Neurophysiological mechanisms of bradykinin-evoked mucosal chloride secretion in guinea pig small intestine.

PubMed

Qu, Mei-Hua; Ji, Wan-Sheng; Zhao, Ting-Kun; Fang, Chun-Yan; Mao, Shu-Mei; Gao, Zhi-Qin

2016-02-15

To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.

Performance of vegetative and fruits Zn/Cu based electrochemical cell

NASA Astrophysics Data System (ADS)

Khan, Md. Kamrul Alam, Prof. _., Dr.

2017-01-01

We have studied the performance of PKL, Aloe Vera, Tomato and Lemon juice electrochemical Cells without load condition for 1:1 Zn/Cu based electrodes. It was studied the variation of Open circuit voltage (Voc), Short current (Isc) and Maximum Power (Pmax) with the variation of time for PKL, Aloe Vera, Tomato and Lemon juice electrochemical Cells. It was seen from the research observation that the discharge characteristic of the PKL electrochemical cell was more efficient than the other three Aloe Vera, Tomato and Lemon juice electrochemical Cells. Because the Open circuit voltage (Voc), Short current (Isc) and Maximum Power (Pmax) are more stable and steady than the others three Aloe Vera, Tomato and Lemon juice electrochemical Cells. Furthermore, to enhance the performance we have also studied the secondary salt effect by using the NaCl as an electrolyte with the PKL, Aloe Vera and Lemon juice electrochemical Cells. Most of the results have been tabulated and graphically discussed. I am grateful to the authority of the Science and technology ministry,Bangladesh for financial support during the research work.

NREL/NASA Internal Short-Circuit Instigator in Lithium Ion Cells; NREL (National Renewable Energy Laboratory)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Long, Dirk; Ireland, John; Pesaran, Ahmad

NREL has developed a device to test one of the most challenging failure mechanisms of lithium-ion (Li-ion) batteries -- a battery internal short circuit. Many members of the technical community believe that this type of failure is caused by a latent flaw that results in a short circuit between electrodes during use. As electric car manufacturers turn to Li-ion batteries for energy storage, solving the short circuit problem becomes more important. To date, no reliable and practical method exists to create on-demand internal shorts in Li-ion cells that produce a response that is relevant to the ones produced by fieldmore » failures. NREL and NASA have worked to establish an improved ISC cell-level test method that simulates an emergent internal short circuit, is capable of triggering the four types of cell internal shorts, and produces consistent and reproducible results. Internal short circuit device design is small, low-profile and implantable into Li-ion cells, preferably during assembly. The key component is an electrolyte-compatible phase change material (PCM). The ISC is triggered by heating the cell above PCM melting temperature (presently 40 degrees C – 60 degrees C). In laboratory testing, the activated device can handle currents in excess of 300 A to simulate hard shorts (< 2 mohms). Phase change from non-conducting to conducting has been 100% successful during trigger tests.« less

Lubiprostone Reverses the Inhibitory Action of Morphine on Mucosal Secretion in Human Small Intestine

PubMed Central

Sun, Xiaohong; Wang, Xiyu; Wang, Guo-Du; Xia, Yun; Liu, Sumei; Qu, Meihua; Needleman, Bradley J.; Mikami, Dean J.; Melvin, W. Scott; Bohn, Laura M.; Ueno, Ryuji; Wood, Jackie D.

2016-01-01

Background and Aims Treatments with morphine or opioid agonists cause constipation. Lubiprostone is approved for treatment of adult idiopathic constipation and constipation-predominant IBS in adult women. We tested whether lubiprostone can reverse morphine-suppression of mucosal secretion in human intestine and explored the mechanism of action. Methods Fresh segments of jejunum discarded during Roux-En-Y gastric bypass surgeries were used. Changes in short-circuit current (ΔIsc) were recorded in Ussing flux chambers as a marker for electrogenic chloride secretion during pharmacological interactions between morphine, prostaglandin receptor antagonists, chloride channel blockers and lubiprostone. Results Morphine suppressed basal Isc. Lubiprostone reversed morphine suppression of basal Isc. Lubiprostone, applied to the mucosa in concentrations ranging from 3 nM to 30 μM, evoked increases in Isc in concentration-dependent manner when applied to the mucosal side of muscle-stripped preparations. Blockade of enteric nerves did not change stimulation of Isc by lubiprostone. Removal of chloride or application of bumetanide or NPPB suppressed or abolished responses to lubiprostone. Antagonists acting at CFTR channels and prostaglandin EP4 receptors, but not at E1, EP1-3 receptors, partially suppressed stimulation of Isc by lubiprostone. Conclusions Antisecretory action of morphine results from suppression of excitability of secretomotor neurons in the enteric nervous system. Lubiprostone, which does not affect enteric neurons directly, bypasses the action of morphine by directly opening mucosal chloride channels. PMID:21181441

Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in human small intestine.

PubMed

Sun, Xiaohong; Wang, Xiyu; Wang, Guo-Du; Xia, Yun; Liu, Sumei; Qu, Meihua; Needleman, Bradley J; Mikami, Dean J; Melvin, W Scott; Bohn, Laura M; Ueno, Ryuji; Wood, Jackie D

2011-02-01

Treatments with morphine or opioid agonists cause constipation. Lubiprostone is approved for treatment of adult idiopathic constipation and constipation-predominant IBS in adult women. We tested whether lubiprostone can reverse morphine-suppression of mucosal secretion in human intestine and explored the mechanism of action. Fresh segments of jejunum discarded during Roux-En-Y gastric bypass surgeries were used. Changes in short-circuit current (ΔIsc) were recorded in Ussing flux chambers as a marker for electrogenic chloride secretion during pharmacological interactions between morphine, prostaglandin receptor antagonists, chloride channel blockers and lubiprostone. Morphine suppressed basal Isc. Lubiprostone reversed morphine suppression of basal Isc. Lubiprostone, applied to the mucosa in concentrations ranging from 3 nM to 30 μM, evoked increases in Isc in concentration-dependent manner when applied to the mucosal side of muscle-stripped preparations. Blockade of enteric nerves did not change stimulation of Isc by lubiprostone. Removal of chloride or application of bumetanide or NPPB suppressed or abolished responses to lubiprostone. Antagonists acting at CFTR channels and prostaglandin EP(4) receptors, but not at E(1), EP(1-3) receptors, partially suppressed stimulation of Isc by lubiprostone. Antisecretory action of morphine results from suppression of excitability of secretomotor neurons in the enteric nervous system. Lubiprostone, which does not affect enteric neurons directly, bypasses the action of morphine by directly opening mucosal chloride channels.

Analysis of the electron-beam-induced current of a polycrystalline p-n junction when the diffusion lengths of the material on either side of a grain boundary differ

NASA Technical Reports Server (NTRS)

Von Roos, O.; Luke, K. L.

1984-01-01

The short circuit current generated by the electron beam of a scanning electron microscope in p-n junctions is reduced by enhanced recombination at grain boundaries in polycrystalline material. Frequently, grain boundaries separate the semiconductor into regions possessing different minority carrier life times. This markedly affects the short circuit current I(sc) as a function of scanning distance from the grain boundary. It will be shown theoretically that (1) the minimum of the I(sc) in crossing the grain boundary with the scanning electron beam is shifted away from the grain boundary toward the region with smaller life time (shorter diffusion length), (2) the magnitude of the minimum differs markedly from those calculated under the assumption of equal diffusion lengths on either side of the grain boundary, and (3) the minimum disappears altogether for small surface recombination velocities (s less than 10,000 cm/s). These effects become negligible, however, for large recombination velocities s at grain boundaries. For p-type silicon this happens for s not less than 100,000 cm/s.

Atrazine increases the sodium absorption in frog (Rana esculenta) skin.

PubMed

Cassano, Giuseppe; Bellantuono, Vito; Ardizzone, Concetta; Lippe, Claudio

2006-02-01

The presence of atrazine in agricultural sites has been linked to the decline in amphibian populations. The efforts of the scientific community generally are directed toward investigating the long-term effect of atrazine on complex functions (reproduction or respiration), but in the present study, we investigated the short-term effect on the short-circuit current (I(sc)), a quantitative measure of the ion transport operated by frog (Rana esculenta) skin. Treatment with 5 microM atrazine (1.08 mg/L) does not affect the transepithelial outfluxes of [14C]mannitol or [14C]urea; therefore, atrazine does not damage the barrier properties of frog skin. Atrazine causes a dose-dependent increase in the short-circuit current, with a minimum of 4.64 +/- 0.76 microA/cm2 (11.05% +/- 1.22%) and a maximum of 12.7 +/- 0.7 microA/cm2 (35% +/- 2.4%) measured at 10 nM and 5 microM, respectively. An increase in Isc also is caused by 5 microM ametryne, prometryn, simazine, terbuthylazine, or terbutryn (other atrazine derivatives). In particular, atrazine increases the transepithelial 22Na+ influx without affecting the outflux. Finally, stimulation of Isc by atrazine is suppressed by SQ 22536, H89, U73122, 2-aminoethoxydiphenyl borate, and W7 (blockers of adenylate cyclase, protein kinase A, phospholipase C, intracellular Ca2+ increase, and calmodulin, respectively), whereas indomethacin and calphostin C (inhibitors of cyclooxygenase and protein kinase C, respectively) have no effect.

Quantifying and Reducing Curve-Fitting Uncertainty in Isc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campanelli, Mark; Duck, Benjamin; Emery, Keith

2015-06-14

Current-voltage (I-V) curve measurements of photovoltaic (PV) devices are used to determine performance parameters and to establish traceable calibration chains. Measurement standards specify localized curve fitting methods, e.g., straight-line interpolation/extrapolation of the I-V curve points near short-circuit current, Isc. By considering such fits as statistical linear regressions, uncertainties in the performance parameters are readily quantified. However, the legitimacy of such a computed uncertainty requires that the model be a valid (local) representation of the I-V curve and that the noise be sufficiently well characterized. Using more data points often has the advantage of lowering the uncertainty. However, more data pointsmore » can make the uncertainty in the fit arbitrarily small, and this fit uncertainty misses the dominant residual uncertainty due to so-called model discrepancy. Using objective Bayesian linear regression for straight-line fits for Isc, we investigate an evidence-based method to automatically choose data windows of I-V points with reduced model discrepancy. We also investigate noise effects. Uncertainties, aligned with the Guide to the Expression of Uncertainty in Measurement (GUM), are quantified throughout.« less

Quantifying and Reducing Curve-Fitting Uncertainty in Isc: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campanelli, Mark; Duck, Benjamin; Emery, Keith

Current-voltage (I-V) curve measurements of photovoltaic (PV) devices are used to determine performance parameters and to establish traceable calibration chains. Measurement standards specify localized curve fitting methods, e.g., straight-line interpolation/extrapolation of the I-V curve points near short-circuit current, Isc. By considering such fits as statistical linear regressions, uncertainties in the performance parameters are readily quantified. However, the legitimacy of such a computed uncertainty requires that the model be a valid (local) representation of the I-V curve and that the noise be sufficiently well characterized. Using more data points often has the advantage of lowering the uncertainty. However, more data pointsmore » can make the uncertainty in the fit arbitrarily small, and this fit uncertainty misses the dominant residual uncertainty due to so-called model discrepancy. Using objective Bayesian linear regression for straight-line fits for Isc, we investigate an evidence-based method to automatically choose data windows of I-V points with reduced model discrepancy. We also investigate noise effects. Uncertainties, aligned with the Guide to the Expression of Uncertainty in Measurement (GUM), are quantified throughout.« less

Development of a digital solar simulator based on full-bridge converter

NASA Astrophysics Data System (ADS)

Liu, Chen; Feng, Jian; Liu, Zhilong; Tong, Weichao; Ji, Yibo

2014-02-01

With the development of solar photovoltaic, distribution schemes utilized in power grid had been commonly application, and photovoltaic (PV) inverter is an essential equipment in grid. In this paper, a digital solar simulator based on full-bridge structure is presented. The output characteristic curve of system is electrically similar to silicon solar cells, which can greatly simplify research methods of PV inverter, improve the efficiency of research and development. The proposed simulator consists on a main control board based on TM320F28335, phase-shifted zero-voltage-switching (ZVS) DC-DC full-bridge converter and voltage and current sampling circuit, that allows emulating the voltage-current curve with the open-circuit voltage (Voc) of 900V and the short-circuit current (Isc) of 18A .When the system connected to a PV inverter, the inverter can quickly track from the open-circuit to the maximum power point and keep stability.

On Demand Internal Short Circuit Device Enables Verification of Safer, Higher Performing Battery Designs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darcy, Eric; Keyser, Matthew

The Internal Short Circuit (ISC) device enables critical battery safety verification. With the aluminum interstitial heat sink between the cells, normal trigger cells cannot be driven into thermal runaway without excessive temperature bias of adjacent cells. With an implantable, on-demand ISC device, thermal runaway tests show that the conductive heat sinks protected adjacent cells from propagation. High heat dissipation and structural support of Al heat sinks show high promise for safer, higher performing batteries.

An EBIC equation for solar cells. [Electron Beam Induced Current

NASA Technical Reports Server (NTRS)

Luke, K. L.; Von Roos, O.

1983-01-01

When an electron beam of a scanning electron microscope (SEM) impinges on an N-P junction, the generation of electron-hole pairs by impact ionization causes a characteristic short circuit current I(sc) to flow. The I(sc), i.e., EBIC (electron beam induced current) depends strongly on the configuration used to investigate the cell's response. In this paper the case where the plane of the junction is perpendicular to the surface is considered. An EBIC equation amenable to numerical computations is derived as a function of cell thickness, source depth, surface recombination velocity, diffusion length, and distance of the junction to the beam-cell interaction point for a cell with an ohmic contact at its back surface. It is shown that the EBIC equation presented here is more general and easier to use than those previously reported. The effects of source depth, ohmic contact, and diffusion length on the normalized EBIC characteristic are discussed.

2017 Year in Review | Transportation Research | NREL

Science.gov Websites

Internal Short Circuit Device Sweeps Awards Around the Globe NREL's patented Battery Internal Short Circuit (ISC) Device allows researchers to simulate true internal short circuits, study the causes of thermal

Research Tool to Evaluate the Safety Response of Lithium Batteries to an Internal Short Circuit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyser, Matthew; Darcy, Eric; Pesaran, Ahmad

Li-ion cells provide the highest specific energy and energy density rechargeable battery with the longest life. Many safety incidents that take place in the field originate due to an internal short that was not detectable or predictable at the point of manufacture. NREL's internal short circuit (ISC) device is capable of simulating shorts and produces consistent and reproducible results. The cell behaves normally until the ISC device is activated wherein a latent defect (i.e., built into the cell during manufacturing) gradually moves into position to create an internal short while the battery is in use, providing relevant data to verifymore » abuse models. The ISC device is an effective tool for studying the safety features of parts of Li-ion batteries.« less

The Extrapolation of High Altitude Solar Cell I(V) Characteristics to AM0

NASA Technical Reports Server (NTRS)

Snyder, David B.; Scheiman, David A.; Jenkins, Phillip P.; Reinke, William; Blankenship, Kurt; Demers, James

2007-01-01

The high altitude aircraft method has been used at NASA GRC since the early 1960's to calibrate solar cell short circuit current, ISC, to Air Mass Zero (AMO). This method extrapolates ISC to AM0 via the Langley plot method, a logarithmic extrapolation to 0 air mass, and includes corrections for the varying Earth-Sun distance to 1.0 AU and compensating for the non-uniform ozone distribution in the atmosphere. However, other characteristics of the solar cell I(V) curve do not extrapolate in the same way. Another approach is needed to extrapolate VOC and the maximum power point (PMAX) to AM0 illumination. As part of the high altitude aircraft method, VOC and PMAX can be obtained as ISC changes during the flight. These values can then the extrapolated, sometimes interpolated, to the ISC(AM0) value. This approach should be valid as long as the shape of the solar spectra in the stratosphere does not change too much from AMO. As a feasibility check, the results are compared to AMO I(V) curves obtained using the NASA GRC X25 based multi-source simulator. This paper investigates the approach on both multi-junction solar cells and sub-cells.

Enteropathogenic E. coli attenuates secretagogue-induced net intestinal ion transport but not Cl- secretion.

PubMed

Hecht, G; Koutsouris, A

1999-03-01

Enteric bacterial pathogens often increase intestinal Cl- secretion. Enteropathogenic Escherichia coli (EPEC) does not stimulate active ion secretion. In fact, EPEC infection decreases net ion transport in response to classic secretagogues. This has been presumed to reflect diminished Cl- secretion. The aim of this study was to investigate the influence of EPEC infection on specific intestinal epithelial ion transport processes. T84 cell monolayers infected with EPEC were used for these studies. EPEC infection significantly decreased short-circuit current (Isc) in response to carbachol and forskolin, yet 125I efflux studies revealed no difference in Cl- channel activity. There was also no alteration in basolateral K+ channel or Na+-K+-2Cl- cotransport activity. Furthermore, net 36Cl- flux was not decreased by EPEC. No alterations in either K+ or Na+ transport could be demonstrated. Instead, removal of basolateral bicarbonate from uninfected monolayers yielded an Isc response approximating that observed with EPEC infection, whereas bicarbonate removal from EPEC-infected monolayers further diminished Isc. These studies suggest that the reduction in stimulated Isc is not secondary to diminished Cl- secretion. Alternatively, bicarbonate-dependent transport processes appear to be perturbed.

High-performance integrated perovskite and organic solar cells with efficient near-infrared harvesting

NASA Astrophysics Data System (ADS)

Kim, Junghwan; Lee, Kwanghee

2016-09-01

The integration of planar-type perovskite (Eg 1.5 eV) solar cells (PSCs) with a bulk-heterojunction (BHJ) composite comprising a near-infrared (NIR) absorbing conjugated polymer (Eg < 1.4 eV) and a fullerene derivative is a promising approach to overcoming the narrow absorption limit of typical PSCs. Nevertheless, integrated solar cells (ISCs) suffer from low fill factors (FFs) and inefficient NIR harvesting, mainly due to poor charge transport in the BHJ films. Here, we successfully demonstrate highly efficient P-I-N perovskite/BHJ ISCs with an enhanced FF and improved NIR harvesting by introducing a novel n-type semiconducting polymer and a new processing additive into the BHJ films. The optimized ISCs exhibit a power conversion efficiency (PCE) of 16.36%, which far surpasses that of the reference PSCs ( 14.70%) due to the increased current density (Jsc 20.04 mA cm-2) resulting from the additional NIR harvesting. Meanwhile, the optimized ISCs maintain a high FF of 77% and an open-circuit voltage (Voc) of 1.06 V. These results indicate that this approach is a versatile means of overcoming the absorption and theoretical efficiency limits of state-ofthe- art PSCs.

Emodin induces chloride secretion in rat distal colon through activation of mast cells and enteric neurons

PubMed Central

Xu, J-D; Liu, S; Wang, W; Li, L-S; Li, X-F; Li, Y; Guo, H; Ji, T; Feng, X-Y; Hou, X-L; Zhang, Y; Zhu, J-X

2012-01-01

BACKGROUND AND PURPOSE Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active component of many herb-based laxatives. However, its mechanism of action is unclear. The aim of the present study was to investigate the role of mast cells and enteric neurons in emodin-induced ion secretion in the rat colon. EXPERIMENTAL APPROACH Short-circuit current (ISC) recording was used to measure epithelial ion transport. A scanning ion-selective electrode technique was used to directly measure Cl- flux (JCl−) across the epithelium. RIA was used to measure emodin-induced histamine release. KEY RESULTS Basolateral addition of emodin induced a concentration-dependent increase in ISC in colonic mucosa/submucosa preparations, EC50 75 µM. The effect of emodin was blocked by apically applied glibenclamide, a Cl- channel blocker, and by basolateral application of bumetanide, an inhibitor of the Na+-K+-2Cl- cotransporter. Emodin-evoked JCl− in mucosa/submucosa preparations was measured by scanning ion-selective electrode technique, which correlated to the increase in ISC and was significantly suppressed by glibenclamide and bumetanide. Pretreatment with tetrodotoxin and the muscarinic receptor antagonist atropine had no effect on emodin-induced ΔISC in mucosa-only preparations, but significantly reduced emodin-induced ΔISC and JCl− in mucosa/submucosa preparations. The COX inhibitor indomethacin, the mast cell stabilizer ketotifen and H1 receptor antagonist pyrilamine significantly reduced emodin-induced ΔISC in mucosa and mucosa/submucosa preparations. The H2 receptor antagonist cimetidine inhibited emodin-induced ΔISC and JCl− only in the mucosa/submucosa preparations. Furthermore, emodin increased histamine release from the colonic mucosa/submucosa tissues. CONCLUSIONS AND IMPLICATIONS The results suggest that emodin-induced colonic Cl- secretion involves mast cell degranulation and activation of cholinergic and non-cholinergic submucosal neurons. PMID:21718311

Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport

PubMed Central

Sayer, Brooke; Lu, Jun; Green, Christina; Söderholm, Johan D; Akhtar, Mahmood; McKay, Derek M

2002-01-01

Neuronal cholinergic input is an important regulator of epithelial electrolyte transport and hence water movement in the gut. In this study, colitis was induced by treating mice with 4% (w v−1) dextran sodium-sulphate (DSS)-water for 5 days followed by 3 days of normal water. Mid-colonic segments were mounted in Ussing chambers and short-circuit current (Isc, indicates net ion movement) responses to the cholinergic agonist, carbachol (CCh; 10−4 M)±tetrodotoxin, atropine (ATR), hexamethonium (HEX), naloxone or phenoxybenzamine were assessed. Tissues from mice with DSS-induced colitis displayed a drop in Isc in response to CCh (−11.3±3.3 μA/cm2), while those from control mice showed a transient increase in Isc (76.3±13.0 μA/cm2). The ΔIsc in colon from DSS-treated mice was tetrodotoxin-sensitive, atropine-insensitive and was reversed by hexamethonium (HEX+CCh=16.7±7.8 μA/cm2), indicating involvement of a nicotinic receptor. CCh induced a drop in Isc in tissues from controls only when they were pretreated with the cholinergic muscarinic receptor blocker, atropine: ATR+CCh=−21.3±7.0 μA/cm2. Nicotine elicited a drop in Isc in Ussing-chambered colon from both control and DSS-treated mice that was TTX-sensitive. The drop in Isc evoked by CCh challenge of colonic tissue from DSS-treated mice or ATR+CCh challenge of control tissue was not significantly affected by blockade of opiate or α-adrenergic receptors by naloxone or phenoxybenzamine, respectively. The data indicate that DSS-colitis reveals a nicotinic receptor that becomes important in cholinergic regulation of ion transport. PMID:11934821

Vibrio cholerae ACE stimulates Ca(2+)-dependent Cl(-)/HCO(3)(-) secretion in T84 cells in vitro.

PubMed

Trucksis, M; Conn, T L; Wasserman, S S; Sears, C L

2000-09-01

ACE, accessory cholera enterotoxin, the third enterotoxin in Vibrio cholerae, has been reported to increase short-circuit current (I(sc)) in rabbit ileum and to cause fluid secretion in ligated rabbit ileal loops. We studied the ACE-induced change in I(sc) and potential difference (PD) in T84 monolayers mounted in modified Ussing chambers, an in vitro model of a Cl(-) secretory cell. ACE added to the apical surface alone stimulated a rapid increase in I(sc) and PD that was concentration dependent and immediately reversed when the toxin was removed. Ion replacement studies established that the current was dependent on Cl(-) and HCO(3)(-). ACE acted synergistically with the Ca(2+)-dependent acetylcholine analog, carbachol, to stimulate secretion in T84 monolayers. In contrast, the secretory response to cAMP or cGMP agonists was not enhanced by ACE. The ACE-stimulated secretion was dependent on extracellular and intracellular Ca(2+) but was not associated with an increase in intracellular cyclic nucleotides. We conclude that the mechanism of secretion by ACE involves Ca(2+) as a second messenger and that this toxin stimulates a novel Ca(2+)-dependent synergy.

Spontaneous water secretion in T84 cells: effects of STa enterotoxin, bumetanide, VIP, forskolin, and A-23187.

PubMed

Toriano, R; Kierbel, A; Ramirez, M A; Malnic, G; Parisi, M

2001-09-01

The regulated Cl(-) secretory apparatus of T84 cells responds to several pharmacological agents via different second messengers (Ca(2+), cAMP, cGMP). However, information about water movements in T84 cells has not been available. In the absence of osmotic or chemical gradient, we observed a net secretory transepithelial volume flux (J(w) = -0.16 +/- 0.02 microl.min(-1).cm(-2)) in parallel with moderate short-circuit current values (I(sc) = 1.55 +/- 0.23 microA/cm(2)). The secretory J(w) reversibly reverted to an absorptive value when A-23187 was added to the serosal bath. Vasoactive intestinal polypeptide increased I(sc), but, unexpectedly, J(w) was not affected. Bumetanide, an inhibitor of basolateral Na(+)-K(+)-2Cl(-) cotransporter, completely blocked secretory J(w) with no change in I(sc). Conversely, serosal forskolin increased I(sc), but J(w) switched from secretory to absorptive values. Escherichia coli heat-stable enterotoxin increased secretory J(w) and I(sc). No difference between the absorptive and secretory unidirectional Cl(-) fluxes was observed in basal conditions, but after STa stimulation, a significant net secretory Cl(-) flux developed. We conclude that, under these conditions, the presence of secretory or absorptive J(w) values cannot be shown by I(sc) and ion flux studies. Furthermore, RT-PCR experiments indicate that aquaporins were not expressed in T84 cells. The molecular pathway for water secretion appears to be transcellular, moving through the lipid bilayer or, as recently proposed, through water-solute cotransporters.

Calcium modulation of the effects of serotonin, carbachol, and histamine on rabbit ileal ion transport.

PubMed Central

Chough, S. P.; Goldenring, J. R.; Hurst, R. D.; Ballantyne, G. H.; Modlin, I. M.

