gurtu, Atul; Kole, Gouranga; Kumar, Sanjeev; Mahakud, Bibhuprasad; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Mitra, Soureek; Mohanty, Gagan Bihari; Parida, Bibhuti; Sarkar, Tanmay; Sur, Nairit; Sutar, Bajrang; Wickramage, Nadeesha; Chauhan, Shubhanshu; Dube, Sourabh; Kothekar, Kunal; Sharma, Seema; Bakhshiansohi, Hamed; Behnamian, Hadi; Etesami, Seyed Mohsen; Fahim, Ali; Goldouzian, Reza; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Rezaei Hosseinabadi, Ferdos; Safarzadeh, Batool; Zeinali, Maryam; Felcini, Marta; Grunewald, Martin; Abbrescia, Marcello; Calabria, Cesare; Caputo, Claudio; Colaleo, Anna; Creanza, Donato; Cristella, Leonardo; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Maggi, Giorgio; Maggi, Marcello; Miniello, Giorgia; My, Salvatore; Nuzzo, Salvatore; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Ranieri, Antonio; Selvaggi, Giovanna; Silvestris, Lucia; Venditti, Rosamaria; Verwilligen, Piet; Abbiendi, Giovanni; Battilana, Carlo; Benvenuti, Alberto; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Chhibra, Simranjit Singh; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Montanari, Alessandro; Navarria, Francesco; Perrotta, Andrea; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Travaglini, Riccardo; Cappello, Gigi; Chiorboli, Massimiliano; Costa, Salvatore; Di Mattia, Alessandro; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Gonzi, Sandro; Gori, Valentina; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Sguazzoni, Giacomo; Tropiano, Antonio; Viliani, Lorenzo; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Primavera, Federica; Calvelli, Valerio; Ferro, Fabrizio; Lo Vetere, Maurizio; Monge, Maria Roberta; Robutti, Enrico; Tosi, Silvano; Brianza, Luca; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Gerosa, Raffaele; Ghezzi, Alessio; Govoni, Pietro; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Marzocchi, Badder; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Ragazzi, Stefano; Redaelli, Nicola; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; Di Guida, Salvatore; Esposito, Marco; Fabozzi, Francesco; Iorio, Alberto Orso Maria; Lanza, Giuseppe; Lista, Luca; Meola, Sabino; Merola, Mario; Paolucci, Pierluigi; Sciacca, Crisostomo; Thyssen, Filip; Bacchetta, Nicola; Bellato, Marco; Benato, Lisa; Bisello, Dario; Boletti, Alessio; Carlin, Roberto; Checchia, Paolo; Dall'Osso, Martino; Dosselli, Umberto; Gasparini, Fabrizio; Gasparini, Ugo; Gozzelino, Andrea; Lacaprara, Stefano; Margoni, Martino; Meneguzzo, Anna Teresa; Montecassiano, Fabio; Passaseo, Marina; Pazzini, Jacopo; Pegoraro, Matteo; Pozzobon, Nicola; Simonetto, Franco; Torassa, Ezio; Tosi, Mia; Vanini, Sara; Ventura, Sandro; Zanetti, Marco; Zotto, Pierluigi; Zucchetta, Alberto; Zumerle, Gianni; Braghieri, Alessandro; Magnani, Alice; Montagna, Paolo; Ratti, Sergio P; Re, Valerio; Riccardi, Cristina; Salvini, Paola; Vai, Ilaria; Vitulo, Paolo; Alunni Solestizi, Luisa; Biasini, Maurizio; Bilei, Gian Mario; Ciangottini, Diego; Fanò, Livio; Lariccia, Paolo; Mantovani, Giancarlo; Menichelli, Mauro; Saha, Anirban; Santocchia, Attilio; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Donato, Silvio; Fedi, Giacomo; Foà, Lorenzo; Giassi, Alessandro; Grippo, Maria Teresa; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Serban, Alin Titus; Spagnolo, Paolo; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Barone, Luciano; Cavallari, Francesca; D'imperio, Giulia; Del Re, Daniele; Diemoz, Marcella; Gelli, Simone; Jorda, Clara; Longo, Egidio; Margaroli, Fabrizio; Meridiani, Paolo; Organtini, Giovanni; Paramatti, Riccardo; Preiato, Federico; Rahatlou, Shahram; Rovelli, Chiara; Santanastasio, Francesco; Traczyk, Piotr; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Costa, Marco; Covarelli, Roberto; Degano, Alessandro; Demaria, Natale; Finco, Linda; Kiani, Bilal; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Monteil, Ennio; Obertino, Maria Margherita; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Pinna Angioni, Gian Luca; Ravera, Fabio; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Solano, Ada; Staiano, Amedeo; Tamponi, Umberto; Belforte, Stefano; Candelise, Vieri; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Gobbo, Benigno; La Licata, Chiara; Marone, Matteo; Schizzi, Andrea; Zanetti, Anna; Kropivnitskaya, Anna; Nam, Soon-Kwon; Kim, Dong Hee; Kim, Gui Nyun; Kim, Min Suk; Kong, Dae Jung; Lee, Sangeun; Oh, Young Do; Sakharov, Alexandre; Son, Dong-Chul; Brochero Cifuentes, Javier Andres; Kim, Hyunsoo; Kim, Tae Jeong; Song, Sanghyeon; Choi, Suyong; Go, Yeonju; Gyun, Dooyeon; Hong, Byung-Sik; Jo, Mihee; Kim, Hyunchul; Kim, Yongsun; Lee, Byounghoon; Lee, Kisoo; Lee, Kyong Sei; Lee, Songkyo; Park, Sung Keun; Roh, Youn; Yoo, Hwi Dong; Choi, Minkyoo; Kim, Hyunyong; Kim, Ji Hyun; Lee, Jason Sang Hun; Park, Inkyu; Ryu, Geonmo; Ryu, Min Sang; Choi, Young-Il; Goh, Junghwan; Kim, Donghyun; Kwon, Eunhyang; Lee, Jongseok; Yu, Intae; Dudenas, Vytautas; Juodagalvis, Andrius; Vaitkus, Juozas; Ahmed, Ijaz; Ibrahim, Zainol Abidin; Komaragiri, Jyothsna Rani; Md Ali, Mohd Adli Bin; Mohamad Idris, Faridah; Wan Abdullah, Wan Ahmad Tajuddin; Yusli, Mohd Nizam; Casimiro Linares, Edgar; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-De La Cruz, Ivan; Hernandez-Almada, Alberto; Lopez-Fernandez, Ricardo; Sánchez Hernández, Alberto; Carrillo Moreno, Salvador; Vazquez Valencia, Fabiola; Pedraza, Isabel; Salazar Ibarguen, Humberto Antonio; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Ahmad, Ashfaq; Ahmad, Muhammad; Hassan, Qamar; Hoorani, Hafeez R; Khan, Wajid Ali; Khurshid, Taimoor; Shoaib, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bożena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Zalewski, Piotr; Brona, Grzegorz; Bunkowski, Karol; Byszuk, Adrian; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Olszewski, Michal; Pozniak, Krzysztof; Walczak, Marek; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Di Francesco, Agostino; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Leonardo, Nuno; Lloret Iglesias, Lara; Nguyen, Federico; Rodrigues Antunes, Joao; Seixas, Joao; Toldaiev, Oleksii; Vadruccio, Daniele; Varela, Joao; Vischia, Pietro; Afanasiev, Serguei; Bunin, Pavel; Gavrilenko, Mikhail; Golutvin, Igor; Gorbunov, Ilya; Kamenev, Alexey; Karjavin, Vladimir; Konoplyanikov, Viktor; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Moisenz, Petr; Palichik, Vladimir; Perelygin, Victor; Shmatov, Sergey; Shulha, Siarhei; Skatchkov, Nikolai; Smirnov, Vitaly; Zarubin, Anatoli; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Kuznetsova, Ekaterina; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Karneyeu, Anton; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Pozdnyakov, Ivan; Safronov, Grigory; Spiridonov, Alexander; Vlasov, Evgueni; Zhokin, Alexander; Bylinkin, Alexander; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Mesyats, Gennady; Rusakov, Sergey V; Baskakov, Alexey; Belyaev, Andrey; Boos, Edouard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Kaminskiy, Alexandre; Klyukhin, Vyacheslav; Kodolova, Olga; Lokhtin, Igor; Miagkov, Igor; Obraztsov, Stepan; Petrushanko, Sergey; Savrin, Viktor; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Tourtchanovitch, Leonid; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Milosevic, Jovan; Rekovic, Vladimir; Alcaraz Maestre, Juan; Calvo, Enrique; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Domínguez Vázquez, Daniel; Escalante Del Valle, Alberto; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Navarro De Martino, Eduardo; Pérez-Calero Yzquierdo, Antonio María; Puerta Pelayo, Jesus; Quintario Olmeda, Adrián; Redondo, Ignacio; Romero, Luciano; Santaolalla, Javier; Senghi Soares, Mara; Albajar, Carmen; de Trocóniz, Jorge F; Missiroli, Marino; Moran, Dermot; Cuevas, Javier; Fernandez Menendez, Javier; Folgueras, Santiago; Gonzalez Caballero, Isidro; Palencia Cortezon, Enrique; Vizan Garcia, Jesus Manuel; Cabrillo, Iban Jose; Calderon, Alicia; Castiñeiras De Saa, Juan Ramon; De Castro Manzano, Pablo; Duarte Campderros, Jordi; Fernandez, Marcos; Garcia-Ferrero, Juan; Gomez, Gervasio; Lopez Virto, Amparo; Marco, Jesus; Marco, Rafael; Martinez Rivero, Celso; Matorras, Francisco; Munoz Sanchez, Francisca Javiela; Piedra Gomez, Jonatan; Rodrigo, Teresa; Rodríguez-Marrero, Ana Yaiza; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Trevisani, Nicolò; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Auzinger, Georg; Bachtis, Michail; Baillon, Paul; Ball, Austin; Barney, David; Benaglia, Andrea; Bendavid, Joshua; Benhabib, Lamia; Benitez, Jose F; Berruti, Gaia Maria; Bloch, Philippe; Bocci, Andrea; Bonato, Alessio; Botta, Cristina; Breuker, Horst; Camporesi, Tiziano; Castello, Roberto; Cerminara, Gianluca; D'Alfonso, Mariarosaria; D'Enterria, David; Dabrowski, Anne; Daponte, Vincenzo; David Tinoco Mendes, Andre; De Gruttola, Michele; De Guio, Federico; De Roeck, Albert; De Visscher, Simon; Di Marco, Emanuele; Dobson, Marc; Dordevic, Milos; Dorney, Brian; Du Pree, Tristan; Dünser, Marc; Dupont, Niels; Elliott-Peisert, Anna; Franzoni, Giovanni; Funk, Wolfgang; Gigi, Dominique; Gill, Karl; Giordano, Domenico; Girone, Maria; Glege, Frank; Guida, Roberto; Gundacker, Stefan; Guthoff, Moritz; Hammer, Josef; Harris, Philip; Hegeman, Jeroen; Innocente, Vincenzo; Janot, Patrick; Kirschenmann, Henning; Kortelainen, Matti J; Kousouris, Konstantinos; Krajczar, Krisztian; Lecoq, Paul; Lourenco, Carlos; Lucchini, Marco Toliman; Magini, Nicolo; Malgeri, Luca; Mannelli, Marcello; Martelli, Arabella; Masetti, Lorenzo; Meijers, Frans; Mersi, Stefano; Meschi, Emilio; Moortgat, Filip; Morovic, Srecko; Mulders, Martijn; Nemallapudi, Mythra Varun; Neugebauer, Hannes; Orfanelli, Styliani; Orsini, Luciano; Pape, Luc; Perez, Emmanuelle; Peruzzi, Marco; Petrilli, Achille; Petrucciani, Giovanni; Pfeiffer, Andreas; Piparo, Danilo; Racz, Attila; Rolandi, Gigi; Rovere, Marco; Ruan, Manqi; Sakulin, Hannes; Schäfer, Christoph; Schwick, Christoph; Seidel, Markus; Sharma, Archana; Silva, Pedro; Simon, Michal; Sphicas, Paraskevas; Steggemann, Jan; Stieger, Benjamin; Stoye, Markus; Takahashi, Yuta; Treille, Daniel; Triossi, Andrea; Tsirou, Andromachi; Veres, Gabor Istvan; Wardle, Nicholas; Wöhri, Hermine Katharina; Zagoździńska, Agnieszka; Zeuner, Wolfram Dietrich; Bertl, Willi; Deiters, Konrad; Erdmann, Wolfram; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; Kotlinski, Danek; Langenegger, Urs; Renker, Dieter; Rohe, Tilman; Bachmair, Felix; Bäni, Lukas; Bianchini, Lorenzo; Casal, Bruno; Dissertori, Günther; Dittmar, Michael; Donegà, Mauro; Eller, Philipp; Grab, Christoph; Heidegger, Constantin; Hits, Dmitry; Hoss, Jan; Kasieczka, Gregor; Lustermann, Werner; Mangano, Boris; Marionneau, Matthieu; Martinez Ruiz del Arbol, Pablo; Masciovecchio, Mario; Meister, Daniel; Micheli, Francesco; Musella, Pasquale; Nessi-Tedaldi, Francesca; Pandolfi, Francesco; Pata, Joosep; Pauss, Felicitas; Perrozzi, Luca; Quittnat, Milena; Rossini, Marco; Starodumov, Andrei; Takahashi, Maiko; Tavolaro, Vittorio Raoul; Theofilatos, Konstantinos; Wallny, Rainer; Aarrestad, Thea Klaeboe; Amsler, Claude; Caminada, Lea; Canelli, Maria Florencia; Chiochia, Vincenzo; De Cosa, Annapaola; Galloni, Camilla; Hinzmann, Andreas; Hreus, Tomas; Kilminster, Benjamin; Lange, Clemens; Ngadiuba, Jennifer; Pinna, Deborah; Robmann, Peter; Ronga, Frederic Jean; Salerno, Daniel; Yang, Yong; Cardaci, Marco; Chen, Kuan-Hsin; Doan, Thi Hien; Jain, Shilpi; Khurana, Raman; Konyushikhin, Maxim; Kuo, Chia-Ming; Lin, Willis; Lu, Yun-Ju; Yu, Shin-Shan; Kumar, Arun; Bartek, Rachel; Chang, Paoti; Chang, You-Hao; Chang, Yu-Wei; Chao, Yuan; Chen, Kai-Feng; Chen, Po-Hsun; Dietz, Charles; Fiori, Francesco; Grundler, Ulysses; Hou, George Wei-Shu; Hsiung, Yee; Liu, Yueh-Feng; Lu, Rong-Shyang; Miñano Moya, Mercedes; Petrakou, Eleni; Tsai, Jui-fa; Tzeng, Yeng-Ming; Asavapibhop, Burin; Kovitanggoon, Kittikul; Singh, Gurpreet; Srimanobhas, Norraphat; Suwonjandee, Narumon; Adiguzel, Aytul; Bakirci, Mustafa Numan; Demiroglu, Zuhal Seyma; Dozen, Candan; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Guler, Yalcin; Gurpinar, Emine; Hos, Ilknur; Kangal, Evrim Ersin; Onengut, Gulsen; Ozdemir, Kadri; Polatoz, Ayse; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Vergili, Mehmet; Zorbilmez, Caglar; Akin, Ilina Vasileva; Bilin, Bugra; Bilmis, Selcuk; Isildak, Bora; Karapinar, Guler; Yalvac, Metin; Zeyrek, Mehmet; Gülmez, Erhan; Kaya, Mithat; Kaya, Ozlem; Yetkin, Elif Asli; Yetkin, Taylan; Cakir, Altan; Cankocak, Kerem; Sen, Sercan; Vardarlı, Fuat Ilkehan; Grynyov, Boris; Levchuk, Leonid; Sorokin, Pavel; Aggleton, Robin; Ball, Fionn; Beck, Lana; Brooke, James John; Clement, Emyr; Cussans, David; Flacher, Henning; Goldstein, Joel; Grimes, Mark; Heath, Greg P; Heath, Helen F; Jacob, Jeson; Kreczko, Lukasz; Lucas, Chris; Meng, Zhaoxia; Newbold, Dave M; Paramesvaran, Sudarshan; Poll, Anthony; Sakuma, Tai; Seif El Nasr-storey, Sarah; Senkin, Sergey; Smith, Dominic; Smith, Vincent J; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Calligaris, Luigi; Cieri, Davide; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Olaiya, Emmanuel; Petyt, David; Shepherd-Themistocleous, Claire; Thea, Alessandro; Tomalin, Ian R; Williams, Thomas; Womersley, William John; Worm, Steven; Baber, Mark; Bainbridge, Robert; Buchmuller, Oliver; Bundock, Aaron; Burton, Darren; Casasso, Stefano; Citron, Matthew; Colling, David; Corpe, Louie; Cripps, Nicholas; Dauncey, Paul; Davies, Gavin; De Wit, Adinda; Della