1993-01-01

In mammalian intestine, a number of secretagogues have been shown to work through either cyclic nucleotide or calcium mediated pathways to elicit ion secretion. Because excessive intestinal electrolyte and fluid secretion is central to the pathogenesis of a variety of diarrheal disorders, understanding of these processes is essential to the development of future clinical treatments. In the current study, the effects of serotonin (5HT), histamine, and carbachol on intestinal ion transport were examined in in vitro preparations of rabbit ileum. All three agonists induced a rapid and transient increase short-circuit current (delta Isc) across ileal mucosa. Inhibition of the delta Isc response of all three agents in chloride-free solution or in the presence of bumetanide confirmed that chloride is the main electrolyte involved in electrogenic ion secretion. Pretreatment of tissue with tetrodotoxin or atropine did not effect secretagogue-mediated electrolyte secretion. While tachyphylaxis of delta Isc response was shown to develop after repeated exposure of a secretagogue to tissue, delta Isc responses after sequential addition of different agonists indicate that cross-tachyphylaxis between agents did not occur. Serotonin, histamine, and carbachol have previously been reported to mediate electrolyte secretion through calcium-dependent pathways. To access the role of extracellular calcium in regulating ion secretion, the effect of verapamil on each agent was tested; verapamil decreased 5HT-induced delta Isc by 65.2% and histamine response by 33.5%, but had no effect on carbachol-elicited chloride secretion. An additive secretory effect was found upon simultaneous exposure of 5HT and carbachol to the system; no other combination of agents produced a significant additive effect. Findings from this study support previous work which has suggested that multiple calcium pathways may be involved in mediating chloride secretion in mammalian intestine. PMID:7716972

Basolateral K channels in an insect epithelium. Channel density, conductance, and block by barium

PubMed Central

Hanrahan, JW; Wills, NK; Phillips, JE; Lewis, SA

1986-01-01

K channels in the basolateral membrane of insect hindgut were studied using current fluctuation analysis and microelectrodes. Locust recta were mounted in Ussing-type chambers containing Cl-free saline and cyclic AMP (cAMP). A transepithelial K current was induced by raising serosal [K] under short-circuit conditions. Adding Ba to the mucosal (luminal) side under these conditions had no effect; however, serosal Ba reversibly inhibited the short-circuit current (Isc), increased transepithelial resistance (Rt), and added a Lorentzian component to power density spectra of the Isc. A nonlinear relationship between corner frequency and serosal [Ba] was observed, which suggests that the rate constant for Ba association with basolateral channels increased as [Ba] was elevated. Microelectrode experiments revealed that the basolateral membrane hyperpolarized when Ba was added: this change in membrane potential could explain the nonlinearity of the 2 pi fc vs. [Ba] relationship if external Ba sensed about three-quarters of the basolateral membrane field. Conventional microelectrodes were used to determine the correspondence between transepithelially measured current noise and basolateral membrane conductance fluctuations, and ion-sensitive microelectrodes were used to measure intracellular K activity (acK). From the relationship between the net electrochemical potential for K across the basolateral membrane and the single channel current calculated from noise analysis, we estimate that the conductance of basolateral K channels is approximately 60 pS, and that there are approximately 180 million channels per square centimeter of tissue area. PMID:2420918

Basolateral K+ channel involvement in forskolin-activated chloride secretion in human colon

PubMed Central

McNamara, Brian; Winter, Desmond C; Cuffe, John E; O'Sullivan, Gerald C; Harvey, Brian J

1999-01-01

In this study we investigated the role of basolateral potassium transport in maintaining cAMP-activated chloride secretion in human colonic epithelium. Ion transport was quantified in isolated human colonic epithelium using the short-circuit current technique. Basolateral potassium transport was studied using nystatin permeabilization. Intracellular calcium measurements were obtained from isolated human colonic crypts using fura-2 spectrofluorescence imaging. In intact isolated colonic strips, forskolin and prostaglandin E2 (PGE2) activated an inward transmembrane current (ISC) consistent with anion secretion (for forskolin ΔISC = 63.8 ± 6.2 μA cm−2, n = 6; for PGE2 ΔISC = 34.3 ± 5.2 μA cm−2, n = 6). This current was inhibited in chloride-free Krebs solution or by inhibiting basolateral chloride uptake with bumetanide and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS). The forskolin- and PGE2-induced chloride secretion was inhibited by basolateral exposure to barium (5 mM), tetrapentylammonium (10 μM) and tetraethylammonium (10 mM). The transepithelial current produced under an apical to serosal K+ gradient in nystatin-perforated colon is generated at the basolateral membrane by K+ transport. Forskolin failed to activate this current under conditions of high or low calcium and failed to increase the levels of intracellular calcium in isolated crypts In conclusion, we propose that potassium recycling through basolateral K+ channels is essential for cAMP-activated chloride secretion. PMID:10432355

Energy Storage Awards | Transportation Research | NREL

Science.gov Websites

storage team has been recognized with three of these top honors. Battery Internal Short-Circuit Device NREL's patented Battery Internal Short-Circuit (ISC) Device is the only diagnostic tool that makes it affect reactions to internal short circuits and pinpoint related safety issues before batteries are in

Second-messenger regulation of sodium transport in mammalian airway epithelia.

PubMed Central

Graham, A; Steel, D M; Alton, E W; Geddes, D M

1992-01-01

1. Sodium absorption is the dominant ion transport process in conducting airways and is a major factor regulating the composition of airway surface liquid. However, little is known about the control of airway sodium transport by intracellular regulatory pathways. 2. In sheep tracheae and human bronchi mounted in Ussing chambers under short circuit conditions, the sodium current can be isolated by pretreating tissues with acetazolamide (100 microM) to inhibit bicarbonate secretion, bumetanide (100 microM) to inhibit chloride secretion and phloridzin (200 microM) to inhibit sodium-glucose cotransport. This sodium current consists of amiloride-sensitive (57%) and amiloride-insensitive (43%) components. 3. The regulation of the isolated sodium current by three second messenger pathways was studied using the calcium ionophore A23187 to elevate intracellular calcium, a combination of forskolin and the phosphodiesterase inhibitor zardaverine to elevate intracellular cyclic AMP, and the phorbol ester 12,13-phorbol dibutyrate (PDB) to stimulate protein kinase C. 4. In sheep trachea, A23187 produces a dose-related inhibition of the sodium current with maximal effect (38% of ISC) at 10 microM and IC50 1 microM. This response affects both the amiloride-sensitive and insensitive components of the sodium current and is not altered by prior stimulation of protein kinase C or elevation of intracellular cyclic AMP. In human bronchi, A23187 (10 microM) produced a significantly greater inhibition of ISC (68%), a response which was unaffected by prior treatment with PDB or forskolin-zardaverine. 5. In sheep trachea, stimulation of protein kinase C with PDB produced a dose-related inhibition of ISC maximal (56% of ISC) at 50 nM (IC50 7 nM). This response was abolished by amiloride (100 microM) pretreatment suggesting a selective effect on the amiloride-sensitive component of the sodium current. The response was not altered by prior elevation of intracellular calcium or cyclic AMP. PDB (10 nM) caused a similar inhibition of ISC in human bronchi (43%). The effect of PKC stimulation following pretreatment with A23187 was diminished in human bronchi. Elevating intracellular cyclic AMP did not alter this response. 6. Addition of forskolin (1 microM) together with the phosphodiesterase inhibitor zardaverine (100 microM) produced a mean 35-fold increase in intracellular cyclic AMP in sheep trachea. This was associated with a small, but significant, 6% transient increase in ISC followed by a significant 4% fall. Neither effect could be abolished by amiloride pretreatment. In human bronchi, a small decrease in ISC which could not be distinguished from that occurring in controls was observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1464841

Differential activation of the HCO3− conductance through the cystic fibrosis transmembrane conductance regulator anion channel by genistein and forskolin in murine duodenum

PubMed Central

Tuo, Biguang; Wen, Guorong; Seidler, Ursula

2009-01-01

Background and purpose: Many cystic fibrosis (CF)-associated mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channels affect CFTR-activated HCO3− transport more than Cl− transport. Targeting the CFTR HCO3− conductance, if possible, may therefore be of major therapeutic benefit. In the present study, we examined the effects of genistein and forskolin on duodenal mucosal HCO3− and Cl− secretion. Experimental approach: Murine duodenal mucosal HCO3− and Cl− secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (Isc) techniques. Key results: Genistein markedly stimulated duodenal HCO3− secretion and Isc in a dose-dependent manner in CFTR wild-type mice, but not in CFTR null mice. CFTRinh-172, a highly specific CFTR inhibitor, inhibited genistein-stimulated duodenal HCO3− secretion and Isc in wild-type mice. Genistein induced 59% net HCO3− increase and 123% net Isc increase over basal value, whereas forskolin, an activator of adenylate cyclase, induced 94% net HCO3− increase and 507% net Isc increase, indicating that, compared with forskolin, genistein induced a relatively high HCO3−/Isc ratio. Further data showed that CFTR HCO3−/Cl− conductance ratio was 1.05 after genistein stimulation, whereas after forskolin stimulation, the CFTR HCO3−/Cl− conductance ratio was 0.27. Conclusions and implications: Genistein stimulates duodenal HCO3− and Cl− secretion through CFTR, and has a relatively high selectivity for the CFTR HCO3− conductance, compared with forskolin. This may indicate the feasibility of selective targeting of the HCO3− conductance of the CFTR channels. PMID:19788494

Rapid elevation of sodium transport through insulin is mediated by AKT in alveolar cells

PubMed Central

Mattes, Charlott; Laube, Mandy; Thome, Ulrich H.

2014-01-01

Abstract Alveolar fluid clearance is driven by vectorial Na+ transport and promotes postnatal lung adaptation. The effect of insulin on alveolar epithelial Na+ transport was studied in isolated alveolar cells from 18–19‐day gestational age rat fetuses. Equivalent short‐circuit currents (ISC) were measured in Ussing chambers and different kinase inhibitors were used to determine the pathway of insulin stimulation. In Western Blot measurements the activation of mediators stimulated by insulin was analyzed. The ISC showed a fast dose‐dependent increase by insulin, which could be attributed to an increased ENaC (epithelial Na+ channel) activity in experiments with permeabilized apical or basolateral membrane. 5‐(N‐Ethyl‐N‐isopropyl)amiloride inhibition of ISC was not affected, however, benzamil‐sensitive ISC was increased in insulin‐stimulated monolayers. The application of LY‐294002 and Akti1/2 both completely blocked the stimulating effect of insulin on ISC. PP242 partly blocked the effect of insulin, whereas Rapamycin evoked no inhibition. Western Blot measurements revealed an increased phosphorylation of AKT after insulin stimulation. SGK1 activity was also increased by insulin as shown by Western Blot of pNDRG1. However, in Ussing chamber measurements, GSK650394, an inhibitor of SGK1 did not prevent the increase in ISC induced by insulin. The application of IGF‐1 mimicked the effect of insulin and increased the ENaC activity. In addition, an increased autophosphorylation of the IGF‐1R/IR was observed after insulin stimulation. We conclude that insulin rapidly increases epithelial Na+ transport by enhancing the activity of endogenous ENaC through activation of PI3K/AKT in alveolar cells. PMID:24760523

Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon

PubMed Central

Zhang, Jin; Halm, Susan T.

2012-01-01

Secretagogues acting at a variety of receptor types activate electrogenic K+ secretion in guinea pig distal colon, often accompanied by Cl− secretion. Distinct blockers of KCa1.1 (BK, Kcnma1), iberiotoxin (IbTx), and paxilline inhibited the negative short-circuit current (Isc) associated with K+ secretion. Mucosal addition of IbTx inhibited epinephrine-activated Isc (epiIsc) and transepithelial conductance (epiGt) consistent with K+ secretion occurring via apical membrane KCa1.1. The concentration dependence of IbTx inhibition of epiIsc yielded an IC50 of 193 nM, with a maximal inhibition of 51%. Similarly, IbTx inhibited epiGt with an IC50 of 220 nM and maximal inhibition of 48%. Mucosally added paxilline (10 μM) inhibited epiIsc and epiGt by ∼50%. IbTx and paxilline also inhibited Isc activated by mucosal ATP, supporting apical KCa1.1 as a requirement for this K+ secretagogue. Responses to IbTx and paxilline indicated that a component of K+ secretion occurred during activation of Cl− secretion by prostaglandin-E2 and cholinergic stimulation. Analysis of KCa1.1α mRNA expression in distal colonic epithelial cells indicated the presence of the ZERO splice variant and three splice variants for the COOH terminus. The presence of the regulatory β-subunits KCaβ1 and KCaβ4 also was demonstrated. Immunolocalization supported the presence of KCa1.1α in apical and basolateral membranes of surface and crypt cells. Together these results support a cellular mechanism for electrogenic K+ secretion involving apical membrane KCa1.1 during activation by several secretagogue types, but the observed K+ secretion likely required the activity of additional K+ channel types in the apical membrane. PMID:23064759

Electrophysiological response of chicken's jejunal epithelium to increasing levels of T-2 toxin.

PubMed

Yunus, Agha Waqar; Kröger, Susan; Tichy, Alexander; Zentek, Jürgen; Böhm, Josef

2013-02-01

The present investigations were conducted to test the effects of T-2 toxin on electrophysiological variables of jejunal epithelium of chicken. Jejunal segments of broilers were monitored in Ussing chambers in the presence of T-2 toxin at the levels of 0 (negative control), 0 (methanol/vehicle control), 0.1, 1, 5, and 10 μg/ml of buffer. T-2 toxin did not affect basal values of short circuit current (I(sc)), transmural potential difference, or tissue conductivity in the jejunal epithelium. T-2 toxin also did not statistically affect glucose-induced electrophysiological variables during the first 3 min of glucose induction. Compared to the vehicle control, the ouabain-sensitive I(sc) was negatively affected (P = 0.008) only under 5 μg of T-2 toxin/ml. Increasing levels of T-2 toxin negatively affected the ouabain-sensitive I(sc) in a cubic (P = 0.007) fashion. These data indicate that acute exposure to moderate levels of T-2 toxin may progressively impair the cation gradient across the jejunal epithelium.

A Regulatory Circuit Composed of a Transcription Factor, IscR, and a Regulatory RNA, RyhB, Controls Fe-S Cluster Delivery.

PubMed

Mandin, Pierre; Chareyre, Sylvia; Barras, Frédéric

2016-09-20

Fe-S clusters are cofactors conserved through all domains of life. Once assembled by dedicated ISC and/or SUF scaffolds, Fe-S clusters are conveyed to their apo-targets via A-type carrier proteins (ATCs). Escherichia coli possesses four such ATCs. ErpA is the only ATC essential under aerobiosis. Recent studies reported a possible regulation of the erpA mRNA by the small RNA (sRNA) RyhB, which controls the expression of many genes under iron starvation. Surprisingly, erpA has not been identified in recent transcriptomic analysis of the iron starvation response, thus bringing into question the actual physiological significance of the putative regulation of erpA by RyhB. Using an sRNA library, we show that among 26 sRNAs, only RyhB represses the expression of an erpA-lacZ translational fusion. We further demonstrate that this repression occurs during iron starvation. Using mutational analysis, we show that RyhB base pairs to the erpA mRNA, inducing its disappearance. In addition, IscR, the master regulator of Fe-S homeostasis, represses expression of erpA at the transcriptional level when iron is abundant, but depleting iron from the medium alleviates this repression. The conjunction of transcriptional derepression by IscR and posttranscriptional repression by RyhB under Fe-limiting conditions is best described as an incoherent regulatory circuit. This double regulation allows full expression of erpA at iron concentrations for which Fe-S biogenesis switches from the ISC to the SUF system. We further provide evidence that this regulatory circuit coordinates ATC usage to iron availability. Regulatory small RNAs (sRNAs) have emerged as major actors in the control of gene expression in the last few decades. Relatively little is known about how these regulators interact with classical transcription factors to coordinate genetic responses. We show here how an sRNA, RyhB, and a transcription factor, IscR, regulate expression of an essential gene, erpA, in the bacterium E. coli ErpA is involved in the biogenesis of Fe-S clusters, an important class of cofactors involved in a plethora of cellular reactions. Interestingly, we show that RyhB and IscR repress expression of erpA under opposite conditions in regard to iron concentration, forming a regulatory circuit called an "incoherent network." This incoherent network serves to maximize expression of erpA at iron concentrations where it is most needed. Altogether, our study paves the way for a better understanding of mixed regulatory networks composed of RNAs and transcription factors. Copyright © 2016 Mandin et al.

Multiple P2Y receptor subtypes in the apical membranes of polarized epithelial cells

PubMed Central

McAlroy, H L; Ahmed, S; Day, S M; Baines, D L; Wong, H Y; Yip, C Y; Ko, W H; Wilson, S M; Collett, A

2000-01-01

Apical ATP, ATP, UTP and UDP evoked transient increases in short circuit current (ISC, a direct measure of transepithelial ion transport) in confluent Caco-2 cells grown on permeable supports. These responses were mediated by a population of at least three pharmacologically distinct receptors. Experiments using cells grown on glass coverslips showed that ATP and UTP consistently increased intracellular free calcium ([Ca2+]i) whilst sensitivity to UDP was variable. Cross desensitization experiments suggested that the responses to UTP and ATP were mediated by a common receptor population. Messenger RNA transcripts corresponding to the P2Y2, P2Y4 and P2Y6 receptors genes were detected in cells grown on Transwell membranes by the reverse transcriptase–polymerase chain reaction. Identical results were obtained for cells grown on glass. Experiments in which ISC and [Ca2+]i were monitored simultaneously in cells on Transwell membranes, confirmed that apical ATP and UTP increased both parameters and showed that the UDP-evoked increase in ISC was accompanied by a [Ca2+]i-signal. Ionomycin consistently increased [Ca2+]i in such polarized cells but caused no discernible change in ISC. However, subsequent application of apical ATP or UTP evoked a small rise in ISC but no rise in [Ca2+]i. UDP evoked no such response. As well as evoking increases in [Ca2+]i, the ATP/UTP-sensitive receptors present in Caco-2 cells thus allow direct control over ion channels in the apical membrane. The UDP-sensitive receptors, however, appear to simply evoke a rise in [Ca2+]i. PMID:11139443

Steroids alter ion transport and absorptive capacity in proximal and distal colon.

PubMed

Sellin, J H; DeSoignie, R C

1985-07-01

Steroids are potent absorbagogues, increasing Na and fluid absorption in a variety of epithelia. This study characterizes the in vitro effects of pharmacological doses of gluco- and mineralocorticoids on transport parameters of rabbit proximal and distal colon. Treatment with methylprednisolone (MP, 40 mg im for 2 days) and desoxycortone acetate (DOCA, 12.5 mg im for 3 days) resulted in a significant increase in short-circuit current (Isc) in distal colon, suggesting an increase in basal Na absorption. Amiloride (10(-4) M) caused a significantly negative Isc in MP-treated tissue, demonstrating a steroid-induced, amiloride-insensitive electrogenic ion transport in distal colon. The effect of two absorbagogues, impermeant anions (SO4-Ringer) and amphotericin, were compared in control and steroid-treated distal colon. In controls, both absorbagogues increased Isc. Impermeant anions caused a rise in Isc in both MP and DOCA tissues, suggesting that the high rate of basal Na absorption had not caused a saturation of the Na pump. The steroid-treated colons, however, did not consistently respond to amphotericin. Amiloride inhibited the entire Isc in MP-treated distal colon that had been exposed to amphotericin; this suggested that amphotericin had not exerted its characteristic effect on the apical membrane of steroid-treated colon. In proximal colon, steroids did not alter basal rates of transport; however, epinephrine-induced Na-Cl absorption was significantly greater in MP-treated vs control (P less than 0.005). Steroids increase the absorptive capacity of both proximal and distal colon for Na, while increasing basal Na absorption only in the distal colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Lubiprostone Reverses the Inhibitory Action of Morphine on Intestinal Secretion in Guinea Pig and Mouse

PubMed Central

Fei, Guijun; Raehal, Kirsten; Liu, Sumei; Qu, Mei-Hua; Sun, Xiaohong; Wang, Guo-Du; Wang, Xi-Yu; Xia, Yun; Schmid, Cullen L.; Bohn, Laura M.

2010-01-01

Lubiprostone activates ClC-2 chloride channels in epithelia. It is approved for treatment of chronic idiopathic constipation in adults and constipation-predominate irritable bowel syndrome in women. We tested a hypothesis that lubiprostone can reverse the constipating action of morphine and investigated the mechanism of action. Short-circuit current (Isc) was recorded in Ussing chambers as a marker for chloride secretion during pharmacological interactions between morphine and lubiprostone. Measurements of fecal wet weight were used to obtain information on morphine-lubiprostone interactions in conscious mice. Morphine decreased basal Isc, with an IC50 of 96.1 nM. The action of dimethylphenylpiperazinium (DMPP), a nicotinic receptor agonist that stimulates neurogenic Isc, was suppressed by morphine. Lubiprostone applied after pretreatment with morphine reversed morphine suppression of both basal Isc and DMPP-evoked chloride secretion. Electrical field stimulation (EFS) of submucosal neurons evoked biphasic increases in Isc. Morphine abolished the first phase and marginally suppressed the second phase. Lubiprostone reversed, in concentration-dependent manner, the action of morphine on the first and second phases of the EFS-evoked responses. Subcutaneous lubiprostone increased fecal wet weight and numbers of pellets expelled. Morphine significantly reduced fecal wet weight and number of pellets. Injection of lubiprostone, 30-min after morphine, reversed morphine-induced suppression of fecal wet weight. We conclude that inhibitory action of morphine on chloride secretion reflects suppression of excitability of cholinergic secretomotor neurons in the enteric nervous system. Lubiprostone, which does not directly affect enteric neurons, bypasses the neurogenic constipating effects of morphine by directly opening chloride channels in the mucosal epithelium. PMID:20406855

Lubiprostone reverses the inhibitory action of morphine on intestinal secretion in guinea pig and mouse.

PubMed

Fei, Guijun; Raehal, Kirsten; Liu, Sumei; Qu, Mei-Hua; Sun, Xiaohong; Wang, Guo-Du; Wang, Xi-Yu; Xia, Yun; Schmid, Cullen L; Bohn, Laura M; Wood, Jackie D

2010-07-01

Lubiprostone activates ClC-2 chloride channels in epithelia. It is approved for treatment of chronic idiopathic constipation in adults and constipation-predominate irritable bowel syndrome in women. We tested a hypothesis that lubiprostone can reverse the constipating action of morphine and investigated the mechanism of action. Short-circuit current (Isc) was recorded in Ussing chambers as a marker for chloride secretion during pharmacological interactions between morphine and lubiprostone. Measurements of fecal wet weight were used to obtain information on morphine-lubiprostone interactions in conscious mice. Morphine decreased basal Isc, with an IC(50) of 96.1 nM. The action of dimethylphenylpiperazinium (DMPP), a nicotinic receptor agonist that stimulates neurogenic Isc, was suppressed by morphine. Lubiprostone applied after pretreatment with morphine reversed morphine suppression of both basal Isc and DMPP-evoked chloride secretion. Electrical field stimulation (EFS) of submucosal neurons evoked biphasic increases in Isc. Morphine abolished the first phase and marginally suppressed the second phase. Lubiprostone reversed, in concentration-dependent manner, the action of morphine on the first and second phases of the EFS-evoked responses. Subcutaneous lubiprostone increased fecal wet weight and numbers of pellets expelled. Morphine significantly reduced fecal wet weight and number of pellets. Injection of lubiprostone, 30-min after morphine, reversed morphine-induced suppression of fecal wet weight. We conclude that inhibitory action of morphine on chloride secretion reflects suppression of excitability of cholinergic secretomotor neurons in the enteric nervous system. Lubiprostone, which does not directly affect enteric neurons, bypasses the neurogenic constipating effects of morphine by directly opening chloride channels in the mucosal epithelium.

Submucosal reflexes: distension-evoked ion transport in the guinea pig distal colon.

PubMed

Frieling, T; Wood, J D; Cooke, H J

1992-07-01

Muscle-stripped segments of distal colon from guinea pigs were mounted in modified flux chambers to determine the effect of distension on mucosal secretion. Ion secretion was monitored as changes in short-circuit current (Isc). Distending forces were pressure gradients established by controlled reduction in liquid volume of the submucosal compartment of the chamber. Volume removal for 10 s or 5 min evoked a monophasic or biphasic increase in Isc, which returned to baseline within 5-20 min. The amplitude of the response correlated with the volume removed and was reduced by bumetanide and Cl-free solutions but not by tetraethylammonium or amiloride. Tetrodotoxin and atropine also suppressed the response. Neither the nicotinic receptor antagonist mecamylamine, the 5-hydroxytryptamine3 (5-HT3) receptor antagonist ICS 205-930, or the prostaglandin synthesis inhibitor piroxicam altered the response. Addition of prostaglandin D2 to the submucosal bath significantly enhanced the response. The results suggest that distension of the colon evokes anion secretion by activation of reflex circuits with cholinergic neurons and muscarinic synapses. Prostaglandins and 5-hydroxytryptamine acting at 5-HT3 receptors appear not to be signal substances in the reflex pathway, which evokes the secretory response to distension.

Fabrication and characterization of anisotype heterojunctions n-TiN/p-CdTe

NASA Astrophysics Data System (ADS)

Solovan, M. M.; Brus, V. V.; Maryanchuk, P. D.; Ilashchuk, M. I.; Rappich, J.; Nickel, N.; Abashin, S. L.

2014-01-01

Photosensitive heterojunctions n-TiN/p-CdTe were fabricated for the first time by means of titanium nitride thin film deposition (n-type conductivity) by the reactive magnetron sputtering onto freshly etched single crystal substrates CdTe (1 1 0) of p-type conductivity. The temperature dependences of the height of the potential barrier and series resistance of the n-TiN/p-CdTe heterojunction were investigated. The dominating current transport mechanisms through the heterojunctions under investigation were determined at forward and reverse bias. The heterojunctions under investigation generate open-circuit voltage Voc = 0.35 V, short-circuit current Isc = 1.88 mA см-2 and fill factor FF = 0.51 under illumination 80 mW сm-2.

Tumour necrosis factor alpha changes porcine intestinal ion transport through a paracrine mechanism involving prostaglandins.

PubMed Central

Kandil, H M; Berschneider, H M; Argenzio, R A

1994-01-01

Prostaglandins stimulate electrogenic anion secretion and inhibit sodium chloride absorption in cryptosporidium induced pig diarrhoea. Because tumour necrosis factor alpha (TNF alpha) is an early mediator of inflammation and stimulates prostaglandin secretion, we investigated its effect on intestinal ion transport. Cryptosporidium infected pig ileum showed higher macrophage infiltration and tissue TNF alpha-like activity than uninfected tissues (p < 0.05, n = 4 and p < 0.05, n = 12, respectively). TNF alpha treatment of control porcine ileal mucosa increased the short circuit current (Isc), a measurement of net anion secretion in this model (p < 0.001, n = 23). This effect was blocked by 10(-6) M indomethacin and Cl- replacement. Neither acute treatment nor preincubation of colonic intestinal epithelial cell monolayers (T84) with TNF alpha stimulated the Isc. However, co-mounting of TNF alpha preincubated pig jejunal fibroblasts (P2JF) monolayers back to back with untreated T84 monolayers dose-dependently induced an indomethacin sensitive increase in Isc compared with values in untreated co-mounted monolayers (p < 0.001, n = 11). These data suggest that in infectious diarrhoea, TNF alpha may induce Cl- secretion through a paracrine mechanism involving prostaglandin release from subepithelial cells, for example fibroblasts. PMID:8063221

Functional characteristics of the porcine colonic epithelium following transportation stress and Salmonella infection.

PubMed

Aschenbach, Jörg R; Ahrens, Frank; Schwelberger, Hubert G; Fürll, Brigitta; Roesler, Uwe; Hensel, Andreas; Gäbel, Gotthold

2007-06-01

Stressful life events and infections contribute to gut disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We used a pig model to analyse whether this could be linked to altered mediator sensitivity of the epithelial lining. Uninfected control pigs or pigs with subclinical Salmonella (S.) typhimurium DT 104 infection were killed either without (ConRest, InfRest) or with prior 8-h transportation (ConTrans, InfTrans). Short-circuit current (I(sc)), tissue conductance (G(t)) and release of mast cell mediators were monitored in isolated colonic epithelia mounted in Ussing chambers. Epithelia were exposed to histamine (100 microM, mucosally), substance P (SP; 1 microM, serosally), calcimycin A23187 (1 microM, serosally) and theophylline (10 mM, bilaterally). Transepithelial flux of histamine and colonic activities of histamine N-methyltransferase (HMT) and diamine oxidase (DAO) were determined. S. infection decreased baseline I(sc), G(t) and histamine fluxes, while transportation had no effect on these values. Mucosal histamine increased I(sc) only in ConTrans pigs. This was not associated with increased mucosal-to-serosal flux of histamine but with a 2-fold increased DAO activity. Serosal SP increased I(sc) only in transported animals, but the increase was six times higher in ConTrans versus InfTrans pigs. Effectiveness of SP was not dependent on the release of histamine or prostaglandin D2. A23187 and theophylline elicited increases in I(sc) that were not different between treatments. Transportation stress facilitates secretory responses of the colonic epithelium to SP and luminal histamine. This is suppressed by subclinical S. infection. Effects of S. infection on porcine colon resemble, in part, the known effects of an oral S. endotoxin application.

The effects of hypoxia on active ionic transport processes in the gill epithelium of hyperregulating crab, Carcinus maneas.