Negra, Michel; Dunne, Patrick; Elwood, Adam; Ferguson, William; Fulcher, Jonathan; Futyan, David; Hall, Geoffrey; Iles, Gregory; Kenzie, Matthew; Lane, Rebecca; Lucas, Robyn; Lyons, Louis; Magnan, Anne-Marie; Malik, Sarah; Nash, Jordan; Nikitenko, Alexander; Pela, Joao; Pesaresi, Mark; Petridis, Konstantinos; Raymond, David Mark; Richards, Alexander; Rose, Andrew; Seez, Christopher; Tapper, Alexander; Uchida, Kirika; Vazquez Acosta, Monica; Virdee, Tejinder; Zenz, Seth Conrad; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Leggat, Duncan; Leslie, Dawn; Reid, Ivan; Symonds, Philip; Teodorescu, Liliana; Turner, Mark; Borzou, Ahmad; Call, Kenneth; Dittmann, Jay; Hatakeyama, Kenichi; Liu, Hongxuan; Pastika, Nathaniel; Charaf, Otman; Cooper, Seth; Henderson, Conor; Rumerio, Paolo; Arcaro, Daniel; Avetisyan, Aram; Bose, Tulika; Fantasia, Cory; Gastler, Daniel; Lawson, Philip; Rankin, Dylan; Richardson, Clint; Rohlf, James; St John, Jason; Sulak, Lawrence; Zou, David; Alimena, Juliette; Berry, Edmund; Bhattacharya, Saptaparna; Cutts, David; Dhingra, Nitish; Ferapontov, Alexey; Garabedian, Alex; Hakala, John; Heintz, Ulrich; Laird, Edward; Landsberg, Greg; Mao, Zaixing; Narain, Meenakshi; Piperov, Stefan; Sagir, Sinan; Syarif, Rizki; Breedon, Richard; Breto, Guillermo; Calderon De La Barca Sanchez, Manuel; Chauhan, Sushil; Chertok, Maxwell; Conway, John; Conway, Rylan; Cox, Peter Timothy; Erbacher, Robin; Gardner, Michael; Ko, Winston; Lander, Richard; Mulhearn, Michael; Pellett, Dave; Pilot, Justin; Ricci-Tam, Francesca; Shalhout, Shalhout; Smith, John; Squires, Michael; Stolp, Dustin; Tripathi, Mani; Wilbur, Scott; Yohay, Rachel; Cousins, Robert; Everaerts, Pieter; Farrell, Chris; Hauser, Jay; Ignatenko, Mikhail; Saltzberg, David; Takasugi, Eric; Valuev, Vyacheslav; Weber, Matthias; Burt, Kira; Clare, Robert; Ellison, John Anthony; Gary, J William; Hanson, Gail; Heilman, Jesse; Paneva, Mirena Ivova; Jandir, Pawandeep; Kennedy, Elizabeth; Lacroix, Florent; Long, Owen Rosser; Luthra, Arun; Malberti, Martina; Olmedo Negrete, Manuel; Shrinivas, Amithabh; Wei, Hua; Wimpenny, Stephen; Yates, Brent; Branson, James G; Cerati, Giuseppe Benedetto; Cittolin, Sergio; D'Agnolo, Raffaele Tito; Derdzinski, Mark; Holzner, André; Kelley, Ryan; Klein, Daniel; Letts, James; Macneill, Ian; Olivito, Dominick; Padhi, Sanjay; Pieri, Marco; Sani, Matteo; Sharma, Vivek; Simon, Sean; Tadel, Matevz; Vartak, Adish; Wasserbaech, Steven; Welke, Charles; Würthwein, Frank; Yagil, Avraham; Zevi Della Porta, Giovanni; Bradmiller-Feld, John; Campagnari, Claudio; Dishaw, Adam; Dutta, Valentina; Flowers, Kristen; Franco Sevilla, Manuel; Geffert, Paul; George, Christopher; Golf, Frank; Gouskos, Loukas; Gran, Jason; Incandela, Joe; Mccoll, Nickolas; Mullin, Sam Daniel; Richman, Jeffrey; Stuart, David; Suarez, Indara; West, Christopher; Yoo, Jaehyeok; Anderson, Dustin; Apresyan, Artur; Bornheim, Adolf; Bunn, Julian; Chen, Yi; Duarte, Javier; Mott, Alexander; Newman, Harvey B; Pena, Cristian; Pierini, Maurizio; Spiropulu, Maria; Vlimant, Jean-Roch; Xie, Si; Zhu, Ren-Yuan; Andrews, Michael Benjamin; Azzolini, Virginia; Calamba, Aristotle; Carlson, Benjamin; Ferguson, Thomas; Paulini, Manfred; Russ, James; Sun, Menglei; Vogel, Helmut; Vorobiev, Igor; Cumalat, John Perry; Ford, William T; Gaz, Alessandro; Jensen, Frank; Johnson, Andrew; Krohn, Michael; Mulholland, Troy; Nauenberg, Uriel; Stenson, Kevin; Wagner, Stephen Robert; Alexander, James; Chatterjee, Avishek; Chaves, Jorge; Chu, Jennifer; Dittmer, Susan; Eggert, Nicholas; Mirman, Nathan; Nicolas Kaufman, Gala; Patterson, Juliet Ritchie; Rinkevicius, Aurelijus; Ryd, Anders; Skinnari, Louise; Soffi, Livia; Sun, Werner; Tan, Shao Min; Teo, Wee Don; Thom, Julia; Thompson, Joshua; Tucker, Jordan; Weng, Yao; Wittich, Peter; Abdullin, Salavat; Albrow, Michael; Anderson, Jacob; Apollinari, Giorgio; Banerjee, Sunanda; Bauerdick, Lothar AT; Beretvas, Andrew; Berryhill, Jeffrey; Bhat, Pushpalatha C; Bolla, Gino; Burkett, Kevin; Butler, Joel Nathan; Cheung, Harry; Chlebana, Frank; Cihangir, Selcuk; Elvira, Victor Daniel; Fisk, Ian; Freeman, Jim; Gottschalk, Erik; Gray, Lindsey; Green, Dan; Grünendahl, Stefan; Gutsche, Oliver; Hanlon, Jim; Hare, Daryl; Harris, Robert M; Hasegawa, Satoshi; Hirschauer, James; Hu, Zhen; Jayatilaka, Bodhitha; Jindariani, Sergo; Johnson, Marvin; Joshi, Umesh; Jung, Andreas Werner; Klima, Boaz; Kreis, Benjamin; Kwan, Simon; Lammel, Stephan; Linacre, Jacob; Lincoln, Don; Lipton, Ron; Liu, Tiehui; Lopes De Sá, Rafael; Lykken, Joseph; Maeshima, Kaori; Marraffino, John Michael; Martinez Outschoorn, Verena Ingrid; Maruyama, Sho; Mason, David; McBride, Patricia; Merkel, Petra; Mishra, Kalanand; Mrenna, Stephen; Nahn, Steve; Newman-Holmes, Catherine; O'Dell, Vivian; Pedro, Kevin; Prokofyev, Oleg; Rakness, Gregory; Sexton-Kennedy, Elizabeth; Soha, Aron; Spalding, William J; Spiegel, Leonard; Taylor, Lucas; Tkaczyk, Slawek; Tran, Nhan Viet; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vernieri, Caterina; Verzocchi, Marco; Vidal, Richard; Weber, Hannsjoerg Artur; Whitbeck, Andrew; Yang, Fan; Acosta, Darin; Avery, Paul; Bortignon, Pierluigi; Bourilkov, Dimitri; Carnes, Andrew; Carver, Matthew; Curry, David; Das, Souvik; Di Giovanni, Gian Piero; Field, Richard D; Furic, Ivan-Kresimir; Gleyzer, Sergei V; Hugon, Justin; Konigsberg, Jacobo; Korytov, Andrey; Low, Jia Fu; Ma, Peisen; Matchev, Konstantin; Mei, Hualin; Milenovic, Predrag; Mitselmakher, Guenakh; Rank, Douglas; Rossin, Roberto; Shchutska, Lesya; Snowball, Matthew; Sperka, David; Terentyev, Nikolay; Thomas, Laurent; Wang, Jian; Wang, Sean-Jiun; Yelton, John; Hewamanage, Samantha; Linn, Stephan; Markowitz, Pete; Martinez, German; Rodriguez, Jorge Luis; Ackert, Andrew; Adams, Jordon Rowe; Adams, Todd; Askew, Andrew; Bochenek, Joseph; Diamond, Brendan; Haas, Jeff; Hagopian, Sharon; Hagopian, Vasken; Johnson, Kurtis F; Khatiwada, Ajeeta; Prosper, Harrison; Weinberg, Marc; Baarmand, Marc M; Bhopatkar, Vallary; Colafranceschi, Stefano; Hohlmann, Marcus; Kalakhety, Himali; Noonan, Daniel; Roy, Titas; Yumiceva, Francisco; Adams, Mark Raymond; Apanasevich, Leonard; Berry, Douglas; Betts, Russell Richard; Bucinskaite, Inga; Cavanaugh, Richard; Evdokimov, Olga; Gauthier, Lucie; Gerber, Cecilia Elena; Hofman, David Jonathan; Kurt, Pelin; O'Brien, Christine; Sandoval Gonzalez, Irving Daniel; Silkworth, Christopher; Turner, Paul; Varelas, Nikos; Wu, Zhenbin; Zakaria, Mohammed; Bilki, Burak; Clarida, Warren; Dilsiz, Kamuran; Durgut, Süleyman; Gandrajula, Reddy Pratap; Haytmyradov, Maksat; Khristenko, Viktor; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Ogul, Hasan; Onel, Yasar; Ozok, Ferhat; Penzo, Aldo; Snyder, Christina; Tiras, Emrah; Wetzel, James; Yi, Kai; Anderson, Ian; Barnett, Bruce Arnold; Blumenfeld, Barry; Eminizer, Nicholas; Fehling, David; Feng, Lei; Gritsan, Andrei; Maksimovic, Petar; Martin, Christopher; Osherson, Marc; Roskes, Jeffrey; Cocoros, Alice; Sarica, Ulascan; Swartz, Morris; Xiao, Meng; Xin, Yongjie; You, Can; Baringer, Philip; Bean, Alice; Benelli, Gabriele; Bruner, Christopher; Kenny III, Raymond Patrick; Majumder, Devdatta; Malek, Magdalena; Murray, Michael; Sanders, Stephen; Stringer, Robert; Wang, Quan; Ivanov, Andrew; Kaadze, Ketino; Khalil, Sadia; Makouski, Mikhail; Maravin, Yurii; Mohammadi, Abdollah; Saini, Lovedeep Kaur; Skhirtladze, Nikoloz; Toda, Sachiko; Lange, David; Rebassoo, Finn; Wright, Douglas; Anelli, Christopher; Baden, Drew; Baron, Owen; Belloni, Alberto; Calvert, Brian; Eno, Sarah Catherine; Ferraioli, Charles; Gomez, Jaime; Hadley, Nicholas John; Jabeen, Shabnam; Kellogg, Richard G; Kolberg, Ted; Kunkle, Joshua; Lu, Ying; Mignerey, Alice; Shin, Young Ho; Skuja, Andris; Tonjes, Marguerite; Tonwar, Suresh C; Apyan, Aram; Barbieri, Richard; Baty, Austin; Bierwagen, Katharina; Brandt, Stephanie; Busza, Wit; Cali, Ivan Amos; Demiragli, Zeynep; Di Matteo, Leonardo; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Gulhan, Doga; Iiyama, Yutaro; Innocenti, Gian Michele; Klute, Markus; Kovalskyi, Dmytro; Lai, Yue Shi; Lee, Yen-Jie; Levin, Andrew; Luckey, Paul David; Marini, Andrea Carlo; Mcginn, Christopher; Mironov, Camelia; Narayanan, Siddharth; Niu, Xinmei; Paus, Christoph; Ralph, Duncan; Roland, Christof; Roland, Gunther; Salfeld-Nebgen, Jakob; Stephans, George; Sumorok, Konstanty; Varma, Mukund; Velicanu, Dragos; Veverka, Jan; Wang, Jing; Wang, Ta-Wei; Wyslouch, Bolek; Yang, Mingming; Zhukova, Victoria; Dahmes, Bryan; Evans, Andrew; Finkel, Alexey; Gude, Alexander; Hansen, Peter; Kalafut, Sean; Kao, Shih-Chuan; Klapoetke, Kevin; Kubota, Yuichi; Lesko, Zachary; Mans, Jeremy; Nourbakhsh, Shervin; Ruckstuhl, Nicole; Rusack, Roger; Tambe, Norbert; Turkewitz, Jared; Acosta, John Gabriel; Oliveros, Sandra; Avdeeva, Ekaterina; Bloom, Kenneth; Bose, Suvadeep; Claes, Daniel R; Dominguez, Aaron; Fangmeier, Caleb; Gonzalez Suarez, Rebeca; Kamalieddin, Rami; Keller, Jason; Knowlton, Dan; Kravchenko, Ilya; Meier, Frank; Monroy, Jose; Ratnikov, Fedor; Siado, Joaquin Emilo; Snow, Gregory R; Alyari, Maral; Dolen, James; George, Jimin; Godshalk, Andrew; Harrington, Charles; Iashvili, Ia; Kaisen, Josh; Kharchilava, Avto; Kumar, Ashish; Rappoccio, Salvatore; Roozbahani, Bahareh; Alverson, George; Barberis, Emanuela; Baumgartel, Darin; Chasco, Matthew; Hortiangtham, Apichart; Massironi, Andrea; Morse, David Michael; Nash, David; Orimoto, Toyoko; Teixeira De Lima, Rafael; Trocino, Daniele; Wang, Ren-Jie; Wood, Darien; Zhang, Jinzhong; Hahn, Kristan Allan; Kubik, Andrew; Mucia, Nicholas; Odell, Nathaniel; Pollack, Brian; Pozdnyakov, Andrey; Schmitt, Michael Henry; Stoynev, Stoyan; Sung, Kevin; Trovato, Marco; Velasco, Mayda; Brinkerhoff, Andrew; Dev, Nabarun; Hildreth, Michael; Jessop, Colin; Karmgard, Daniel John; Kellams, Nathan; Lannon, Kevin; Lynch, Sean; Marinelli, Nancy; Meng, Fanbo; Mueller, Charles; Musienko, Yuri; Pearson, Tessa; Planer, Michael; Reinsvold, Allison; Ruchti, Randy; Smith, Geoffrey; Taroni, Silvia; Valls, Nil; Wayne, Mitchell; Wolf, Matthias; Woodard, Anna; Antonelli, Louis; Brinson, Jessica; Bylsma, Ben; Durkin, Lloyd Stanley; Flowers, Sean; Hart, Andrew; Hill, Christopher; Hughes, Richard; Ji, Weifeng; Kotov, Khristian; Ling, Ta-Yung; Liu, Bingxuan; Luo, Wuming; Puigh, Darren; Rodenburg, Marissa; Winer, Brian L; Wulsin, Howard Wells; Driga, Olga; Elmer, Peter; Hardenbrook, Joshua; Hebda, Philip; Koay, Sue Ann; Lujan, Paul; Marlow, Daniel; Medvedeva, Tatiana; Mooney, Michael; Olsen, James; Palmer, Christopher; Piroué, Pierre; Saka, Halil; Stickland, David; Tully, Christopher; Zuranski, Andrzej; Malik, Sudhir; Barnes, Virgil E; Benedetti, Daniele; Bortoletto, Daniela; Gutay, Laszlo; Jha, Manoj; Jones, Matthew; Jung, Kurt; Miller, David Harry; Neumeister, Norbert; Radburn-Smith, Benjamin Charles; Shi, Xin; Shipsey, Ian; Silvers, David; Sun, Jian; Svyatkovskiy, Alexey; Wang, Fuqiang; Xie, Wei; Xu, Lingshan; Parashar, Neeti; Stupak, John; Adair, Antony; Akgun, Bora; Chen, Zhenyu; Ecklund, Karl Matthew; Geurts, Frank JM; Guilbaud, Maxime; Li, Wei; Michlin, Benjamin; Northup, Michael; Padley, Brian Paul; Redjimi, Radia; Roberts, Jay; Rorie, Jamal; Tu, Zhoudunming; Zabel, James; Betchart, Burton; Bodek, Arie; de Barbaro, Pawel; Demina, Regina; Eshaq, Yossof; Ferbel, Thomas; Galanti, Mario; Garcia-Bellido, Aran; Han, Jiyeon; Harel, Amnon; Hindrichs, Otto; Khukhunaishvili, Aleko; Petrillo, Gianluca; Tan, Ping; Verzetti, Mauro; Arora, Sanjay; Barker, Anthony; Chou, John Paul; Contreras-Campana, Christian; Contreras-Campana, Emmanuel; Duggan, Daniel; Ferencek, Dinko; Gershtein, Yuri; Gray, Richard; Halkiadakis, Eva; Hidas, Dean; Hughes, Elliot; Kaplan, Steven; Kunnawalkam Elayavalli, Raghav; Lath, Amitabh; Nash, Kevin; Panwalkar, Shruti; Park, Michael; Salur, Sevil; Schnetzer, Steve; Sheffield, David; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Thomassen, Peter; Walker, Matthew; Foerster, Mark; Riley, Grant; Rose, Keith; Spanier, Stefan; York, Andrew; Bouhali, Othmane; Castaneda Hernandez, Alfredo; Dalchenko, Mykhailo; De Mattia, Marco; Delgado, Andrea; Dildick, Sven; Eusebi, Ricardo; Gilmore, Jason; Kamon, Teruki; Krutelyov, Vyacheslav; Mueller, Ryan; Osipenkov, Ilya; Pakhotin, Yuriy; Patel, Rishi; Perloff, Alexx; Rose, Anthony; Safonov, Alexei; Tatarinov, Aysen; Ulmer, Keith; Akchurin, Nural; Cowden, Christopher; Damgov, Jordan; Dragoiu, Cosmin; Dudero, Phillip Russell; Faulkner, James; Kunori, Shuichi; Lamichhane, Kamal; Lee, Sung Won; Libeiro, Terence; Undleeb, Sonaina; Volobouev, Igor; Appelt, Eric; Delannoy, Andrés G; Greene, Senta; Gurrola, Alfredo; Janjam, Ravi; Johns, Willard; Maguire, Charles; Mao, Yaxian; Melo, Andrew; Ni, Hong; Sheldon, Paul; Snook, Benjamin; Tuo, Shengquan; Velkovska, Julia; Xu, Qiao; Arenton, Michael Wayne; Cox, Bradley; Francis, Brian; Goodell, Joseph; Hirosky, Robert; Ledovskoy, Alexander; Li, Hengne; Lin, Chuanzhe; Neu, Christopher; Sinthuprasith, Tutanon; Sun, Xin; Wang, Yanchu; Wolfe, Evan; Wood, John; Xia, Fan; Clarke, Christopher; Harr, Robert; Karchin, Paul Edmund; Kottachchi Kankanamge Don, Chamath; Lamichhane, Pramod; Sturdy, Jared; Belknap, Donald; Carlsmith, Duncan; Cepeda, Maria; Dasu, Sridhara; Dodd, Laura; Duric, Senka; Gomber, Bhawna; Grothe, Monika; Hall-Wilton, Richard; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Lanaro, Armando; Levine, Aaron; Long, Kenneth; Loveless, Richard; Mohapatra, Ajit; Ojalvo, Isabel; Perry, Thomas; Pierro, Giuseppe Antonio; Polese, Giovanni; Ruggles, Tyler; Sarangi, Tapas; Savin, Alexander; Sharma, Archana; Smith, Nicholas; Smith, Wesley H; Taylor, Devin; Woods, Nathaniel


    This paper describes the CMS trigger system and its performance during Run 1 of the LHC. The trigger system consists of two levels designed to select events of potential physics interest from a GHz (MHz) interaction rate of proton-proton (heavy ion) collisions. The first level of the trigger is implemented in hardware, and selects events containing detector signals consistent with an electron, photon, muon, $\\tau$ lepton, jet, or missing transverse energy. A programmable menu of up to 128 object-based algorithms is used to select events for subsequent processing. The trigger thresholds are adjusted to the LHC instantaneous luminosity during data taking in order to restrict the output rate to 100 kHz, the upper limit imposed by the CMS readout electronics. The second level, implemented in software, further refines the purity of the output stream, selecting an average rate of 400 Hz for offline event storage. The objectives, strategy and performance of the trigger system during the LHC Run 1 are described.

  14. Trigger Monitoring at ATLAS

    CERN Document Server

    Sidoti, A; The ATLAS collaboration


    The Trigger and Data Acquisition system for the ATLAS experiment has to reduce the 40 MHz of LHC bunch crossing rate to ~200 Hz of recording rate. This is achieved through a complex distributed system composed by $sim$ 1.000 CPUs, about a third of the expected final size of the system. Monitoring the trigger behavior through all the trigger level is of fundamental importance to assess the quality of the data taken, to give fast feedback for the trigger configuration design and to monitor the stability of the HLT farm components. In this paper we will present the online monitoring framework and the various tools available in the ATLAS trigger system going from the ones that build the basic monitoring infrastructure and test the basic functionalities of the system to the more elaborated ones that checks the quality of the data taking looking at physics variables reconstructed online. The early experience in the 2009 cosmics data taking period will also be shown.

  15. Stimulus conflict triggers behavioral avoidance. (United States)

    Dignath, David; Eder, Andreas B


    According to a recent extension of the conflict-monitoring theory, conflict between two competing response tendencies is registered as an aversive event and triggers a motivation to avoid the source of conflict. In the present study, we tested this assumption. Over five experiments, we examined whether conflict is associated with an avoidance motivation and whether stimulus conflict or response conflict triggers an avoidance tendency. Participants first performed a color Stroop task. In a subsequent motivation test, participants responded to Stroop stimuli with approach- and avoidance-related lever movements. These results showed that Stroop-conflict stimuli increased the frequency of avoidance responses in a free-choice motivation test, and also increased the speed of avoidance relative to approach responses in a forced-choice test. High and low proportions of response conflict in the Stroop task had no effect on avoidance in the motivation test. Avoidance of conflict was, however, obtained even with new conflict stimuli that had not been presented before in a Stroop task, and when the Stroop task was replaced with an unrelated filler task. Taken together, these results suggest that stimulus conflict is sufficient to trigger avoidance.

  16. Calcium phosphates for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Canillas, M.; Pena, P.; Aza, A.H. de; Rodriguez, M.A.


    The history of calcium phosphates in the medicine field starts in 1769 when the first evidence of its existence in the bone tissue is discovered. Since then, the interest for calcium phosphates has increased among the scientific community. Their study has been developed in parallel with new advances in materials sciences, medicine or tissue engineering areas. Bone tissue engineering is the field where calcium phosphates have had a great importance. While the first bioceramics are selected according to bioinert, biocompatibility and mechanical properties with the aim to replace bone tissue damaged, calcium phosphates open the way to the bone tissue regeneration challenge. Nowadays, they are present in the majority of commercial products directed to repair or regenerate damaged bone tissue. Finally, in the last few decades, they have been suggested and studied as drug delivering devices and as vehicles of DNA and RNA for the future generation therapies. (Author)

  17. [Calcium metabolism after the menopause]. (United States)

    Kanovitch, D; Klotz, H P


    The authors recall the antagonism between estradiol and parathormone. Estradiol tends to lower serum calcium and fix calcium in the bones as shown by one of us 25 years ago. The mechanism of this action of estrogen on calcium metabolism has been determined by numerous authors but some points are still not clear, e.g. the interferences between estrogen and calcitonin. Classically, parathormone is known to increase bony reabsorption and raise serum calcium. After the menopause the gradual reduction in estradiol secretion leads to post-menopausal osteoporosis. It is better to administer estrogens prophylactically to women after the menopause provided a cervical smear and mammography have been carried out to eliminate latent carcinoma of the breast or uterine cervix.

  18. Developmental Trigger Thumb. (United States)

    Twu, Jonathan; Angeles, Jovito


    Developmental trigger thumb, although uncommon, can be easily identifiable in the pediatric outpatient visit. Patients often present with their thumb locked in flexion and a firm nodule at the base of the thumb. The thumb is usually passively correctable and nonpainful. It is important to examine the opposite thumb as bilateral trigger thumbs occur at a rate of 25% to 30%. Nonsurgical options have been proposed in the past including watchful waiting, extension exercises, splinting, and steroid injections with mixed results. Surgical intervention is indicated when there is painful triggering or the thumb is not passively correctable. Surgical treatment is an outpatient procedure that involves releasing the thumb flexor tendon from a small fibrous sheath called the A1 pulley. The overall recurrence rate after surgery is 1.4%. Our recommendation is for early referral to a pediatric orthopedic surgeon to evaluate for the need for surgical intervention. Copyright 2016, SLACK Incorporated.

  19. The ATLAS Tau Trigger

    CERN Document Server

    Rados, PK; The ATLAS collaboration


    Physics processes involving tau leptons play a crucial role in understanding particle physics at the high energy frontier. The ability to efficiently trigger on events containing hadronic tau decays is therefore of particular importance to the ATLAS experiment. During the 2012 run, the Large Hadronic Collder (LHC) reached instantaneous luminosities of nearly $10^{34} cm^{-2}s^{-1}$ with bunch crossings occurring every $50 ns$. This resulted in a huge event rate and a high probability of overlapping interactions per bunch crossing (pile-up). With this in mind it was necessary to design an ATLAS tau trigger system that could reduce the event rate to a manageable level, while efficiently extracting the most interesting physics events in a pile-up robust manner. In this poster the ATLAS tau trigger is described, its performance during 2012 is presented, and the outlook for the LHC Run II is briefly summarized.

  20. Microfabricated triggered vacuum switch (United States)

    Roesler, Alexander W [Tijeras, NM; Schare, Joshua M [Albuquerque, NM; Bunch, Kyle [Albuquerque, NM


    A microfabricated vacuum switch is disclosed which includes a substrate upon which an anode, cathode and trigger electrode are located. A cover is sealed over the substrate under vacuum to complete the vacuum switch. In some embodiments of the present invention, a metal cover can be used in place of the trigger electrode on the substrate. Materials used for the vacuum switch are compatible with high vacuum, relatively high temperature processing. These materials include molybdenum, niobium, copper, tungsten, aluminum and alloys thereof for the anode and cathode. Carbon in the form of graphitic carbon, a diamond-like material, or carbon nanotubes can be used in the trigger electrode. Channels can be optionally formed in the substrate to mitigate against surface breakdown.

  1. ALICE High Level Trigger

    CERN Multimedia

    Alt, T


    The ALICE High Level Trigger (HLT) is a computing farm designed and build for the real-time, online processing of the raw data produced by the ALICE detectors. Events are fully reconstructed from the raw data, analyzed and compressed. The analysis summary together with the compressed data and a trigger decision is sent to the DAQ. In addition the reconstruction of the events allows for on-line monitoring of physical observables and this information is provided to the Data Quality Monitor (DQM). The HLT can process event rates of up to 2 kHz for proton-proton and 200 Hz for Pb-Pb central collisions.

  2. Revisiting Pneumatic Nail Gun Trigger Recommendations. (United States)

    Albers, James; Lowe, Brian; Lipscomb, Hester; Hudock, Stephen; Dement, John; Evanoff, Bradley; Fullen, Mark; Gillen, Matt; Kaskutas, Vicki; Nolan, James; Patterson, Dennis; Platner, James; Pompeii, Lisa; Schoenfisch, Ashley


    Use of a pneumatic nail gun with a sequential actuation trigger (SAT) significantly diminishes the risk for acute traumatic injury compared to use of a contact actuation trigger (CAT) nail gun. A theoretically-based increased risk of work-related musculoskeletal disorders from use of a SAT nail gun, relative to CAT, appears unlikely and remains unproven. Based on current knowledge, the use of CAT nail guns cannot be justified as a safe alternative to SAT nail guns. This letter provides a perspective of ergonomists and occupational safety researchers recommending the use of the sequential actuation trigger for all nail gun tasks in the construction industry.

  3. Diuretics and disorders of calcium homeostasis. (United States)

    Grieff, Marvin; Bushinsky, David A


    Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Muon Trigger for Mobile Phones (United States)

    Borisyak, M.; Usvyatsov, M.; Mulhearn, M.; Shimmin, C.; Ustyuzhanin, A.


    The CRAYFIS experiment proposes to use privately owned mobile phones as a ground detector array for Ultra High Energy Cosmic Rays. Upon interacting with Earth’s atmosphere, these events produce extensive particle showers which can be detected by cameras on mobile phones. A typical shower contains minimally-ionizing particles such as muons. As these particles interact with CMOS image sensors, they may leave tracks of faintly-activated pixels that are sometimes hard to distinguish from random detector noise. Triggers that rely on the presence of very bright pixels within an image frame are not efficient in this case. We present a trigger algorithm based on Convolutional Neural Networks which selects images containing such tracks and are evaluated in a lazy manner: the response of each successive layer is computed only if activation of the current layer satisfies a continuation criterion. Usage of neural networks increases the sensitivity considerably comparable with image thresholding, while the lazy evaluation allows for execution of the trigger under the limited computational power of mobile phones.

  5. Calcium dependence of inactivation of calcium release from the sarcoplasmic reticulum in skeletal muscle fibers. (United States)

    Simon, B J; Klein, M G; Schneider, M F


    inactivation. Thus, equilibrium inactivation of calcium release appears to be produced by rather modest increases in [Ca2+] above the resting level and in a steeply calcium-dependent manner. However, the inactivation develops relatively slowly even during marked elevation of [Ca2+], indicating that a calcium-independent transition appears to occur after the initial calcium-binding step.

  6. Calcium affects on vascular endpoints

    Directory of Open Access Journals (Sweden)

    Patel Vaishali B


    Full Text Available Abstract Calcium is one of the most abundant minerals in the body and its metabolism is one of the basic biologic processes in humans. Although historically linked primarily to bone structural development and maintenance, calcium is now recognized as a key component of many physiologic pathways necessary for optimum health including cardiovascular, neurological, endocrine, renal, and gastrointestinal systems. A recent meta-analysis published in August 2011 showed a potential increase in cardiovascular events related to calcium supplementation. The possible mechanism of action of this correlation has not been well elucidated. This topic has generated intense interest due to the widespread use of calcium supplements, particularly among the middle aged and elderly who are at the most risk from cardiac events. Prior studies did not control for potential confounding factors such as the use of statins, aspirin or other medications. These controversial results warrant additional well-designed studies to investigate the relationship between calcium supplementation and cardiovascular outcomes. The purpose of this review is to highlight the current literature in regards to calcium supplementation and cardiovascular health; and to identify areas of future research.

  7. Multitrophic effects of calcium availability on invasive alien plants, birds, and bird prey items (United States)

    Vince D' Amico; Greg Shriver; Jake Bowman; Meg Ballard; Whitney Wiest; Liz Tymkiw; Melissa. Miller


    Acid rain alters forest soil calcium concentrations in two ways: (1) hydrogen ions displace exchangeable calcium adsorbed to soil surfaces, and (2) aluminum is released to soil water by acid rain and displaces adsorbed calcium. This increases the absorption of aluminum by plant roots, and decreases the absorption of calcium, causing calcium to be more readily leached...

  8. The ATLAS Electron and Photon Trigger

    CERN Document Server

    Jones, Samuel David; The ATLAS collaboration


    Electron and photon triggers covering transverse energies from 5 GeV to several TeV are essential for signal selection in a wide variety of ATLAS physics analyses to study Standard Model processes and to search for new phenomena. Final states including leptons and photons had, for example, an important role in the discovery and measurement of the Higgs boson. Dedicated triggers are also used to collect data for calibration, efficiency and fake rate measurements. The ATLAS trigger system is divided in a hardware-based Level-1 trigger and a software-based high-level trigger, both of which were upgraded during the LHC shutdown in preparation for Run-2 operation. To cope with the increasing luminosity and more challenging pile-up conditions at a center-of-mass energy of 13 TeV, the trigger selections at each level are optimized to control the rates and keep efficiencies high. To achieve this goal multivariate analysis techniques are used. The ATLAS electron and photon triggers and their performance with Run 2 dat...

  9. The ATLAS Electron and Photon Trigger

    CERN Document Server

    Jones, Samuel David; The ATLAS collaboration


    Electron and photon triggers covering transverse energies from 5 GeV to several TeV are essential for signal selection in a wide variety of ATLAS physics analyses to study Standard Model processes and to search for new phenomena. Final states including leptons and photons had, for example, an important role in the discovery and measurement of the Higgs boson. Dedicated triggers are also used to collect data for calibration, efficiency and fake rate measurements. The ATLAS trigger system is divided in a hardware-based Level-1 trigger and a software-based high-level trigger, both of which were upgraded during the LHC shutdown in preparation for Run-2 operation. To cope with the increasing luminosity and more challenging pile-up conditions at a center-of-mass energy of 13 TeV, the trigger selections at each level are optimized to control the rates and keep efficiencies high. To achieve this goal multivariate analysis techniques are used. The ATLAS electron and photon triggers and their performance with Run 2 dat...

  10. Upgrade of the CMS Global Muon Trigger

    CERN Document Server

    Jeitler, Manfred; Rabady, Dinyar; Sakulin, Hannes; Stahl, Achim


    The increase in center-of-mass energy and luminosity for Run-II of the Large Hadron Collider poses new challenges for the trigger systems of the experiments. To keep triggering with a similar performance as in Run-I, the CMS muon trigger is currently being upgraded. The new algorithms will provide higher resolution, especially for the muon transverse momentum and will make use of isolation criteria that combine calorimeter with muon information already in the level-1 trigger. The demands of the new algorithms can only be met by upgrading the level-1 trigger system to new powerful FPGAs with high bandwidth I/O. The processing boards will be based on the new μTCA standard. We report on the planned algorithms for the upgraded Global Muon Trigger (μGMT) which sorts and removes duplicates from boundaries of the muon trigger sub-systems. Furthermore, it determines how isolated the muon candidates are based on calorimetric energy deposits. The μGMT will be implemented using a processing board that features a larg...

  11. The ATLAS Trigger Performance and Evolution

    CERN Document Server

    Petersen, B A; The ATLAS collaboration


    During the data taking period from 2009 until 2012, the ATLAS trigger has been very successfully used to collect proton-proton data at LHC centre-of-mass energies between 900 GeV and 8 TeV. The three-level trigger system reduces the event rate from the design bunch-crossing rate of 40 MHz to an average recording rate of about 300 Hz. Using custom electronics with input from the calorimeter and muon detectors, the first level rejects most background collisions in less than 2.5 microseconds. Then follow two levels of software-based triggers. The trigger system is designed to select events by identifying muons, electrons, photons, taus, jets and B hadron candidates, as well as using global event signatures, such as missing transverse energy. We give an overview of the strategy and performance of the different trigger selections based mainly on the experience during the 2011-2012 LHC run, where the trigger menu needed quick adaptations to the continuous increase of luminosity. Examples of trigger efficiencies and...

  12. The Role of Calcium in Osteoporosis (United States)

    Arnaud, C. D.; Sanchez, S. D.


    Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

  13. Substitutions in Calcium Aluminates and Calcium Aluminoferrites. (United States)


  14. The Risks and Benefits of Calcium Supplementation

    Directory of Open Access Journals (Sweden)

    Chan Soo Shin


    Full Text Available The association between calcium supplementation and adverse cardiovascular events has recently become a topic of debate due to the publication of two epidemiological studies and one meta-analysis of randomized controlled clinical trials. The reports indicate that there is a significant increase in adverse cardiovascular events following supplementation with calcium; however, a number of experts have raised several issues with these reports such as inconsistencies in attempts to reproduce the findings in other populations and questions concerning the validity of the data due to low compliance, biases in case ascertainment, and/or a lack of adjustment. Additionally, the Auckland Calcium Study, the Women's Health Initiative, and many other studies included in the meta-analysis obtained data from calcium-replete subjects and it is not clear whether the same risk profile would be observed in populations with low calcium intakes. Dietary calcium intake varies widely throughout the world and it is especially low in East Asia, although the risk of cardiovascular events is less prominent in this region. Therefore, clarification is necessary regarding the occurrence of adverse cardiovascular events following calcium supplementation and whether this relationship can be generalized to populations with low calcium intakes. Additionally, the skeletal benefits from calcium supplementation are greater in subjects with low calcium intakes and, therefore, the risk-benefit ratio of calcium supplementation is likely to differ based on the dietary calcium intake and risks of osteoporosis and cardiovascular diseases of various populations. Further studies investigating the risk-benefit profiles of calcium supplementation in various populations are required to develop population-specific guidelines for individuals of different genders, ages, ethnicities, and risk profiles around the world.

  15. Electroconvulsive stimulations prevent chronic stress-induced increases in L-type calcium channel mRNAs in the hippocampus and basolateral amygdala

    DEFF Research Database (Denmark)

    Maigaard, Katrine; Pedersen, Ida Hageman; Jørgensen, Anders


    in the brain. We find that stress tended to upregulate Ca(v)1.2 and Ca(v)1.3 channels in a brain region specific manner, while ECS tended to normalise this effect. This was more pronounced for Ca(v)1.2 channels, where stress clearly increased expression in both the basolateral amygdala, dentate gyrus and CA3...

  16. Monocytes from spontaneously hypertensive rats show increased store-operated and second messenger-operated calcium influx mediated by transient receptor potential canonical Type 3 channels

    DEFF Research Database (Denmark)

    Liu, Dao Yan; Scholze, Alexandra; Kreutz, Reinhold


    We recently showed that increased expression of the transient receptor potential canonical Type 3 (TRPC3) channel is associated with genetic hypertension. It is unknown whether store-operated TRPC3 channels, which are activated after depletion of intracellular stores, or second messenger-operated...

  17. Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity. (United States)

    Lau, K; Langman, C B; Gafter, U; Dudeja, P K; Brasitus, T A


    Changes in Ca absorption have been described in the spontaneously hypertensive rat (SHR) compared with Wistar-Kyoto (WKy) rats. In 3.5-wk-old SHR and age-matched WKy controls, we measured direct arterial blood pressure, Ca absorption, and serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels and small intestine brush border membrane (BBM) fluidity and lipid composition. The two objectives were (a) to define the nature of the absorptive changes before detectable hypertension and (b) to evaluate the potential mechanism(s). We found that even at this normotensive stage (106 +/- 4 vs. 107 +/- 2 torr for the female and 109 +/- 3 vs. 104 +/- 3 torr for the male), the SHR (a) absorbed more Ca (1.46 +/- 0.06 vs. 1.14 +/- 0.08 mmol/d and 1.53 +/- 0.06 vs. 1.28 +/- 0.06 mmol/d, respectively) and retained more Ca, (b) had higher serum 1,25(OH)2D3 levels (340 +/- 36 vs. 160 +/- 18 pg/ml and 230 +/- 25 vs. 150 +/- 16 pg/ml, respectively), and (c) possessed BBM with increased fluidity and with reduced fatty acyl saturation index owing to decreased stearic (32.2 +/- 2.6% vs. 38.2 +/- 0.9%) but increased linoleic acids (12.2 +/- 2.0% vs. 7.6 +/- 1.6%). These results demonstrate increased Ca absorption in prehypertensive SHR associated with increased serum 1,25(OH)2D3 levels, increased intestinal BBM fluidity, and reduced saturation index, which singly or in combination could produce the changes in intestinal Ca transport.