PubMed

Lucu, Čedomil; Ziegler, Andreas

2017-09-01

Effects of hypoxia on the osmorespiratory functions of the posterior gills of the shore crab Carcinus maenas acclimated to 12ppt seawater (DSW) were studied. Short-circuit current (Isc) across the hemilamella (one epithelium layer supported by cuticle) was substantially reduced under exposure to 1.6, 2.0, or 2.5mg O 2 /L hypoxic saline (both sides of epithelium) and fully recovered after reoxygenation. Isc was reduced equally in the epithelium exposed to 1.6mg O 2 /L on both sides and when the apical side was oxygenated and the basolateral side solely exposed to hypoxia. Under 1.6mg O 2 /L, at the level of maximum inhibition of Isc, conductance was decreased from 40.0mScm -2 to 34.7mScm -2 and fully recovered after reoxygenation. Isc inhibition under hypoxia and reduced 86 Rb + (K + ) fluxes across apically located K + channels were caused preferentially by reversible inhibition of basolaterally located and ouabain sensitive Na + ,K + -ATPase mediated electrogenic transport. Reversible inhibition of Isc is discussed as decline in active transport energy supply down regulating metabolic processes and saving energy during oxygen deprivation. In response to a 4day exposure of Carcinus to 2.0mg O 2 /L, hemolymph Na + and Cl - concentration decreased, i.e. hyperosmoregulation was weakened. Variations of the oxygen concentration level and exposure time to hypoxia lead to an increase of the surface of mitochondria per epithelium area and might in part compensate for the decrease in oxygen availability under hypoxic conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Prostaglandin E2 induces chloride secretion through crosstalk between cAMP and calcium signaling in mouse inner medullary collecting duct cells

PubMed Central

Rajagopal, Madhumitha; Thomas, Sheela V.; Kathpalia, Paru P.; Chen, Yu

2013-01-01

Under conditions of high dietary salt intake, prostaglandin E2 (PGE2) production is increased in the collecting duct and promotes urinary sodium chloride (NaCl) excretion; however, the molecular mechanisms by which PGE2 increases NaCl excretion in this context have not been clearly defined. We used the mouse inner medullary collecting duct (mIMCD)-K2 cell line to characterize mechanisms underlying PGE2-regulated NaCl transport. When epithelial Na+ channels were inhibited, PGE2 exclusively stimulated basolateral EP4 receptors to increase short-circuit current (IscPGE2). We found that IscPGE2 was sensitive to inhibition by H-89 and CFTR-172, indicating that EP4 receptors signal through protein kinase A to induce Cl− secretion via cystic fibrosis transmembrane conductance regulator (CFTR). Unexpectedly, we also found that IscPGE2 was sensitive to inhibition by BAPTA-AM (Ca2+ chelator), 2-aminoethoxydiphenyl borate (2-APB) (inositol triphosphate receptor blocker), and flufenamic acid (FFA) [Ca2+-activated Cl− channel (CACC) inhibitor], suggesting that EP4 receptors also signal through Ca2+ to induce Cl− secretion via CACC. Additionally, we observed that PGE2 stimulated an increase in Isc through crosstalk between cAMP and Ca2+ signaling; BAPTA-AM or 2-APB inhibited a component of IscPGE2 that was sensitive to CFTR-172 inhibition; H-89 inhibited a component of IscPGE2 that was sensitive to FFA inhibition. Together, our findings indicate that PGE2 activates basolateral EP4 receptors and signals through both cAMP and Ca2+ to stimulate Cl− secretion in IMCD-K2 cells. We propose that these signaling pathways, and the crosstalk between them, may provide a concerted mechanism for enhancing urinary NaCl excretion under conditions of high dietary NaCl intake. PMID:24284792

Acute ENaC Stimulation by cAMP in a Kidney Cell Line is Mediated by Exocytic Insertion from a Recycling Channel Pool

PubMed Central

Butterworth, Michael B.; Edinger, Robert S.; Johnson, John P.; Frizzell, Raymond A.

2005-01-01

Acute hormonal regulation of the epithelial sodium channel (ENaC) in tight epithelia increases transcellular Na+ transport via trafficking of intracellular channels to the apical surface. The fate of the channels removed from the apical surface following agonist washout is less clear. By repetitively stimulating polarized mouse cortical collecting duct (mCCD, MPKCCD14) epithelia, we evaluated the hypothesis that ENaC recycles through an intracellular pool to be available for reinsertion into the apical membrane. Short circuit current (ISC), membrane capacitance (CT), and conductance (GT) were recorded from mCCD epithelia mounted in modified Ussing chambers. Surface biotinylation of ENaC demonstrated an increase in channel number in the apical membrane following cAMP stimulation. This increase was accompanied by a 83 ± 6% (n = 31) increase in ISC and a 15.3 ± 1.5% (n = 15) increase in CT. Selective membrane permeabilization demonstrated that the CT increase was due to an increase in apical membrane capacitance. ISC and CT declined to basal levels on stimulus washout. Repetitive cAMP stimulation and washout (∼1 h each cycle) resulted in response fatigue; ΔISC decreased ∼10% per stimulation–recovery cycle. When channel production was blocked by cycloheximide, ΔISC decreased ∼15% per stimulation cycle, indicating that newly synthesized ENaC contributed a relatively small fraction of the channels mobilized to the apical membrane. Selective block of surface ENaC by benzamil demonstrated that channels inserted from a subapical pool made up >90% of the stimulated ISC, and that on restimulation a large proportion of channels retrieved from the apical surface were reinserted into the apical membrane. Channel recycling was disrupted by brefeldin A, which inhibited ENaC exocytosis, by chloroquine, which inhibited ENaC endocytosis and recycling, and by latrunculin A, which blocked ENaC exocytosis. A compartment model featuring channel populations in the apical membrane and intracellular recycling pool provided an adequate kinetic description of the ISC responses to repetitive stimulation. The model supports the concept of ENaC recycling in response to repetitive cAMP stimulation. PMID:15623897

Apical P2XR contribute to [Ca2+]i signaling and Isc in mouse renal MCD.

PubMed

Li, Liuzhe; Lynch, I Jeanette; Zheng, Wencui; Cash, Melanie N; Teng, Xueling; Wingo, Charles S; Verlander, Jill W; Xia, Shen-Ling

2007-08-03

We examined P2X receptor expression and distribution in the mouse collecting duct (CD) and their functional role in Ca(2+) signaling. Both P2X(1) and P2X(4) were detected by RT-PCR and Western blot. Immunohistochemistry demonstrated apical P2X(1) and P2X(4) immunoreactivity in principal cells in the outer medullary CD (OMCD) and inner medullary CD (IMCD). Luminal ATP induced an increase in Ca(2+) signaling in native medullary CD (MCD) as measured by fluorescence imaging. ATP also induced an increase in Ca(2+) signaling in MCD cells grown in primary culture but not in the presence of P2XR antagonist PPNDS. Short circuit current (I(sc)) measurement with mouse IMCD cells showed that P2XR agonist BzATP induced a larger I(sc) than did P2YR agonist UTP in the apical membrane. Our data reveal for the first time that P2X(1) and P2X(4) are cell-specific with prominent immunoreactivity in the apical area of MCD cells. The finding that P2XR blockade inhibits ATP-induced Ca(2+) signaling suggests that activation of P2XR is a key step in Ca(2+)-dependent purinergic signaling. The result that activation of P2XR produces large I(sc) indicates the necessity of P2XR in renal CD ion transport.

Leukotrienes-mediated effects of water extracts from Sargassum horneri, a marine brown alga, on Cl- absorption in isolated rat colon.

PubMed

Sakai, Hideki; Uchiumi, Takaoki; Lee, Jung-Bum; Ohira, Yuta; Ohkura, Jun-ichi; Suzuki, Tomoyuki; Hayashi, Toshimitsu; Takeguchi, Noriaki

2004-02-01

Sargassum horneri is an edible marine brown alga distributed along the seacoast of Japan. Here we examined effects on the water-soluble (ethanol-insoluble) extracts (EIS) from Sargassum horneri on ion transports across the isolated rat colonic mucosa set in Ussing chambers. The nonpolysaccharide fraction of EIS (EIS-2) significantly decreased short-circuit current (Isc) across the mucosa, and increased the tissue conductance (Gt). The half-maximal effect of EIS-2 was obtained at 20 microg/ml. In contrast, the polysaccharide fraction of EIS (EIS-1; 100 microg/ml) had little effect on Isc and Gt. The effect of EIS-2 depended on the presence of Cl- and HCO3- but not K+ in the bathing solution. These results suggest that EIS-2 stimulates Cl)absorption in the colonic mucosa. The EIS-2-induced changes in Isc and Gt were inhibited by 3-(1-[p-chlorobenzyl]-5-[isopropyl]-3-t-butylthioindol-2-yl)-2,2-dimethyl-propanoic acid sodium (MK-886; 10 microM), a 5-lipoxygenase-activating protein inhibitor, and 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB; 100 microM), a Cl- channel blocker. EIS-2 attenuated the prostaglandin E2 (0.5 microM)-increased Isc, and the half-maximal effect of EIS-2 was obtained at 50 microg/ml. The present study suggests that the EIS-2 stimulates Cl- absorption mediated by basolateral leukotriene-sensitive Cl- channels and apical Cl-/HCO3- exchanger in the rat colonic mucosa.

Structural, electrical, and photoelectric properties of p-NiO/n-CdTe heterojunctions

NASA Astrophysics Data System (ADS)

Parkhomenko, Hryhorii; Solovan, Mykhaylo; Brus, Viktor; Maystruk, Eduard; Maryanchuk, Pavlo

2018-01-01

p-NiO/n-CdTe-photosensitive heterojunctions were prepared by the deposition of nickel oxide thin films onto n-type single-crystal CdTe substrates by DC reactive magnetron sputtering. The analysis of capacitance-voltage (C-V) characteristics, measured at different frequencies of the small amplitude AC signal and corrected by the effect of the series resistance, provided evidence of the presence of electrically charged interface states, which significantly affect the measured capacitance. The dominant current transport mechanisms in the heterojunctions were determined at forward and reverse biases. Using "light" I-V characteristics, we determined the open-circuit voltage Voc=0.42 V, the short-circuit current Isc=57.5 μA/cm2, and the fill factor FF=0.24 under white light illumination with the intensity of 80 mW.

Effect of TiO2 nanoparticle-accumulated bilayer photoelectrode and condenser lens-assisted solar concentrator on light harvesting in dye-sensitized solar cells.

PubMed

Moon, Kook Joo; Lee, Sun Woo; Lee, Yong Hun; Kim, Ji Hoon; Ahn, Ji Young; Lee, Seung Jun; Lee, Deug Woo; Kim, Soo Hyung

2013-06-12

TiO2 nanoparticles (NPs) with a size of 240 nm (T240), used as a light-scattering layer, were applied on 25-nm-sized TiO2 NPs (T25) that were used as a dye-absorbing layer in the photoelectrodes of dye-sensitized solar cells (DSSCs). In addition, the incident light was concentrated via a condenser lens, and the effect of light concentration on the capacity of the light-scattering layer was systematically investigated. At the optimized focal length of the condenser lens, T25/T240 double layer (DL)-based DSSCs with the photoactive area of 0.36 cm2 were found to have the short circuit current (Isc) of 11.92 mA, the open circuit voltage (Voc) of 0.74 V, and power conversion efficiency (PCE) of approximately 4.11%, which is significantly improved when they were compared to the T25 single layer (SL)-based DSSCs without using a solar concentrator (the corresponding values were the Isc of 2.53 mA, the Voc of 0.69, and the PCE of 3.57%). Thus, the use of the optimized light harvesting structure in the photoelectrodes of DSSCs in conjunction with light concentration was found to significantly enhance the power output of DSSCs.

Dye-Sensitized Solar Cells for Space Power

NASA Technical Reports Server (NTRS)

Harris, Jerry D.; Hehemann, David G.; Duraj, Stan A.

2003-01-01

During the course of this grant, dye-sensitized solar cells were prepared and characterized. The solar cells were prepared using materials (dyes, electrolytes, transparent conductive oxide coated glass, nanocrystalline TiO2) entirely prepared in-house, as well as prepared using materials available commercially. Complete cells were characterized under simulated AM0 illumination. The best cell prepared at NASA had an AM0 efficiency of 1.22% for a 1.1 sq cm cell. Short circuit current (Isc), open circuit voltage (Voc) and fill factor (FF) for the cell were 6.95 mA, 618 mV and 42.8%, respectively. For comparison purposes, two commercially prepared dye-sensitized solar cells were obtained from Solaronix SA, Aubonne, Switzerland. The Solaronix cells were also characterized under simulated AM0 illumination. The best cell from Solaronix had an active area of 3.71 sq cm and measured an AM0 efficiency of 3.16%. with Isc, Voc and FF of 45.80 mA, 669.6 mV and 52.3%, respectively. Both cells from Solaronix were rapid thermal cycled between -80 C and 80 C. Thermal cycling led to a 4.6% loss of efficiency in one of the cells and led to nearly a complete failure in the second cell.

Electrical transport characterization of PEDOT:PSS/n-Si Schottky diodes and their applications in solar cells.

PubMed

Khurelbaatar, Zagarzusem; Hyung, Jung-Hwan; Kim, Gil-Sung; Park, No-Won; Shim, Kyu-Hwan; Lee, Sang-Kwon

2014-06-01

We demonstrate locally contacted PEDOT:PSS Schottky diodes with excellent rectifying behavior, fabricated on n-type Si substrates using a spin-coating process and a reactive-ion etching process. Electrical transport characterizations of these Schottky diodes were investigated by both current-voltage (I-V) and capacitance-voltage (C-V) measurements. We found that these devices exhibit excellent modulation in the current with an on/off ratio of - 10(6). Schottky junction solar cells composed of PEDOT:PSS and n-Si structures were also examined. From the current density-voltage (J-V) measurement of a solar cell under illumination, the short circuit current (I(sc)), open circuit voltage (V(oc)), and conversion efficiency (eta) were - 19.7 mA/cm2, - 578.5 mV, and - 6.5%, respectively. The simple and low-cost fabrication process of the PEDOT:PSS/n-Si Schottky junctions makes them a promising candidate for further high performance solar cell applications.

Bicarbonate-dependent chloride transport drives fluid secretion by the human airway epithelial cell line Calu-3

PubMed Central

Shan, Jiajie; Liao, Jie; Huang, Junwei; Robert, Renaud; Palmer, Melissa L; Fahrenkrug, Scott C; O'Grady, Scott M; Hanrahan, John W

2012-01-01

Anion and fluid secretion are both defective in cystic fibrosis (CF); however, the transport mechanisms are not well understood. In this study, Cl− and HCO3− secretion was measured using genetically matched CF transmembrane conductance regulator (CFTR)-deficient and CFTR-expressing cell lines derived from the human airway epithelial cell line Calu-3. Forskolin stimulated the short-circuit current (Isc) across voltage-clamped monolayers, and also increased the equivalent short-circuit current (Ieq) calculated under open-circuit conditions. Isc was equivalent to the HCO3− net flux measured using the pH-stat technique, whereas Ieq was the sum of the Cl− and HCO3− net fluxes. Ieq and HCO3− fluxes were increased by bafilomycin and ZnCl2, suggesting that some secreted HCO3− is neutralized by parallel electrogenic H+ secretion. Ieq and fluid secretion were dependent on the presence of both Na+ and HCO3−. The carbonic anhydrase inhibitor acetazolamide abolished forskolin stimulation of Ieq and HCO3− secretion, suggesting that HCO3− transport under these conditions requires catalysed synthesis of carbonic acid. Cl− was the predominant anion in secretions under all conditions studied and thus drives most of the fluid transport. Nevertheless, 50–70% of Cl− and fluid transport was bumetanide-insensitive, suggesting basolateral Cl− loading by a sodium–potassium–chloride cotransporter 1 (NKCC1)-independent mechanism. Imposing a transepithelial HCO3− gradient across basolaterally permeabilized Calu-3 cells sustained a forskolin-stimulated current, which was sensitive to CFTR inhibitors and drastically reduced in CFTR-deficient cells. Net HCO3− secretion was increased by bilateral Cl− removal and therefore did not require apical Cl−/HCO3− exchange. The results suggest a model in which most HCO3− is recycled basolaterally by exchange with Cl−, and the resulting HCO3−-dependent Cl− transport provides an osmotic driving force for fluid secretion. PMID:22777674

Effects of tumor promoters on sodium ion transport across frog skin.

PubMed

Civan, M M; Rubenstein, D; Mauro, T; O'Brien, T G

1985-05-01

Phorbol esters are tumor promoters and mitogens whose effects may be mediated by changes in ion transport across membranes. Clarification of the transport effects of these agents should be facilitated by using a well-characterized model epithelial system whose intracellular and transmural parameters are readily measurable. The current results constitute a preliminary study of the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol-12,13-dibutyrate (PDBU), and phorbol on the short-circuit current (Isc) across frog skin. TPA produced two effects: a stimulation of Isc of variable magnitude and a far more constant inhibition of the natriferic action of vasopressin. These effects appear related to the action of TPA as a tumor promoter insofar as PDBU (an active ester) also inhibited the natriferic response to vasopressin, whereas phorbol (inactive as a tumor promoter) had no significant effect. TPA is largely active from the mucosal medium, inhibits the natriferic response to adenosine 3',5'-cyclic monophosphate (cAMP) as well as that to vasopressin, and does not stimulate Isc in the presence of 10(-4) M mucosal amiloride. Inhibition of prostaglandin E1 production by indomethacin had no effect on the actions of TPA. The results indicate that frog skin is a promising model for studying the transport effects of the phorbol esters. The data further suggest that TPA acts on frog skin by activating the physiological amiloride- and cAMP-sensitive channels gating apical Na+ entry from the mucosal medium into the epithelial cells.

Properties of p-n-junctions formed by a laser irradiation of a surface of n-Cd1-xZnxTe single crystal

NASA Astrophysics Data System (ADS)

Khomyak, V. V.; Ilashchuk, M. I.; Shtepliuk, I. I.

2015-03-01

Photosensitive barrier structures were fabricated by high-power pulsed laser irradiation of a freshly-cleaved surface of п-type bulk Cd1-xZnxTe substrates. Their electrical properties were investigated and discussed. Dominant carrier mechanisms at a forward and a reverse bias in terms of a recombination and tunnel-recombination model were analyzed. At the illumination reaching 100 mW · cm-2, these surface-barrier р-Cd1-хZnхTe/п-Cd1-хZnхTe structures were possessed by the following photoelectric parameters: open-circuit voltage Voc = 0.61 V, short-circuit current Isc = 0.21 mА and fill factor FF = 0.49, respectively.

Stimulation of Murine Intestinal Secretion by Daily Genistein Injections: Gender-dependent Differences

PubMed Central

Al-Nakkash, Layla; Batia, Lyn; Bhakta, Minoti; Peterson, Amity; Hale, Nathan; Skinner, Ryan; Sears, Steven; Jensen, Jesse

2011-01-01

Background/Aims The effect of daily injections with genistein (naturally occurring phytoestrogen) on intestinal chloride (Cl−) secretion was measured with Ussing chamber short circuit current (Isc, μA/cm2), in C57BL/6J male and female mice, using 600 mg/kg genistein/day (600G), 300 mg/kg genistein/day (300G), 150 mg/kg genistein/day (150G) or genistein-free vehicle control (0G) for 1- or 2-weeks. Methods and Results Injecting with 600G elicited significant increases in basal Isc in females after 1-week (ñ70 μA/cm2, n=15, p < 0.05) and in males after 2-weeks (ñ80 μA/cm2, n=5, p < 0.05) compared to their 0G counterparts. Chloride-free ringer significantly reduced basal Isc by 65% in 600G males and 72% in 600G females, suggesting that Cl− was the major anion comprising the genistein-stimulated secretion. The forskolin-stimulated (10 μM) Isc was significantly inhibited by the CFTR chloride channel inhibitors, glibenclamide (500 μM) and CFTRinh-172 (100 μM) in 600G males and females, suggesting some contribution by genistein-dependent CFTR-mediated Cl− secretion. We found no associated changes in intestinal morphology, nor change in total CFTR protein with 600G. There was a 5% increase in apical/subapical ratio in 600G males compared to controls (no change in females). Conclusion These data suggest that male and female mice both exhibit increased Cl- secretion with 600G, however, the mechanisms mediating this are gender-dependent. PMID:21865731

A Newton-Raphson Method Approach to Adjusting Multi-Source Solar Simulators

NASA Technical Reports Server (NTRS)

Snyder, David B.; Wolford, David S.

2012-01-01

NASA Glenn Research Center has been using an in house designed X25 based multi-source solar simulator since 2003. The simulator is set up for triple junction solar cells prior to measurements b y adjusting the three sources to produce the correct short circuit current, lsc, in each of three AM0 calibrated sub-cells. The past practice has been to adjust one source on one sub-cell at a time, iterating until all the sub-cells have the calibrated Isc. The new approach is to create a matrix of measured lsc for small source changes on each sub-cell. A matrix, A, is produced. This is normalized to unit changes in the sources so that Ax(delta)s = (delta)isc. This matrix can now be inverted and used with the known Isc differences from the AM0 calibrated values to indicate changes in the source settings, (delta)s = A ·'x.(delta)isc This approach is still an iterative one, but all sources are changed during each iteration step. It typically takes four to six steps to converge on the calibrated lsc values. Even though the source lamps may degrade over time, the initial matrix evaluation i s not performed each time, since measurement matrix needs to be only approximate. Because an iterative approach is used the method will still continue to be valid. This method may become more important as state-of-the-art solar cell junction responses overlap the sources of the simulator. Also, as the number of cell junctions and sources increase, this method should remain applicable.

Methadone but not morphine inhibits lubiprostone-stimulated Cl- currents in T84 intestinal cells and recombinant human ClC-2, but not CFTR Cl- currents.

PubMed

Cuppoletti, John; Chakrabarti, Jayati; Tewari, Kirti; Malinowska, Danuta H

2013-05-01

In clinical trials, methadone, but not morphine, appeared to prevent beneficial effects of lubiprostone, a ClC-2 Cl(-) channel activator, on opioid-induced constipation. Effects of methadone and morphine on lubiprostone-stimulated Cl(-) currents were measured by short circuit current (Isc) across T84 cells. Whole cell patch clamp of human ClC-2 (hClC-2) stably expressed in HEK293 cells and in a high expression cell line (HEK293EBNA) as well as human CFTR (hCFTR) stably expressed in HEK293 cells was used to study methadone and morphine effects on recombinant hClC-2 and hCFTR Cl(-) currents. Methadone but not morphine inhibited lubiprostone-stimulated Isc in T84 cells with half-maximal inhibition at 100 nM. Naloxone did not affect lubiprostone stimulation or methadone inhibition of Isc. Lubiprostone-stimulated Cl(-) currents in hClC-2/HEK293 cells, but not forskolin/IBMX-stimulated Cl(-) currents in hCFTR/HEK293 cells, were inhibited by methadone, but not morphine. HEK293EBNA cells expressing hClC-2 showed time-dependent, voltage-activated, CdCl2-inhibited Cl(-) currents in the absence (control) and the presence of lubiprostone. Methadone, but not morphine, inhibited control and lubiprostone-stimulated hClC-2 Cl(-) currents with half-maximal inhibition at 100 and 200-230 nM, respectively. Forskolin/IBMX-stimulated hClC-2 Cl(-) currents were also inhibited by methadone. Myristoylated protein kinase inhibitor (a specific PKA inhibitor) inhibited forskolin/IBMX- but not lubiprostone-stimulated hClC-2 Cl(-) currents. Methadone caused greater inhibition of lubiprostone-stimulated currents added before patching (66.1 %) compared with after patching (28.7 %). Methadone caused inhibition of lubiprostone-stimulated Cl(-) currents in T84 cells and control; lubiprostone- and forskolin/IBMX-stimulated recombinant hClC-2 Cl(-) currents may be the basis for reduced efficacy of lubiprostone in methadone-treated patients.

An analytical-numerical approach for parameter determination of a five-parameter single-diode model of photovoltaic cells and modules

NASA Astrophysics Data System (ADS)

Hejri, Mohammad; Mokhtari, Hossein; Azizian, Mohammad Reza; Söder, Lennart

2016-04-01

Parameter extraction of the five-parameter single-diode model of solar cells and modules from experimental data is a challenging problem. These parameters are evaluated from a set of nonlinear equations that cannot be solved analytically. On the other hand, a numerical solution of such equations needs a suitable initial guess to converge to a solution. This paper presents a new set of approximate analytical solutions for the parameters of a five-parameter single-diode model of photovoltaic (PV) cells and modules. The proposed solutions provide a good initial point which guarantees numerical analysis convergence. The proposed technique needs only a few data from the PV current-voltage characteristics, i.e. open circuit voltage Voc, short circuit current Isc and maximum power point current and voltage Im; Vm making it a fast and low cost parameter determination technique. The accuracy of the presented theoretical I-V curves is verified by experimental data.

Altered ion transport by thyroid epithelia from CFTR−/− pigs suggests mechanisms for hypothyroidism in Cystic Fibrosis

PubMed Central

Li, Hui; Ganta, Suhasini; Fong, Peying

2010-01-01

Subclinical hypothyroidism has been linked to Cystic Fibrosis (CF), and the cystic fibrosis transmembrane conductance regulator (CFTR) shown to be expressed in the thyroid. The thyroid epithelium secretes Cl− and absorbs Na+ in response to cAMP. Chloride secretion may provide a counter-ion for the SLC26A4 (Pendrin)-mediated I− secretion which is required for the first step of thyroid hormonogenesis, thyroglobulin iodination. In contrast, few models exist to explain a role for Na+ absorption. Whether CFTR mediates the secretory Cl− current in thyroid epithelium has not been directly addressed. We used thyroids from a novel pig CFTR−/− model, generated primary pig thyroid epithelial cell cultures (pThECs), analyzed these cultures for preservation of thyroid-specific transcripts and proteins, and monitored 1) the Cl− secretory response to the cAMP agonist, isoproterenol and 2) the amiloride-sensitive Na+ current. Baseline short-circuit current (Isc) did not differ between CFTR+/+ and CFTR−/− cultures. Serosal isoproterenol increased Isc in CFTR+/+, but not CFTR−/−, monolayers. Compared to CFTR+/+ thyroid cultures, amiloride-sensitive Na+ absorption measured in CFTR−/− pThECs represented a greater fraction of the resting Isc. However, levels of transcripts encoding ENaC subunits did not differ between CFTR+/+ and CFTR−/− pThECs. Immunoblot analysis verified ENaC subunit protein expression, but quantification indicated no difference in expression levels. Our studies definitively demonstrate that CFTR mediates cAMP-stimulated Cl− secretion in a well-differentiated thyroid culture model, and that knockout of CFTR promotes increased Na+ absorption by a mechanism other than increased ENaC expression. These findings suggest several models for the mechanism of CF-associated hypothyroidism. PMID:20729267

Bioelectric characterization of epithelia from neonatal CFTR knockout ferrets.

PubMed

Fisher, John T; Tyler, Scott R; Zhang, Yulong; Lee, Ben J; Liu, Xiaoming; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Luo, Meihui; Xie, Weiliang; Yi, Yaling; Zhou, Weihong; Song, Yi; Keiser, Nicholas; Wang, Kai; de Jonge, Hugo R; Engelhardt, John F

2013-11-01

Cystic fibrosis (CF) is a life-shortening, recessive, multiorgan genetic disorder caused by the loss of CF transmembrane conductance regulator (CFTR) chloride channel function found in many types of epithelia. Animal models that recapitulate the human disease phenotype are critical to understanding pathophysiology in CF and developing therapies. CFTR knockout ferrets manifest many of the phenotypes observed in the human disease, including lung infections, pancreatic disease and diabetes, liver disease, malnutrition, and meconium ileus. In the present study, we have characterized abnormalities in the bioelectric properties of the trachea, stomach, intestine, and gallbladder of newborn CF ferrets. Short-circuit current (ISC) analysis of CF and wild-type (WT) tracheas revealed the following similarities and differences: (1) amiloride-sensitive sodium currents were similar between genotypes; (2) responses to 4,4'-diisothiocyano-2,2'-stilbene disulphonic acid were 3.3-fold greater in CF animals, suggesting elevated baseline chloride transport through non-CFTR channels in a subset of CF animals; and (3) a lack of 3-isobutyl-1-methylxanthine (IBMX)/forskolin-stimulated and N-(2-Naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene)glycine hydrazide (GlyH-101)-inhibited currents in CF animals due to the lack of CFTR. CFTR mRNA was present throughout all levels of the WT ferret and IBMX/forskolin-inducible ISC was only observed in WT animals. However, despite the lack of CFTR function in the knockout ferret, the luminal pH of the CF ferret gallbladder, stomach, and intestines was not significantly changed relative to WT. The WT stomach and gallbladder exhibited significantly enhanced IBMX/forskolin ISC responses and inhibition by GlyH-101 relative to CF samples. These findings demonstrate that multiple organs affected by disease in the CF ferret have bioelectric abnormalities consistent with the lack of cAMP-mediated chloride transport.