  18. The ATLAS Tau Trigger

    CERN Document Server

    Rados, PK; The ATLAS collaboration


    The tau lepton plays a crucial role in understanding particle physics at the Tera scale. One of the most promising probes of the Higgs boson coupling to fermions is with detector signatures involving taus. In addition, many theories beyond the Standard Model, such as supersymmetry and exotic particles (Wʹ and Zʹ), predict new physics with large couplings to taus. The ability to trigger on hadronic tau decays is therefore critical to achieving the physics goals of the ATLAS experiment. The higher instantaneous luminosities of proton-proton collisions achieved by the Large Hadron Collider (LHC) in 2012 resulted in a larger probability of overlap (pile-up) between bunch crossings, and so it was critical for ATLAS to have an effective tau trigger strategy. The details of this strategy are summarized in this paper, and the results of the latest performance measurements are presented.

  19. The ATLAS Tau Trigger

    CERN Document Server

    Rados, PK; The ATLAS collaboration


    The tau lepton plays a crucial role in understanding particle physics at the Tera scale. One of the most promising probes of the Higgs boson coupling to fermions is with detector signatures involving taus. In addition, many theories beyond the Standard Model, such as supersymmetry and exotic particles (Wʹ′ and Zʹ′), predict new physics with large couplings to taus. The ability to trigger on hadronic tau decays is therefore critical to achieving the physics goals of the ATLAS experiment. The higher instantaneous luminosities of proton-proton collisions achieved by the Large Hadron Collider (LHC) in 2012 resulted in a larger probability of overlap (pile-up) between bunch crossings, and so it was critical for ATLAS to have an effective tau trigger strategy. The details of this strategy are summarized in this poster, and the latest performance measurements are presented.

  20. Peanut (Arachis hypogaea L.) Cultivar Response to Prohexadione Calcium (United States)

    Peanut digging efficiency can be reduced if row visibility is limited by excessive vegetation. The plant growth regulator prohexadione calcium retards vegetative growth and improves row visibility by inhibiting internode elongation. In some instances, prohexadione calcium also increases pod yield....

  1. New Fast Interaction Trigger for ALICE (United States)

    Trzaska, Wladyslaw Henryk


    The LHC heavy-ion luminosity and collision rate from 2021 onwards will considerably exceed the design parameters of the present ALICE forward trigger detectors and the introduction of the Muon Forward Tracker (MFT) will significantly reduce the space available for the new trigger detectors. To comply with these conditions a new Fast Interaction Trigger (FIT) will be built. FIT will be the main forward trigger, luminometer, and interaction-time detector. It will also determine multiplicity, centrality, and reaction plane of heavy-ion collisions. FIT will consist of two arrays of Cherenkov quartz radiators with MCP-PMT sensors and of a plastic scintillator ring. By increasing the overall acceptance of FIT, the scintillator will improve centrality and event plane resolution. It will also add sensitivity for the detection of beam-gas events and provide some degree of redundancy. FIT is currently undergoing an intense R&D and prototyping period. It is scheduled for installation in ALICE during 2020.

  2. New Fast Interaction Trigger for ALICE

    Energy Technology Data Exchange (ETDEWEB)

    Trzaska, Wladyslaw Henryk


    The LHC heavy-ion luminosity and collision rate from 2021 onwards will considerably exceed the design parameters of the present ALICE forward trigger detectors and the introduction of the Muon Forward Tracker (MFT) will significantly reduce the space available for the new trigger detectors. To comply with these conditions a new Fast Interaction Trigger (FIT) will be built. FIT will be the main forward trigger, luminometer, and interaction-time detector. It will also determine multiplicity, centrality, and reaction plane of heavy-ion collisions. FIT will consist of two arrays of Cherenkov quartz radiators with MCP-PMT sensors and of a plastic scintillator ring. By increasing the overall acceptance of FIT, the scintillator will improve centrality and event plane resolution. It will also add sensitivity for the detection of beam-gas events and provide some degree of redundancy. FIT is currently undergoing an intense R&D and prototyping period. It is scheduled for installation in ALICE during 2020.


    Polyakova, E P; Ksenofontov, D A; Revyakin, A O; Ivanov, A A


    Experiments on goats and rabbits showed that zinc supplement to the diet leads to calcium concentration rise in muscle, bone and blood of animals. However, this rise was not adequate to increase in.zinc consumption. The bulk of alimentary zinc stayed in soluble fraction, dense endogen fraction and infusoria fraction of digesta and stimulated calcium release from food particles, it's accumulation in digesta fractions and calcium utilization on the whole. Authors estimate animal digesta as homeostatic, spatial organized, endogenic formation in which zinc and calcium are functionally dependent through enteral mucosa.

  4. Physics issues on triggering

    Indian Academy of Sciences (India)

    The detector at the international linear collider (ILC) should be able to run 'trig- gerless' which means that all events can be read out and then be analysed with the offline reconstruction program in a trigger farm. The event rates for 'high Q2' events like W-pairs or q¯q are low, about 0.1/train. However, there is a significant.

  5. Neural networks for triggering

    Energy Technology Data Exchange (ETDEWEB)

    Denby, B. (Fermi National Accelerator Lab., Batavia, IL (USA)); Campbell, M. (Michigan Univ., Ann Arbor, MI (USA)); Bedeschi, F. (Istituto Nazionale di Fisica Nucleare, Pisa (Italy)); Chriss, N.; Bowers, C. (Chicago Univ., IL (USA)); Nesti, F. (Scuola Normale Superiore, Pisa (Italy))


    Two types of neural network beauty trigger architectures, based on identification of electrons in jets and recognition of secondary vertices, have been simulated in the environment of the Fermilab CDF experiment. The efficiencies for B's and rejection of background obtained are encouraging. If hardware tests are successful, the electron identification architecture will be tested in the 1991 run of CDF. 10 refs., 5 figs., 1 tab.

  6. [Regulatory mechanism of calcium metabolism. (United States)

    Ozono, Keiichi

    It is often difficult for terrestrial animals to take enough calcium. To maintain serum or extracellular calcium levels is very important for muscle and nerve function. Two major regulators to increase the serum calcium levels are parathyroid hormone(PTH)and vitamin D. PTH binds to the G protein coupling receptor, PTH1R, and increases intracellular cAMP levels. Impirement in the PTH signalling causes many diseases such as pseudohypoparathyroidism and acrodysostosis with hormone resistance. Vitamin D is activated to 1,25-dihydroxyvitamin D[1,25(OH)2D]by two steps of hydroxylation which occurs in the Liver and Kidney. Then, 1,25(OH)2D binds to vitamin D receptor(VDR), which works as a ligand-dependent transcription factor. Hypocalcemia and hypercalcemia are caused by various disorders including abnormal regulation of PTH and vitamin D production and their signal transduction.

  7. Simulation of the ATLAS New Small Wheel Trigger Sysmtem

    CERN Document Server

    Saito, Tomoyuki; The ATLAS collaboration


    The instantaneous luminosity of the Large Hadron Collider (LHC) at CERN will be increased up to a factor of five with respect to the original design value to explore higher energy scale. In order to benefit from the expected high luminosity performance, the first station of the ATLAS muon end-cap Small Wheel system will be replaced by a New Small Wheel (NSW) detector. The NSW provide precise track segment information to the muon Level-1 trigger to reduce fake triggers. This contribution will summarize a detail of the NSW trigger decision system, track reconstruction algorithm implemented into the trigger processor and results of performance studies on the trigger system.

  8. Relative bioavailability of calcium-rich dietary sources in the elderly. (United States)

    Martini, Ligia; Wood, Richard J


    The recent increase in the dietary calcium recommendation from 800 to 1200 mg/d for persons aged > 51 y has made it important to identify alternative high-calcium dietary sources that the elderly can use in meeting their calcium requirement. We determined the bioavailability of calcium from 3 different sources: orange juice fortified with calcium-citrate malate, skim milk, and a calcium carbonate supplement. Twelve subjects [9 women and 3 men with a mean (+/- SEM) age of 70 +/- 3 and 76 +/- 6 y, respectively] consumed low-calcium (300 mg/d) and high-calcium (1300 mg/d) diets for three 1-wk periods each during a 6-wk crossover study. The acute biochemical response to calcium from each of the 3 sources was assessed during a 4-h period after the initial breakfast meal of the high-calcium diet. Postprandial suppression of serum parathyroid hormone did not differ significantly between the test meals containing calcium-fortified orange juice, the calcium carbonate supplement, and milk. This finding suggests that the calcium bioavailability from the 3 sources was equivalent. During the 1-wk high-calcium diet periods, fasting serum calcium increased by 3% (P calcium diet period. However, no differences among the supplemental calcium sources were found in these calcium-responsive measures or fasting serum parathyroid hormone concentration. In elderly subjects, the calcium bioavailability of the 3 high-calcium dietary sources tested was equivalent, during both the acute postprandial and longer-term periods.

  9. Effects of modulation of calcium levels and calcium fluxes on ABA- induced gene expression in barley aleurone

    NARCIS (Netherlands)

    Meulen, R.M. van der; Visser, K.; Wang, M.


    We present data to elucidate the involvement of calcium ions in abscisic acid (ABA)-induced gene expression. Modulation of external calcium concentrations was able to affect ABA-induced specific RAB gene expression. At a constant ABA level with increasing extracellular calcium level, an increasing

  10. Modulation of L-type calcium channels by sodium ions.


    Balke, C W; Wier, W G


    It is universally believed that the removal of external sodium ions is without effect on calcium current. We now report that in enzymatically isolated guinea pig ventricular cells, the replacement of external sodium ions with certain other cations causes a 3- to 6-fold increase in peak L-type calcium current. The increase in current is reversibly blocked by L-type calcium-channel antagonists, not mediated by changes in internal calcium, and is inhibited by intracellular 5'-adenylyl imidodipho...

  11. Isolating Triggered Star Formation

    Energy Technology Data Exchange (ETDEWEB)

    Barton, Elizabeth J.; Arnold, Jacob A.; /UC, Irvine; Zentner, Andrew R.; /KICP, Chicago /Chicago U., EFI; Bullock, James S.; /UC, Irvine; Wechsler, Risa H.; /KIPAC, Menlo


    Galaxy pairs provide a potentially powerful means of studying triggered star formation from galaxy interactions. We use a large cosmological N-body simulation coupled with a well-tested semi-analytic substructure model to demonstrate that the majority of galaxies in close pairs reside within cluster or group-size halos and therefore represent a biased population, poorly suited for direct comparison to 'field' galaxies. Thus, the frequent observation that some types of galaxies in pairs have redder colors than 'field' galaxies is primarily a selection effect. We use our simulations to devise a means to select galaxy pairs that are isolated in their dark matter halos with respect to other massive subhalos (N= 2 halos) and to select a control sample of isolated galaxies (N= 1 halos) for comparison. We then apply these selection criteria to a volume-limited subset of the 2dF Galaxy Redshift Survey with M{sub B,j} {le} -19 and obtain the first clean measure of the typical fraction of galaxies affected by triggered star formation and the average elevation in the star formation rate. We find that 24% (30.5 %) of these L* and sub-L* galaxies in isolated 50 (30) h{sup -1} kpc pairs exhibit star formation that is boosted by a factor of {approx}> 5 above their average past value, while only 10% of isolated galaxies in the control sample show this level of enhancement. Thus, 14% (20 %) of the galaxies in these close pairs show clear triggered star formation. Our orbit models suggest that 12% (16%) of 50 (30) h{sup -1} kpc close pairs that are isolated according to our definition have had a close ({le} 30 h{sup -1} kpc) pass within the last Gyr. Thus, the data are broadly consistent with a scenario in which most or all close passes of isolated pairs result in triggered star formation. The isolation criteria we develop provide a means to constrain star formation and feedback prescriptions in hydrodynamic simulations and a very general method of understanding

  12. Cytoplasmic calcium increase via fusion with inactivated Sendai virus induces apoptosis in human multiple myeloma cells by downregulation of c-Myc oncogene. (United States)

    Jiang, Yingzhe; Saga, Kotaro; Miyamoto, Yasuhide; Kaneda, Yasufumi


    Because the emergence of drug resistance is a major limitation of current treatments for multiple myeloma (MM), it is necessary to continuously develop novel anticancer strategies. Here, using an inactivated Sendai virus (Hemagglutinating Virus of Japan; HVJ) envelope (HVJ-E), we discovered that increase of cytoplasmic Ca2+ by virus-cell fusion significantly induced apoptosis against human MM cells but not peripheral blood mononuclear cells from healthy donors. Interaction of F protein of HVJ-E with MM cells increased intracellular Ca2+ level of MMs by the induction of Ca2+ efflux from endoplasmic reticulum but not influx from extracellular region. The elevation of the Ca2+ cytoplasmic level induced SMAD1/5/8 phosphorylation and translocation into the nucleus, and SMAD1/5/8 and SMAD4 complex suppressed c-Myc transcription. Meanwhile, HVJ-E decreases S62 phosphorylation of c-Myc and promotes c-Myc protein degradation. Thus, HVJ-E-induced cell death of MM resulted from suppression of c-Myc by both destabilization of c-Myc protein and downregulation of c-Myc transcription. This study indicates that HVJ-E will be a promising tool for MM therapy.

  13. Performance of the ATLAS Muon Trigger and Phase-1 Upgrade of Level-1 Endcap Muon Trigger

    CERN Document Server

    Mizukami, Atsushi; The ATLAS collaboration


    The ATLAS experiment utilises a trigger system to efficiently record interesting events. It consists of first-level and high-level triggers. The first-level trigger is implemented with custom-built hardware to reduce the event rate from 40 MHz to100 kHz. Then the software-based high-level triggers refine the trigger decisions reducing the output rate down to 1 kHz. Events with muons in the final state are an important signature for many physics topics at the LHC. An efficient trigger on muons and a detailed understanding of its performance are required. Trigger efficiencies are, for example, obtained from the muon decay of Z boson, with a Tag&Probe method, using proton-proton collision data collected in 2016 at a centre-of-mass energy of 13 TeV. The LHC is expected to increase its instantaneous luminosity to $3\\times10^{34} \\rm{cm^{-2}s^{-1}}$ after the phase-1 upgrade between 2018-2020. The upgrade of the ATLAS trigger system is mandatory to cope with this high-luminosity. In the phase-1 upgrade, new det...

  14. Calcium channel blocker overdose (United States)

    ... page: // Calcium-channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium-channel blockers are a type of medicine used to ...

  15. Fenoprofen calcium overdose (United States)

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

  16. Increase vs. decrease of calcium uptake by isolated heart cells induced by H/sub 2/O/sub 2/ vs. HOCl

    Energy Technology Data Exchange (ETDEWEB)

    Kaminishi, T.; Matsuoka, T.; Yanagishita, T.; Kako, K.J.


    Adult rat heart myocytes were labeled rapidly with exogenous (45Ca2+). Addition of 2.5 mM H2O2 to the heart cell suspension raised the content of rapidly exchangeable intracellular Ca2+ twofold, whereas addition of 1-30 mM HOCl decreased the Ca2+ content. The H2O2-induced increase in Ca2+ content was dependent on the medium Na+, pH, and temperature but was not significantly affected by addition of verapamil, diltiazem, amiloride, or 3-aminobenzamide. The (3H)ouabain binding to myocytes was suppressed by H2O2, whereas the Ca2+ efflux from myocytes was not influenced. An uncoupler, carbonyl cyanide m-chlorophenylhydrazone, reduced Ca2+ content, implying that the H2O2-induced change in Ca2+ content was not directly related to ATP depletion. On the other hand, the H2O2-induced Ca2+ accumulation in myocytes was prevented by deferoxamine or o-phenanthroline. These results suggest that H2O2 inhibited Na+-K+-ATPase, resulting in an increase in intracellular Na+ concentration and stimulation of sarcolemmal Na+-Ca2+ exchange activity, which caused a transient net Ca2+ influx into myocytes. By contrast, HOCl decreased the Ca2+ content of the rapidly exchangeable pool below control levels and this action of HOCl was antagonized by 1,4-dithiothreitol. HOCl accelerated Ca2+ efflux from myocytes. Ca2+ uptake and Ca2+-ATPase of the isolated sarcoplasmic reticular (SR) fraction were highly sensitive to the action of HOCl. Ca2+ uptake by intracellular sites, studied with myocytes permeabilized with digitonin, was inhibited by both H2O2 and HOCl. Thus these results suggest that HOCl inhibits the SR Ca2+ pump, resulting in the observed acceleration of Ca2+ efflux from and decline in Ca2+ content of myocytes.

  17. Role of calcium in selenium cataract. (United States)

    Shearer, T R; David, L L

    The purpose of this research was to test the role of certain minerals in the formation of cataract caused by an overdose of selenium. Several pieces of information indicated that lenticular calcium may play an important role in selenite cataractogenesis: 1) Lens calcium concentrations in selenite treated rats were increased more than 5-fold, and the increase in lens calcium was localized in the nucleus. 2) Lens calcium concentrations were elevated at least one full day before actual formation of nuclear cataract, but serum calcium levels were not changed. 3) In older rats not susceptible to selenite cataract, lens calcium was not significantly increased. 4) No evidence was found for a generalized disruption in lens permeability, since no major changes in lens water, sodium, and potassium levels were observed, and 5) when levels of calcium observed in selenite cataract were added to solutions of soluble proteins from rat lenses, light scattering was increased. Selenium-overdose cataracts may provide an important model for studies on the role of calcium in cataractogenesis.

  18. Adding calcium improves lithium ferrite core (United States)

    Lessoff, H.


    Adding calcium increases uniformity of grain growth over a wide range of sintering temperatures and reduces porosity within the grain. Ferrite cores containing calcium have square hysteresis loops and high curie temperatures, making them useful in coincident current memories of digital electronic computers.

  19. Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium–calcium overload


    Noble, D; Noble, P J


    Late sodium current in cardiac cells is very small compared with the fast component, but as it flows throughout the action potential it may make a substantial contribution to sodium loading during each cardiac cycle. Late sodium current may contribute to triggering arrhythmia in two ways: by causing repolarisation failure (early afterdepolarisations); and by triggering late afterdepolarisations attributable to calcium oscillations in sodium–calcium overload conditions. Reduction of late sodiu...