DETANO and Nitrated Lipids Increase Chloride Secretion across Lung Airway Cells

PubMed Central

Chen, Lan; Bosworth, Charles A.; Pico, Tristant; Collawn, James F.; Varga, Karoly; Gao, Zhiqian; Clancy, John Paul; Fortenberry, James A.; Lancaster, Jack R.; Matalon, Sadis

2008-01-01

We investigated the cellular mechanisms by which nitric oxide (NO) increases chloride (Cl−) secretion across lung epithelial cells in vitro and in vivo. Addition of (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETANONOate [DETANO];1–1,000 μM) into apical compartments of Ussing chambers containing Calu-3 cells increased short-circuit currents (Isc) from 5.2 ± 0.8 to 15.0 ± 2.1 μA/cm2 (X ± 1 SE; n = 7; P < 0.001). NO generated from two nitrated lipids (nitrolinoleic and nitrooleic acids; 1–10 μM) also increased Isc by about 100%. Similar effects were noted across basolaterally, but not apically, permeabilized Calu-3 cells. None of these NO donors increased Isc in Calu-3 cells pretreated with 10 μM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase). Scavenging of NO either prevented or reversed the increase of Isc. These data indicate that NO stimulation of soluble guanylyl cyclase was sufficient and necessary for the increase of Isc via stimulation of the apical cystic fibrosis transmembrane regulator (CFTR). Both Calu-3 and alveolar type II (ATII) cells contained CFTR, as demonstrated by in vitro phosphorylation of immunoprecipitated CFTR by protein kinase (PK) A. PKGII (but not PKGI) phosphorylated CFTR immuniprecipitated from Calu-3 cells. Corresponding values in ATII cells were below the threshold of detection. Furthermore, DETANO, 8-Br-cGMP, or 8-(4-chlorophenylthio)-cGMP (up to 2 mM each) did not increase Cl− secretion across amiloride-treated ATII cells in vitro. Measurements of nasal potential differences in anesthetized mice showed that perfusion of the nares with DETANO activated glybenclamide-sensitive Cl− secretion. These findings suggest that small concentrations of NO donors may prove beneficial in stimulating Cl− secretion across airway cells without promoting alveolar edema. PMID:18314534

DETANO and nitrated lipids increase chloride secretion across lung airway cells.

PubMed

Chen, Lan; Bosworth, Charles A; Pico, Tristant; Collawn, James F; Varga, Karoly; Gao, Zhiqian; Clancy, John Paul; Fortenberry, James A; Lancaster, Jack R; Matalon, Sadis

2008-08-01

We investigated the cellular mechanisms by which nitric oxide (NO) increases chloride (Cl-) secretion across lung epithelial cells in vitro and in vivo. Addition of (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETANONOate [DETANO];1-1,000 microM) into apical compartments of Ussing chambers containing Calu-3 cells increased short-circuit currents (I(sc)) from 5.2 +/- 0.8 to 15.0 +/- 2.1 microA/cm(2) (X +/- 1 SE; n = 7; P < 0.001). NO generated from two nitrated lipids (nitrolinoleic and nitrooleic acids; 1-10 microM) also increased I(sc) by about 100%. Similar effects were noted across basolaterally, but not apically, permeabilized Calu-3 cells. None of these NO donors increased I(sc) in Calu-3 cells pretreated with 10 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase). Scavenging of NO either prevented or reversed the increase of I(sc). These data indicate that NO stimulation of soluble guanylyl cyclase was sufficient and necessary for the increase of I(sc) via stimulation of the apical cystic fibrosis transmembrane regulator (CFTR). Both Calu-3 and alveolar type II (ATII) cells contained CFTR, as demonstrated by in vitro phosphorylation of immunoprecipitated CFTR by protein kinase (PK) A. PKGII (but not PKGI) phosphorylated CFTR immuniprecipitated from Calu-3 cells. Corresponding values in ATII cells were below the threshold of detection. Furthermore, DETANO, 8-Br-cGMP, or 8-(4-chlorophenylthio)-cGMP (up to 2 mM each) did not increase Cl- secretion across amiloride-treated ATII cells in vitro. Measurements of nasal potential differences in anesthetized mice showed that perfusion of the nares with DETANO activated glybenclamide-sensitive Cl- secretion. These findings suggest that small concentrations of NO donors may prove beneficial in stimulating Cl- secretion across airway cells without promoting alveolar edema.

Na(+)/Ca(2+) exchange regulates Ca(2+)-dependent duodenal mucosal ion transport and HCO(3)(-) secretion in mice.

PubMed

Dong, Hui; Sellers, Zachary M; Smith, Anders; Chow, Jimmy Y C; Barrett, Kim E

2005-03-01

Stimulation of muscarinic receptors in duodenal mucosa raises intracellular Ca(2+), which regulates ion transport, including HCO(3)(-) secretion. However, the underlying Ca(2+) handling mechanisms are poorly understood. The aim of the present study was to determine whether Na(+)/Ca(2+) exchanger (NCX) plays a role in the regulation of duodenal mucosal ion transport and HCO(3)(-) secretion by controlling Ca(2+) homeostasis. Mouse duodenal mucosa was mounted in Ussing chambers. Net ion transport was assessed as short-circuit current (I(sc)), and HCO(3)(-) secretion was determined by pH-stat. Expression of NCX in duodenal mucosae was analyzed by Western blot, and cytosolic Ca(2+) in duodenocytes was measured by fura 2. Carbachol (100 muM) increased I(sc) in a biphasic manner: an initial transient peak within 2 min and a later sustained plateau starting at 10 min. Carbachol-induced HCO(3)(-) secretion peaked at 10 min. 2-Aminoethoxydiphenylborate (2-APB, 100 muM) or LiCl (30 mM) significantly reduced the initial peak in I(sc) by 51 or 47%, respectively, and abolished the plateau phase of I(sc) without affecting HCO(3)(-) secretion induced by carbachol. Ryanodine (100 muM), caffeine (10 mM), and nifedipine (10 muM) had no effect on either response to carbachol. In contrast, nickel (5 mM) and KB-R7943 (10-30 muM) significantly inhibited carbachol-induced increases in duodenal mucosal I(sc) and HCO(3)(-) secretion. Western blot analysis showed expression of NCX1 proteins in duodenal mucosae, and functional NCX in duodenocytes was demonstrated in Ca(2+) imaging experiments where Na(+) depletion elicited Ca(2+) entry via the reversed mode of NCX. These results indicate that NCX contributes to the regulation of Ca(2+)-dependent duodenal mucosal ion transport and HCO(3)(-) secretion that results from stimulation of muscarinic receptors.

Fabrication and Characterization of Organic Photovoltaic Cell using Keithley 2400 SMU for efficient solar cell

NASA Astrophysics Data System (ADS)

Hafeez, Hafeez Y.; Iro, Zaharaddeen S.; Adam, Bala I.; Mohammed, J.

2018-04-01

An organic solar cell device or organic photovoltaic cell (OPV) is a class of solar cell that uses conductive organic polymers or small organic molecules for light absorption and charge transport. In this study, we fabricate and characterize an organic photovoltaic cell device and estimated important parameters of the device such as Open Circuit Voltage Voc of 0.28V, Short-Circuit Current Isc of 4.0 × 10-5 A, Maximum Power Pmax of 2.4 × 10-6 W, Fill Factor of 0.214 and the energy conversion efficiency of η=0.00239% were tested using Keithley 2400,source meter under A.M 1.5 (1000/m2) illumination from a Newport Class A solar simulator. Also the I-V characteristics for OPV were drawn.

The role of low light intensity: A step towards understanding the connection between light, optic/lens and photovoltaic behavior for Sb2S3 thin-film solar cells

NASA Astrophysics Data System (ADS)

Lojpur, Vesna; Mitrić, Miodrag; Validžić, Ivana Lj

2018-05-01

We report here an optic/lens system that we used so far, for cooling the surface of solar cells, the reduction of light intensity and the change of light distribution that reaches the surface of the solar cell. The objective was to improve photovoltaic characteristics under very low light illumination, as well as to understand the connection between light, optic/lens and photovoltaic behavior for Sb2S3 thin-film solar cells. It was found that for all so far designed thin-film solar cells made and based on the synthesized Sb2S3, optics/lens system causes an increase in open circuit voltage (VOC) and short circuit current (ISC) and thus the efficiencies of made solar devices. Values of energy gaps for the thin-films made devices were in the range from 1.4 to 2 eV. Improvements of the photovoltaic response of the designed devices are found to be better at the lower light intensity (5% sun), than at higher intensities of light. For the same intensity of light used optic/lens improves the efficiency of the devices, by changing the light distribution. Other processes that are related to the optics/lens system, leading to an increase in ISC and VOC and consequently to an increase in efficiencies of the designed devices, are investigated.

Effect of TiO2 nanoparticle-accumulated bilayer photoelectrode and condenser lens-assisted solar concentrator on light harvesting in dye-sensitized solar cells

PubMed Central

2013-01-01

TiO2 nanoparticles (NPs) with a size of 240 nm (T240), used as a light-scattering layer, were applied on 25-nm-sized TiO2 NPs (T25) that were used as a dye-absorbing layer in the photoelectrodes of dye-sensitized solar cells (DSSCs). In addition, the incident light was concentrated via a condenser lens, and the effect of light concentration on the capacity of the light-scattering layer was systematically investigated. At the optimized focal length of the condenser lens, T25/T240 double layer (DL)-based DSSCs with the photoactive area of 0.36 cm2 were found to have the short circuit current (Isc) of 11.92 mA, the open circuit voltage (Voc) of 0.74 V, and power conversion efficiency (PCE) of approximately 4.11%, which is significantly improved when they were compared to the T25 single layer (SL)-based DSSCs without using a solar concentrator (the corresponding values were the Isc of 2.53 mA, the Voc of 0.69, and the PCE of 3.57%). Thus, the use of the optimized light harvesting structure in the photoelectrodes of DSSCs in conjunction with light concentration was found to significantly enhance the power output of DSSCs. PMID:23758633

Fusion-activated cation entry (FACE) via P2X₄ couples surfactant secretion and alveolar fluid transport.

PubMed

Thompson, Kristin E; Korbmacher, Jonas P; Hecht, Elena; Hobi, Nina; Wittekindt, Oliver H; Dietl, Paul; Kranz, Christine; Frick, Manfred

2013-04-01

Two fundamental mechanisms within alveoli are essential for lung function: regulated fluid transport and secretion of surfactant. Surfactant is secreted via exocytosis of lamellar bodies (LBs) in alveolar type II (ATII) cells. We recently reported that LB exocytosis results in fusion-activated cation entry (FACE) via P2X₄ receptors on LBs. We propose that FACE, in addition to facilitating surfactant secretion, modulates alveolar fluid transport. Correlative fluorescence and atomic force microscopy revealed that FACE-dependent water influx correlated with individual fusion events in rat primary ATII cells. Moreover, ATII cell monolayers grown at air-liquid interface exhibited increases in short-circuit current (Isc) on stimulation with ATP or UTP. Both are potent agonists for LB exocytosis, but only ATP activates FACE. ATP, not UTP, elicited additional fusion-dependent increases in Isc. Overexpressing dominant-negative P2X₄ abrogated this effect by ∼50%, whereas potentiating P2X4 lead to ∼80% increase in Isc. Finally, we monitored changes in alveolar surface liquid (ASL) on ATII monolayers by confocal microscopy. Only stimulation with ATP, not UTP, led to a significant, fusion-dependent, 20% decrease in ASL, indicating apical-to-basolateral fluid transport across ATII monolayers. Our data support the first direct link between LB exocytosis, regulation of surfactant secretion, and transalveolar fluid resorption via FACE.

Inhibition of airway surface fluid absorption by cholinergic stimulation

PubMed Central

Joo, Nam Soo; Krouse, Mauri E.; Choi, Jae Young; Cho, Hyung-Ju; Wine, Jeffrey J.

2016-01-01

In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20–70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways. PMID:26846701

Inhibition of Na+ transport in lung epithelial cells by respiratory syncytial virus infection.

PubMed

Chen, Lan; Song, Weifeng; Davis, Ian C; Shrestha, Kedar; Schwiebert, Erik; Sullender, Wayne M; Matalon, Sadis

2009-05-01

We investigated the mechanisms by which respiratory syncytial virus (RSV) infection decreases vectorial Na+ transport across respiratory epithelial cells. Mouse tracheal epithelial (MTE) cells from either BALB/c or C57BL/6 mice and human airway H441 cells were grown on semipermeable supports under an air-liquid interface. Cells were infected with RSV-A2 and mounted in Ussing chambers for measurements of short-circuit currents (I(sc)). Infection with RSV for 24 hours (multiplicity of infection = 1) resulted in positive immunofluorescence for RSV antigen in less than 10% of MTE or H441 cells. In spite of the limited number of cells infected, RSV reduced both basal and amiloride-sensitive I(sc) in both MTE and H441 cells by approximately 50%, without causing a concomitant reduction in transepithelial resistance. Agents that increased intracellular cAMP (forskolin, cpt-CAMP, and IBMX) increased mainly Cl(-) secretion in MTE cells and Na+ absorption in H441 cells. RSV infection for 24 hours blunted both variables. In contrast, ouabain sensitive I(sc), measured across apically permeabilized H441 monolayers, remained unchanged. Western blot analysis of H441 cell lysates demonstrated reductions in alpha- but not gamma-ENaC subunit protein levels at 24 hours after RSV infection. The reduction in amiloride-sensitive I(sc) in H441 cells was prevented by pretreatment with inhibitors of de novo pyrimidine or purine synthesis (A77-1726 and 6-MP, respectively, 50 microM). Our results suggest that infection of both murine and human respiratory epithelial cells with RSV inhibits vectorial Na+ transport via nucleotide release. These findings are consistent with our previous studies showing reduced alveolar fluid clearance after RSV infection of BALB/c mice.

Nerve growth factor reduces amiloride‐sensitive Na+ transport in human airway epithelial cells

PubMed Central

Shimko, Michael J.; Zaccone, Eric J.; Thompson, Janet A.; Schwegler‐Berry, Diane; Kashon, Michael L.; Fedan, Jeffrey S.

2014-01-01

Abstract Nerve growth factor (NGF) is overexpressed in patients with inflammatory lung diseases, including virus infections. Airway surface liquid (ASL), which is regulated by epithelial cell ion transport, is essential for normal lung function. No information is available regarding the effect of NGF on ion transport of airway epithelium. To investigate whether NGF can affect ion transport, human primary air‐interface cultured epithelial cells were placed in Ussing chambers to obtain transepithelial voltage (−7.1 ± 3.4 mV), short‐circuit current (Isc, 5.9 ± 1.0 μA), and transepithelial resistance (750 Ω·cm2), and to measure responses to ion transport inhibitors. Amiloride (apical, 3.5 × 10−5 mol/L) decreased Isc by 55.3%. Apically applied NGF (1 ng/mL) reduced Isc by 5.3% in 5 min; basolaterally applied NGF had no effect. The response to amiloride was reduced (41.6%) in the presence of NGF. K‐252a (10 nmol/L, apical) did not itself affect Na+ transport, but it attenuated the NGF‐induced reduction in Na+ transport, indicating the participation of the trkA receptor in the NGF‐induced reduction in Na+ transport. PD‐98059 (30 μmol/L, apical and basolateral) did not itself affect Na+ transport, but attenuated the NGF‐induced reduction in Na+ transport, indicating that trkA activated the Erk 1/2 signaling cascade. NGF stimulated phosphorylation of Erk 1/2 and the β‐subunit of ENaC. K‐252a and PD‐98059 inhibited these responses. NGF had no effect on Isc in the presence of apical nystatin (50 μmol/L). These results indicate that NGF inhibits Na+ transport through a trkA‐Erk 1/2‐activated signaling pathway linked to ENaC phosphorylation. PMID:25347857

Hydrostatic pressure activates ATP-sensitive K+ channels in lung epithelium by ATP release through pannexin and connexin hemichannels.

PubMed

Richter, Katrin; Kiefer, Kevin P; Grzesik, Benno A; Clauss, Wolfgang G; Fronius, Martin

2014-01-01

Lungs of air-breathing vertebrates are constantly exposed to mechanical forces and therefore are suitable for investigation of mechanotransduction processes in nonexcitable cells and tissues. Freshly dissected Xenopus laevis lungs were used for transepithelial short-circuit current (ISC) recordings and were exposed to increased hydrostatic pressure (HP; 5 cm fluid column, modified Ussing chamber). I(SC) values obtained under HP (I(5cm)) were normalized to values before HP (I(0cm)) application (I(5cm)/I(0cm)). Under control conditions, HP decreased I(SC) (I(5cm)/I(0cm)=0.84; n=68; P<0.0001). This effect was reversible and repeatable ≥30 times. Preincubation with ATP-sensitive K(+) channel (K(ATP)) inhibitors (HMR1098 and glibenclamide) prevented the decrease in I(SC) (I(5cm)/I(0cm): HMR1098=1.19, P<0.0001; glibenclamide=1.11, P<0.0001). Similar effects were observed with hemichannel inhibitors (I(5cm)/I(0cm): meclofenamic acid=1.09, P<0.0001; probenecid=1.0, P<0.0001). The HP effect was accompanied by release of ATP (P<0.05), determined by luciferin-luciferase luminescence in perfusion solution from the luminal side of an Ussing chamber. ATP release was abrogated by both meclofenamic acid and probenecid. RT-PCR experiments revealed the expression of pannexin and connexin hemichannels and KATP subunit transcripts in X. laevis lung. These data show an activation of KATP in pulmonary epithelial cells in response to HP that is induced by ATP release through mechanosensitive pannexin and connexin hemichannels. These findings represent a novel mechanism of mechanotransduction in nonexcitable cells.

K(Ca)3.1 channels facilitate K+ secretion or Na+ absorption depending on apical or basolateral P2Y receptor stimulation.

PubMed

Palmer, Melissa L; Peitzman, Elizabeth R; Maniak, Peter J; Sieck, Gary C; Prakash, Y S; O'Grady, Scott M

2011-07-15

Human mammary epithelial (HME) cells express several P2Y receptor subtypes located in both apical and basolateral membranes. Apical UTP or ATP-γ-S stimulation of monolayers mounted in Ussing chambers evoked a rapid, but transient decrease in short circuit current (I(sc)), consistent with activation of an apical K+ conductance. In contrast, basolateral P2Y receptor stimulation activated basolateral K+ channels and increased transepithelial Na+ absorption. Chelating intracellular Ca2+ using the membrane-permeable compound BAPTA-AM, abolished the effects of purinoceptor activation on I(sc). Apical pretreatment with charybdotoxin also blocked the I(sc) decrease by >90% and similar magnitudes of inhibition were observed with clotrimazole and TRAM-34. In contrast, iberiotoxin and apamin did not block the effects of apical P2Y receptor stimulation. Silencing the expression of K(Ca)3.1 produced ∼70% inhibition of mRNA expression and a similar reduction in the effects of apical purinoceptor agonists on I(sc). In addition, silencing P2Y2 receptors reduced the level of P2Y2 mRNA by 75% and blocked the effects of ATP-γ-S by 65%. These results suggest that P2Y2 receptors mediate the effects of purinoceptor agonists on K+ secretion by regulating the activity of K(Ca)3.1 channels expressed in the apical membrane of HME cells. The results also indicate that release of ATP or UTP across the apical or basolateral membrane elicits qualitatively different effects on ion transport that may ultimately determine the [Na+]/[K+] composition of fluid within the mammary ductal network.

Titanium-containing zeolites and microporous molecular sieves as photovoltaic solar cells.

PubMed

Atienzar, Pedro; Valencia, Susana; Corma, Avelino; García, Hermenegildo

2007-05-14

Four titanium-containing zeolites and microporous molecular sieves differing on the crystal structure and particle size (Ti/Beta, Ti/Beta-60, TS-1 and ETS-10) are prepared, and their activity for solar cells after incorporating N3 (a commercially available ruthenium polypyridyl dye) is tested. All the zeolites exhibit photovoltaic activity, and the photoresponse is quite independent of the zeolite pore dimensions or particle size. The photoresponse increases with titanium content in the range 1-7% wt. In this way, cells are obtained that have open-circuit voltage Voc=560 mV and maximum short-circuit photocurrent density Isc=100 microA, measured for 1x1 cm2 surfaces with a solar simulator at 1000 W through and AM 1.5 filter. These values are promising and comparable to those obtained for current dye-sensitized titania solar cells.

An enhanced mangiferaindica for dye sensitized solar cell application

NASA Astrophysics Data System (ADS)

Uno, U. E.; Emetere, M. E.; Fadipe, L. A.; Oluranti, Jonathan

2016-02-01

Titanium dioxide (T1O2) is preferred to Zinc oxide as mesoporous oxide layer because it raised the efficiency of DSSCs from 1% to 7%. The chemistry of the process however seem rigorous to allow the light induced electron injection from the adsorbed dye into the nanocrystallites i.e. which renders the TiO2 conductive. The DSSC fabricated consist of 2.25 cm2 active area of titanium dioxide coated on FTO glass (fluorine tin oxide) immersed in ethanol solution of natural dye extracted as an anode (electrode) and counter electrode. These two electrodes were coupled together and the space between them was filled with the Iodolyte AN-50 as solid electrolyte or redox mediator. The photo electrochemical parameters of the dye extracted (Mango fruit Peel) from the results obtained are short circuit current (Isc)= 1.22×10-2, current density (Jsc)=4.07×10-2, open circuit voltage (voc) =0.53V, fill factor (FF) of 0.16 and the overall conversion efficiency (Eff) =0.345%.

GI stem cells – new insights into roles in physiology and pathophysiology

PubMed Central

von Furstenberg, Richard J.

2016-01-01

Abstract This overview gives a brief historical summary of key discoveries regarding stem cells of the small intestine. The current concept is that there are two pools of intestinal stem cells (ISCs): an actively cycling pool that is marked by Lgr5, is relatively homogeneous and is responsible for daily turnover of the epithelium; and a slowly cycling or quiescent pool that functions as reserve ISCs. The latter pool appears to be quite heterogeneous and may include partially differentiated epithelial lineages that can reacquire stem cell characteristics following injury to the intestine. Markers and methods of isolation for active and quiescent ISC populations are described as well as the numerous important advances that have been made in approaches to the in vitro culture of ISCs and crypts. Factors regulating ISC biology are briefly summarized and both known and unknown aspects of the ISC niche are discussed. Although most of our current knowledge regarding ISC physiology and pathophysiology has come from studies with mice, recent work with human tissue highlights the potential translational applications arising from this field of research. Many of these topics are further elaborated in the following articles. PMID:27107928

Interferometry science center

NASA Technical Reports Server (NTRS)

Sargent, A. I.

2002-01-01

The Interferometry Science Center (ISC) is operated jointly by Caltech and JPL and is part of NASA's Navigator Program. The ISC has been created to facilitate the timely and successful execution of scientific investigations within the Navigator program, particularly those that rely on observations from NASA's interferometer projects. Currently, ISC is expected to provide full life cycle support for the Keck Interferometer, the Starlight mission, the Space Interferometry Mission, and the Terrestrial Planet Finder Mission. The nature and goals of ISc will be described.

Effect of solution concentration on MEH-PPV thin films

NASA Astrophysics Data System (ADS)

Affendi, I. H. H.; Sarah, M. S. P.; Alrokayan, Salman A. H.; Khan, Haseeb A.; Rusop, M.

2018-05-01

MEH-PPV thin films were prepared with a mixture of THF (tetrahydrofuran) solution deposited by spin coating method. The surface topology of MEH-PPV thin film were characterize by atomic force microscopy (AFM) and optical properties of absorption spectra were characterized by using Ultraviolet-visible-near-infrared (UV-Vis-NIR). The MEH-PPV concentration variation affects the surface and optical properties of the thin film where 0.5 mg/ml MEH-PPV concentration have a good surface topology provided the same film also gives the highest absorption coefficient were then deposited to a TiO2 thin film forming composite layer. The composite layer then shows low current flow of short circuit current of Isc = -5.313E-7 A.

A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa

PubMed Central

Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F

2015-01-01

Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (Isc). Subsequent Isc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. Isc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704

Acute ENaC stimulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool.

PubMed

Butterworth, Michael B; Edinger, Robert S; Johnson, John P; Frizzell, Raymond A

2005-01-01

Acute hormonal regulation of the epithelial sodium channel (ENaC) in tight epithelia increases transcellular Na(+) transport via trafficking of intracellular channels to the apical surface. The fate of the channels removed from the apical surface following agonist washout is less clear. By repetitively stimulating polarized mouse cortical collecting duct (mCCD, (MPK)CCD(14)) epithelia, we evaluated the hypothesis that ENaC recycles through an intracellular pool to be available for reinsertion into the apical membrane. Short circuit current (I(SC)), membrane capacitance (C(T)), and conductance (G(T)) were recorded from mCCD epithelia mounted in modified Ussing chambers. Surface biotinylation of ENaC demonstrated an increase in channel number in the apical membrane following cAMP stimulation. This increase was accompanied by a 83 +/- 6% (n = 31) increase in I(SC) and a 15.3 +/- 1.5% (n = 15) increase in C(T). Selective membrane permeabilization demonstrated that the C(T) increase was due to an increase in apical membrane capacitance. I(SC) and C(T) declined to basal levels on stimulus washout. Repetitive cAMP stimulation and washout (approximately 1 h each cycle) resulted in response fatigue; DeltaI(SC) decreased approximately 10% per stimulation-recovery cycle. When channel production was blocked by cycloheximide, DeltaI(SC) decreased approximately 15% per stimulation cycle, indicating that newly synthesized ENaC contributed a relatively small fraction of the channels mobilized to the apical membrane. Selective block of surface ENaC by benzamil demonstrated that channels inserted from a subapical pool made up >90% of the stimulated I(SC), and that on restimulation a large proportion of channels retrieved from the apical surface were reinserted into the apical membrane. Channel recycling was disrupted by brefeldin A, which inhibited ENaC exocytosis, by chloroquine, which inhibited ENaC endocytosis and recycling, and by latrunculin A, which blocked ENaC exocytosis. A compartment model featuring channel populations in the apical membrane and intracellular recycling pool provided an adequate kinetic description of the I(SC) responses to repetitive stimulation. The model supports the concept of ENaC recycling in response to repetitive cAMP stimulation.

Effects of ε-viniferin, a dehydrodimer of resveratrol, on transepithelial active ion transport and ion permeability in the rat small and large intestinal mucosa.

PubMed

Karaki, Shin-Ichiro; Ishikawa, Junji; Tomizawa, Yuka; Kuwahara, Atsukazu

2016-05-01

ε-Viniferin is a dehydrodimer of resveratrol, a polyphenol synthesized in many plants, including grapevine. The present study investigated the effects of ε-viniferin and resveratrol on epithelial secretory and barrier functions in isolated rat small and large intestinal mucosa. Mucosa-submucosa tissue preparations of various segments of the rat large and small intestines were mounted on Ussing chambers, and short-circuit current (Isc) and tissue conductance (Gt) were continuously measured. The mucosal addition of ε-viniferin (>10(-5) mol/L) and resveratrol (>10(-4) mol/L) to the cecal mucosa, which was the most sensitive region, induced an increase in Isc and a rapid phase decrease (P-1) followed by rapid (P-2) and broad (P-3) peak increases in Gt in concentration-dependent manners. Mucosal ε-viniferin (10(-4) mol/L), but not resveratrol (10(-4) mol/L), increased the permeability of FITC-conjugated dextran (4 kDa). The mucosal ε-viniferin-evoked changes in Isc (Cl(-) secretion), but not in Gt, were attenuated by a selective cyclooxygenase (COX)-1 inhibitor and a selective EP4 prostaglandin receptor. The mucosal ε-viniferin-evoked increase in Isc was partially attenuated, and P-2, but not P-1 or P-3, change in Gt was abolished by a transient receptor potential cation channel, subfamily A, member 1 (TRPA1) inhibitor. Moreover, the mucosal ε-viniferin concentration-dependently attenuated the mucosal propionate (1 mmol/L)-evoked increases in Isc and Gt Immunohistochemical studies revealed COX-1-immunoreactive epithelial cells in the cecal crypt. The present study showed that mucosal ε-viniferin modulated transepithelial ion transport and permeability, possibly by activating sensory epithelial cells expressing COX-1 and TRPA1. Moreover, mucosal ε-viniferin decreased mucosal sensitivity to other luminal molecules such as short-chain fatty acids. In conclusion, these results suggest that ε-viniferin modifies intestinal mucosal transport and barrier functions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Single crystal CVD diamond membranes for betavoltaic cells

NASA Astrophysics Data System (ADS)

Delfaure, C.; Pomorski, M.; de Sanoit, J.; Bergonzo, P.; Saada, S.