  20. Converging roles of ion channels, calcium, metabolic stress, and activity pattern of Substantia nigra dopaminergic neurons in health and Parkinson's disease. (United States)

    Duda, Johanna; Pötschke, Christina; Liss, Birgit


    Dopamine-releasing neurons within the Substantia nigra (SN DA) are particularly vulnerable to degeneration compared to other dopaminergic neurons. The age-dependent, progressive loss of these neurons is a pathological hallmark of Parkinson's disease (PD), as the resulting loss of striatal dopamine causes its major movement-related symptoms. SN DA neurons release dopamine from their axonal terminals within the dorsal striatum, and also from their cell bodies and dendrites within the midbrain in a calcium- and activity-dependent manner. Their intrinsically generated and metabolically challenging activity is created and modulated by the orchestrated function of different ion channels and dopamine D2-autoreceptors. Here, we review increasing evidence that the mechanisms that control activity patterns and calcium homeostasis of SN DA neurons are not only crucial for their dopamine release within a physiological range but also modulate their mitochondrial and lysosomal activity, their metabolic stress levels, and their vulnerability to degeneration in PD. Indeed, impaired calcium homeostasis, lysosomal and mitochondrial dysfunction, and metabolic stress in SN DA neurons represent central converging trigger factors for idiopathic and familial PD. We summarize double-edged roles of ion channels, activity patterns, calcium homeostasis, and related feedback/feed-forward signaling mechanisms in SN DA neurons for maintaining and modulating their physiological function, but also for contributing to their vulnerability in PD-paradigms. We focus on the emerging roles of maintained neuronal activity and calcium homeostasis within a physiological bandwidth, and its modulation by PD-triggers, as well as on bidirectional functions of voltage-gated L-type calcium channels and metabolically gated ATP-sensitive potassium (K-ATP) channels, and their probable interplay in health and PD. We propose that SN DA neurons possess several feedback and feed-forward mechanisms to protect and adapt

  1. Mechanism for Triggered Waves in Atrial Myocytes. (United States)

    Shiferaw, Yohannes; Aistrup, Gary L; Wasserstrom, J Andrew


    Excitation-contraction coupling in atrial cells is mediated by calcium (Ca) signaling between L-type Ca channels and Ryanodine receptors that occurs mainly at the cell boundary. This unique architecture dictates essential aspects of Ca signaling under both normal and diseased conditions. In this study we apply laser scanning confocal microscopy, along with an experimentally based computational model, to understand the Ca cycling dynamics of an atrial cell subjected to rapid pacing. Our main finding is that when an atrial cell is paced under Ca overload conditions, Ca waves can then nucleate on the cell boundary and propagate to the cell interior. These propagating Ca waves are referred to as "triggered waves" because they are initiated by L-type Ca channel openings during the action potential. These excitations are distinct from spontaneous Ca waves originating from random fluctuations of Ryanodine receptor channels, and which occur after much longer waiting times. Furthermore, we argue that the onset of these triggered waves is a highly nonlinear function of the sarcoplasmic reticulum Ca load. This strong nonlinearity leads to aperiodic response of Ca at rapid pacing rates that is caused by the complex interplay between paced Ca release and triggered waves. We argue further that this feature of atrial cells leads to dynamic instabilities that may underlie atrial arrhythmias. These studies will serve as a starting point to explore the nonlinear dynamics of atrial cells and will yield insights into the trigger and maintenance of atrial fibrillation. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Calcium and Mitosis (United States)

    Hepler, P.


    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.

  3. Preparation of calcium chloride-loaded solid lipid particles and heat-triggered calcium ion release

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Huangying; Kim, Jin-Chul [Kangwon National University, Chunchon (Korea, Republic of)


    CaCl{sub 2}-loaded solid lipid particles (SLPs) were prepared by a melt/emulsification/solidification method. CaCl{sub 2} microparticles (1-5 μm) could be obtained in a mortar with aid of the dispersant (Tween 80/Span80 (35/65, w/w)) when the ratio of CaCl{sub 2} to dispersant was 2 : 0.1 (w/w). SLP was prepared by dispersing 0.42 g of micronized CaCl{sub 2} particles in 2 g of molten PBSA, emulsifying the mixture at 85 .deg. C in 40 ml of Tween 20 solution (0.5% w/v), and quenching the emulsion in an ice bath. The diameter of CaCl{sub 2}-loaded SLP was 10-150 μm. The unenveloped CaCl{sub 2} could be removed by dialysis and the specific loading of CaCl{sub 2} in SLP was 0.036mg/mg. An EDS spectrum of CaCl{sub 2}-loaded SLP, which was dialyzed, showed that the unenveloped CaCl{sub 2} was completely removed. Any excipients (dispersant, Tween 20, CaCl{sub 2}) had little effect on the melting point of SLPs. No appreciable amount of Ca2+ was released in 20-50 .deg. C for 22 h. But the release degree at 60 .deg. C was significant (about 2.3%) during the same period. The matrix of the lipid particle was in a liquid state at 60 .deg. C, so CaCl{sub 2} particles could move freely and contact the surrounding water, leading to the release. At 70 .deg. C, the release degree at a given time was a few times higher than that obtained at 60 .deg. C.

  4. Increasing physical activity and decreasing sedentary activity in adolescent girls – The Incorporating More Physical Activity and Calcium in Teens (IMPACT study

    Directory of Open Access Journals (Sweden)

    Hergenroeder Albert


    Full Text Available Abstract Background Lack of regular physical activity and consequent sub-optimal bone mass acquisition in youth has been implicated as a primary cause of adult-onset osteoporosis. IMPACT was a behavioral theory-based 1 1/2 year randomized controlled field study aimed at increasing bone accretion in middle school girls. The objective of this study was to determine the intervention effects of the IMPACT program upon key physical and sedentary activity endpoints among schools that participated in the IMPACT study. Endpoints examined included weight bearing physical activity (WBPA; moderate to vigorous physical activity (MVPA; vigorous physical activity (VPA; MET (metabolic equivalent – weighted WBPA and MVPA; sedentary activity; before/after-school physical activity; and weekend physical activity. Methods Primary data analysis using a pretest-posttest control group design was conducted utilizing mixed model analysis of covariance. Data gathered from the IMPACT cohort from 2000–2002 were analyzed to determine baseline versus follow-up differences in activity endpoints. Confounders investigated included ethnicity, body mass index, menarcheal status, participation in 7th grade PE/athletics, friend/familial support and neighborhood safety. Results Follow-up means were higher for participating intervention schools relative to control schools for all physical activity variables but were statistically significant only for the following variables: daily minutes of vigorous physical activity (mean difference between Intervention (I and Control (C = 6.00↑ minutes, 95% CI = 5.82–6.18, p = 0.05, daily after school activity minutes (mean difference between I and C = 8.95↑ minutes, 95% CI = 8.69–9.21, p = 0.04, and daily weekend activity minutes (mean difference between I and C = 19.00↑ minutes, 95% CI = 18.40–19.60, p = 0.05. The intervention significantly reduced duration of student daily TV/Video watching (mean difference between I and C = 12

  5. Calcium- and Phosphorus-Supplemented Diet Increases Bone Mass after Short-Term Exercise and Increases Bone Mass and Structural Strength after Long-Term Exercise in Adult Mice: e0151995

    National Research Council Canada - National Science Library

    Michael A Friedman; Alyssa M Bailey; Matthew J Rondon; Erin M McNerny; Nadder D Sahar; David H Kohn


    .... Long-term exercise of 6-12 weeks in rodents increases bone mass and bone strength. However, in growing mice, a short-term exercise program of 3 weeks can limit increases in bone mass and structural strength, compared to non-exercised controls...

  6. Noradrenaline-induced increases in calcium and tension in skeletal muscle conductance and resistance arteries from rats with post-infarction heart failure

    DEFF Research Database (Denmark)

    Trautner, Simon; Amtorp, Ole; Boesgaard, Soren


    We tested the hypothesis that arterial reactivity to noradrenaline is augmented in congestive heart failure (CHF), which could contribute to the deleterious changes in peripheral vascular resistance and compliance in this condition. From male Wistar rats with post-infarction CHF and sham-operated......We tested the hypothesis that arterial reactivity to noradrenaline is augmented in congestive heart failure (CHF), which could contribute to the deleterious changes in peripheral vascular resistance and compliance in this condition. From male Wistar rats with post-infarction CHF and sham......-operated rats, skeletal muscle conductance and resistance arteries (mean lumen diameters: 514 and 186 microm) were isolated and mounted on wire myographs, and wall tension was recorded in response to cumulative application of acetylcholine and noradrenaline to the vessel segments. In a subset of experiments....... In the resistance arteries of CHF rats, the noradrenaline-induced increases in [Ca(2+)](i) were significantly enhanced (P=0.003). Despite the augmented [Ca(2+)](i) levels, the tension responses to noradrenaline were unaltered in these arteries. In the conductance arteries, there were no significant differences...

  7. Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention.

    Directory of Open Access Journals (Sweden)

    Ziying Han


    Full Text Available Hemorrhagic fever viruses, including the filoviruses (Ebola and Marburg and arenaviruses (Lassa and Junín viruses, are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines. Importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. Consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. An important cellular signal implicated previously in EBOV budding is calcium. Indeed, host cell calcium signals are increasingly being recognized to play a role in steps of entry, replication, and transmission for a range of viruses, but if and how filoviruses and arenaviruses mobilize calcium and the precise stage of virus transmission regulated by calcium have not been defined. Here we demonstrate that expression of matrix proteins from both filoviruses and arenaviruses triggers an increase in host cytoplasmic Ca2+ concentration by a mechanism that requires host Orai1 channels. Furthermore, we demonstrate that Orai1 regulates both VLP and infectious filovirus and arenavirus production and spread. Notably, suppression of the protein that triggers Orai activation (Stromal Interaction Molecule 1, STIM1 and genetic inactivation or pharmacological blockade of Orai1 channels inhibits VLP and infectious virus egress. These findings are highly significant as they expand our understanding of host mechanisms that may broadly control enveloped RNA virus budding, and they establish Orai and STIM1 as novel targets for broad-spectrum host-oriented therapeutics to combat these emerging BSL-4 pathogens and potentially other enveloped RNA viruses that bud via similar mechanisms.

  8. Calcium en cardioplegie

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Meijler, F.L.


    Coronary perfusion with a calcium-free solution, followed by reperfusion with a calcium containing solution, may result in acute myocardial cell death and in irreversible loss of the e1ectrical and mechanical activity of the heart. This phenomenon is known as the calcium paradox. A number of

  9. Khz-cp (crude polysaccharide extract obtained from the fusion of Ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis by increasing intracellular calcium levels and activating P38 and NADPH oxidase-dependent generation of reactive oxygen species in SNU-1 cells. (United States)

    Kim, Tae Hwan; Kim, Ju Sung; Kim, Zoo Haye; Huang, Ren Bin; Chae, Young Lye; Wang, Ren Sheng


    Khz-cp is a crude polysaccharide extract that is obtained after nuclear fusion in Ganoderma lucidum and Polyporus umbellatus mycelia (Khz). It inhibits the growth of cancer cells. Khz-cp was extracted by solvent extraction. The anti-proliferative activity of Khz-cp was confirmed by using Annexin-V/PI-flow cytometry analysis. Intracellular calcium increase and measurement of intracellular reactive oxygen species (ROS) were performed by using flow cytometry and inverted microscope. SNU-1 cells were treated with p38, Bcl-2 and Nox family siRNA. siRNA transfected cells was employed to investigate the expression of apoptotic, growth and survival genes in SNU-1 cells. Western blot analysis was performed to confirm the expression of the genes. In the present study, Khz-cp induced apoptosis preferentially in transformed cells and had only minimal effects on non-transformed cells. Furthermore, Khz-cp was found to induce apoptosis by increasing the intracellular Ca2+ concentration ([Ca2+]i) and activating P38 to generate reactive oxygen species (ROS) via NADPH oxidase and the mitochondria. Khz-cp-induced apoptosis was caspase dependent and occurred via a mitochondrial pathway. ROS generation by NADPH oxidase was critical for Khz-cp-induced apoptosis, and although mitochondrial ROS production was also required, it appeared to occur secondary to ROS generation by NADPH oxidase. Activation of NADPH oxidase was shown by the translocation of the regulatory subunits p47phox and p67phox to the cell membrane and was necessary for ROS generation by Khz-cp. Khz-cp triggered a rapid and sustained increase in [Ca2+]i that activated P38. P38 was considered to play a key role in the activation of NADPH oxidase because inhibition of its expression or activity abrogated membrane translocation of the p47phox and p67phox subunits and ROS generation. In summary, these data indicate that Khz-cp preferentially induces apoptosis in cancer cells and that the signaling mechanisms involve an

  10. Calcium content of different compositions of gallstones and pathogenesis of calcium carbonate gallstones. (United States)

    Yu, Ji-Kuen; Pan, Huichin; Huang, Shing-Moo; Huang, Nan-Lan; Yao, Chung-Chin; Hsiao, Kuang-Ming; Wu, Chew-Wun


    Our aim was to investigate the calcium content of different gallstone compositions and the pathogenic mechanisms of calcium carbonate gallstones. Between August 2001 and July 2007, gallstones from 481 patients, including 68 calcium carbonate gallstones, were analyzed for total calcium content. Gallbladder bile samples from 33 cases and six controls were analyzed for pH, carbonate anion level, free-ionized calcium concentration and saturation index for calcium carbonate. Total calcium content averaged 75.6 %, 11.8 %, and 4.2 % for calcium carbonate, calcium bilirubinate and cholesterol gallstones. In 29.4 % of patients, chronic and/or intermittent cystic duct obstructions were caused by polypoid lesions in the neck region and 70.6 % were caused by stones. A total of 82 % of patients had chronic low-grade inflammation of the gallbladder wall and 18.0 % had acute inflammatory exacerbations. In the bile, we found the mean pH, mean carbonate anion, free-ionized calcium concentrations, and mean saturation index for calcium carbonate to be elevated in comparison to controls. From our study, we found chronic and/or intermittent cystic duct obstructions and low-grade GB wall inflammation lead to GB epithelium hydrogen secretion dysfunction. Increased calcium ion efflux into the GB lumen combined with increased carbonate anion presence increases SI_CaCO(3) from 1 to 22.4. Thus, in an alkaline milieu with pH 7.8, calcium carbonate begins to aggregate and precipitate. Copyright © 2012. Published by Elsevier B.V.

  11. Level-1 Jets and Sums Trigger Performance

    CERN Document Server

    CMS Collaboration


    After the first long shutdown, the LHC has restarted at a centre-of-mass energy of 13 TeV. The LHC is expected to achieve an instantaneous luminosity larger than $10^{34} \\rm{cm}^{-2} \\rm{s}^{-1}$ and an average number of pile-up interactions of at least 40. The CMS Level-1 trigger architecture has undergone a full upgrade in order to maintain and improve the trigger performance under these new conditions. It will allow CMS to keep the trigger rate under control and to avoid a significant increase in trigger thresholds that would have a negative impact on the CMS physics programme. First studies of the performance of the calorimeter trigger upgrade for jets and energy sums are shown. Details of the algorithms and commissioning may be found in CMS-DP-2015-051 and the CMS Technical Design Report for the Level-1 Trigger upgrade: CERN-LHCC-2013-011, CMS-TDR-12 (2013)

  12. The spatial pattern of atrial cardiomyocyte calcium signalling modulates contraction. (United States)

    Mackenzie, Lauren; Roderick, H Llewelyn; Berridge, Michael J; Conway, Stuart J; Bootman, Martin D


    We examined the regulation of calcium signalling in atrial cardiomyocytes during excitation-contraction coupling, and how changes in the distribution of calcium impacts on contractility. Under control conditions, calcium transients originated in subsarcolemmal locations and showed local regeneration through activation of calcium-induced calcium release from ryanodine receptors. Despite functional ryanodine receptors being expressed at regular (approximately 2 microm) intervals throughout atrial myocytes, the subsarcolemmal calcium signal did not spread in a fully regenerative manner through the interior of a cell. Rather, there was a diminishing centripetal propagation of calcium. The lack of regeneration was due to mitochondria and SERCA pumps preventing the inward movement of calcium. Inhibiting these calcium buffering mechanisms allowed the globalisation of action potential-evoked responses. In addition, physiological positive inotropic agents, such as endothelin-1 and beta-adrenergic agonists, as well as enhanced calcium current, calcium store loading and inositol 1,4,5-trisphosphate infusion also led to regenerative global responses. The consequence of globalising calcium signals was a significant increase in cellular contraction. These data indicate how calcium signals and their consequences are determined by the interplay of multiple subcellular calcium management systems.

  13. Relationship of calcium absorption with 25(OH)D and calcium intake in children with rickets. (United States)

    Thacher, Tom D; Abrams, Steven A


    Nutritional rickets has long been considered a disease caused by vitamin D deficiency, but recent data indicate that inadequate dietary calcium intake is an important cause of rickets, particularly in tropical countries. Children with rickets due to calcium deficiency do not have very low 25(OH)D concentrations, and serum 1,25(OH)(2) D values are markedly elevated. Studies of Nigerian children with rickets demonstrated they have high fractional calcium absorption. A high-phytate diet was demonstrated to increase calcium absorption compared with the fasting state, and enzymatic dephytinization did not significantly improve calcium absorption. When given vitamin D, children with rickets have a marked increase in 1,25(OH)(2) D concentrations without any change in fractional calcium absorption. No positive relationship was found between fractional calcium absorption and serum 25(OH)D concentrations in children on low-calcium diets. More research is needed to understand the interaction between calcium and vitamin D and the role of vitamin D in calcium absorption. © 2010 International Life Sciences Institute.

  14. Tuning local calcium availability: cell-type-specific immobile calcium buffer capacity in hippocampal neurons. (United States)

    Matthews, Elizabeth A; Schoch, Susanne; Dietrich, Dirk


    It has remained difficult to ascribe a specific functional role to immobile or fixed intracellular calcium buffers in central neurons because the amount of these buffers is unknown. Here, we explicitly isolated the fixed buffer fraction by prolonged whole-cell patch-clamp dialysis and quantified its buffering capacity in murine hippocampal slices using confocal calcium imaging and the "added-buffer" approach. In dentate granule cells, the calcium binding ratio (κ) after complete washout of calbindin D28k (Cb), κfixed, displayed a substantial value of ∼100. In contrast, in CA1 oriens lacunosum moleculare (OLM) interneurons, which do not contain any known calcium-binding protein(s), κfixed amounted to only ∼30. Based on these values, a theoretical analysis of dendritic spread of calcium after local entry showed that fixed buffers, in the absence of mobile species, decrease intracellular calcium mobility 100- and 30-fold in granule cells and OLM cells, respectively, and thereby strongly slow calcium signals. Although the large κfixed alone strongly delays the spread of calcium in granule cells, this value optimizes the benefits of additionally expressing the mobile calcium binding protein Cb. With such high κfixed, Cb effectively increases the propagation velocity to levels seen in OLM cells and, contrary to expectation, does not affect the peak calcium concentration close to the source but sharpens the spatial and temporal calcium gradients. The data suggest that the amount of fixed buffers determines the temporal availability of calcium for calcium-binding partners and plays a pivotal role in setting the repertoire of cellular calcium signaling regimens.

  15. Synthesis of Trigger Properties (United States)

    Kupferman, Orna; Vardi, Moshe Y.