2016-06-01

A single crystal diamond large area thin membrane was assembled as a p-doped/Intrinsic/Metal (PIM) structure and used in a betavoltaic configuration. When tested with a 20 keV electron beam from a high resolution scanning electron microscope, we measured an open circuit voltage (Voc) of 1.85 V, a charge collection efficiency (CCE) of 98%, a fill-factor of 80%, and a total conversion efficiency of 9.4%. These parameters are inherently linked to the diamond membrane PIM structure that allows full device depletion even at 0 V and are among the highest reported up to now for any other material tested for betavoltaic devices. It enables to drive a high short-circuit current Isc up to 7.12 μA, to reach a maximum power Pmax of 10.48 μW, a remarkable value demonstrating the high-benefit of diamond for the realization of long-life radioisotope based micro-batteries.

Bioelectric Characterization of Epithelia from Neonatal CFTR Knockout Ferrets

PubMed Central

Fisher, John T.; Tyler, Scott R.; Zhang, Yulong; Lee, Ben J.; Liu, Xiaoming; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Luo, Meihui; Xie, Weiliang; Yi, Yaling; Zhou, Weihong; Song, Yi; Keiser, Nicholas; Wang, Kai; de Jonge, Hugo R.

2013-01-01

Cystic fibrosis (CF) is a life-shortening, recessive, multiorgan genetic disorder caused by the loss of CF transmembrane conductance regulator (CFTR) chloride channel function found in many types of epithelia. Animal models that recapitulate the human disease phenotype are critical to understanding pathophysiology in CF and developing therapies. CFTR knockout ferrets manifest many of the phenotypes observed in the human disease, including lung infections, pancreatic disease and diabetes, liver disease, malnutrition, and meconium ileus. In the present study, we have characterized abnormalities in the bioelectric properties of the trachea, stomach, intestine, and gallbladder of newborn CF ferrets. Short-circuit current (ISC) analysis of CF and wild-type (WT) tracheas revealed the following similarities and differences: (1) amiloride-sensitive sodium currents were similar between genotypes; (2) responses to 4,4′-diisothiocyano-2,2′-stilbene disulphonic acid were 3.3-fold greater in CF animals, suggesting elevated baseline chloride transport through non-CFTR channels in a subset of CF animals; and (3) a lack of 3-isobutyl-1-methylxanthine (IBMX)/forskolin–stimulated and N-(2-Naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene)glycine hydrazide (GlyH-101)–inhibited currents in CF animals due to the lack of CFTR. CFTR mRNA was present throughout all levels of the WT ferret and IBMX/forskolin–inducible ISC was only observed in WT animals. However, despite the lack of CFTR function in the knockout ferret, the luminal pH of the CF ferret gallbladder, stomach, and intestines was not significantly changed relative to WT. The WT stomach and gallbladder exhibited significantly enhanced IBMX/forskolin ISC responses and inhibition by GlyH-101 relative to CF samples. These findings demonstrate that multiple organs affected by disease in the CF ferret have bioelectric abnormalities consistent with the lack of cAMP-mediated chloride transport. PMID:23782101

Islamic World Science Citation Center (ISC): Evaluating Scholary Journals Based on Citation Analysis

PubMed Central

Mehrad, Jaffar; Arastoopoor, Sholeh

2012-01-01

Introduction: Citation analysis is currently one of the most widely used metrics for analyzing the scientific contribution in different fields. The Islamic World Science Citation Center (ISC) aims at promoting technical cooperation among Muslim scientists and their respected centers based on these theories. It also facilitates the accessibility of knowledge and research contribution among them. This paper aims at revealing some of the outmost features of ISC databases, in order to give a fairly clear view of what it is and what are its products. The paper consists of three major parts. After an introduction about the Islamic World Science Citation Center, the paper deals with major tools and products of ISC. In the third part ISCs’ journal Submission system is presented as an automatic means, by which users can upload journals’ papers into the respected databases. Conclusion: Some complementary remarks have been made regarding the current state of ISC and its future plans. PMID:23322953

Characterization of active ion transport across primary rabbit corneal epithelial cell layers (RCrECL) cultured at an air-interface.

PubMed

Chang-Lin, Joan-En; Kim, Kwang-Jin; Lee, Vincent H L

2005-06-01

Previously, we reported the development of a primary culture model of tight rabbit corneal epithelial cell layers (RCrECL) characterizing bioelectric parameters, morphology, cytokeratin, and passive permeability. In the present study, we specifically evaluated the active ion transport processes of RCrECL cultured from either pigmented or albino rabbits. Primary cultured RCrECL were grown at an air-interface on Clear-Snapwells precoated with collagen/fibronectin/laminin and mounted in a modified Ussing-type chamber for the evaluation of their active ion transport processes under short-circuited conditions. Contribution of active Na(+) and Cl(-) transport to overall short-circuit current (I(sc)) was evaluated by removing Na(+) and Cl(-), respectively, from bathing fluids of RCrECL and measurements of net fluxes of Na(+) and Cl(-) using (22)Na and (36)Cl, respectively. Amiloride and benzamil were used to determine the role of apical Na(+)-channel activities to net Na(+) fluxes. N-phenylanthranilic acid (NPAA), ouabain, BaCl(2) and bumetanide were used to determine the role of basolateral Na,K-ATPase, apical Cl(-)-channel, and basolateral K(+)-channel and Na(+)(K(+))2Cl(-)-cotransporter activities, respectively, in active ion transport across RCrECL. I(sc) of RCrECL derived from pigmented rabbits was comprised of 64+/-2% and 44+/-5% for active Na(+) and Cl(-) transport, respectively, consistent with net Na(+) absorption and Cl(-) secretion of 0.062+/-0.006 and 0.046+/-0.008 muEq/cm(2)/hr estimated from radionuclide fluxes. Apical amiloride and benzamil inhibited I(sc) by up to approximately 50% with an IC(50) of 1 and 0.1 microm, respectively, consistent with participation of apical epithelial Na(+)-channels to net Na(+) absorption across RCrECL cultured from pigmented rabbits. Addition of ouabain to the basolateral, NPAA to the apical, BaCl(2) to the basolateral and bumetanide to basolateral fluid decreased I(sc) by 86+/-1.5%, 53+/-3%, 18+/-1.8% and 13+/-1.9% in RCrECL cultured from pigmented rabbits, while 85+/-0.7%, 36+/-1.6%, 38+/-1.8% and 15+/-3.5% decreases are observed for RCrECL from albino rabbits, respectively. Air-interface cultured RCrECL from either pigmented or albino rabbits exhibited active ion transport properties similar to those present in excised tissues. This primary culture system may be a reliable in-vitro model for mechanistic characterization of corneal epithelial function and regulation of transport properties.

The ISC Contribution to Monitoring Research

NASA Astrophysics Data System (ADS)

Storchak, D. A.; Bondar, I.; Harris, J.; Gaspà Rebull, O.

2010-12-01

The International Seismological Centre (ISC) is a non-governmental organization charged with production of the ISC Bulletin - the definitive global summary of seismicity based on reports from over 4.5 thousand seismic stations worldwide. The ISC data have been extensively used in preparation of the Comprehensive Test Ban Treaty (CTBT). They are now used by the CTBTO Preparatory Technical Secretariat (PTS) and the State Parties as an important benchmark for assessing and monitoring detection capabilities of the International Monitoring System (IMS). The ISC also provides a valuable collection of reviewed waveform readings at academic and operational sites co-located with the IMS stations. To improve the timeliness of its Bulletin, the ISC is making a special effort in collecting preliminary bulletins from a growing number of networks worldwide that become available soon after seismic events occur. Preliminary bulletins are later substituted with the final analysis data once these become available to the ISC from each network. The ISC also collects and maintains data sets that are useful for monitoring research. These are the IASPEI Reference Event List of globally distributed GT0-5 events, the groomed ISC bulletin (EHB), the IDC REB, USArray phase picking data. In cooperation with the World Data Center for Seismology, Denver (USGS), the ISC also maintains the International Seismographic Station Registry that holds parameters of seismic stations used in the international data exchange. The UK Foreign and Commonwealth Office along with partners from several Nordic countries are currently funding a project to make the ISC database securely linked with the computer facilities at PTS and National Data Centres. The ISC Bulletin data are made available via a dedicated software link designed to offer the ISC data in a way convenient to monitoring community.

An enhanced mangiferaindica for dye sensitized solar cell application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uno, U. E., E-mail: moses.emetere@covenantuniversity.edu.ng; Emetere, M. E., E-mail: uno-essang@yahoo.co.uk; Fadipe, L. A.

Titanium dioxide (T1O2) is preferred to Zinc oxide as mesoporous oxide layer because it raised the efficiency of DSSCs from 1% to 7%. The chemistry of the process however seem rigorous to allow the light induced electron injection from the adsorbed dye into the nanocrystallites i.e. which renders the TiO{sub 2} conductive. The DSSC fabricated consist of 2.25 cm{sup 2} active area of titanium dioxide coated on FTO glass (fluorine tin oxide) immersed in ethanol solution of natural dye extracted as an anode (electrode) and counter electrode. These two electrodes were coupled together and the space between them was filledmore » with the Iodolyte AN-50 as solid electrolyte or redox mediator. The photo electrochemical parameters of the dye extracted (Mango fruit Peel) from the results obtained are short circuit current (Isc)= 1.22×10{sup −2}, current density (Jsc)=4.07×10{sup −2}, open circuit voltage (voc) =0.53V, fill factor (FF) of 0.16 and the overall conversion efficiency (Eff) =0.345%.« less

Propofol inhibits carbachol-induced chloride secretion by directly targeting the basolateral K+ channel in rat ileum epithelium.

PubMed

Tang, S-H; Wang, H-Y; Sun, H; An, N; Xiao, L; Sun, Q; Zhao, D-B

2017-02-01

Propofol is a widely used intravenous general anesthetic. Acetylcholine (ACh) is critical in controlling epithelial ion transport. This study was to investigate the effects of propofol on ACh-evoked secretion in rat ileum epithelium. The Ussing chamber technique was used to investigate the effects of propofol on carbachol (CCh)-evoked short-circuit currents (Isc). Propofol (10 -2 -10 -6  mol/L) attenuated CCh-evoked Isc of rat ileum mucosa in a dose-dependent manner. The inhibitory effect of propofol was only evident after application to the serosal side. Pretreatment with tetrodotoxin (TTX, 0.3 μmol/L, n=5) had no effect on propofol-induced inhibitory effect, whereas serosal application of K + channel inhibitor, glibenclamide, but not, an ATP-sensitive K + channel inhibitor, largely reduced the inhibitory effect of propofol. In addition, pretreatment with either hexamethonium bromide (HB, nicotinic nACh receptor antagonist) or Cl - channel blockers niflumic acid and cystic fibrosis transmembrane conductance regulator (inh)-172 did not produce any effect on the propofol-induced inhibitory effect. Propofol inhibits CCh-induced intestinal secretion by directly targeting basolateral K + channels. © 2016 John Wiley & Sons Ltd.

Identification of transport abnormalities in duodenal mucosa and duodenal enterocytes from patients with cystic fibrosis.

PubMed

Pratha, V S; Hogan, D L; Martensson, B A; Bernard, J; Zhou, R; Isenberg, J I

2000-06-01

The duodenum is a cystic fibrosis transmembrane conductance regulator (CFTR)-expressing epithelium with high bicarbonate secretory capacity. We aimed to define the role of CFTR in human duodenal epithelial bicarbonate secretion in normal (NL) subjects and patients with cystic fibrosis (CF). Endoscopic biopsy specimens of the duodenal bulb were obtained from 9 CF patients and 16 volunteers. Tissues were mounted in modified Ussing chambers. Bicarbonate secretion and short-circuit current (Isc) were quantitated under basal conditions and in response to dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP), carbachol, and the heat-stable toxin of Escherichia coli (STa). Duodenocytes were also isolated and loaded with the pH-sensitive fluoroprobe BCECF/AM, and intracellular pH (pH(i)) was measured at rest and after intracellular acidification and alkalinization. Basal HCO(3)(-) secretion and Isc were significantly lower in the CF vs. NL duodenal mucosa. In contrast to NL, db-cAMP failed to alter either HCO(3)(-) or Isc in CF tissues. However, in CF, carbachol resulted in an electroneutral HCO(3)(-) secretion, whereas STa induced electrogenic HCO(3)(-) secretion that was similar to NL. In CF and NL duodenocytes, basal pH(i) and recovery from an acid load were comparable, but pH(i) recovery after an alkaline load in CF duodenocytes was Cl(-) dependent, whereas in NL duodenocytes it was Cl(-) independent. These findings implicate CFTR in NL duodenal alkaline transport and its absence in CF. Although duodenal bicarbonate secretion is impaired in CF tissues, alternate pathway(s) likely exist that can be activated by carbachol and STa.

In vitro effects of hydrochloric acid and various concentrations of acetic, propionic, butyric, or valeric acids on bioelectric properties of equine gastric squamous mucosa.

PubMed

Andrews, Frank M; Buchanan, Benjamin R; Smith, Sionagh H; Elliott, Sarah B; Saxton, Arnold M

2006-11-01

To compare the effects of hydrochloric acid (HCl) and various concentrations of volatile fatty acids (VFAs) on tissue bioelectric properties of equine stomach nonglandular (NG) mucosa. Gastric tissues obtained from 48 adult horses. NG gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference (PD) were measured and electrical resistance (R) and conductance calculated for tissues after addition of HCl and VFAs (5, 10, 20, and 40 mM) in normal Ringer's solution (NRS). Mucosa exposed to HCl in NRS (pH of 1.5 and, to a lesser extent, 4.0) had a significant decrease in Isc, PD, and R, whereas tissues exposed to acetic acid at a pH of < 4.0, propionic and butyric acids at a pH of

QWIPs at IRnova, a status update

NASA Astrophysics Data System (ADS)

Martijn, Henk; Gamfeldt, Anders; Asplund, Carl; Smuk, Sergiy; Kataria, Himanshu; Costard, Eric

2016-05-01

IRnova has a long history of producing QWIPs for the LWIR band. In this paper we give an overview of the current products (FPAs with 640x480 and 384x288 pixels respectively, and 25 μm pitch) and their performance. Their superior stability and uniformity inherent to detectors based on III/V material system will be demonstrated. Furthermore, an IDCA specifically designed for hand-held systems used for the detection of SF6 gas using a 0.5 W cooler will be presented. The detector format is 320x256 pixels with 30 μm pitch using the ISC9705 read out circuit. The peak wavelength is at 10.55 μm and the NETD is 22 mK.

A versatile software package for inter-subject correlation based analyses of fMRI.

PubMed

Kauppi, Jukka-Pekka; Pajula, Juha; Tohka, Jussi

2014-01-01

In the inter-subject correlation (ISC) based analysis of the functional magnetic resonance imaging (fMRI) data, the extent of shared processing across subjects during the experiment is determined by calculating correlation coefficients between the fMRI time series of the subjects in the corresponding brain locations. This implies that ISC can be used to analyze fMRI data without explicitly modeling the stimulus and thus ISC is a potential method to analyze fMRI data acquired under complex naturalistic stimuli. Despite of the suitability of ISC based approach to analyze complex fMRI data, no generic software tools have been made available for this purpose, limiting a widespread use of ISC based analysis techniques among neuroimaging community. In this paper, we present a graphical user interface (GUI) based software package, ISC Toolbox, implemented in Matlab for computing various ISC based analyses. Many advanced computations such as comparison of ISCs between different stimuli, time window ISC, and inter-subject phase synchronization are supported by the toolbox. The analyses are coupled with re-sampling based statistical inference. The ISC based analyses are data and computation intensive and the ISC toolbox is equipped with mechanisms to execute the parallel computations in a cluster environment automatically and with an automatic detection of the cluster environment in use. Currently, SGE-based (Oracle Grid Engine, Son of a Grid Engine, or Open Grid Scheduler) and Slurm environments are supported. In this paper, we present a detailed account on the methods behind the ISC Toolbox, the implementation of the toolbox and demonstrate the possible use of the toolbox by summarizing selected example applications. We also report the computation time experiments both using a single desktop computer and two grid environments demonstrating that parallelization effectively reduces the computing time. The ISC Toolbox is available in https://code.google.com/p/isc-toolbox/

A versatile software package for inter-subject correlation based analyses of fMRI

PubMed Central

Kauppi, Jukka-Pekka; Pajula, Juha; Tohka, Jussi

2014-01-01

In the inter-subject correlation (ISC) based analysis of the functional magnetic resonance imaging (fMRI) data, the extent of shared processing across subjects during the experiment is determined by calculating correlation coefficients between the fMRI time series of the subjects in the corresponding brain locations. This implies that ISC can be used to analyze fMRI data without explicitly modeling the stimulus and thus ISC is a potential method to analyze fMRI data acquired under complex naturalistic stimuli. Despite of the suitability of ISC based approach to analyze complex fMRI data, no generic software tools have been made available for this purpose, limiting a widespread use of ISC based analysis techniques among neuroimaging community. In this paper, we present a graphical user interface (GUI) based software package, ISC Toolbox, implemented in Matlab for computing various ISC based analyses. Many advanced computations such as comparison of ISCs between different stimuli, time window ISC, and inter-subject phase synchronization are supported by the toolbox. The analyses are coupled with re-sampling based statistical inference. The ISC based analyses are data and computation intensive and the ISC toolbox is equipped with mechanisms to execute the parallel computations in a cluster environment automatically and with an automatic detection of the cluster environment in use. Currently, SGE-based (Oracle Grid Engine, Son of a Grid Engine, or Open Grid Scheduler) and Slurm environments are supported. In this paper, we present a detailed account on the methods behind the ISC Toolbox, the implementation of the toolbox and demonstrate the possible use of the toolbox by summarizing selected example applications. We also report the computation time experiments both using a single desktop computer and two grid environments demonstrating that parallelization effectively reduces the computing time. The ISC Toolbox is available in https://code.google.com/p/isc-toolbox/ PMID:24550818

Drosophila Perlecan Regulates Intestinal Stem Cell Activity via Cell-Matrix Attachment

PubMed Central

You, Jia; Zhang, Yan; Li, Zhouhua; Lou, Zhefeng; Jin, Longjin; Lin, Xinhua

2014-01-01

Summary Stem cells require specialized local microenvironments, termed niches, for normal retention, proliferation, and multipotency. Niches are composed of cells together with their associated extracellular matrix (ECM). Currently, the roles of ECM in regulating niche functions are poorly understood. Here, we demonstrate that Perlecan (Pcan), a highly conserved ECM component, controls intestinal stem cell (ISC) activities and ISC-ECM attachment in Drosophila adult posterior midgut. Loss of Pcan from ISCs, but not other surrounding cells, causes ISCs to detach from underlying ECM, lose their identity, and fail to proliferate. These defects are not a result of a loss of epidermal growth factor receptor (EGFR) or Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling activity but partially depend on integrin signaling activity. We propose that Pcan secreted by ISCs confers niche properties to the adjacent ECM that is required for ISC maintenance of stem cell identity, activity, and anchorage to the niche. PMID:24936464

Ultra-high aspect ratio titania nanoflakes for dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Lee, Yang-Yao; El-Shall, Hassan

2017-12-01

Micron sized titania flakes with thickness about 40 nm were used in the titania pastes to assemble dye-sensitized solar cells (DSSCs). Using the same deposition method, better particle dispersion of titania flakes resulted in well bonded and integral films comparing to cracking of Degussa P25 nanoparticle films during the evaporation and sintering processes. There are two features of titania flakes which leads to improved conversion efficiency of DSSC: (1) Higher and stronger adsorption of N-719 dyes due to high specific surface area (2) Stronger light scattering of visible light spectrum because of micron scale wide in two dimensions of the flakes. The thickness of the conducting TiO2 was critical to the IV characteristics of DSSC such as the short-circuit current density (Isc) and open-circuit voltage (Voc). Under the same thickness basis, calcined titania flakes provided 5 times higher efficiency than the photoelectrodes consisted of Degussa P25 nanoparticles (7.4% vs. 1.2%).

Fine-tuning device performances of small molecule solar cells via the more polarized DPP-attached donor units.

PubMed

Huang, Jianhua; Jia, Hui; Li, Liangjie; Lu, Zhenhuan; Zhang, Wenqing; He, Weiwei; Jiang, Bo; Tang, Ailing; Tan, Zhan'ao; Zhan, Chuanlang; Li, Yongfang; Yao, Jiannian

2012-11-07

Three solution-processable small molecules of DPPT, DPPSe and DPPTT were synthesized by Stille coupling through attaching donor units of thiophene (T), selenophene (Se) and thieno[3,2-b]thiophene (TT) to the diketopyrrolopyrrole (DPP) core, respectively. Replacement of the T donors with the more polarized Se units results in a balance between the a and b direction packing and an obvious increase of the power conversion efficiency (PCE) from 1.90% to 2.33% with the increase of the short-circuit current (I(sc)) from 5.59 to 5.81 mA cm(-2) and the open-circuit voltage (V(oc)) from 0.78 V to 0.86 under the small molecule/acceptor ratio of 3 : 1. However, introduction of the conjugation-enlarged TT groups (versus the T units) leads to a decrease of the PCE, down to 1.70%, with a significant decrease of the fill factor (FF) (38% versus 44%), due to its poor film-forming characteristics.

Employment of single-diode model to elucidate the variations in photovoltaic parameters under different electrical and thermal conditions

PubMed Central

Hameed, Shilan S.; Aziz, Fakhra; Sulaiman, Khaulah; Ahmad, Zubair

2017-01-01

In this research work, numerical simulations are performed to correlate the photovoltaic parameters with various internal and external factors influencing the performance of solar cells. Single-diode modeling approach is utilized for this purpose and theoretical investigations are compared with the reported experimental evidences for organic and inorganic solar cells at various electrical and thermal conditions. Electrical parameters include parasitic resistances (Rs and Rp) and ideality factor (n), while thermal parameters can be defined by the cells temperature (T). A comprehensive analysis concerning broad spectral variations in the short circuit current (Isc), open circuit voltage (Voc), fill factor (FF) and efficiency (η) is presented and discussed. It was generally concluded that there exists a good agreement between the simulated results and experimental findings. Nevertheless, the controversial consequence of temperature impact on the performance of organic solar cells necessitates the development of a complementary model which is capable of well simulating the temperature impact on these devices performance. PMID:28793325

Simulation study of air and water cooled photovoltaic panel using ANSYS

NASA Astrophysics Data System (ADS)

Syafiqah, Z.; Amin, N. A. M.; Irwan, Y. M.; Majid, M. S. A.; Aziz, N. A.

2017-10-01

Demand for alternative energy is growing due to decrease of fossil fuels sources. One of the promising and popular renewable energy technology is a photovoltaic (PV) technology. During the actual operation of PV cells, only around 15% of solar irradiance is converted to electricity, while the rest is converted into heat. The electrical efficiency decreases with the increment in PV panel’s temperature. This electrical energy is referring to the open-circuit voltage (Voc), short-circuit current (Isc) and output power generate. This paper examines and discusses the PV panel with water and air cooling system. The air cooling system was installed at the back of PV panel while water cooling system at front surface. The analyses of both cooling systems were done by using ANSYS CFX and PSPICE software. The highest temperature of PV panel without cooling system is 66.3 °C. There is a decrement of 19.2% and 53.2% in temperature with the air and water cooling system applied to PV panel.

Glutamine supplementation improves intestinal barrier function in a weaned piglet model of Escherichia coli infection.

PubMed

Ewaschuk, Julia B; Murdoch, Gordon K; Johnson, Ian R; Madsen, Karen L; Field, Catherine J

2011-09-01

The weaning period is associated with an increased prevalence of gastrointestinal infection in many species. Glutamine (Gln) has been shown to improve intestinal barrier function and immune function in both in vivo and in vitro models. The objective of the present study was to determine the effect of dietary Gln supplementation on intestinal barrier function and intestinal cytokines in a model of Escherichia coli infection. We randomised 21-d-old piglets (n 20) to nutritionally complete isonitrogenous diets with or without Gln (4·4 %, w/w) for 2 weeks. Intestinal loops were isolated from anaesthetised pigs and inoculated with either saline or one of the two E. coli (K88AC or K88 wild-type)-containing solutions. Intestinal tissue was studied for permeability, cytokine expression, fluid secretion and tight-junction protein expression. Animals receiving Gln supplementation had decreased potential difference (PD) and short-circuit current (I(sc)) in E. coli-inoculated intestinal loops (PD 0·628 (SEM 0·151) mV; I(sc) 13·0 (SEM 3·07) μA/cm(2)) compared with control-fed animals (PD 1·36 (SEM 0·227) mV; I(sc) 22·4 (SEM 2·24) μA/cm(2)). Intestinal tissue from control, but not from Gln-supplemented, animals responded to E. coli with a significant increase in mucosal cytokine mRNA (IL-1β, IL-6, transforming growth factor-β and IL-10). Tight-junction protein expression (claudin-1 and occludin) was reduced with exposure to E. coli in control-fed animals and was not influenced in Gln-supplemented piglets. Gln supplementation may be useful in reducing the severity of weaning-related gastrointestinal infections, by reducing the mucosal cytokine response and altering intestinal barrier function.

K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport

PubMed Central

2010-01-01

Background Lung epithelial Na+ channels (ENaC) are regulated by cell Ca2+ signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K+ channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K+ channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC) by up-regulating both apical and basolateral ion transport. Methods Verapamil-induced depression of heterologously expressed human αβγ ENaC in Xenopus oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441), and in vivo alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca2+ signal in H441 cells was analyzed using Fluo 4AM. Results The rate of in vivo AFC was reduced significantly (40.6 ± 6.3% of control, P < 0.05, n = 12) in mice intratracheally administrated verapamil. KCa3.1 (1-EBIO) and KATP (minoxidil) channel openers significantly recovered AFC. In addition to short-circuit current (Isc) in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca2+ signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca2+ in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, KV (pyrithione-Na), K Ca3.1 (1-EBIO), and KATP (minoxidil) channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na+ and K+ transport pathways. Conclusions Our observations demonstrate that K+ channel openers are capable of rescuing reduced vectorial Na+ transport across lung epithelial cells with impaired Ca2+ signal. PMID:20507598

Anti-Diarrheal Mechanism of the Traditional Remedy Uzara via Reduction of Active Chloride Secretion

PubMed Central

Fromm, Anja; Günzel, Dorothee

2011-01-01

Background and Purpose The root extract of the African Uzara plant is used in traditional medicine as anti-diarrheal drug. It is known to act via inhibition of intestinal motility, but malabsorptive or antisecretory mechanisms are unknown yet. Experimental Approach HT-29/B6 cells and human colonic biopsies were studied in Ussing experiments in vitro. Uzara was tested on basal as well as on forskolin- or cholera toxin-induced Cl− secretion by measuring short-circuit current (ISC) and tracer fluxes of 22Na+ and 36Cl−. Para- and transcellular resistances were determined by two-path impedance spectroscopy. Enzymatic activity of the Na+/K+-ATPase and intracellular cAMP levels (ELISA) were measured. Key Results In HT-29/B6 cells, Uzara inhibited forskolin- as well as cholera toxin-induced ISC within 60 minutes indicating reduced active chloride secretion. Similar results were obtained in human colonic biopsies pre-stimulated with forskolin. In HT-29/B6, the effect of Uzara on the forskolin-induced ISC was time- and dose-dependent. Analyses of the cellular mechanisms of this Uzara effect revealed inhibition of the Na+/K+-ATPase, a decrease in forskolin-induced cAMP production and a decrease in paracellular resistance. Tracer flux experiments indicate that the dominant effect is the inhibition of the Na+/K+-ATPase. Conclusion and Implications Uzara exerts anti-diarrheal effects via inhibition of active chloride secretion. This inhibition is mainly due to an inhibition of the Na+/K+-ATPase and to a lesser extent to a decrease in intracellular cAMP responses and paracellular resistance. The results imply that Uzara is suitable for treating acute secretory diarrhea. PMID:21479205

Effect of entacapone on colon motility and ion transport in a rat model of Parkinson's disease.

PubMed

Li, Li-Sheng; Liu, Chen-Zhe; Xu, Jing-Dong; Zheng, Li-Fei; Feng, Xiao-Yan; Zhang, Yue; Zhu, Jin-Xia

2015-03-28

To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease (PD) rats. Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC ) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl(-) channel blocker diphenylamine-2, 2'-dicarboxylic acid, basolateral application of Na(+)-K(+)-2Cl(-)co-transporter antagonist bumetanide, elimination of Cl(-) from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl(-) flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl(-) secretion in the PD rat.

Choline acetyltransferase and organic cation transporters are responsible for synthesis and propionate-induced release of acetylcholine in colon epithelium.

PubMed

Bader, Sandra; Klein, Jochen; Diener, Martin

2014-06-15

Acetylcholine is not only a neurotransmitter, but is found in a variety of non-neuronal cells. For example, the enzyme choline acetyltransferase (ChAT), catalyzing acetylcholine synthesis, is expressed by the colonic epithelium of different species. These cells release acetylcholine across the basolateral membrane after luminal exposure to propionate, a short-chain fatty acid. The functional consequence is the induction of chloride secretion, measurable as increase in short-circuit current (Isc) in Ussing chamber experiments. It is unclear how acetylcholine is produced and released by colonic epithelium. Therefore, the aim of the present study was the identification (on mRNA and protein level) and functional characterization (in Ussing chamber experiments combined with HPLC detection of acetylcholine) of transporters/enzymes in the cholinergic system of rat colonic epithelium. Immunohistochemical staining as well as RT-PCR revealed the expression of high-affinity choline transporter, ChAT, carnitine acetyltransferase (CarAT), vesicular acetylcholine transporter (VAChT), and organic cation transporters (OCT 1, 2, 3) in colonic epithelium. In contrast to blockade of ChAT with bromoacetylcholine, inhibition of CarAT with mildronate did not inhibit the propionate-induced increase in Isc, suggesting a predominant synthesis of epithelial acetylcholine by ChAT. Although being expressed, blockade of VAChT with vesamicol was ineffective, whereas inhibition of OCTs with omeprazole and corticosterone inhibited propionate-induced Isc and the release of acetylcholine into the basolateral compartment. In summary, OCTs seem to be involved in regulated acetylcholine release by colonic epithelium, which is assumed to be involved in chemosensing of luminal short-chain fatty acids by the intestinal epithelium. Copyright © 2014 Elsevier B.V. All rights reserved.

Orexins control intestinal glucose transport by distinct neuronal, endocrine, and direct epithelial pathways.

PubMed

Ducroc, Robert; Voisin, Thierry; El Firar, Aadil; Laburthe, Marc

2007-10-01

Orexins are neuropeptides involved in energy homeostasis. We investigated the effect of orexin A (OxA) and orexin B (OxB) on intestinal glucose transport in the rat. Injection of orexins led to a decrease in the blood glucose level in oral glucose tolerance tests (OGTTs). Effects of orexins on glucose entry were analyzed in Ussing chambers using the Na(+)-dependent increase in short-circuit current (Isc) to quantify jejunal glucose transport. The rapid and marked increase in Isc induced by luminal glucose was inhibited by 10 nmol/l OxA or OxB (53 and 59%, respectively). Response curves to OxA and OxB were not significantly different with half-maximal inhibitory concentrations at 0.9 and 0.4 nmol/l, respectively. On the one hand, OxA-induced inhibition of Isc was reduced by the neuronal blocker tetrodotoxin (TTX) and by a cholecystokinin (CCK) 2R antagonist, indicating involvement of neuronal and endocrine CCK-releasing cells. The OX(1)R antagonist SB334867 had no effect on OxA-induced inhibition, which is likely to occur via a neuronal and/or endocrine OX(2)R. On the other hand, SB334867 induced a significant right shift of the concentration-effect curve for OxB. This OxB-preferring OX(1)R pathway was not sensitive to TTX or to CCKR antagonists, suggesting that OxB may act directly on enterocytic OX(1)R. These distinct effects of OxA and OxB are consistent with the expression of OX(1)R and OX(2)R mRNA in the epithelial and nonepithelial tissues, respectively. Our data delineate a new function for orexins as inhibitors of intestinal glucose absorption and provide a new basis for orexin-induced short-term control of energy homeostasis.

Bradykinin-Stimulated Cyclooxygenase Activity Stimulates Vas Deferens Epithelial Anion Secretion In Vitro in Swine and Humans1

PubMed Central

Pierucci-Alves, Fernando; Schultz, Bruce D.

2008-01-01

Epithelia lining the male reproductive duct modulate fertility by altering the luminal environment to which sperm are exposed. Although vas deferens epithelial cells reportedly express high levels of cyclooxygenases (Ptgs), and activation of bradykinin (BK) receptors can lead to upregulation of PTGS activity in epididymal epithelia, it remains unknown whether BKs and/or PTGSs have any role in modulating epithelial ion transport across vas deferens epithelia. Porcine and human vas deferens epithelial cell primary cultures and the PVD9902 cell line responded to lysylbradykinin with an increase in short circuit current (ISC; indicating net anion secretion), an effect that was 60%–93% reduced by indomethacin. The BK effect was inhibited by the B2 receptor subtype (BDKRB2) antagonist HOE140, whereas the B1 receptor subtype agonist des-Arg9-BK had no effect. BDKRB2 immunoreactivity was documented in most epithelial cells composing the native epithelium and on Western blots derived from cultured cells. Gene expression analysis revealed that the PTGS2 transcript is 20 times more abundant than its PTGS1 counterpart in cultured porcine vas deferens epithelia and that BDKRB2 mRNA is likewise highly expressed. Subsequent experiments revealed that prostaglandin E2, 1-OH prostaglandin E1 (prostaglandin E receptor 4 [PTGER4] agonist) and butaprost (PTGER2 agonist) increase ISC in a concentration-dependent manner, whereas sulprostone (mixed PTGER1 and PTGER3 agonist) produced no change in ISC. These results demonstrate that autacoids can affect epithelial cells to acutely modulate the luminal environment to which sperm are exposed in the vas deferens by enhancing PTGS activity, leading to the production of prostaglandins that act at PTGER4 and/or PTGER2 to induce or enhance anion secretion. PMID:18480467

Transmittance of selected nanostructurized solar glasses designated via relative change in electrical parameters of silicon solar cells

NASA Astrophysics Data System (ADS)

Pociask-Bialy, Malgorzata; Kalwas, Kornelia

2017-01-01

Photovoltaics is one of the most promising technologies for electricity production. In the future, photovoltaics could be an effective and safe source of energy. In this work were present the results of the analysis of a special solar glasses transmissivity coefficient used as protective cover of photovoltaic cell. Antireflective glass due to its unique physical properties eliminate reflections and significantly increasing light transmission. The study of the relative change in the electrical parameters of photovoltaic cells ,with and without coats, as open-circuit current ISC and the maximum power point MPP are presented in this paper. Research were undertaken with using the solar simulator QuickSun130CA, Class AAA+, under Standard Test Conditions.

Regulation of transepithelial ion transport in the rat late distal colon by the sympathetic nervous system.

PubMed

Zhang, X; Li, Y; Zhang, X; Duan, Z; Zhu, J

2015-01-01

The colorectum (late distal colon) is innervated by the sympathetic nervous system, and many colorectal diseases are related to disorders of the sympathetic nervous system. The sympathetic regulation of colorectal ion transport is rarely reported. The present study aims to investigate the effect of norepinephrine (NE) in the normal and catecholamine-depleted condition to clarify the regulation of the sympathetic adrenergic system in ion transport in the rat colorectum. NE-induced ion transport in the rats colorectum was measured by short-circuit current (I(sc)) recording; the expression of beta-adrenoceptors and NE transporter (NET) were quantified by real-time PCR, and western blotting. When the endogenous catecholamine was depleted by reserpine, the baseline I(sc) in the colorectum was increased significantly comparing to controls. NE evoked downward deltaI(sc) in colorectum of treated rats was 1.8-fold of controls. The expression of beta(2)-adrenoceptor protein in the colorectal mucosa was greater than the control, though the mRNA level was reduced. However, NET expression was significantly lower in catecholamine-depleted rats compared to the controls. In conclusion, the sympathetic nervous system plays an important role in regulating basal ion transport in the colorectum. Disorders of sympathetic neurotransmitters result in abnormal ion transport, beta-adrenoceptor and NET are involved in the process.

Rebuild of the Bulletin of the International Seismological Centre (ISC), part 1: 1964-1979

NASA Astrophysics Data System (ADS)

Storchak, Dmitry A.; Harris, James; Brown, Lonn; Lieser, Kathrin; Shumba, Blessing; Verney, Rebecca; Di Giacomo, Domenico; Korger, Edith I. M.

2017-12-01

The data from the Bulletin of the International Seismological Centre (ISC) have always been and still remain in demand for a wide range of studies in Geosciences. The unique features of the Bulletin include long-term coverage (1904-present), the most comprehensive set of included seismic data from the majority of permanent seismic networks at any given time in the history of instrumental recording (currently 150) and homogeneity of the data and their representation. In order to preserve this homogeneity, the ISC has followed its own standard seismic event processing procedures that have not substantially changed until the early 2000s. Several considerable and necessary advancements in the ISC data collection and seismic event location procedures have created a need to rebuild the data for preceding years in line with the new procedures. Thus was set up a project to rebuild the ISC Bulletin for the period from the beginning of the ISC data till the end of data year 2010. The project is known as the Rebuild of the ISC Bulletin. From data month of January 2011, the ISC data have already been processed with the fully tested and established new procedures and do not require an alteration. It was inconceivable even to think about such a project for many tens of years, but great advances in computer power and increased support by the ISC Member-Institutions and Sponsors have given us a chance to perform this project. Having obtained a lot of experience on the way, we believe that within a few years the entire period of the ISC data will be reprocessed and extended for the entire period of instrumental seismological recordings from 1904 till present. The purpose of this article is to describe the work on reprocessing the ISC Bulletin data under the Rebuild project. We also announce the release of the rebuilt ISC Bulletin for the period 1964-1979 with all seismic events reprocessed and relocated in line with the modern ISC procedures, 68,000 new events, 255 new stations, 815,000 new seismic phases, more robust and reliable mb and M S magnitude evaluations and the addition of 2700 new M S magnitudes.

NREL Blows Up Batteries to Make the World Safer | News | NREL

Science.gov Websites

lithium-ion batteries safer for earthlings and astronauts is something NREL excels at. In this video . Matt and his team study battery failure using innovative technologies, such as the award-winning Battery Internal Short Circuit (ISC) Device that can precisely identify weak spots in battery cells. This

Tritiated amorphous silicon films and devices

NASA Astrophysics Data System (ADS)

Kosteski, Tome

The do saddle-field glow discharge deposition technique has been used to bond tritium within an amorphous silicon thin film network using silane and elemental tritium in the glow discharge. The concentration of tritium is approximately 7 at. %. Minimal outgassing of tritium from tritiated hydrogenated amorphous silicon (a-Si:H:T) at room temperature suggests that tritium is bonded stably. Tritium effusion only occurred at temperatures above the film's growth temperature. The radioactive decay of tritium results in the production of high-energy beta particles. Each beta particle can generate on average approximately 1300 electron-hole pairs in a-Si:H:T. Electrical conductivity of a-Si:H:T is shown to be due to a thermally activated process and due to the generation of excess carriers by the beta particles. p-i-n betavoltaic devices have been made with a-Si:H:T in the intrinsic (i-) region. The i-region consisted of either a-Si:H:T, or a thin section of a-Si:H:T (a Delta layer) sandwiched between undoped hydrogenated amorphous silicon (a-Si:H). The excess carriers generated in the i-region are separated by the device's built-in electric field. Short-circuit currents (Isc ), open-circuit voltages (Voc), and power have been measured and correlated to the generation of excess carriers in the i-region. Good devices were made at a substrate temperature of 250°C and relatively large flow rates of silane and tritium; this ensures that there are more monohydride bonds than dihydride bonds. Under dark conditions, Isc, and Voc have been found to decrease rapidly. This is consistent with the production of silicon neutral dangling bonds (5 x 1017cm-3 per day) from the loss of tritium due to its transmutation into helium. Dangling bonds reduce carrier lifetime and weaken the electric field in the i-region. The short-circuit current from Delta layer devices decreased more slowly and settled to higher values for narrower Delta layers. This is because the dangling bonds are isolated to the Delta layer and the lifetime of excess carriers generated in the a-Si:H remains unaffected. Annealing a-Si:H:T at 120°C for approximately one hour is shown to remove dangling bonds produced from the decay of bonded tritium.

Extending the ISC-GEM Global Earthquake Instrumental Catalogue

NASA Astrophysics Data System (ADS)

Di Giacomo, Domenico; Engdhal, Bob; Storchak, Dmitry; Villaseñor, Antonio; Harris, James

2015-04-01

After a 27-month project funded by the GEM Foundation (www.globalquakemodel.org), in January 2013 we released the ISC-GEM Global Instrumental Earthquake Catalogue (1900 2009) (www.isc.ac.uk/iscgem/index.php) as a special product to use for seismic hazard studies. The new catalogue was necessary as improved seismic hazard studies necessitate that earthquake catalogues are homogeneous (to the largest extent possible) over time in their fundamental parameters, such as location and magnitude. Due to time and resource limitation, the ISC-GEM catalogue (1900-2009) included earthquakes selected according to the following time-variable cut-off magnitudes: Ms=7.5 for earthquakes occurring before 1918; Ms=6.25 between 1918 and 1963; and Ms=5.5 from 1964 onwards. Because of the importance of having a reliable seismic input for seismic hazard studies, funding from GEM and two commercial companies in the US and UK allowed us to start working on the extension of the ISC-GEM catalogue both for earthquakes that occurred beyond 2009 and for earthquakes listed in the International Seismological Summary (ISS) which fell below the cut-off magnitude of 6.25. This extension is part of a four-year program that aims at including in the ISC-GEM catalogue large global earthquakes that occurred before the beginning of the ISC Bulletin in 1964. In this contribution we present the updated ISC GEM catalogue, which will include over 1000 more earthquakes that occurred in 2010 2011 and several hundreds more between 1950 and 1959. The catalogue extension between 1935 and 1949 is currently underway. The extension of the ISC-GEM catalogue will also be helpful for regional cross border seismic hazard studies as the ISC-GEM catalogue should be used as basis for cross-checking the consistency in location and magnitude of those earthquakes listed both in the ISC GEM global catalogue and regional catalogues.

Modulation of chloride, potassium and bicarbonate transport by muscarinic receptors in a human adenocarcinoma cell line.

PubMed

Holliday, N D; Cox, H M

1999-01-01

1. Short-circuit current (I(SC)) responses to carbachol (CCh) were investigated in Colony 1 epithelia, a subpopulation of the HCA-7 adenocarcinoma cell line. In Krebs-Henseleit (KH) buffer, CCh responses consisted of three I(SC) components: an unusual rapid decrease (the 10 s spike) followed by an upward spike at 30 s and a slower transient increase (the 2 min peak). This response was not potentiated by forskolin; rather, CCh inhibited cyclic AMP-stimulated I(SC). 2. In HCO3- free buffer, the decrease in forskolin-elevated I(SC) after CCh was reduced, although the interactions between CCh and forskolin remained at best additive rather than synergistic. When Cl- anions were replaced by gluconate, both Ca2+- and cyclic AMP-mediated electrogenic responses were significantly inhibited. 3. Basolateral Ba2+ (1-10 mM) and 293B (10 microM) selectively inhibited forskolin stimulation of I(SC), without altering the effects of CCh. Under Ba2+- or 293B-treated conditions, CCh responses were potentiated by pretreatment with forskolin. 4. Basolateral charybdotoxin (50 nM) significantly increased the size of the 10 s spike of CCh responses in both KH and HCO3- free medium, without affecting the 2 min peak. The enhanced 10 s spike was inhibited by prior addition of 5 mM apical Ba2+. Charybdotoxin did not affect forskolin responses. 5. In epithelial layers prestimulated with forskolin, the muscarinic antagonists atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, both at 100 nM) abolished subsequent 10 microM CCh responses. Following addition of p-fluoro hexahydro-sila-difenidol (pF-HHSiD, 10 microM) or pirenzepine (1 microM), qualitative changes in the CCh response time-profile also indicated a rightward shift of the agonist concentration-response curve; however, 1 microM gallamine had no effect. These results suggest that a single M3-like receptor subtype mediates the secretory response to CCh. 6. It is concluded that CCh and forskolin activate discrete populations of basolateral K+ channels gated by either Ca2+ or cyclic AMP, but that the Cl- permeability of the apical membrane may limit their combined effects on electrogenic Cl- secretion. In addition, CCh activates a Ba2+-sensitive apical K+ conductance leading to electrogenic K+ transport. Both agents may also modulate HCO3- secretion through a mechanism at least partially dependent on carbonic anhydrase.

Transfer of sulfur from IscS to IscU during Fe/S cluster assembly.

PubMed

Urbina, H D; Silberg, J J; Hoff, K G; Vickery, L E

2001-11-30

The cysteine desulfurase enzymes NifS and IscS provide sulfur for the biosynthesis of Fe/S proteins. NifU and IscU have been proposed to serve as template or scaffold proteins in the initial Fe/S cluster assembly events, but the mechanism of sulfur transfer from NifS or IscS to NifU or IscU has not been elucidated. We have employed [(35)S]cysteine radiotracer studies to monitor sulfur transfer between IscS and IscU from Escherichia coli and have used direct binding measurements to investigate interactions between the proteins. IscS catalyzed transfer of (35)S from [(35)S]cysteine to IscU in the absence of additional thiol reagents, suggesting that transfer can occur directly and without involvement of an intermediate carrier. Surface plasmon resonance studies and isothermal titration calorimetry measurements further revealed that IscU binds to IscS with high affinity (K(d) approximately 2 microm) in support of a direct transfer mechanism. Transfer was inhibited by treatment of IscU with iodoacetamide, and (35)S was released by reducing reagents, suggesting that transfer of persulfide sulfur occurs to cysteinyl groups of IscU. A deletion mutant of IscS lacking C-terminal residues 376-413 (IscSDelta376-413) displayed cysteine desulfurase activity similar to the full-length protein but exhibited lower binding affinity for IscU, decreased ability to transfer (35)S to IscU, and reduced activity in assays of Fe/S cluster assembly on IscU. The findings with IscSDelta376-413 provide additional support for a mechanism of sulfur transfer involving a direct interaction between IscS and IscU and suggest that the C-terminal region of IscS may be important for binding IscU.

Lateral MoS2 p-n junction formed by chemical doping for use in high-performance optoelectronics.

PubMed

Choi, Min Sup; Qu, Deshun; Lee, Daeyeong; Liu, Xiaochi; Watanabe, Kenji; Taniguchi, Takashi; Yoo, Won Jong

2014-09-23

This paper demonstrates a technique to form a lateral homogeneous 2D MoS2 p-n junction by partially stacking 2D h-BN as a mask to p-dope MoS2. The fabricated lateral MoS2 p-n junction with asymmetric electrodes of Pd and Cr/Au displayed a highly efficient photoresponse (maximum external quantum efficiency of ∼7000%, specific detectivity of ∼5 × 10(10) Jones, and light switching ratio of ∼10(3)) and ideal rectifying behavior. The enhanced photoresponse and generation of open-circuit voltage (VOC) and short-circuit current (ISC) were understood to originate from the formation of a p-n junction after chemical doping. Due to the high photoresponse at low VD and VG attributed to its built-in potential, our MoS2 p-n diode made progress toward the realization of low-power operating photodevices. Thus, this study suggests an effective way to form a lateral p-n junction by the h-BN hard masking technique and to improve the photoresponse of MoS2 by the chemical doping process.

A water-soluble hybrid material of single-walled carbon nanotubes with an amphiphilic poly(phenyleneethynylene): preparation, characterization, and photovoltaic properties.

PubMed

Mao, Jie; Liu, Qian; Lv, Xin; Liu, Zunfeng; Huang, Yi; Ma, Yanfeng; Chen, Yongsheng; Yin, Shougen

2007-08-01

A novel rigid linear polymer poly(phenyleneethynylene) (PPE) was synthesized and the polymer exhibits good solubility in both water and common organic solvents. The interaction at both ground and excited state between this polymer and single-walled carbon nanotubes (SWNTs) was studied and a water-soluble nano-scale PPE/SWNTs hybrid was fabricated, where the water solubility of SWNTs was enhanced to 1.8 mg/ml. Steady state fluorescence spectra and fluorescence lifetime decay measurements showed that the emissions from PPEs in this hybrid at excited state were efficiently quenched by the attachment of SWNTs, where an efficient energy transfer happened from PPEs to SWNTs as the electron acceptor. Using this hybrid as the active layer we fabricated a photovoltaic cell with the bulk heterojunction configuration, and it showed a photoresponse with an open circuit voltage (Voc) of 105 mV and a short circuit current density (Isc) of 28.7 microA/cm2 under standard AM 1.5 illumination (100 mW/cm2).

Emotions promote social interaction by synchronizing brain activity across individuals

PubMed Central

Nummenmaa, Lauri; Glerean, Enrico; Viinikainen, Mikko; Jääskeläinen, Iiro P.; Hari, Riitta; Sams, Mikko

2012-01-01

Sharing others’ emotional states may facilitate understanding their intentions and actions. Here we show that networks of brain areas “tick together” in participants who are viewing similar emotional events in a movie. Participants’ brain activity was measured with functional MRI while they watched movies depicting unpleasant, neutral, and pleasant emotions. After scanning, participants watched the movies again and continuously rated their experience of pleasantness–unpleasantness (i.e., valence) and of arousal–calmness. Pearson’s correlation coefficient was used to derive multisubject voxelwise similarity measures [intersubject correlations (ISCs)] of functional MRI data. Valence and arousal time series were used to predict the moment-to-moment ISCs computed using a 17-s moving average. During movie viewing, participants' brain activity was synchronized in lower- and higher-order sensory areas and in corticolimbic emotion circuits. Negative valence was associated with increased ISC in the emotion-processing network (thalamus, ventral striatum, insula) and in the default-mode network (precuneus, temporoparietal junction, medial prefrontal cortex, posterior superior temporal sulcus). High arousal was associated with increased ISC in the somatosensory cortices and visual and dorsal attention networks comprising the visual cortex, bilateral intraparietal sulci, and frontal eye fields. Seed-voxel–based correlation analysis confirmed that these sets of regions constitute dissociable, functional networks. We propose that negative valence synchronizes individuals’ brain areas supporting emotional sensations and understanding of another’s actions, whereas high arousal directs individuals’ attention to similar features of the environment. By enhancing the synchrony of brain activity across individuals, emotions may promote social interaction and facilitate interpersonal understanding. PMID:22623534

Intestinal bicarbonate secretion in Amphiuma measured by pH stat in vitro: relationship with metabolism and transport of sodium and chloride ions.

PubMed Central

Imon, M A; White, J F

1981-01-01

1. Isolated Amphiuma small intestine exposed on both surfaces to buffered or unbuffered media generated gradients of pH under short-circuited conditions consistent with secretion of HCO3(-). 2. When unbuffered mucosal medium was maintained at pH 7.4 by addition of acid, alkalinization of the mucosal medium occurred at a rate of 1-2 microequiv/hr cm2 under short-circuit conditions (Isc) and was reduced by anoxia, acetazolamide or removal of CO2. 3. The rate of HCO3(-) secretion (JHCO3(-)) was reduced at a mucosal pH above or below 7.4 and was proportional to serosal HCO3(-). 4. JHCO3(-) was reduced in Na+-free (choline) and Cl-free (SO4(2-) media and after exposure to the stilbene SITS. 5. The difference JHCO3(-)--Isc was consistent with net Cl- absorption. 6. The tissue resistance (Rt) was elevated upon exposure to serosal HCO3(-) and lowered by mucosal HCO3(-). 7. The intestinal mucosa exhibited carbonic anhydrase activity that was sensitive to ethoxazolamide. 8. It is concluded that HCO3(-) secretion is active, influenced by intracellular carbonic anhydrase activity and coupled to Cl- and possibly Na+ absorption. PMID:7310697

Intestinal bicarbonate secretion in Amphiuma measured by pH stat in vitro: relationship with metabolism and transport of sodium and chloride ions.

PubMed

Imon, M A; White, J F

1981-05-01

1. Isolated Amphiuma small intestine exposed on both surfaces to buffered or unbuffered media generated gradients of pH under short-circuited conditions consistent with secretion of HCO3(-). 2. When unbuffered mucosal medium was maintained at pH 7.4 by addition of acid, alkalinization of the mucosal medium occurred at a rate of 1-2 microequiv/hr cm2 under short-circuit conditions (Isc) and was reduced by anoxia, acetazolamide or removal of CO2. 3. The rate of HCO3(-) secretion (JHCO3(-)) was reduced at a mucosal pH above or below 7.4 and was proportional to serosal HCO3(-). 4. JHCO3(-) was reduced in Na+-free (choline) and Cl-free (SO4(2-) media and after exposure to the stilbene SITS. 5. The difference JHCO3(-)--Isc was consistent with net Cl- absorption. 6. The tissue resistance (Rt) was elevated upon exposure to serosal HCO3(-) and lowered by mucosal HCO3(-). 7. The intestinal mucosa exhibited carbonic anhydrase activity that was sensitive to ethoxazolamide. 8. It is concluded that HCO3(-) secretion is active, influenced by intracellular carbonic anhydrase activity and coupled to Cl- and possibly Na+ absorption.

Na+/H+ exchanger 3 inhibitor diminishes the amino-acid-enhanced transepithelial calcium transport across the rat duodenum.

PubMed

Thammayon, Nithipak; Wongdee, Kannikar; Lertsuwan, Kornkamon; Suntornsaratoon, Panan; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2017-04-01

Na + /H + exchanger (NHE)-3 is important for intestinal absorption of nutrients and minerals, including calcium. The previous investigations have shown that the intestinal calcium absorption is also dependent on luminal nutrients, but whether aliphatic amino acids and glucose, which are abundant in the luminal fluid during a meal, similarly enhance calcium transport remains elusive. Herein, we used the in vitro Ussing chamber technique to determine epithelial electrical parameters, i.e., potential difference (PD), short-circuit current (Isc), and transepithelial resistance, as well as 45 Ca flux in the rat duodenum directly exposed on the mucosal side to glucose or various amino acids. We found that mucosal glucose exposure led to the enhanced calcium transport, PD, and Isc, all of which were insensitive to NHE3 inhibitor (100 nM tenapanor). In the absence of mucosal glucose, several amino acids (12 mM in the mucosal side), i.e., alanine, isoleucine, leucine, proline, and hydroxyproline, markedly increased the duodenal calcium transport. An inhibitor for NHE3 exposure on the mucosal side completely abolished proline- and leucine-enhanced calcium transport, but not transepithelial transport of both amino acids themselves. In conclusion, glucose and certain amino acids in the mucosal side were potent stimulators of the duodenal calcium absorption, but only amino-acid-enhanced calcium transport was NHE3-dependent.

The adrenergic receptor subtypes present in frog (Rana esculenta) skin.

PubMed

Bellantuono, Vito; Cassano, Giuseppe; Lippe, Claudio

2008-08-01

Frog skin transports ions and water under hormonal control. In spite of the fundamental role played by adrenergic stimulation in maintaining the water balance of the organism, the receptor subtype(s) present in the skin have not been identified yet. We measured the increase in short-circuit current (ISC, an estimate of ion transport) induced by cirazoline, clonidine, xamoterol, formoterol, or BRL 37344, in order to verify the presence of alpha1, alpha2, beta1, beta2, or beta3 receptor subtypes, respectively. Only after treatment with formoterol, BRL 37344 and, to a lesser extent, cirazoline was measured a significant increase in ISC (57%, 33.2%, and 4.7%, respectively). The formoterol and BRL 37344 concentrations producing half-maximal effect (EC50) were 1.12 and 70.1 nM, respectively. Moreover, the formoterol effect was inhibited by treatment with ICI 118551 (antagonist of beta2 receptors) while SR 59230A (antagonist of beta3 receptors) had no effect; opposite findings were obtained when the BRL 37344 stimulation was investigated. Finally, by measuring the transepithelial fluxes of 22Na+ and 36Cl-, we demonstrated that Na+ absorption is increased by activation of beta2 and beta3 and is cAMP-sensitive, whereas the Cl- secretion is only increased by activation of beta2 receptors and is cAMP- and calmodulin-sensitive.