    In automated synthesis, we transform a specification into a system that is guaranteed to satisfy the specification. In spite of the rich theory developed for temporal synthesis, little of this theory has been reduced to practice. This is in contrast with model-checking theory, which has led to industrial development and use of formal verification tools. We address this problem here by considering a certain class of PSL properties; this class covers most of the properties used in practice by system designers. We refer to this class as the class of trigger properties.

  16. The ATLAS Trigger Algorithms for General Purpose Graphics Processor Units

    CERN Document Server

    Tavares Delgado, Ademar; The ATLAS collaboration


    The ATLAS Trigger Algorithms for General Purpose Graphics Processor Units Type: Talk Abstract: We present the ATLAS Trigger algorithms developed to exploit General­ Purpose Graphics Processor Units. ATLAS is a particle physics experiment located on the LHC collider at CERN. The ATLAS Trigger system has two levels, hardware-­based Level 1 and the High Level Trigger implemented in software running on a farm of commodity CPU. Performing the trigger event selection within the available farm resources presents a significant challenge that will increase future LHC upgrades. are being evaluated as a potential solution for trigger algorithms acceleration. Key factors determining the potential benefit of this new technology are the relative execution speedup, the number of GPUs required and the relative financial cost of the selected GPU. We have developed a trigger demonstrator which includes algorithms for reconstructing tracks in the Inner Detector and Muon Spectrometer and clusters of energy deposited in the Cal...

  17. Biotic Nitrogen Enrichment Regulates Calcium Sources to Forests (United States)

    Pett-Ridge, J. C.; Perakis, S. S.; Hynicka, J. D.


    Calcium is an essential nutrient in forest ecosystems that is susceptible to leaching loss and depletion. Calcium depletion can affect plant and animal productivity, soil acid buffering capacity, and fluxes of carbon and water. Excess nitrogen supply and associated soil acidification are often implicated in short-term calcium loss from soils, but the long-term role of nitrogen enrichment on calcium sources and resupply is unknown. Here we use strontium isotopes (87Sr/86Sr) as a proxy for calcium to investigate how soil nitrogen enrichment from biological nitrogen fixation interacts with bedrock calcium to regulate both short-term available supplies and the long-term sources of calcium in montane conifer forests. Our study examines 22 sites in western Oregon, spanning a 20-fold range of bedrock calcium on sedimentary and basaltic lithologies. In contrast to previous studies emphasizing abiotic control of weathering as a determinant of long-term ecosystem calcium dynamics and sources (via bedrock fertility, climate, or topographic/tectonic controls) we find instead that that biotic nitrogen enrichment of soil can strongly regulate calcium sources and supplies in forest ecosystems. For forests on calcium-rich basaltic bedrock, increasing nitrogen enrichment causes calcium sources to shift from rock-weathering to atmospheric dominance, with minimal influence from other major soil forming factors, despite regionally high rates of tectonic uplift and erosion that can rejuvenate weathering supply of soil minerals. For forests on calcium-poor sedimentary bedrock, we find that atmospheric inputs dominate regardless of degree of nitrogen enrichment. Short-term measures of soil and ecosystem calcium fertility are decoupled from calcium source sustainability, with fundamental implications for understanding nitrogen impacts, both in natural ecosystems and in the context of global change. Our finding that long-term nitrogen enrichment increases forest reliance on atmospheric

  18. A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties

    Directory of Open Access Journals (Sweden)

    Christine Dorothee Schmeitz


    Full Text Available Fate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic or initiates apoptosis depends on extracellular triggers and intracellular signalling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modelling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.

  19. Calcium sources applied to soil can replace leaf application in ‘Fuji’ apple tree


    Moeses Andrigo Danner; Silvia Scariotto; Idemir Citadin; Gener Augusto Penso; Luís César Cassol


    Calcium increases postharvest conservation of apples. Consequently, several calcium foliar sprays are generally applied to apple trees. Due to the low mobility of calcium in the phloem, foliar sprays may have low efficiency to supply calcium in the fruits. This study aimed to evaluate the efficiency of different sources of calcium applied to the soil, compared to the foliar application, on the content of calcium in the soil, leaves and fruits, on yield and fruit quality of ‘Fuji’ apple trees....

  20. Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders. (United States)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine; Dimke, Henrik; Eladari, Dominique


    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis. Copyright © 2016 by the American Society of Nephrology.

  1. Protons Trigger Mitochondrial Flashes. (United States)

    Wang, Xianhua; Zhang, Xing; Huang, Zhanglong; Wu, Di; Liu, Beibei; Zhang, Rufeng; Yin, Rongkang; Hou, Tingting; Jian, Chongshu; Xu, Jiejia; Zhao, Yan; Wang, Yanru; Gao, Feng; Cheng, Heping


    Emerging evidence indicates that mitochondrial flashes (mitoflashes) are highly conserved elemental mitochondrial signaling events. However, which signal controls their ignition and how they are integrated with other mitochondrial signals and functions remain elusive. In this study, we aimed to further delineate the signal components of the mitoflash and determine the mitoflash trigger mechanism. Using multiple biosensors and chemical probes as well as label-free autofluorescence, we found that the mitoflash reflects chemical and electrical excitation at the single-organelle level, comprising bursting superoxide production, oxidative redox shift, and matrix alkalinization as well as transient membrane depolarization. Both electroneutral H(+)/K(+) or H(+)/Na(+) antiport and matrix proton uncaging elicited immediate and robust mitoflash responses over a broad dynamic range in cardiomyocytes and HeLa cells. However, charge-uncompensated proton transport, which depolarizes mitochondria, caused the opposite effect, and steady matrix acidification mildly inhibited mitoflashes. Based on a numerical simulation, we estimated a mean proton lifetime of 1.42 ns and diffusion distance of 2.06 nm in the matrix. We conclude that nanodomain protons act as a novel, to our knowledge, trigger of mitoflashes in energized mitochondria. This finding suggests that mitoflash genesis is functionally and mechanistically integrated with mitochondrial energy metabolism. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Serum Calcium Level is Associated with Lipids in Young Nigerian ...

    African Journals Online (AJOL)

    cholesterol (VLDL‑c), total lipids and total calcium were assayed in 160 young women (110 OCP users and 50 controls) using colorimetric ... Emokpae and Uadia: Serum calcium correlates with lipid levels in women using low dose oral contraceptive pills ..... by increasing calcium absorption from diet in the intestine.

  3. Remote Dynamic Earthquake Triggering in Shale Gas Basins in Canada and Implications for Triggering Mechanisms (United States)

    Harrington, Rebecca M.; Liu, Yajing; Wang, Bei; Kao, Honn; Yu, Hongyu


    Here we investigate the occurrence of remote dynamic triggering in three sedimentary basins in Canada where recent fluid injection activity is correlated with increasing numbers of earthquakes. In efforts to count as many small, local earthquakes as possible for the statistical test of triggering, we apply a multi-station matched-filter detection method to continuous waveforms to detect uncataloged local earthquakes in 10-day time windows surrounding triggering mainshocks occurring between 2013-2015 with an estimated local peak ground velocity exceeding 0.01 cm/s. We count the number of earthquakes in 24-hour bins and use a statistical p-value test to determine if the changes in seismicity levels after the mainshock waves have passed are statistically significant. The p-value tests show occurrences of triggering following transient stress perturbations of sites that suggest local faults may remain critically stressed over periods similar to the time frame of our study ( 2 years) or longer, potentially due to maintained high pore pressures in tight shale formations following injection. The time window over which seismicity rates change varies at each site, with more delayed triggering occurring at sites where production history is longer. The observations combined with new modeling results suggest that the poroelastic response of the medium may be the dominant factor influencing instantaneous triggering, particularly in low-permeability tight shales. At sites where production history is longer and permeabilities have been increased, both pore pressure diffusion and the poroelastic response of the medium may work together to promote both instantaneous and delayed triggering. Not only does the interplay of the poroelastic response of the medium and pore pressure diffusion have implications for triggering induced earthquakes near injection sites, but it may be a plausible explanation for observations of instantaneous and delayed earthquake triggering in general.

  4. Data analysis at the CMS level-1 trigger: migrating complex selection algorithms from offline analysis and high-level trigger to the trigger electronics

    CERN Document Server

    Wulz, Claudia


    With ever increasing luminosity at the LHC, optimum online data selection is becoming more and more important. While in the case of some experiments (LHCb and ALICE) this task is being completely transferred to computer farms, the others -- ATLAS and CMS -- will not be able to do this in the medium-term future for technological, detector-related reasons. Therefore, these experiments pursue the complementary approach of migrating more and more of the offline and high-level trigger intelligence into the trigger electronics. The presentation illustrates how the level-1 trigger of the CMS experiment and in particular its concluding stage, the so-called ``Global Trigger", take up this challenge.

  5. Ryanodine-, IP3- and NAADP-dependent calcium stores control acetylcholine release. (United States)

    Chameau, P; Van de Vrede, Y; Fossier, P; Baux, G


    Injections of inositol trisphosphate (IP3) or nicotinamide adenine dinucleotide phosphate (NAADP) into the presynaptic neurone of an identified cholinergic synapse in the buccal ganglion of Aplysia californica increased the amplitude of the inhibitory postsynaptic current evoked by a presynaptic action potential. This suggests that Ca2+ release from various Ca2+ stores can modulate acetylcholine (ACh) release. Specific blockade of the calcium-induced calcium release (CICR) mechanism with ryanodine, or of IP3-induced calcium release with heparin, abolished the effects of IP3, but not the effects of NAADP, suggesting the presence of an intracellular Ca2+ pool independent of those containing ryanodine receptors (RyR) or IP3 receptors. To reinforce electrophysiological observations, intracellular [Ca2+]i changes were measured using the fluorescent dye rhod-2. Injections of cyclic ADP-ribose (an activator of RyR), IP3 or NAADP into the presynaptic neurone induced transient increases in the free intracellular Ca2+ concentration. RyR- and IP3-induced increases were prevented by application of respective selective antagonists but not NAADP-induced increases. Our results show that RyR-dependent, IP3-dependent, and NAADP-dependent Ca2+ stores are present in the same presynaptic terminal but are differently involved in the regulation of the presynaptic Ca2+ concentration that triggers transmitter release.

  6. Graphical processors for HEP trigger systems

    Energy Technology Data Exchange (ETDEWEB)

    Ammendola, R. [INFN Sezione di Roma Tor Vergata, Via della Ricerca Scientifica, 1, 00133 Roma (Italy); Biagioni, A. [INFN Sezione di Roma, P.le Aldo Moro, 2, 00185 Roma (Italy); Chiozzi, S.; Cotta Ramusino, A. [INFN Sezione di Ferrara, Via Saragat, 1, 44122 Ferrara (Italy); Di Lorenzo, S. [INFN Sezione di Pisa, L. Bruno Pontecorvo, 3, 56127 Pisa (Italy); Università di Pisa, Lungarno Pacinotti 43, 56126 Pisa (Italy); Fantechi, R. [INFN Sezione di Pisa, L. Bruno Pontecorvo, 3, 56127 Pisa (Italy); Fiorini, M. [INFN Sezione di Ferrara, Via Saragat, 1, 44122 Ferrara (Italy); Università di Ferrara, Via Ludovico Ariosto 35, 44121 Ferrara (Italy); Frezza, O. [INFN Sezione di Roma, P.le Aldo Moro, 2, 00185 Roma (Italy); Lamanna, G. [INFN, Laboratori Nazionali di Frascati (Italy); Lo Cicero, F.; Lonardo, A.; Martinelli, M.; Neri, I.; Paolucci, P.S.; Pastorelli, E. [INFN Sezione di Roma, P.le Aldo Moro, 2, 00185 Roma (Italy); Piandani, R. [INFN Sezione di Pisa, L. Bruno Pontecorvo, 3, 56127 Pisa (Italy); Pontisso, L., E-mail: [INFN Sezione di Pisa, L. Bruno Pontecorvo, 3, 56127 Pisa (Italy); Rossetti, D. [NVIDIA Corp., Santa Clara, CA (United States); Simula, F. [INFN Sezione di Roma, P.le Aldo Moro, 2, 00185 Roma (Italy); Sozzi, M. [INFN Sezione di Pisa, L. Bruno Pontecorvo, 3, 56127 Pisa (Italy); Università di Pisa, Lungarno Pacinotti 43, 56126 Pisa (Italy); and others


    General-purpose computing on GPUs is emerging as a new paradigm in several fields of science, although so far applications have been tailored to employ GPUs as accelerators in offline computations. With the steady decrease of GPU latencies and the increase in link and memory throughputs, time is ripe for real-time applications using GPUs in high-energy physics data acquisition and trigger systems. We will discuss the use of online parallel computing on GPUs for synchronous low level trigger systems, focusing on tests performed on the trigger of the CERN NA62 experiment. Latencies of all components need analysing, networking being the most critical. To keep it under control, we envisioned NaNet, an FPGA-based PCIe Network Interface Card (NIC) enabling GPUDirect connection. Moreover, we discuss how specific trigger algorithms can be parallelised and thus benefit from a GPU implementation, in terms of increased execution speed. Such improvements are particularly relevant for the foreseen LHC luminosity upgrade where highly selective algorithms will be crucial to maintain sustainable trigger rates with very high pileup.

  7. Upgrades of the ATLAS trigger system

    CERN Document Server

    Pastore, Francesca; The ATLAS collaboration


    In coming years the LHC is expected to undergo upgrades to increase both the energy of proton-proton collisions and the instantaneous luminosity. In order to cope with these more challenging LHC conditions, upgrades of the ATLAS trigger system will be required. This talk will focus on some of the key aspects of these upgrades. Firstly, the upgrade period between 2019-2021 will see an increase in instantaneous luminosity to $3\\times10^{34} \\rm{cm^{-2}s^{-1}}$. Upgrades to the Level 1 trigger system during this time will include improvements for both the muon and calorimeter triggers. These include the upgrade of the first-level Endcap Muon trigger, the calorimeter trigger electronics and the addition of new calorimeter feature extractor hardware, such as the Global Feature Extractor (gFEX). An overview will be given on the design and development status the aforementioned systems, along with the latest testing and validation results. \\\\ By 2026, the High Luminosity LHC will be able to deliver 14 TeV collisions ...

  8. Graphical processors for HEP trigger systems (United States)

    Ammendola, R.; Biagioni, A.; Chiozzi, S.; Cotta Ramusino, A.; Di Lorenzo, S.; Fantechi, R.; Fiorini, M.; Frezza, O.; Lamanna, G.; Lo Cicero, F.; Lonardo, A.; Martinelli, M.; Neri, I.; Paolucci, P. S.; Pastorelli, E.; Piandani, R.; Pontisso, L.; Rossetti, D.; Simula, F.; Sozzi, M.; Vicini, P.


    General-purpose computing on GPUs is emerging as a new paradigm in several fields of science, although so far applications have been tailored to employ GPUs as accelerators in offline computations. With the steady decrease of GPU latencies and the increase in link and memory throughputs, time is ripe for real-time applications using GPUs in high-energy physics data acquisition and trigger systems. We will discuss the use of online parallel computing on GPUs for synchronous low level trigger systems, focusing on tests performed on the trigger of the CERN NA62 experiment. Latencies of all components need analysing, networking being the most critical. To keep it under control, we envisioned NaNet, an FPGA-based PCIe Network Interface Card (NIC) enabling GPUDirect connection. Moreover, we discuss how specific trigger algorithms can be parallelised and thus benefit from a GPU implementation, in terms of increased execution speed. Such improvements are particularly relevant for the foreseen LHC luminosity upgrade where highly selective algorithms will be crucial to maintain sustainable trigger rates with very high pileup.

  9. Inhibition of calcium/calmodulin-dependent protein kinase kinase β and calcium/calmodulin-dependent protein kinase IV is detrimental in cerebral ischemia. (United States)

    McCullough, Louise D; Tarabishy, Sami; Liu, Lin; Benashski, Sharon; Xu, Yan; Ribar, Thomas; Means, Anthony; Li, Jun


    Elevation of intracellular calcium was traditionally thought to be detrimental in stroke pathology. However, clinical trials testing treatments that block calcium signaling have failed to improve outcomes in ischemic stroke. Emerging data suggest that calcium may also trigger endogenous protective pathways after stroke. Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is a major kinase activated by rising intracellular calcium. Compelling evidence has suggested that CaMKK and its downstream kinase CaMK IV are critical in neuronal survival when cells are under ischemic stress. We examined the functional role of CaMKK/CaMK IV signaling in stroke. We used a middle cerebral artery occlusion model in mice. Our data demonstrated that pharmacological and genetic inhibition of CaMKK aggravated stroke injury. Additionally, deletion of CaMKK β, one of the 2 CaMKK isoforms, reduced CaMK IV activation, and CaMK IV deletion in mice worsened stroke outcome. Finally, CaMKK β or CaMK IV knockout mice had exacerbated blood-brain barrier disruption evidenced by increased hemorrhagic transformation and activation of matrix metalloproteinase. We observed transcriptional inactivation including reduced levels of histone deacetylase 4 phosphorylation in mice with CaMKK β or CaMK IV deletion after stroke. Our data have established that the CaMKK/CaMK IV pathway is a key endogenous protective mechanism in ischemia. Our results suggest that this pathway serves as an important regulator of blood-brain barrier integrity and transcriptional activation of neuroprotective molecules in stroke.

  10. Level 1 Tau trigger performance in 2016 data and VBF seeds at Level 1 trigger

    CERN Document Server

    CMS Collaboration


    After the first long shutdown, the LHC has restarted at a centre-of-mass energy of 13 TeV. In 2016, the LHC achieved an instantaneous luminosity larger than $10^{34}$ $\\mathrm{cm}^{-2}\\cdot \\mathrm{s}^{-1}$ and a peak average pile-up of more than 40. The CMS Level-1 trigger architecture has undergone a full upgrade in order to maintain and improve the trigger performance under these new conditions. It allows CMS to keep the trigger rate under control and to avoid a significant increase in trigger thresholds that would have a negative impact on the CMS physics program. Studies of the performance of the calorimeter trigger upgrade for tau leptons, using the full 2016 dataset (35.9 $\\mathrm{fb}^{-1}$), are shown. Details of the Level-1 trigger algorithms and commissioning may be found in CMS-DP-2015-009, CMS-DP-2015-003, CMS-DP-2015-051 and the CMS Technical Design Report for the Level-1 Trigger upgrade: CERN-LHCC-2013-011, CMS-TDR-12 (2013). Previous performance results, based on the ICHEP 2016 dataset (12.9 ...

  11. Latent myofascial trigger points. (United States)

    Ge, Hong-You; Arendt-Nielsen, Lars


    A latent myofascial trigger point (MTP) is defined as a focus of hyperirritability in a muscle taut band that is clinically associated with local twitch response and tenderness and/or referred pain upon manual examination. Current evidence suggests that the temporal profile of the spontaneous electrical activity at an MTP is similar to focal muscle fiber contraction and/or muscle cramp potentials, which contribute significantly to the induction of local tenderness and pain and motor dysfunctions. This review highlights the potential mechanisms underlying the sensory-motor dysfunctions associated with latent MTPs and discusses the contribution of central sensitization associated with latent MTPs and the MTP network to the spatial propagation of pain and motor dysfunctions. Treating latent MTPs in patients with musculoskeletal pain may not only decrease pain sensitivity and improve motor functions, but also prevent latent MTPs from transforming into active MTPs, and hence, prevent the development of myofascial pain syndrome.

  12. Voltage-gated calcium flux mediatesEscherichia colimechanosensation. (United States)

    Bruni, Giancarlo N; Weekley, R Andrew; Dodd, Benjamin J T; Kralj, Joel M


    Electrically excitable cells harness voltage-coupled calcium influx to transmit intracellular signals, typically studied in neurons and cardiomyocytes. Despite intense study in higher organisms, investigations of voltage and calcium signaling in bacteria have lagged due to their small size and a lack of sensitive tools. Only recently were bacteria shown to modulate their membrane potential on the timescale of seconds, and little is known about the downstream effects from this modulation. In this paper, we report on the effects of electrophysiology in individual bacteria. A genetically encoded calcium sensor expressed in Escherichia coli revealed calcium transients in single cells. A fusion sensor that simultaneously reports voltage and calcium indicated that calcium influx is induced by voltage depolarizations, similar to metazoan action potentials. Cytoplasmic calcium levels and transients increased upon mechanical stimulation with a hydrogel, and single cells altered protein concentrations dependent on the mechanical environment. Blocking voltage and calcium flux altered mechanically induced changes in protein concentration, while inducing calcium flux reproduced these changes. Thus, voltage and calcium relay a bacterial sense of touch and alter cellular lifestyle. Although the calcium effectors remain unknown, these data open a host of new questions about E. coli , including the identity of the underlying molecular players, as well as other signals conveyed by voltage and calcium. These data also provide evidence that dynamic voltage and calcium exists as a signaling modality in the oldest domain of life, and therefore studying electrophysiology beyond canonical electrically excitable cells could yield exciting new findings.

  13. Plant Calcium Content: Ready to Remodel

    Directory of Open Access Journals (Sweden)

    Mary Lou Guerinot


    Full Text Available By identifying the relationship between calcium location in the plant cell and nutrient bioavailability, the plant characteristics leading to maximal calcium absorption by humans can be identified. Knowledge of plant cellular and molecular targets controlling calcium location in plants is emerging. These insights should allow for better strategies for increasing the nutritional content of foods. In particular, the use of preparation-free elemental imaging technologies such as synchrotron X-ray fluorescence (SXRF microscopy in plant biology may allow researchers to understand the relationship between subcellular location and nutrient bioavailability. These approaches may lead to better strategies for altering the location of calcium within the plant to maximize its absorption from fruits and vegetables. These modified foods could be part of a diet for children and adults identified as at-risk for low calcium intake or absorption with the ultimate goal of decreasing the incidence and severity of inadequate bone mineralization.

  14. Endoplasmic reticulum calcium stores in dendritic spines. (United States)

    Segal, Menahem; Korkotian, Eduard


    Despite decades of research, the role of calcium stores in dendritic spines structure, function and plasticity is still debated. The reasons for this may have to do with the multitude of overlapping calcium handling machineries in the neuron, including stores, voltage and ligand gated channels, pumps and transporters. Also, different cells in the brain are endowed with calcium stores that are activated by different receptor types, and their differential compartmentalization in dendrites, spines and presynaptic terminals complicates their analysis. In the present review we address several key issues, including the role of calcium stores in synaptic plasticity, their role during development, in stress and in neurodegenerative diseases. Apparently, there is increasing evidence for a crucial role of calcium stores, especially of the ryanodine species, in synaptic plasticity and neuronal survival.

  15. Plant Calcium Content: Ready to Remodel (United States)

    Yang, Jian; Punshon, Tracy; Guerinot, Mary Lou; Hirschi, Kendal D.


    By identifying the relationship between calcium location in the plant cell and nutrient bioavailability, the plant characteristics leading to maximal calcium absorption by humans can be identified. Knowledge of plant cellular and molecular targets controlling calcium location in plants is emerging. These insights should allow for better strategies for increasing the nutritional content of foods. In particular, the use of preparation-free elemental imaging technologies such as synchrotron X-ray fluorescence (SXRF) microscopy in plant biology may allow researchers to understand the relationship between subcellular location and nutrient bioavailability. These approaches may lead to better strategies for altering the location of calcium within the plant to maximize its absorption from fruits and vegetables. These modified foods could be part of a diet for children and adults identified as at-risk for low calcium intake or absorption with the ultimate goal of decreasing the incidence and severity of inadequate bone mineralization. PMID:23016135

  16. The calcium and vitamin D controversy

    DEFF Research Database (Denmark)

    Abrahamsen, Bo


    or subanalyses while maintaining balancing. Though large clinical RCTs currently evaluate the effects of higher vitamin D doses (equivalent to 50–83 μg/d) there is no current research effort regarding the calcium controversy. In the absence of such studies it is not possible to provide clinicians with evidence......Areas of the world where vitamin D levels are low for months of the year and intakes of calcium are high have a high prevalence of osteoporosis and cardiovascular disease. This suggests a public health message of avoiding calcium supplements and increasing vitamin D intake. No message could be more...... welcome as vitamin D can be given as a bolus while calcium must be taken daily and may be poorly tolerated. This approach is based on no evidence from intervention studies. Randomized controlled trials (RCTs) suggest that vitamin D given with calcium elicits a small reduction in fracture risk and deaths...

  17. Astrocyte calcium signalling orchestrates neuronal synchronization in organotypic hippocampal slices (United States)

    Sasaki, Takuya; Ishikawa, Tomoe; Abe, Reimi; Nakayama, Ryota; Asada, Akiko; Matsuki, Norio; Ikegaya, Yuji


    Astrocytes are thought to detect neuronal activity in the form of intracellular calcium elevations; thereby, astrocytes can regulate neuronal excitability and synaptic transmission. Little is known, however, about how the astrocyte calcium signal regulates the activity of neuronal populations. In this study, we addressed this issue using functional multineuron calcium imaging in hippocampal slice cultures. Under normal conditions, CA3 neuronal networks exhibited temporally correlated activity patterns, occasionally generating large synchronization among a subset of cells. The synchronized neuronal activity was correlated with astrocyte calcium events. Calcium buffering by an intracellular injection of a calcium chelator into multiple astrocytes reduced the synaptic strength of unitary transmission between pairs of surrounding pyramidal cells and caused desynchronization of the neuronal networks. Uncaging the calcium in the astrocytes increased the frequency of neuronal synchronization. These data suggest an essential role of the astrocyte calcium signal in the maintenance of basal neuronal function at the circuit level. PMID:24710057

  18. The signaling module cAMP/Epac/Rap1/PLCε/IP3 mobilizes acrosomal calcium during sperm exocytosis. (United States)

    Lucchesi, Ornella; Ruete, María C; Bustos, Matías A; Quevedo, María F; Tomes, Claudia N


    Exocytosis of the sperm's single secretory granule, or acrosome, is a regulated exocytosis triggered by components of the egg's investments. In addition to external calcium, sperm exocytosis (termed the acrosome reaction) requires cAMP synthesized endogenously and calcium mobilized from the acrosome through IP3-sensitive channels. The relevant cAMP target is Epac. In the first part of this paper, we present a novel tool (the TAT-cAMP sponge) to investigate cAMP-related signaling pathways in response to progesterone as acrosome reaction trigger. The TAT-cAMP sponge consists of the cAMP-binding sites of protein kinase A regulatory subunit RIβ fused to the protein transduction domain TAT of the human immunodeficiency virus-1. The sponge permeated into sperm, sequestered endogenous cAMP, and blocked exocytosis. Progesterone increased the population of sperm with Rap1-GTP, Rab3-GTP, and Rab27-GTP in the acrosomal region; pretreatment with the TAT-cAMP sponge prevented the activation of all three GTPases. In the second part of this manuscript, we show that phospholipase Cε (PLCε) is required for the acrosome reaction downstream of Rap1 and upstream of intra-acrosomal calcium mobilization. Last, we present direct evidence that cAMP, Epac, Rap1, and PLCε are necessary for calcium mobilization from sperm's secretory granule. In summary, we describe here a pathway that connects cAMP to calcium mobilization from the acrosome during sperm exocytosis. Never before had direct evidence for each step of the cascade been put together in the same study. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Towards a Level-1 tracking trigger for the ATLAS experiment

    CERN Document Server

    Cerri, A; The ATLAS collaboration


    The future plans for the LHC accelerator allow, through a schedule of phased upgrades, an increase in the average instantaneous luminosity by a factor 5 with respect to the original design luminosity. The ATLAS experiment at the LHC will be able to maximise the physics potential from this higher luminosity only if the detector, trigger and DAQ infrastructure are adapted to handle the sustained increase in particle production rates. In this paper the changes expected to be required to the ATLAS detectors and trigger system to fulfill the requirement for working in such high luminosity scenario are described. The increased number of interactions per bunch crossing will result in higher occupancy in the detectors and increased rates at each level of the trigger system. The trigger selection will improve the selectivity partly from increased granularity for the sub detectors and the consequent higher resolution. One of the largest challenges will be the provision of tracking information at the first trigger level...

  20. The ATLAS hadronic tau trigger

    CERN Document Server

    Black, C; The ATLAS collaboration


    With the high luminosities of proton-proton collisions achieved at the LHC, the strategies for triggering have become more important than ever for physics analysis. The naive inclusive single tau lepton triggers now suffer from severe rate limitations. To allow for a large program of physics analyses with taus, the development of topological triggers that combine tau signatures with other measured quantities in the event is required. These combined triggers open many opportunities to study new physics beyond the Standard Model and to search for the Standard Model Higgs. We present the status and performance of the hadronic tau trigger in ATLAS. We demonstrate that the ATLAS tau trigger ran remarkably well over 2011, and how the lessons learned from 2011 led to numerous improvements in the preparation of the 2012 run. These improvements include the introduction of tau selection criteria that are robust against varying pileup scenarios, and the implementation of multivariate selection techniques in the tau trig...

  1. The ATLAS hadronic tau trigger

    CERN Document Server

    Black, C; The ATLAS collaboration


    With the high luminosities of proton-proton collisions achieved at the LHC, the strategies for triggering have become more important than ever for physics analysis. The naïve inclusive single tau lepton triggers now suffer from severe rate limitations. To allow for a large program of physics analyses with taus, the development of topological triggers that combine tau signatures with other measured quantities in the event is required. These combined triggers open many opportunities to study new physics beyond the Standard Model and to search for the Standard Model Higgs. We present the status and performance of the hadronic tau trigger in ATLAS. We demonstrate that the ATLAS tau trigger ran remarkably well over 2011, and how the lessons learned from 2011 led to numerous improvements in the preparation of the 2012 run. These improvements include the introduction of tau selection criteria that are robust against varying pileup scenarios, and the implementation of multivariate selection techniques in the tau tri...

  2. Differential effects of thapsigargin analogues on apoptosis of prostate cancer cells: complex regulation by intracellular calcium. (United States)

    Dubois, Charlotte; Vanden Abeele, Fabien; Sehgal, Pankaj; Olesen, Claus; Junker, Steffen; Christensen, Søren B; Prevarskaya, Natalia; Møller, Jesper V


    The inhibition of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) by thapsigargin (Tg) and Tg-type analogues is considered to trigger cell death by activation of apoptotic pathways. Some of these analogues may be useful as antineoplastic agents after appropriate targeting as peptide conjugated prodrugs to cancer cells. With this in mind, this study evaluates the effect on LNCaP androgen-sensitive cancer cells of thapsigargin substituted with 12-aminododecanoyl linkers and Leu (Leu-8ADT), aspartate (Asp-8ADT) or Boc-8ADT. Our results show that both Leu-8ADT and Asp-8ADT result in rapid ER calcium depletion and an influx of calcium across the plasma membrane by activation of store-operated calcium entry. By contrast, ER Ca(2+) depletion by Boc-8ADT is a very slow process that does not perceptibly increase cytosolic Ca(2+) and activate store-operated calcium entry, because the inhibition of SERCA with this compound is very slow. Nevertheless, we find that Boc-8ADT is a more efficient inducer of apoptosis than both Tg and Leu-8ADT. Compared with Tg and the other analogues, apoptosis induced by Asp-8ADT is very modest, although this compound also activates store-operated calcium entry and at high concentrations (1 μm) causes severe morphological changes, reflecting decreased cell viability. We conclude that many factors need to be considered for optimization of these compounds in antineoplastic drug design. Among these ER stress induced by Ca(2+) endoplasmic reticulum mobilization seems particularly important, whereas the early cytosolic increase of Ca(2+) concentration preceding the executive phase of apoptosis appears to be of no, or little, consequence for a subsequent apoptotic effect. © 2013 FEBS.

  3. Run 2 ATLAS Trigger and Detector Performance

    CERN Document Server

    Solovyanov, Oleg; The ATLAS collaboration


    The 2nd LHC run has started in June 2015 with a proton-proton centre-of-mass collision energy of 13 TeV. During the years 2016 and 2017, LHC delivered an unprecedented amount of luminosity under the ever-increasing challenging conditions in terms of peak luminosity, pile-up and trigger rates. In this talk, the LHC running conditions and the improvements made to the ATLAS experiment in the course of Run 2 will be discussed, and the latest ATLAS detector and ATLAS trigger performance results from the Run 2 will be presented.

  4. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar


    Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

  5. Flexible trigger menu implementation on the Global Trigger for the CMS Level-1 trigger upgrade (United States)

    MATSUSHITA, Takashi; CMS Collaboration


    The CMS experiment at the Large Hadron Collider (LHC) has continued to explore physics at the high-energy frontier in 2016. The integrated luminosity delivered by the LHC in 2016 was 41 fb‑1 with a peak luminosity of 1.5 × 1034 cm‑2s‑1 and peak mean pile-up of about 50, all exceeding the initial estimations for 2016. The CMS experiment has upgraded its hardware-based Level-1 trigger system to maintain its performance for new physics searches and precision measurements at high luminosities. The Global Trigger is the final step of the CMS Level-1 trigger and implements a trigger menu, a set of selection requirements applied to the final list of objects from calorimeter and muon triggers, for reducing the 40 MHz collision rate to 100 kHz. The Global Trigger has been upgraded with state-of-the-art FPGA processors on Advanced Mezzanine Cards with optical links running at 10 GHz in a MicroTCA crate. The powerful processing resources of the upgraded system enable implementation of more algorithms at a time than previously possible, allowing CMS to be more flexible in how it handles the available trigger bandwidth. Algorithms for a trigger menu, including topological requirements on multi-objects, can be realised in the Global Trigger using the newly developed trigger menu specification grammar. Analysis-like trigger algorithms can be represented in an intuitive manner and the algorithms are translated to corresponding VHDL code blocks to build a firmware. The grammar can be extended in future as the needs arise. The experience of implementing trigger menus on the upgraded Global Trigger system will be presented.

  6. Calcium Intake in Elderly Australian Women Is Inadequate

    Directory of Open Access Journals (Sweden)

    Colin W. Binns


    Full Text Available The role of calcium in the prevention of bone loss in later life has been well established but little data exist on the adequacy of calcium intakes in elderly Australian women. The aim of this study was to compare the dietary intake including calcium of elderly Australian women with the Australian dietary recommendation, and to investigate the prevalence of calcium supplement use in this population. Community-dwelling women aged 70–80 years were randomly recruited using the Electoral Roll for a 2-year protein intervention study in Western Australia. Dietary intake was assessed at baseline by a 3-day weighed food record and analysed for energy, calcium and other nutrients. A total of 218 women were included in the analysis. Mean energy intake was 7,140 ± 1,518 kJ/day and protein provided 19 ± 4% of energy. Mean dietary calcium intake was 852 ± 298 mg/day, which is below Australian recommendations. Less than one quarter of women reported taking calcium supplements and only 3% reported taking vitamin D supplements. Calcium supplements by average provided calcium 122 ± 427 mg/day and when this was taken into account, total calcium intake increased to 955 ± 504 mg/day, which remained 13% lower than the Estimated Average Requirement (EAR, 1,100 mg/day for women of this age group. The women taking calcium supplements had a higher calcium intake (1501 ± 573 mg compared with the women on diet alone (813 ± 347 mg. The results of this study indicate that the majority of elderly women were not meeting their calcium requirements from diet alone. In order to achieve the recommended dietary calcium intake, better strategies for promoting increased calcium, from both diet and calcium supplements appears to be needed.

  7. Muon triggers in the High Level Trigger of LHCb

    CERN Document Server

    Aaij, Roel


    The muon trigger selections for both levels of the LHCb software trigger (HLT1 and 2) are described and their performance is evaluated using $B^{+} \\to J/\\psi K^{+}$ signals reconstructed in 330 pb$^{-1}$ of data which were collected in the first half 2011.