A pacemaker powered by an implantable biofuel cell operating under conditions mimicking the human blood circulatory system--battery not included.

PubMed

Southcott, Mark; MacVittie, Kevin; Halámek, Jan; Halámková, Lenka; Jemison, William D; Lobel, Robert; Katz, Evgeny

2013-05-07

Biocatalytic electrodes made of buckypaper were modified with PQQ-dependent glucose dehydrogenase on the anode and with laccase on the cathode and were assembled in a flow biofuel cell filled with serum solution mimicking the human blood circulatory system. The biofuel cell generated an open circuitry voltage, Voc, of ca. 470 mV and a short circuitry current, Isc, of ca. 5 mA (a current density of 0.83 mA cm(-2)). The power generated by the implantable biofuel cell was used to activate a pacemaker connected to the cell via a charge pump and a DC-DC converter interface circuit to adjust the voltage produced by the biofuel cell to the value required by the pacemaker. The voltage-current dependencies were analyzed for the biofuel cell connected to an Ohmic load and to the electronic loads composed of the interface circuit, or the power converter, and the pacemaker to study their operation. The correct pacemaker operation was confirmed using a medical device - an implantable loop recorder. Sustainable operation of the pacemaker was achieved with the system closely mimicking human physiological conditions using a single biofuel cell. This first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body.

Rebuilding the Bulletin of the International Seismological Centre (ISC)

NASA Astrophysics Data System (ADS)

Brown, L. N.; Lieser, K.; Harris, J.; Shumba, B.; Verney, R.; Storchak, D. A.; Di Giacomo, D.; Delahaye, E.

2017-12-01

Currently, the published International Seismological Centre (ISC) locations represent a mixture of algorithms (Reviser, ISCloc), velocity models (Jeffreys-Bullen, ak135), and phases (P-wave only, P&S, and finally all available ak135 phases starting in 2009). Thus, the primary goal of the Rebuild Project is to modernize the ISC bulletin by homogenizing our methods, procedures, and quality standards across more than four decades (1964-2010) of prior relocations at the ISC. We are also incorporating many new historical datasets from both temporary and permanent networks which were not available to us at the time of first relocation. Additionally, event magnitudes are determined in a more robust way - no longer will magnitudes be calculated using only one or two station readings, but instead recomputed with an alpha-trimmed median and requiring a minimum of three station readings. Employing the newest version of the ISC locator (ISCloc, Bondar & Storchak, 2011), all events in the bulletin are relocated using the ak135 global velocity model using all available phases. Then, using an internally developed and tested set of event quality criteria, our team of analysts works carefully with each event that has been flagged as requiring additional review. After each data month has been processed, an updated set of quality checks are run, and any further issues are consequently resolved. Our current predictions indicate that more than 150,000 flagged events will be reviewed by our analysts over the forty-six data-year period of the project. Once the Rebuild Project is finished, the ISC Bulletin will be the most complete and modern database of global seismicity freely available anywhere in the world. At present, we have finished work on sixteen years of historical data (1964-1979), and we show our preliminary results here.

Solar Cell Short Circuit Current Errors and Uncertainties During High Altitude Calibrations

NASA Technical Reports Server (NTRS)

Snyder, David D.

2012-01-01

High altitude balloon based facilities can make solar cell calibration measurements above 99.5% of the atmosphere to use for adjusting laboratory solar simulators. While close to on-orbit illumination, the small attenuation to the spectra may result in under measurements of solar cell parameters. Variations of stratospheric weather, may produce flight-to-flight measurement variations. To support the NSCAP effort, this work quantifies some of the effects on solar cell short circuit current (Isc) measurements on triple junction sub-cells. This work looks at several types of high altitude methods, direct high altitude meas urements near 120 kft, and lower stratospheric Langley plots from aircraft. It also looks at Langley extrapolation from altitudes above most of the ozone, for potential small balloon payloads. A convolution of the sub-cell spectral response with the standard solar spectrum modified by several absorption processes is used to determine the relative change from AMO, lscllsc(AMO). Rayleigh scattering, molecular scatterin g from uniformly mixed gases, Ozone, and water vapor, are included in this analysis. A range of atmosph eric pressures are examined, from 0. 05 to 0.25 Atm to cover the range of atmospheric altitudes where solar cell calibrations a reperformed. Generally these errors and uncertainties are less than 0.2%

Fabrication, Optimization and Characterization of Natural Dye Sensitized Solar Cell

PubMed Central

Ghann, William; Kang, Hyeonggon; Sheikh, Tajbik; Yadav, Sunil; Chavez-Gil, Tulio; Nesbitt, Fred; Uddin, Jamal

2017-01-01

The dyes extracted from pomegranate and berry fruits were successfully used in the fabrication of natural dye sensitized solar cells (NDSSC). The morphology, porosity, surface roughness, thickness, absorption and emission characteristics of the pomegranate dye sensitized photo-anode were studied using various analytical techniques including FESEM, EDS, TEM, AFM, FTIR, Raman, Fluorescence and Absorption Spectroscopy. Pomegranate dye extract has been shown to contain anthocyanin which is an excellent light harvesting pigment needed for the generation of charge carriers for the production of electricity. The solar cell’s photovoltic performance in terms of efficiency, voltage, and current was tested with a standard illumination of air-mass 1.5 global (AM 1.5 G) having an irradiance of 100 mW/cm2. After optimization of the photo-anode and counter electrode, a photoelectric conversion efficiency (η) of 2%, an open-circuit voltage (Voc) of 0.39 mV, and a short-circuit current density (Isc) of 12.2 mA/cm2 were obtained. Impedance determination showed a relatively low charge-transfer resistance (17.44 Ω) and a long lifetime, signifying a reduction in recombination losses. The relatively enhanced efficiency is attributable in part to the use of a highly concentrated pomegranate dye, graphite counter electrode and TiCl4 treatment of the photo-anode. PMID:28128369

Fabrication, Optimization and Characterization of Natural Dye Sensitized Solar Cell

NASA Astrophysics Data System (ADS)

Ghann, William; Kang, Hyeonggon; Sheikh, Tajbik; Yadav, Sunil; Chavez-Gil, Tulio; Nesbitt, Fred; Uddin, Jamal

2017-01-01

The dyes extracted from pomegranate and berry fruits were successfully used in the fabrication of natural dye sensitized solar cells (NDSSC). The morphology, porosity, surface roughness, thickness, absorption and emission characteristics of the pomegranate dye sensitized photo-anode were studied using various analytical techniques including FESEM, EDS, TEM, AFM, FTIR, Raman, Fluorescence and Absorption Spectroscopy. Pomegranate dye extract has been shown to contain anthocyanin which is an excellent light harvesting pigment needed for the generation of charge carriers for the production of electricity. The solar cell’s photovoltic performance in terms of efficiency, voltage, and current was tested with a standard illumination of air-mass 1.5 global (AM 1.5 G) having an irradiance of 100 mW/cm2. After optimization of the photo-anode and counter electrode, a photoelectric conversion efficiency (η) of 2%, an open-circuit voltage (Voc) of 0.39 mV, and a short-circuit current density (Isc) of 12.2 mA/cm2 were obtained. Impedance determination showed a relatively low charge-transfer resistance (17.44 Ω) and a long lifetime, signifying a reduction in recombination losses. The relatively enhanced efficiency is attributable in part to the use of a highly concentrated pomegranate dye, graphite counter electrode and TiCl4 treatment of the photo-anode.

Turning Escherichia coli into a Frataxin-Dependent Organism

PubMed Central

Roche, Béatrice; Agrebi, Rym; Huguenot, Allison; Ollagnier de Choudens, Sandrine; Barras, Frédéric; Py, Béatrice

2015-01-01

Fe-S bound proteins are ubiquitous and contribute to most basic cellular processes. A defect in the ISC components catalyzing Fe-S cluster biogenesis leads to drastic phenotypes in both eukaryotes and prokaryotes. In this context, the Frataxin protein (FXN) stands out as an exception. In eukaryotes, a defect in FXN results in severe defects in Fe-S cluster biogenesis, and in humans, this is associated with Friedreich’s ataxia, a neurodegenerative disease. In contrast, prokaryotes deficient in the FXN homolog CyaY are fully viable, despite the clear involvement of CyaY in ISC-catalyzed Fe-S cluster formation. The molecular basis of the differing importance in the contribution of FXN remains enigmatic. Here, we have demonstrated that a single mutation in the scaffold protein IscU rendered E. coli viability strictly dependent upon a functional CyaY. Remarkably, this mutation changed an Ile residue, conserved in prokaryotes at position 108, into a Met residue, conserved in eukaryotes. We found that in the double mutant IscUIM ΔcyaY, the ISC pathway was completely abolished, becoming equivalent to the ΔiscU deletion strain and recapitulating the drastic phenotype caused by FXN deletion in eukaryotes. Biochemical analyses of the “eukaryotic-like” IscUIM scaffold revealed that it exhibited a reduced capacity to form Fe-S clusters. Finally, bioinformatic studies of prokaryotic IscU proteins allowed us to trace back the source of FXN-dependency as it occurs in present-day eukaryotes. We propose an evolutionary scenario in which the current mitochondrial Isu proteins originated from the IscUIM version present in the ancestor of the Rickettsiae. Subsequent acquisition of SUF, the second Fe-S cluster biogenesis system, in bacteria, was accompanied by diminished contribution of CyaY in prokaryotic Fe-S cluster biogenesis, and increased tolerance to change in the amino acid present at the 108th position of the scaffold. PMID:25996492

Coordinate regulation of the Suf and Isc Fe-S cluster biogenesis pathways by IscR is essential for viability of Escherichia coli.

PubMed

Mettert, Erin L; Kiley, Patricia J

2014-12-01

Fe-S cluster biogenesis is essential for the viability of most organisms. In Escherichia coli, this process requires either the housekeeping Isc or the stress-induced Suf pathway. The global regulator IscR coordinates cluster synthesis by repressing transcription of the isc operon by [2Fe-2S]-IscR and activating expression of the suf operon. We show that either [2Fe-2S]-IscR or apo-IscR can activate suf, making expression sensitive to mainly IscR levels and not the cluster state, unlike isc expression. We also demonstrate that in the absence of isc, IscR-dependent suf activation is essential since strains lacking both the Isc pathway and IscR were not viable unless Suf was expressed ectopically. Similarly, removal of the IscR binding site in the sufA promoter also led to a requirement for isc. Furthermore, suf expression was increased in a Δisc mutant, presumably due to increased IscR levels in this mutant. This was surprising because the iron-dependent repressor Fur, whose higher-affinity binding at the sufA promoter should occlude IscR binding, showed only partial repression. In addition, Fur derepression was not sufficient for viability in the absence of IscR and the Isc pathway, highlighting the importance of direct IscR activation. Finally, a mutant lacking Fur and the Isc pathway increased suf expression to the highest observed levels and nearly restored [2Fe-2S]-IscR activity, providing a mechanism for regulating IscR activity under stress conditions. Together, these findings have enhanced our understanding of the homeostatic mechanism by which cells use one regulator, IscR, to differentially control Fe-S cluster biogenesis pathways to ensure viability. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Effect of entacapone on colon motility and ion transport in a rat model of Parkinson’s disease

PubMed Central

Li, Li-Sheng; Liu, Chen-Zhe; Xu, Jing-Dong; Zheng, Li-Fei; Feng, Xiao-Yan; Zhang, Yue; Zhu, Jin-Xia

2015-01-01

AIM: To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson’s disease (PD) rats. METHODS: Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. RESULTS: COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl- channel blocker diphenylamine-2, 2’-dicarboxylic acid, basolateral application of Na+-K+-2Cl-co-transporter antagonist bumetanide, elimination of Cl- from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl- flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. CONCLUSION: COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl- secretion in the PD rat. PMID:25834315

Effect of 5-hydroxytryptamine on duodenal mucosal bicarbonate secretion in mice.

PubMed

Tuo, Bi-Guang; Isenberg, Jon I

2003-09-01

5-hydroxytryptamine (5-HT) is an important neurotransmitter and intercellular messenger that modulates many gastrointestinal functions. Because little is known about the role of 5-HT in the regulation of duodenal bicarbonate secretion, we examined the role of 5-HT on duodenal bicarbonate secretion and define neural pathways involved in the actions of 5-HT. Duodenal mucosa from National Institutes of Health Swiss mice was stripped of seromuscular layers and mounted in Ussing chambers. The effect of 5-HT on duodenal bicarbonate secretion was determined by the pH stat technique. Acetylcholine (ACh) release from duodenal mucosa was assessed by preincubating the tissue with [(3)H] choline and measuring 5-HT-evoked release of tritium. 5-HT added to the serosal bath markedly stimulated duodenal bicarbonate secretion and short circuit current (Isc) in a dose-dependent manner (10(-7) mol/L to 10(-3) mol/L; P < 0.0001), whereas mucosally added 5-HT was without effect. 5-HT-stimulated bicarbonate secretion was independent of luminal Cl(-). Pretreatment with tetrodotoxin (TTX) (10(-6) mol/L) or atropine (10(-5) mol/L) markedly reduced 5-HT-stimulated duodenal bicarbonate secretion (by 60% and 65%, respectively; P < 0.001) and Isc (by 45% and 27%, respectively; P < 0.001 and P < 0.05). Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME) (10(-3) mol/L), propranolol (10(-5) mol/L), or phentolamine (10(-5) mol/L) did not significantly alter 5-HT-stimulated duodenal mucosal bicarbonate secretion or Isc. 5-HT concentration-dependently evoked ACh release from duodenal mucosal preparations (P < 0.0001). TTX markedly inhibited 5-HT-evoked ACh release (P < 0.001). 5-HT is a potent activator of duodenal mucosal bicarbonate secretion in mice. Duodenal bicarbonate secretion induced by 5-HT in vitro occurs principally via a cholinergic neural pathway.

2,4-Dichlorophenoxyacetic acid alters intracellular pH and ion transport in the outer mantle epithelium of the bivalve Anodonta cygnea.

PubMed

Alves, Marco G; Oliveira, Pedro F

2014-09-01

Bivalve molluscs, due to their sedentary mode of life and filter-feeding behavior, are very susceptible to pollutant bioaccumulation and used as sentinel organisms in the assessment of environment pollution. Herein we aimed to determine the in vivo, ex vivo and in vitro effects of 2,4-dichlorophenoxyacetic acid (2,4-D), a widely used herbicide, in Anodonta cygnea shell growth mechanisms. For that, we evaluated the effect of 2,4-D (100 μM) exposure on the transepithelial short-circuit current (Isc), potential (Vt) and conductance (Gt), as well as on OME ion transport systems and intracellular pH (pHi). In vivo exposure to 2,4-D caused an increase of 50% on the Isc generated by OME and ex vivo addition of that compound to the apical side of OME also induced an Isc increase. Furthermore, 2,4-D was able to cause a pHi increase in isolated cells of OME. Noteworthy, when 2,4-D was added following the exposure to specific inhibitors of several membrane transporters identified as responsible for pHi maintenance in these cells, no significant effect was observed on pHi except when the V-type ATPase inhibitor was used, indicating an overlap with the effect of 2,4-D. Thus, we concluded that 2,4-D is able of enhancing the activity of the V-ATPases present on the OME of A. cygnea and that this effect seems to be due to a direct stimulation of those H(+) transporters present on the apical portion of the membrane of OME cells, which are vital for shell maintenance and growth. This study allows us to better understand the molecular mechanisms behind 2,4-D toxicity and its deleterious effect in aquatic ecosystems, with particular emphasis on those involved in shell formation of bivalves. Copyright © 2014 Elsevier B.V. All rights reserved.

The ISC Seismic Event Bibliography

NASA Astrophysics Data System (ADS)

Di Giacomo, Domenico; Storchak, Dmitry

2015-04-01

The International Seismological Centre (ISC) is a not-for-profit organization operating in the UK for the last 50 years and producing the ISC Bulletin - the definitive worldwide summary of seismic events, both natural and anthropogenic - starting from the beginning of 20th century. Often researchers need to gather information related to specific seismic events for various reasons. To facilitate such task, in 2012 we set up a new database linking earthquakes and other seismic events in the ISC Bulletin to bibliographic records of scientific articles (mostly peer-reviewed journals) that describe those events. Such association allows users of the ISC Event Bibliography (www.isc.ac.uk/event_bibliography/index.php) to run searches for publications via a map-based web interface and, optionally, selecting scientific publications related to either specific events or events in the area of interest. Some of the greatest earthquakes were described in several hundreds of articles published over a period of few years. The journals included in our database are not limited to seismology but bring together a variety of fields in geosciences (e.g., engineering seismology, geodesy and remote sensing, tectonophysics, monitoring research, tsunami, geology, geochemistry, hydrogeology, atmospheric sciences, etc.) making this service useful in multidisciplinary studies. Usually papers dealing with large data set are not included (e.g., papers describing a seismic catalogue). Currently the ISC Event Bibliography includes over 17,000 individual publications from about 500 titles related to over 14,000 events that occurred in last 100+ years. The bibliographic records in the Event Bibliography start in the 1950s, and it is updated as new publications become available.

Role of IscX in Iron-Sulfur Cluster Biogenesis in Escherichia coli

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jin Hae; Bothe, Jameson R.; Frederick, Ronnie O.

2014-08-20

The Escherichia coli isc operon encodes key proteins involved in the biosynthesis of iron–sulfur (Fe–S) clusters. Whereas extensive studies of most ISC proteins have revealed their functional properties, the role of IscX (also dubbed YfhJ), a small acidic protein encoded by the last gene in the operon, has remained in question. Previous studies showed that IscX binds iron ions and interacts with the cysteine desulfurase (IscS) and the scaffold protein for cluster assembly (IscU), and it has been proposed that IscX functions either as an iron supplier or a regulator of Fe–S cluster biogenesis. We have used a combination ofmore » NMR spectroscopy, small-angle X-ray scattering (SAXS), chemical cross-linking, and enzymatic assays to enlarge our understanding of the interactions of IscX with iron ions, IscU, and IscS. We used chemical shift perturbation to identify the binding interfaces of IscX and IscU in their complex. NMR studies showed that Fe 2+ from added ferrous ammonium sulfate binds IscX much more avidly than does Fe 3+ from added ferric ammonium citrate and that Fe 2+ strengthens the interaction between IscX and IscU. We found that the addition of IscX to the IscU–IscS binary complex led to the formation of a ternary complex with reduced cysteine desulfurase activity, and we determined a low-resolution model for that complex from a combination of NMR and SAXS data. We postulate that the inhibition of cysteine desulfurase activity by IscX serves to reduce unproductive conversion of cysteine to alanine. By incorporating these new findings with results from prior studies, we propose a detailed mechanism for Fe–S cluster assembly in which IscX serves both as a donor of Fe 2+ and as a regulator of cysteine desulfurase activity.« less

Ischemic stroke in patients with cancer: is it different from usual strokes?

PubMed

Lee, Eun-Jae; Nah, Hyun-Wook; Kwon, Joo-Young; Kang, Dong-Wha; Kwon, Sun U; Kim, Jong S

2014-06-01

It remains unclear whether the characteristics of ischemic stroke in patients with cancer (ISC) differ from usual ischemic strokes (non-ISC). Although a small number of studies have been conducted to characterize ISC, the status of cancer has rarely been considered seriously. We aimed to investigate the features of ISC according to the status of cancer, and compare their characteristics with those of non-ISC. We assessed and classified 204 ISC patients into two groups: 104 with active (ISC-active) and 100 with inactive (ISC-inactive) cancer. For each ISC patient, two age- and gender-matched ischemic stroke patients without history of cancer were selected as non-ISC control subjects. We compared the clinical/laboratory data, stroke mechanisms, and diffusion weighted imaging (DWI) lesion patterns between ISC-active and non-ISC patients, and between ISC-inactive and non-ISC patients. ISC-active patients demonstrated higher C-reactive protein (CRP) and D-dimer, more frequent cryptogenic stroke and patterns of multiple DWI lesions (in bilateral anterior or in anterior and posterior circulations), and less prevalent conventional risk factors than non-ISC patients, while ISC-inactive patients revealed no such marked differences. Among ISC-active patients, both elevated CRP and D-dimer levels were associated with cryptogenic mechanism and multiple lesion patterns. Furthermore, ISC-active patients with cryptogenic strokes tended to have multiple lesion patterns and metastasis. ISC-active, but not ISC-inactive, is distinct in terms of risk factors, stroke mechanisms, and lesion patterns. Chronic inflammation and an activated coagulation system may contribute to the pathogenic mechanism of strokes, the extent of each depending on the activity and severity of cancer. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Large magneto-conductance and magneto-electroluminescence in exciplex-based organic light-emitting diodes at room temperature

NASA Astrophysics Data System (ADS)

Ling, Yongzhou; Lei, Yanlian; Zhang, Qiaoming; Chen, Lixiang; Song, Qunliang; Xiong, Zuhong

2015-11-01

In this work, we report on large magneto-conductance (MC) over 60% and magneto-electroluminescence (MEL) as high as 112% at room temperature in an exciplex-based organic light-emitting diode (OLED) with efficient reverse intersystem crossing (ISC). The large MC and MEL are individually confirmed by the current density-voltage characteristics and the electroluminescence spectra under various magnetic fields. We proposed that this type of magnetic field effect (MFE) is governed by the field-modulated reverse ISC between the singlet and triplet exciplex. The temperature-dependent MFEs reveal that the small activation energy of reverse ISC accounts for the large MFEs in the present exciplex-based OLEDs.

Understanding the role of dynamics in the iron sulfur cluster molecular machine.

PubMed

di Maio, Danilo; Chandramouli, Balasubramanian; Yan, Robert; Brancato, Giuseppe; Pastore, Annalisa

2017-01-01

The bacterial proteins IscS, IscU and CyaY, the bacterial orthologue of frataxin, play an essential role in the biological machine that assembles the prosthetic FeS cluster groups on proteins. They form functionally binary and ternary complexes both in vivo and in vitro. Yet, the mechanism by which they work remains unclear. We carried out extensive molecular dynamics simulations to understand the nature of their interactions and the role of dynamics starting from the crystal structure of a IscS-IscU complex and the experimentally-based model of a ternary IscS-IscU-CyaY complex and used nuclear magnetic resonance to experimentally test the interface. We show that, while being firmly anchored to IscS, IscU has a pivotal motion around the interface. Our results also describe how the catalytic loop of IscS can flip conformation to allow FeS cluster assembly. This motion is hampered in the ternary complex explaining its inhibitory properties in cluster formation. We conclude that the observed 'fluid' IscS-IscU interface provides the binary complex with a functional adaptability exploited in partner recognition and unravels the molecular determinants of the reported inhibitory action of CyaY in the IscS-IscU-CyaY complex explained in terms of the hampering effect on specific IscU-IscS movements. Our study provides the first mechanistic basis to explain how the IscS-IscU complex selects its binding partners and supports the inhibitory role of CyaY in the ternary complex. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

NREL Multiphysics Modeling Tools and ISC Device for Designing Safer Li-Ion Batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pesaran, Ahmad A.; Yang, Chuanbo

2016-03-24

The National Renewable Energy Laboratory has developed a portfolio of multiphysics modeling tools to aid battery designers better understand the response of lithium ion batteries to abusive conditions. We will discuss this portfolio, which includes coupled electrical, thermal, chemical, electrochemical, and mechanical modeling. These models can simulate the response of a cell to overheating, overcharge, mechanical deformation, nail penetration, and internal short circuit. Cell-to-cell thermal propagation modeling will be discussed.

TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification

PubMed Central

Kozmin, Stanislav G; Stepchenkova, Elena I; Schaaper, Roel M

2013-01-01

Lack of molybdenum cofactor (Moco) in Escherichia coli leads to hypersensitivity to the mutagenic and toxic effects of N-hydroxylated base analogs, such as 6-N-hydroxylaminopurine (HAP). This phenotype is due to the loss of two Moco-dependent activities, YcbX and YiiM, that are capable of reducing HAP to adenine. Here, we describe two novel HAP-sensitive mutants containing a defect in iscS or tusA (yhhP) gene. IscS is a major L-cysteine desulfurase involved in iron–sulfur cluster synthesis, thiamine synthesis, and tRNA thiomodification. TusA is a small sulfur-carrier protein that interacts with IscS. We show that both IscS and TusA operate within the Moco-dependent pathway. Like other Moco-deficient strains, tusA and iscS mutants are HAP sensitive and resistant to chlorate under anaerobic conditions. The base-analog sensitivity of iscS or tusA strains could be suppressed by supplying exogenous L-cysteine or sulfide or by an increase in endogenous sulfur donors (cysB constitutive mutant). The data suggest that iscS and tusA mutants have a defect in the mobilization of sulfur required for active YcbX/YiiM proteins as well as nitrate reductase, presumably due to lack of functional Moco. Overall, our data imply a novel and indispensable role of the IscS/TusA complex in the activity of several molybdoenzymes. PMID:23894086

Efficient perovskite/organic integrated solar cells with extended photoresponse to 930 nm and enhanced near-infrared external quantum efficiency of over 50.

PubMed

Guo, Qiang; Liu, Hao; Shi, Zhenzhen; Wang, Fuzhi; Zhou, Erjun; Bian, Xingming; Zhang, Bing; Alsaedi, Ahmed; Hayat, Tasawar; Tan, Zhan'ao

2018-02-15

Enhancing the light-harvesting activity is an effective way to improve the power conversion efficiency of solar cells. Although rapid enhancement in the PCE up to a value of 22.1% has been achieved for perovskite solar cells, only part of the sunlight, i.e., with wavelengths below 800-850 nm is utilized due to the limited bandgap of the perovskite materials, resulting in most of the near infrared light being wasted. To broaden the photoresponse of perovskite solar cells, we demonstrate an efficient perovskite/organic integrated solar cell containing both CH 3 NH 3 PbI 3 perovskite and PBDTTT-E-T:IEICO organic photoactive layers. By integrating a low band gap PBDTTT-E-T:IEICO active layer on a perovskite layer, the maximum wavelength for light harvesting of the ISC increased to 930 nm, sharply increasing the utilization of near infrared radiation. In addition, the external quantum efficiency of the integrated device exceeded 50% in the near infrared range. The MAPbI 3 /PBDTTT-E-T:IEICO ISCs show an enhanced short-circuit current density of over 24 mA cm -2 , which is the highest existing value among perovskite/organic integrated solar cells and much higher than the traditional MAPbI 3 based perovskite solar cells. The results reveal that a perovskite/organic integrated structure is a promising strategy to extend and enhance sunlight utilization for perovskite solar cells.

Mechanisms underlying the inhibitory effect of the feed contaminant deoxynivalenol on glucose absorption in broiler chickens.

PubMed

Awad, W A; Ghareeb, K; Zentek, J

2014-10-01

Deoxynivalenol (DON), a major contaminant of cereals and grains, is of public health concern worldwide and has been shown to reduce the electrogenic transport of glucose. However, the full effects of Fusarium mycotoxins on nutrient absorption are still not clear. The aim of this study was to investigate whether decreased nutrient absorption was due to specific effects on transporter trafficking in the intestine and whether inhibition of phosphoinositol-3-kinase (PI-3-kinase) affected the electrogenic jejunal transport of glucose. Jejunal mucosa of 6-week-old broiler chickens were mounted in Ussing chambers and treated with DON, wortmannin (a specific inhibitor of PI-3-kinase), DON + wortmannin, phlorizin and cytochalasin B. DON was found to decrease the short-circuit current (Isc) after glucose addition. A similar decline in Isc after glucose addition was observed following pre-application of wortmannin, or phlorizin (Na(+)/glucose co-transporter, SGLT1 inhibitor). The results indicate that DON decreased glucose absorption in the absence of wortmannin or phlorizin but had no additional effect on glucose absorption in their presence. Glucose transport was not affected by cytochalasin B (facilitative glucose transporter, GLUT2 inhibitor). The study provides evidence that the suppressive effect of DON on the electrogenic transport of glucose may be due to an inhibitory activity of the PI3 kinase pathway and intestinal SGLT1. Furthermore, the effect of cytochalasin B on glucose transport in chicken tissues differs from that in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Specification of regional intestinal stem cell identity during Drosophila metamorphosis.