  8. Embryonic mobilization of calcium in a viviparous reptile: evidence for a novel pattern of placental calcium secretion. (United States)

    Fregoso, Santiago P; Stewart, James R; Ecay, Tom W


    Yolk reserves supply the majority of embryonic nutrition in squamate reptiles, including calcium. Embryos of oviparous squamates exploit the eggshell for supplemental calcium, while embryos of viviparous species may receive additional calcium via the placenta. Developmental uptake of calcium in oviparous snakes increases during the interval of greatest embryonic growth (stage 35 to parturition). However, the pattern of embryonic calcium acquisition is unknown for viviparous snakes. Furthermore, while the uterus of oviparous species transports calcium early in embryonic development during mineralization of the eggshell, the timing of uterine calcium secretion in viviparous snakes is unknown. We studied a viviparous snake, Virginia striatula, to determine the ontogenetic pattern of yolk and embryonic calcium content. The pattern of embryonic calcium uptake of V. striatula is similar to that of oviparous snakes but the sources of calcium differ. In contrast to oviparous species, embryos of V. striatula acquire half of total neonatal calcium via placental provision, of which 71% is mobilized between stage 35 and parturition. Furthermore, we report for the first time in a viviparous squamate an increase in yolk calcium content during early stages of embryonic development, indicating that uterine secretion of calcium occurs in V. striatula coincident with shelling in oviparous squamates. Thus, uterine calcium secretion in this viviparous species may either occur continuously or in two phases, coincident with the timing of shelling in oviparous species and again during the last stages of development. Whereas, the pattern of embryonic calcium acquisition in V. striatula is plesiomorphic for squamates, the pattern of uterine calcium secretion includes both retention of a plesiomorphic trait and the evolution of a novel trait. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Vitamin d deficiency is associated with insulin resistance independent of intracellular calcium, dietary calcium and serum levels of parathormone, calcitriol and calcium in premenopausal women. (United States)

    Ferreira, Thaís da Silva; Rocha, Tatiana Martins; Klein, Márcia Regina Simas Torres; Sanjuliani, Antonio Felipe


    There is evidence that vitamin D deficiency is associated with increased risk of cardiovascular disease. However, it is not known if this association is independent of dietary calcium, intracellular calcium and serum levels of parathormone, calcitriol and calcium. To investigate the independent relationship of vitamin D deficiency with insulin resistance, lipid profile, inflammatory status, blood pressure and endothelial function. Cross-sectional study conducted with 73 healthy Brazilian premenopausal women aged 18 - 50 years. All participants were evaluated for: 25 hydroxyvitamin D serum levels, anthropometric parameters, body composition, calcium metabolism, insulin resistance, lipoprotein profile, inflammatory status, blood pressure and endothelial function. Endothelial function was assessed by reactive hyperemia index using Endo-PAT 2000®. Women were stratified in two groups: with vitamin D deficiency (25 hydroxyvitamin D independent of dietary calcium, intracellular calcium and serum levels of parathormone, calcitriol and calcium in healthy premenopausal women. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  10. Trigger and data acquisition

    CERN Multimedia

    CERN. Geneva; Gaspar, C


    Past LEP experiments generate data at 0.5 MByte/s from particle detectors with over a quarter of a million readout channels. The process of reading out the electronic channels, treating them, and storing the date produced by each collision for further analysis by the physicists is called "Data Acquisition". Not all beam crossings produce interesting physics "events", picking the interesting ones is the task of the "Trigger" system. In order to make sure that the data is collected in good conditions the experiment's operation has to be constantly verified. In all, at LEP experiments over 100 000 parameters were monitored, controlled, and synchronized by the "Monotoring and control" system. In the future, LHC experiments will produce as much data in a single day as a LEP detector did in a full year's running with a raw data rate of 10 - 100 MBytes/s and will have to cope with some 800 million proton-proton collisions a second of these collisions only one in 100 million million is interesting for new particle se...

  11. Simulation of the ATLAS New Small Wheel Trigger

    CERN Document Server

    Saito, Tomoyuki; The ATLAS collaboration


    The instantaneous luminosity of the LHC will be increased by up to a factor of seven with respect to the original design value to explore physics at higher energy scale. The inner station of the ATLAS muon end-cap system (Small Wheel) needs to be replaced by the New Small Wheel (NSW) to benefit from the high luminosity. The NSW provides precise track-segment information to the Level-1 trigger system in order to suppress the trigger rate from fake muon tracks. This article summarizes the NSW trigger decision system, track-segment finding algorithm implemented in the trigger processor and discusses results of performance studies on the trigger system. The results demonstrate that the NSW trigger system is capable of working with good performance satisfying the requirements.

  12. The upgrade of the ATLAS first-level calorimeter trigger

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00227035; The ATLAS collaboration


    The first-level calorimeter trigger (L1Calo) had operated successfully through the first data taking phase of the ATLAS experiment at the CERN Large Hadron Collider. Toward forthcoming LHC runs, a series of upgrades is planned for L1Calo to face new challenges posed by the upcoming increases of the beam energy and the luminosity. This article reviews the ATLAS L1Calo trigger upgrade project that introduces new architectures for the liquid-argon calorimeter trigger readout and the L1Calo trigger processing system.

  13. Upgrade trigger: Biannual performance update

    CERN Document Server

    Aaij, Roel; Couturier, Ben; Esen, Sevda; De Cian, Michel; De Vries, Jacco Andreas; Dziurda, Agnieszka; Fitzpatrick, Conor; Fontana, Marianna; Grillo, Lucia; Hasse, Christoph; Jones, Christopher Rob; Le Gac, Renaud; Matev, Rosen; Neufeld, Niko; Nikodem, Thomas; Polci, Francesco; Del Buono, Luigi; Quagliani, Renato; Schwemmer, Rainer; Seyfert, Paul; Stahl, Sascha; Szumlak, Tomasz; Vesterinen, Mika Anton; Wanczyk, Joanna; Williams, Mark Richard James; Yin, Hang; Zacharjasz, Emilia Anna


    This document presents the performance of the LHCb Upgrade trigger reconstruction sequence, incorporating changes to the underlying reconstruction algorithms and detector description since the Trigger and Online Upgrade TDR. An updated extrapolation is presented using the most recent example of an Event Filter Farm node.

  14. Photon-triggered nanowire transistors (United States)

    Kim, Jungkil; Lee, Hoo-Cheol; Kim, Kyoung-Ho; Hwang, Min-Soo; Park, Jin-Sung; Lee, Jung Min; So, Jae-Pil; Choi, Jae-Hyuck; Kwon, Soon-Hong; Barrelet, Carl J.; Park, Hong-Gyu


    Photon-triggered electronic circuits have been a long-standing goal of photonics. Recent demonstrations include either all-optical transistors in which photons control other photons or phototransistors with the gate response tuned or enhanced by photons. However, only a few studies report on devices in which electronic currents are optically switched and amplified without an electrical gate. Here we show photon-triggered nanowire (NW) transistors, photon-triggered NW logic gates and a single NW photodetection system. NWs are synthesized with long crystalline silicon (CSi) segments connected by short porous silicon (PSi) segments. In a fabricated device, the electrical contacts on both ends of the NW are connected to a single PSi segment in the middle. Exposing the PSi segment to light triggers a current in the NW with a high on/off ratio of >8 × 106. A device that contains two PSi segments along the NW can be triggered using two independent optical input signals. Using localized pump lasers, we demonstrate photon-triggered logic gates including AND, OR and NAND gates. A photon-triggered NW transistor of diameter 25 nm with a single 100 nm PSi segment requires less than 300 pW of power. Furthermore, we take advantage of the high photosensitivity and fabricate a submicrometre-resolution photodetection system. Photon-triggered transistors offer a new venue towards multifunctional device applications such as programmable logic elements and ultrasensitive photodetectors.

  15. GnRH agonist triggering

    DEFF Research Database (Denmark)

    Kol, Shahar; Humaidan, Peter; Al Humaidan, Peter Samir Heskjær


    The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. Recent developments in the area strengthen this premise. GnRHa trigger offers important advantages,...

  16. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. (United States)

    Tian, Lin; Hires, S Andrew; Mao, Tianyi; Huber, Daniel; Chiappe, M Eugenia; Chalasani, Sreekanth H; Petreanu, Leopoldo; Akerboom, Jasper; McKinney, Sean A; Schreiter, Eric R; Bargmann, Cornelia I; Jayaraman, Vivek; Svoboda, Karel; Looger, Loren L


    Genetically encoded calcium indicators (GECIs) can be used to image activity in defined neuronal populations. However, current GECIs produce inferior signals compared to synthetic indicators and recording electrodes, precluding detection of low firing rates. We developed a single-wavelength GCaMP2-based GECI (GCaMP3), with increased baseline fluorescence (3-fold), increased dynamic range (3-fold) and higher affinity for calcium (1.3-fold). We detected GCaMP3 fluorescence changes triggered by single action potentials in pyramidal cell dendrites, with signal-to-noise ratio and photostability substantially better than those of GCaMP2, D3cpVenus and TN-XXL. In Caenorhabditis elegans chemosensory neurons and the Drosophila melanogaster antennal lobe, sensory stimulation-evoked fluorescence responses were significantly enhanced with GCaMP3 (4-6-fold). In somatosensory and motor cortical neurons in the intact mouse, GCaMP3 detected calcium transients with amplitudes linearly dependent on action potential number. Long-term imaging in the motor cortex of behaving mice revealed large fluorescence changes in imaged neurons over months.

  17. Weaning triggers a maturation step of pancreatic β cells

    DEFF Research Database (Denmark)

    Stolovich-Rain, Miri; Enk, Jonatan; Vikesa, Jonas


    -stimulated oxidative phosphorylation and insulin secretion from islets. Transcriptome analysis reveals that weaning increases the expression of genes involved in replication licensing, suggesting a mechanism for increased responsiveness to the mitogenic activity of high glucose. We propose that weaning triggers...

  18. Consumption of calcium-fortified cereal bars to improve dietary calcium intake of healthy women: randomized controlled feasibility study.

    Directory of Open Access Journals (Sweden)

    Jennifer T Lee

    Full Text Available Calcium is an important structural component of the skeletal system. Although an adequate intake of calcium helps to maintain bone health and reduce the risk of osteoporosis, many women do not meet recommended daily intakes of calcium. Previous interventions studies designed to increase dietary intake of women have utilized primarily dairy sources of calcium or supplements. However, lactose intolerance, milk protein allergies, or food preferences may lead many women to exclude important dairy sources of dietary calcium. Therefore, we undertook a 9 week randomized crossover design trial to examine the potential benefit of including a non-dairy source of calcium in the diet of women. Following a 3 week run-in baseline period, 35 healthy women > 18 years were randomized by crossover design into either Group I or Group II. Group I added 2 calcium-fortified cereal bars daily (total of 400 mg calcium/day (intervention to their usual diet and Group II continued their usual diet (control. At the end of 3 weeks, diets were switched for another 3 weeks. Intakes of calcium and energy were estimated from 3-day diet and supplemental diaries. Wilcoxon signed-rank tests were used for within group comparisons and Mann Whitney U tests were used for between group comparisons of calcium and energy intake. Dietary calcium was significantly higher during intervention (1071 mg/d when participants consumed 2 calcium-fortified cereal bars daily than during the baseline (720 mg/d, P <0.0001 or control diets (775 mg/d, P = 0.0001 periods. Furthermore, the addition of 2 calcium-fortified cereal bars daily for the 3 week intervention did not significantly increase total energy intake or result in weight gain. In conclusion, consumption of calcium-fortified cereal bars significantly increased calcium intake of women. Further research examining the potential ability of fortified cereal bars to help maintain and improve bone health of women is NCT

  19. Triggering requirements for SSC physics

    Energy Technology Data Exchange (ETDEWEB)

    Gilchriese, M.G.D. [Lawrence Berkeley Lab., CA (United States)


    Some aspects of triggering requirements for high P{sub T} physics processes at the Superconducting Super Collider (SSC) are described. A very wide range of trigger types will be required to enable detection of the large number of potential physics signatures possible at the SSC. Although in many cases trigger rates are not now well understood, it is possible to conclude that the ability to trigger on transverse energy, number and energy of jets, number and energy of leptons (electrons and muons), missing energy and combinations of these will be required. An SSC trigger system must be both highly flexible and redundant to ensure reliable detection of many new physics processes at the SSC.

  20. Ca2+ ionophores trigger membrane remodeling without a need for store-operated Ca2+ entry. (United States)

    Galitzine, Marie; Capiod, Thierry; Le Deist, Françoise; Meyer, Dominique; Freyssinet, Jean-Marie; Kerbiriou-Nabias, Danièle


    Calcium (Ca2+) ionophores are the most effective agents able to elicit rapid membrane remodeling in vitro. This process exposes aminophospholipids at the surface of platelets and blood cells, thus providing a catalytic surface for coagulation. To explore the underlying mechanism, we examined if cytosolic Ca2+ ([Ca2+]i) increase through store-operated Ca2+ entry (SOCE) was necessary for the potent effect of ionophores. Recent studies have demonstrated that the Ca2+-ATPase inhibitor thapsigargin, although able to elevate [Ca2+]i through SOCE, does not trigger the rapid membrane remodeling. However, it was not known if the additional effect of ionophores to promote the process required SOCE or could it occur independently. We took advantage of two mutant B lymphoblast cell lines, characterized either by defective SOCE or altered membrane remodeling, to simultaneously assess [Ca2+]i increase and membrane remodeling in the presence of ionophores or thapsigargin. Results imply that ionophores trigger membrane remodeling without the requirement for a functional SOCE.

  1. Calcium and bones (United States)

    ... eat in their diet. Vitamin D is the hormone that helps the gut absorb more calcium. Many older adults have common risks that make bone health worse. Calcium intake in the diet (milk, cheese, yogurt) is low. Vitamin D levels are ...

  2. Extracellular Calcium and Magnesium

    African Journals Online (AJOL)

    ABSTRACT. The cause of preeclampsia remains unknown and calcium and magnesium supplement are being suggested as means of prevention. The objective of this study was to assess magnesium and calcium in the plasma and cerebrospinal fluid of Nigerian women with preedamp sia and eclampsia. Setting was ...

  3. Apatite Formation from Amorphous Calcium Phosphate and Mixed Amorphous Calcium Phosphate/Amorphous Calcium Carbonate. (United States)

    Ibsen, Casper J S; Chernyshov, Dmitry; Birkedal, Henrik


    Crystallization from amorphous phases is an emerging pathway for making advanced materials. Biology has made use of amorphous precursor phases for eons and used them to produce structures with remarkable properties. Herein, we show how the design of the amorphous phase greatly influences the nanocrystals formed therefrom. We investigate the transformation of mixed amorphous calcium phosphate/amorphous calcium carbonate phases into bone-like nanocrystalline apatite using in situ synchrotron X-ray diffraction and IR spectroscopy. The speciation of phosphate was controlled by pH to favor HPO4 (2-) . In a carbonate free system, the reaction produces anisotropic apatite crystallites with large aspect ratios. The first formed crystallites are highly calcium deficient and hydrogen phosphate rich, consistent with thin octacalcium phosphate (OCP)-like needles. During growth, the crystallites become increasingly stoichiometric, which indicates that the crystallites grow through addition of near-stoichiometric apatite to the OCP-like initial crystals through a process that involves either crystallite fusion/aggregation or Ostwald ripening. The mixed amorphous phases were found to be more stable against phase transformations, hence, the crystallization was inhibited. The resulting crystallites were smaller and less anisotropic. This is rationalized by the idea that a local phosphate-depletion zone formed around the growing crystal until it was surrounded by amorphous calcium carbonate, which stopped the crystallization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Effectiveness and Safety of a Clinical Decision Rule to Reduce Repeat Ionized Calcium Testing: A Pre/Post Test Intervention. (United States)

    Salman, Momina; Pike, Donna Comins; Wu, Rong; Oncken, Cheryl


    The American Recovery and Reinvestment Act authorizes the Centers for Medicare and Medicaid Services to reimburse hospitals that demonstrate meaningful use of certified electronic health record technology. We sought to demonstrate meaningful use by developing and implementing one clinical decision support rule in the computerized physician order entry system that targets clinician-ordered repeat ionized calcium measurement at the University of Connecticut Health Center. The rule consists of a pop-up computer reminder that is triggered by ordering a second ionized calcium test within 72 hours after an initial normal test, with no clear indication for repeat testing. We implemented the rule on December 14, 2010, and have reviewed all data collected through December 2014. We found that the number of repeat tests decreased from 46% to 14% with no significant increase in the number of serious adverse events. We conclude that computerized reminders can decrease unnecessary repeat testing in the inpatient setting.

  5. The CMS Barrel Muon Trigger Upgrade

    CERN Document Server

    Triossi, Andrea


    ABSTRACT: The increase of luminosity expected by LHC during Phase 1 will impose several constrains for rate reduction while maintaining high efficiency in the CMS Level 1 trigger system. The TwinMux system is the early layer of the muon barrel region that concentrates the information from different subdetectors DT, RPC and HO. It arranges and fan-out the slow optical trigger links from the detector chambers into faster links (10 Gbps) that are sent to the track finders. Results, from collision runs, that confirm the satisfactory operation of the trigger system up to the output of the barrel track finder, will be shown. SUMMARY: In view of the increase of luminosity during phase 1 upgrade of LHC, the muon trigger chain of the Compact Muon Solenoid (CMS) experiment underwent considerable improvements. The muon detector was designed for preserving the complementarity and redundancy of three separate muon detection systems, Cathode Strip Chambers (CSC), Drift Tubes (DT) and Resistive Plate Chambers (RPC), until ...

  6. Myofacial trigger points in advanced cancer patients

    Directory of Open Access Journals (Sweden)

    Hideaki Hasuo


    Full Text Available Myofascial pain syndrome is started to be recognized as one of important factors of pain in cancer patients. However, no reports on features of myofascial trigger points were found in terminally-ill cancer populations. This time, we encountered 5 patients with myofascial pain syndrome and terminal cancer in whom delirium developed due to increased doses of opioid without a diagnosis of myofascial pain syndrome on initial presentation. The delirium subsided with dose reductions of opioid and treatment of myofascial pain syndrome. The common reason for a delayed diagnosis among the patients included an incomplete palpation of the painful sites, which led to unsuccessful myofascial trigger points identification. The features of myofascial trigger points included single onset in the cancer pain management site with opioid and the contralateral abdominal side muscles of the non-common sites. Withdrawal reflexes associated with cancer pain in the supine position, which are increasingly seen in the terminal cancer patients, were considered to have contributed to this siuation.We consider that careful palpation of the painful site is important, in order to obtain greater knowledge and understanding of the features of myofascial trigger points.

  7. Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture* (United States)

    Mauceri, Daniela; Hagenston, Anna M.; Schramm, Kathrin; Weiss, Ursula; Bading, Hilmar


    Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines. PMID:26231212

  8. In vitro antioxidant properties of calcium dobesilate. (United States)

    Brunet, J; Farine, J C; Garay, R P; Hannaert, P


    Calcium dobesilate, a vascular protective agent, was tested in vitro for its scavenging action against oxygen free radicals. Calcium dobesilate was as potent as rutin to scavenge hydroxyl radicals (IC50 = 1.1 vs 0.7 microM, respectively). It was also able to scavenge superoxide radicals, but with 23 times less potency than rutin (IC50 = 682 vs 30 microM, respectively). Calcium dobesilate significantly reduced platelet activating factor (PAF)-induced chemiluminescence in human PMN cells and lipid peroxidation by oxygen free radicals in human erythrocyte membranes, although these actions required calcium dobesilate concentrations > or = 50 microM. Finally, in cultured bovine aortic endothelial cells, magnesium dobesilate reduced the increase in cytosolic free calcium induced by hydrogen peroxide and inhibited phenazine methosulfate-induced cell potassium loss. In conclusion, calcium dobesilate was effective in scavenging hydroxyl radicals in vitro, at therapeutically relevant concentrations. Conversely, higher concentrations of the compound were required to scavenge superoxide radicals or to protect the cells against the deleterious effects of intracellular reactive oxygen species. Further studies in vivo are required to determine if these antioxidant properties of calcium dobesilate can play a role in its vascular protective mechanisms.

  9. The ATLAS Missing ET trigger

    CERN Document Server

    Beauchemin, P; The ATLAS collaboration


    Over the last few months, the ATLAS detector collected 900 GeV LHC collision events which allowed for the study the performance of the ATLAS Trigger and Data Acquisition system (TDAQ). With the 7 TeV collision data collected recently, the performance studies of the trigger system are critical for a successful physics program. In particular a large spectrum of physics results will rely on the capa