PubMed

Driver, Ian; Ohlstein, Benjamin

2014-05-01

In the adult Drosophila midgut the bone morphogenetic protein (BMP) signaling pathway is required to specify and maintain the acid-secreting region of the midgut known as the copper cell region (CCR). BMP signaling is also involved in the modulation of intestinal stem cell (ISC) proliferation in response to injury. How ISCs are able to respond to the same signaling pathway in a regionally different manner is currently unknown. Here, we show that dual use of the BMP signaling pathway in the midgut is possible because BMP signals are only capable of transforming ISC and enterocyte identity during a defined window of metamorphosis. ISC heterogeneity is established prior to adulthood and then maintained in cooperation with regional signals from surrounding tissue. Our data provide a conceptual framework for how other tissues maintained by regional stem cells might be patterned and establishes the pupal and adult midgut as a novel genetic platform for identifying genes necessary for regional stem cell specification and maintenance.

Activation of adenosine low-affinity A3 receptors inhibits the enteric short interplexus neural circuit triggered by histamine.

PubMed

Bozarov, Andrey; Wang, Yu-Zhong; Yu, Jun Ge; Wunderlich, Jacqueline; Hassanain, Hamdy H; Alhaj, Mazin; Cooke, Helen J; Grants, Iveta; Ren, Tianhua; Christofi, Fievos L

2009-12-01

We tested the novel hypothesis that endogenous adenosine (eADO) activates low-affinity A3 receptors in a model of neurogenic diarrhea in the guinea pig colon. Dimaprit activation of H2 receptors was used to trigger a cyclic coordinated response of contraction and Cl(-) secretion. Contraction-relaxation was monitored by sonomicrometry (via intracrystal distance) simultaneously with short-circuit current (I(sc), Cl(-) secretion). The short interplexus reflex coordinated response was attenuated or abolished by antagonists at H2 (cimetidine), 5-hydroxytryptamine 4 receptor (RS39604), neurokinin-1 receptor (GR82334), or nicotinic (mecamylamine) receptors. The A1 agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) abolished coordinated responses, and A1 antagonists could restore normal responses. A1-selective antagonists alone [8-cyclopentyltheophylline (CPT), 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX), or 8-cyclopentyl-N(3)-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-xanthine (FSCPX)] caused a concentration-dependent augmentation of crypt cell secretion or contraction and acted at nanomolar concentrations. The A3 agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) abolished coordinated responses and the A3 antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191) could restore and further augment responses. The IB-MECA effect was resistant to knockdown of adenosine A1 receptor with the irreversible antagonist FSCPX; the IC(50) for IB-MECA was 0.8 microM. MRS1191 alone could augment or unmask coordinated responses to dimaprit, and IB-MECA suppressed them. MRS1191 augmented distension-evoked reflex I(sc) responses. Adenosine deaminase mimicked actions of adenosine receptor antagonists. A3 receptor immunoreactivity was differentially expressed in enteric neurons of different parts of colon. After tetrodotoxin, IB-MECA caused circular muscle relaxation. The data support the novel concept that eADO acts at low-affinity A3 receptors in addition to high-affinity A1 receptors to suppress coordinated responses triggered by immune-histamine H2 receptor activation. The short interplexus circuit activated by histamine involves adenosine, acetylcholine, substance P, and serotonin. We postulate that A3 receptor modulation may occur in gut inflammatory diseases or allergic responses involving mast cell and histamine release.

Activation of adenosine low-affinity A3 receptors inhibits the enteric short interplexus neural circuit triggered by histamine

PubMed Central

Bozarov, Andrey; Wang, Yu-Zhong; Yu, Jun Ge; Wunderlich, Jacqueline; Hassanain, Hamdy H.; Alhaj, Mazin; Cooke, Helen J.; Grants, Iveta; Ren, Tianhua

2009-01-01

We tested the novel hypothesis that endogenous adenosine (eADO) activates low-affinity A3 receptors in a model of neurogenic diarrhea in the guinea pig colon. Dimaprit activation of H2 receptors was used to trigger a cyclic coordinated response of contraction and Cl− secretion. Contraction-relaxation was monitored by sonomicrometry (via intracrystal distance) simultaneously with short-circuit current (Isc, Cl− secretion). The short interplexus reflex coordinated response was attenuated or abolished by antagonists at H2 (cimetidine), 5-hydroxytryptamine 4 receptor (RS39604), neurokinin-1 receptor (GR82334), or nicotinic (mecamylamine) receptors. The A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA) abolished coordinated responses, and A1 antagonists could restore normal responses. A1-selective antagonists alone [8-cyclopentyltheophylline (CPT), 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX), or 8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-xanthine (FSCPX)] caused a concentration-dependent augmentation of crypt cell secretion or contraction and acted at nanomolar concentrations. The A3 agonist N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA) abolished coordinated responses and the A3 antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS1191) could restore and further augment responses. The IB-MECA effect was resistant to knockdown of adenosine A1 receptor with the irreversible antagonist FSCPX; the IC50 for IB-MECA was 0.8 μM. MRS1191 alone could augment or unmask coordinated responses to dimaprit, and IB-MECA suppressed them. MRS1191 augmented distension-evoked reflex Isc responses. Adenosine deaminase mimicked actions of adenosine receptor antagonists. A3 receptor immunoreactivity was differentially expressed in enteric neurons of different parts of colon. After tetrodotoxin, IB-MECA caused circular muscle relaxation. The data support the novel concept that eADO acts at low-affinity A3 receptors in addition to high-affinity A1 receptors to suppress coordinated responses triggered by immune-histamine H2 receptor activation. The short interplexus circuit activated by histamine involves adenosine, acetylcholine, substance P, and serotonin. We postulate that A3 receptor modulation may occur in gut inflammatory diseases or allergic responses involving mast cell and histamine release. PMID:19808660

ISC-EHB: Reconstruction of a robust earthquake dataset

NASA Astrophysics Data System (ADS)

Weston, J.; Engdahl, E. R.; Harris, J.; Di Giacomo, D.; Storchak, D. A.

2018-04-01

The EHB Bulletin of hypocentres and associated travel-time residuals was originally developed with procedures described by Engdahl, Van der Hilst and Buland (1998) and currently ends in 2008. It is a widely used seismological dataset, which is now expanded and reconstructed, partly by exploiting updated procedures at the International Seismological Centre (ISC), to produce the ISC-EHB. The reconstruction begins in the modern period (2000-2013) to which new and more rigorous procedures for event selection, data preparation, processing, and relocation are applied. The selection criteria minimise the location bias produced by unmodelled 3D Earth structure, resulting in events that are relatively well located in any given region. Depths of the selected events are significantly improved by a more comprehensive review of near station and secondary phase travel-time residuals based on ISC data, especially for the depth phases pP, pwP and sP, as well as by a rigorous review of the event depths in subduction zone cross sections. The resulting cross sections and associated maps are shown to provide details of seismicity in subduction zones in much greater detail than previously achievable. The new ISC-EHB dataset will be especially useful for global seismicity studies and high-frequency regional and global tomographic inversions.

The innovation scorecard for continuous improvement applied to translational science.

PubMed

Kotarba, Joseph A; Wooten, Kevin

2017-10-01

This paper reports on the baseline stage of a qualitative evaluation of the application of the Innovative Scorecard (ISC) to the Clinical and Translational Science Award (CTSA) at the University of Texas Medical Branch (UTMB) at Galveston. The ISC is adopted from the established Balanced Scorecard system for strategic planning and performance management. In formulating the evaluation, we focused on the organizational identity literature. The initial evaluation consisted of a series of semi-structured interviews with 22 participants of the ISC Boot Camp conducted in July 2015. The logic of grounded theory pointed to the clustering of perceptions of the ISC around respondents' occupational locations at UTMB. Administrators anticipate the expansion of planning activities to include a wider range of participants under the current CTSA award period (2015-2020) than under our first CTSA approval period (2009-2014). A common viewpoint among the senior scientists was that the scientific value of their work will continue to speak for itself without requiring the language of business. Junior scientists looked forward to the ISC's emphasis on increasingly horizontal leadership that will give them more access to and more control over their work and resources. Postdocs and senior staff welcomed increased involvement in the total research process at UTMB. The report concludes with strategies for future follow-up.

100+ years of instrumental seismology: the example of the ISC-GEM Global Earthquake Instrumental Catalogue

NASA Astrophysics Data System (ADS)

Storchak, Dmitry; Di Giacomo, Domenico

2015-04-01

Systematic seismological observations of earthquakes using seismic instruments on a global scale began more than 100 years ago. Since then seismologists made many discoveries about the Earth interior and the physics of the earthquakes, also thanks to major developments in the seismic instrumentation deployed around the world. Besides, since the establishment of the first global networks (Milne and Jesuit networks), seismologists around the world stored and exchanged the results of routine observations (e.g., picking of arrival times, amplitude-period measurements, etc.) or more sophisticated analyses (e.g., moment tensor inversion) in seismological bulletins/catalogues. With a project funded by the GEM Foundation (www.globalquakemodel.org), the ISC and the Team of International Experts released a new global earthquake catalogue, the ISC-GEM Global Instrumental Earthquake Catalogue (1900 2009) (www.isc.ac.uk/iscgem/index.php), which, differently from previous global seismic catalogues, has the unique feature of covering the entire period of instrumental seismology with locations and magnitude re-assessed using modern approaches for the global earthquakes selected for processing (in the current version approximately 21,000). During the 110 years covered by the ISC-GEM catalogue many seismological developments occurred in terms of instrumentation, seismological practice and knowledge of the physics of the earthquakes. In this contribution we give a brief overview of the major milestones characterizing the last 100+ years of instrumental seismology that were relevant for the production of the ISC-GEM catalogue and the major challenges we faced to obtain a catalogue as homogenous as possible.

The InSAR Scientific Computing Environment (ISCE): A Python Framework for Earth Science

NASA Astrophysics Data System (ADS)

Rosen, P. A.; Gurrola, E. M.; Agram, P. S.; Sacco, G. F.; Lavalle, M.

2015-12-01

The InSAR Scientific Computing Environment (ISCE, funded by NASA ESTO) provides a modern computing framework for geodetic image processing of InSAR data from a diverse array of radar satellites and aircraft. ISCE is both a modular, flexible, and extensible framework for building software components and applications as well as a toolbox of applications for processing raw or focused InSAR and Polarimetric InSAR data. The ISCE framework contains object-oriented Python components layered to construct Python InSAR components that manage legacy Fortran/C InSAR programs. Components are independently configurable in a layered manner to provide maximum control. Polymorphism is used to define a workflow in terms of abstract facilities for each processing step that are realized by specific components at run-time. This enables a single workflow to work on either raw or focused data from all sensors. ISCE can serve as the core of a production center to process Level-0 radar data to Level-3 products, but is amenable to interactive processing approaches that allow scientists to experiment with data to explore new ways of doing science with InSAR data. The NASA-ISRO SAR (NISAR) Mission will deliver data of unprecedented quantity and quality, making possible global-scale studies in climate research, natural hazards, and Earth's ecosystems. ISCE is planned as the foundational element in processing NISAR data, enabling a new class of analyses that take greater advantage of the long time and large spatial scales of these new data. NISAR will be but one mission in a constellation of radar satellites in the future delivering such data. ISCE currently supports all publicly available strip map mode space-borne SAR data since ERS and is expected to include support for upcoming missions. ISCE has been incorporated into two prototype cloud-based systems that have demonstrated its elasticity in addressing larger data processing problems in a "production" context and its ability to be controlled by individual science users on the cloud for large data problems. ISCE has been downloaded by over 200 users by a license for WinSAR members through the Unavco.org website. Others may apply directly to JPL for a license at download.jpl.nasa.gov.

Cpe1786/IscR of Clostridium perfringens represses expression of genes involved in Fe-S cluster biogenesis.

PubMed

André, Gaelle; Haudecoeur, Elise; Courtois, Emmanuelle; Monot, Marc; Dupuy, Bruno; Rodionov, Dmitry A; Martin-Verstraete, Isabelle

2017-05-01

Cpe1786 of Clostridium perfringens is an Rrf2-type regulator containing the three-cysteine residues coordinating a Fe-S in IscR, the repressor controlling Fe-S homeostasis in enterobacteria. The cpe1786 gene formed an operon with iscSU involved in Fe-S biogenesis and tmrU. This operon was transcribed from a σ A -dependent promoter. We showed that in the heterologous host Bacillus subtilis, Cpe1786, renamed IscR Cp , negatively controlled its own transcription. We constructed an iscR mutant in C. perfringens. We then compared the expression profile of strain 13 and of the iscR mutant. IscR Cp controlled expression of genes involved in Fe-S biogenesis, in amino acid or sugar metabolisms, in fermentation pathways and in host compound utilization. We then demonstrated, using a ChIP-PCR experiment, that IscR Cp interacted with its promoter region in vivo in C. perfringens and with the promoter of cpe2093 encoding an amino acid ABC transporter. We utilized a comparative genomic approach to infer a candidate IscR binding motif and reconstruct IscR regulons in clostridia. We showed that point mutations in the conserved motif of 29 bp identified upstream of iscR decreased the cysteine-dependent repression of iscR mediated by IscR Cp . Copyright © 2016 Institut Pasteur. All rights reserved.

Low free drug concentration prevents inhibition of F508del CFTR functional expression by the potentiator VX-770 (ivacaftor).

PubMed

Matthes, Elizabeth; Goepp, Julie; Carlile, Graeme W; Luo, Yishan; Dejgaard, Kurt; Billet, Arnaud; Robert, Renaud; Thomas, David Y; Hanrahan, John W

2016-02-01

The most common cystic fibrosis (CF) mutation F508del inhibits the gating and surface expression of CFTR, a plasma membrane anion channel. Optimal pharmacotherapies will probably require both a 'potentiator' to increase channel open probability and a 'corrector' that improves folding and trafficking of the mutant protein and its stability at the cell surface. Interaction between CF drugs has been reported but remains poorly understood. CF bronchial epithelial cells were exposed to the corrector VX-809 (lumacaftor) and potentiator VX-770 (ivacaftor) individually or in combination. Functional expression of CFTR was assayed as the forskolin-stimulated short-circuit current (Isc ) across airway epithelial monolayers expressing F508del CFTR. The potentiated Isc response during forskolin stimulation was increased sixfold after pretreatment with VX-809 alone and reached ~11% that measured across non-CF monolayers. VX-770 (100 nM) and genistein (50 μM) caused similar levels of potentiation, which were not additive and were abolished by the CFTR inhibitor CFTRinh -172. The unbound fraction of VX-770 in plasma was 0.13 ± 0.04%, which together with previous measurements in patients given 250 mg p.o. twice daily, suggests a peak free plasma concentration of 1.5-8.5 nM. Chronic exposure to high VX-770 concentrations (>1 μM) inhibited functional correction by VX-809 but not in the presence of physiological protein levels (20-40 mg·mL(-1) ). Chronic exposure to a low concentration of VX-770 (100 nM) together with VX-809 (1 μM) also did not reduce the forskolin-stimulated Isc , relative to cells chronically exposed to VX-809 alone, provided it was assayed acutely using the same, clinically relevant concentration of potentiator. Chronic exposure to clinically relevant concentrations of VX-770 did not reduce F508del CFTR function. Therapeutic benefit of VX-770 + VX-809 (Orkambi) is probably limited by the efficacy of VX-809 rather than by inhibition by VX-770. © 2015 The British Pharmacological Society.

Comparison of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Ciliary Beat Frequency Activation by the CFTR Modulators Genistein, VRT-532, and UCCF-152 in Primary Sinonasal Epithelial Cultures

PubMed Central

Conger, Bryant T.; Zhang, Shaoyan; Skinner, Daniel; Hicks, Stephen B.; Sorscher, Eric J.; Rowe, Steven M.; Woodworth, Bradford A.

2014-01-01

IMPORTANCE Pharmacologic activation of mucociliary clearance (MCC) represents an emerging therapeutic strategy for patients with chronic rhinosinusitis, even in the absence of congenital mutations of the CFTR gene. Drug discovery efforts have identified small molecules that activate the cystic fibrosis transmembrane conductance regulator (CFTR), including potentiators under development for treatment of cystic fibrosis. OBJECTIVE To evaluate the properties of CFTR modulators and their effects on ciliary beat frequency (CBF) in human sinonasal epithelium (HSNE). DESIGN Primary HSNE cultures (wild type and F508del/F508del) were used to compare stimulation of CFTR-mediated Cl− conductance and CBF by the CFTR modulators genistein, VRT-532, and UCCF-152. MAIN OUTCOMES AND MEASURES Increase in CFTR-dependent anion transport and CBF. RESULTS HSNE cultures were analyzed using pharmacologic manipulation of ion transport (change in short-circuit current [ΔISC]) and high-speed digital imaging (CBF). Activation of CFTR-dependent anion transport was significantly different among agonists (P < .001), with genistein exerting the greatest effect (mean [SD] ΔISC, genistein, 23.1 [1.8] µA/cm2 > VRT-532, 8.1 [1.0] µA/cm2 > UCCF-152, 3.4 [1.4] µA/cm2 > control, 0.7 [0.2] µA/cm2; Tukey-Kramer P < .05) in the absence of forskolin. Genistein and UCCF-152 augmented CBF (under submerged conditions) significantly better (Tukey-Kramer P < .05) than cells treated with VRT-532 or dimethyl sulfoxide vehicle control (mean [SD] fold change over baseline, genistein, 1.63 [0.06]; UCCF-152, 1.56 [0.06]; VRT-532, 1.38 [0.08]; control, 1.27 [0.02]). Activation of CBF was blunted in F508del/F508del HSNE cultures. CONCLUSIONS AND RELEVANCE The degree of CBF stimulation was not dependent on the magnitude of Cl− secretion, suggesting that different mechanisms of action may underlie MCC activation by these small molecule potentiators. Agents that activate both CFTR-dependent ISC and CBF are particularly attractive as therapeutics because they may address 2 independent pathways that contribute to deficient MCC in chronic rhinosinusitis. PMID:23949358

Comparison of cystic fibrosis transmembrane conductance regulator (CFTR) and ciliary beat frequency activation by the CFTR Modulators Genistein, VRT-532, and UCCF-152 in primary sinonasal epithelial cultures.

PubMed

Conger, Bryant T; Zhang, Shaoyan; Skinner, Daniel; Hicks, Stephen B; Sorscher, Eric J; Rowe, Steven M; Woodworth, Bradford A

2013-08-01

Pharmacologic activation of mucociliary clearance (MCC) represents an emerging therapeutic strategy for patients with chronic rhinosinusitis, even in the absence of congenital mutations of the CFTR gene. Drug discovery efforts have identified small molecules that activate the cystic fibrosis transmembrane conductance regulator (CFTR), including potentiators under development for treatment of cystic fibrosis. To evaluate the properties of CFTR modulators and their effects on ciliary beat frequency (CBF) in human sinonasal epithelium (HSNE). Primary HSNE cultures (wild type and F508del/F508del) were used to compare stimulation of CFTR-mediated Cl- conductance and CBF by the CFTR modulators genistein, VRT-532, and UCCF-152. Increase in CFTR-dependent anion transport and CBF. HSNE cultures were analyzed using pharmacologic manipulation of ion transport (change in short-circuit current [∆ISC]) and high-speed digital imaging (CBF). Activation of CFTR-dependent anion transport was significantly different among agonists (P < .001), with genistein exerting the greatest effect (mean [SD] ∆ISC, genistein, 23.1 [1.8] μA/cm2² > VRT-532, 8.1 [1.0] μA/cm² > UCCF-152, 3.4 [1.4] μA/cm² > control, 0.7 [0.2] μA/cm²; Tukey-Kramer P < .05) in the absence of forskolin. Genistein and UCCF-152 augmented CBF (under submerged conditions) significantly better (Tukey-Kramer P < .05) than cells treated with VRT-532 or dimethyl sulfoxide vehicle control (mean [SD] fold change over baseline, genistein, 1.63 [0.06]; UCCF-152, 1.56 [0.06]; VRT-532, 1.38 [0.08]; control, 1.27 [0.02]). Activation of CBF was blunted in F508del/F508del HSNE cultures. The degree of CBF stimulation was not dependent on the magnitude of Cl- secretion, suggesting that different mechanisms of action may underlie MCC activation by these small molecule potentiators. Agents that activate both CFTR-dependent ISC and CBF are particularly attractive as therapeutics because they may address 2 independent pathways that contribute to deficient MCC in chronic rhinosinusitis.

ISC-GEM: Global Instrumental Earthquake Catalogue (1900-2009), III. Re-computed MS and mb, proxy MW, final magnitude composition and completeness assessment

NASA Astrophysics Data System (ADS)

Di Giacomo, Domenico; Bondár, István; Storchak, Dmitry A.; Engdahl, E. Robert; Bormann, Peter; Harris, James

2015-02-01

This paper outlines the re-computation and compilation of the magnitudes now contained in the final ISC-GEM Reference Global Instrumental Earthquake Catalogue (1900-2009). The catalogue is available via the ISC website (http://www.isc.ac.uk/iscgem/). The available re-computed MS and mb provided an ideal basis for deriving new conversion relationships to moment magnitude MW. Therefore, rather than using previously published regression models, we derived new empirical relationships using both generalized orthogonal linear and exponential non-linear models to obtain MW proxies from MS and mb. The new models were tested against true values of MW, and the newly derived exponential models were then preferred to the linear ones in computing MW proxies. For the final magnitude composition of the ISC-GEM catalogue, we preferred directly measured MW values as published by the Global CMT project for the period 1976-2009 (plus intermediate-depth earthquakes between 1962 and 1975). In addition, over 1000 publications have been examined to obtain direct seismic moment M0 and, therefore, also MW estimates for 967 large earthquakes during 1900-1978 (Lee and Engdahl, 2015) by various alternative methods to the current GCMT procedure. In all other instances we computed MW proxy values by converting our re-computed MS and mb values into MW, using the newly derived non-linear regression models. The final magnitude composition is an improvement in terms of magnitude homogeneity compared to previous catalogues. The magnitude completeness is not homogeneous over the 110 years covered by the ISC-GEM catalogue. Therefore, seismicity rate estimates may be strongly affected without a careful time window selection. In particular, the ISC-GEM catalogue appears to be complete down to MW 5.6 starting from 1964, whereas for the early instrumental period the completeness varies from ∼7.5 to 6.2. Further time and resources would be necessary to homogenize the magnitude of completeness over the entire catalogue length.

Towards a defined ECM and small molecule based monolayer culture system for the expansion of mouse and human intestinal stem cells.

PubMed

Tong, Zhixiang; Martyn, Keir; Yang, Andy; Yin, Xiaolei; Mead, Benjamin E; Joshi, Nitin; Sherman, Nicholas E; Langer, Robert S; Karp, Jeffrey M

2018-02-01

Current ISC culture systems face significant challenges such as animal-derived or undefined matrix compositions, batch-to-batch variability (e.g. Matrigel-based organoid culture), and complexity of assaying cell aggregates such as organoids which renders the research and clinical translation of ISCs challenging. Here, through screening for suitable ECM components, we report a defined, collagen based monolayer culture system that supports the growth of mouse and human intestinal epithelial cells (IECs) enriched for an Lgr5 + population comparable or higher to the levels found in a standard Matrigel-based organoid culture. The system, referred to as the Bolstering Lgr5 Transformational (BLT) Sandwich culture, comprises a collagen IV-coated porous substrate and a collagen I gel overlay which sandwich an IEC monolayer in between. The distinct collagen cues synergistically regulate IEC attachment, proliferation, and Lgr5 expression through maximizing the engagement of distinct cell surface adhesion receptors (i.e. integrin α2β1, integrin β4) and cell polarity. Further, we apply our BLT Sandwich system to identify that the addition of a bone morphogenetic protein (BMP) receptor inhibitor (LDN-193189) improves the expansion of Lgr5-GFP + cells from mouse small intestinal crypts by nearly 2.5-fold. Notably, the BLT Sandwich culture is capable of expanding human-derived IECs with higher LGR5 mRNA levels than conventional Matrigel culture, providing superior expansion of human LGR5 + ISCs. Considering the key roles Lgr5 + ISCs play in intestinal epithelial homeostasis and regeneration, we envision that our BLT Sandwich culture system holds great potential for understanding and manipulating ISC biology in vitro (e.g. for modeling ISC-mediated gut diseases) or for expanding a large number of ISCs for clinical utility (e.g. for stem cell therapy). Copyright © 2017 Elsevier Ltd. All rights reserved.

Spectroscopic and functional characterization of iron-sulfur cluster-bound forms of Azotobacter vinelandii (Nif)IscA.

PubMed

Mapolelo, Daphne T; Zhang, Bo; Naik, Sunil G; Huynh, Boi Hanh; Johnson, Michael K

2012-10-16

The mechanism of [4Fe-4S] cluster assembly on A-type Fe-S cluster assembly proteins, in general, and the specific role of (Nif)IscA in the maturation of nitrogen fixation proteins are currently unknown. To address these questions, in vitro spectroscopic studies (UV-visible absorption/CD, resonance Raman and Mössbauer) have been used to investigate the mechanism of [4Fe-4S] cluster assembly on Azotobacter vinelandii(Nif)IscA, and the ability of (Nif)IscA to accept clusters from NifU and to donate clusters to the apo form of the nitrogenase Fe-protein. The results show that (Nif)IscA can rapidly and reversibly cycle between forms containing one [2Fe-2S](2+) and one [4Fe-4S](2+) cluster per homodimer via DTT-induced two-electron reductive coupling of two [2Fe-2S](2+) clusters and O(2)-induced [4Fe-4S](2+) oxidative cleavage. This unique type of cluster interconversion in response to cellular redox status and oxygen levels is likely to be important for the specific role of A-type proteins in the maturation of [4Fe-4S] cluster-containing proteins under aerobic growth or oxidative stress conditions. Only the [4Fe-4S](2+)-(Nif)IscA was competent for rapid activation of apo-nitrogenase Fe protein under anaerobic conditions. Apo-(Nif)IscA was shown to accept clusters from [4Fe-4S] cluster-bound NifU via rapid intact cluster transfer, indicating a potential role as a cluster carrier for delivery of clusters assembled on NifU. Overall the results support the proposal that A-type proteins can function as carrier proteins for clusters assembled on U-type proteins and suggest that they are likely to supply [2Fe-2S] clusters rather than [4Fe-4S] for the maturation of [4Fe-4S] cluster-containing proteins under aerobic or oxidative stress growth conditions.

Spectroscopic and Functional Characterization of Iron-Sulfur Cluster-Bound Forms of Azotobacter vinelandii NifIscA†

PubMed Central

Mapolelo, Daphne T.; Zhang, Bo; Naik, Sunil G.; Huynh, Boi Hanh; Johnson, Michael K.

2012-01-01

The mechanism of [4Fe-4S] cluster assembly on A-type Fe-S cluster assembly proteins, in general, and the specific role of NifIscA in the maturation of nitrogen fixation proteins are currently unknown. To address these questions, in vitro spectroscopic studies (UV–visible absorption/CD, resonance Raman and Mössbauer) have been used to investigate the mechanism of [4Fe-4S] cluster assembly on Azotobacter vinelandii NifIscA, and the ability of NifIscA to accept clusters from NifU and to donate clusters to the apo form of the nitrogenase Fe-protein. The results show that NifIscA can rapidly and reversibly cycle between forms containing one [2Fe-2S]2+ and one [4Fe-4S]2+ cluster per homodimer via DTT-induced two-electron reductive coupling of two [2Fe-2S]2+ clusters and O2-induced [4Fe-4S]2+ oxidative cleavage. This unique type of cluster interconversion in response to cellular redox status and oxygen levels is likely to be important for the specific role of A-type proteins in the maturation of [4Fe-4S] cluster-containing proteins under aerobic growth or oxidative stress conditions. Only the [4Fe-4S]2+-NifIscA was competent for rapid activation of apo-nitrogenase Fe protein under anaerobic conditions. Apo-NifIscA was shown to accept clusters from [4Fe-4S] cluster-bound NifU via rapid intact cluster transfer, indicating a potential role as a cluster carrier for delivery of clusters assembled on NifU. Overall the results support the proposal that A-type proteins can function as carrier proteins for clusters assembled on U-type proteins and suggest that they are likely to supply [2Fe-2S] clusters rather than [4Fe-4S] for the maturation of [4Fe-4S] cluster-containing proteins under aerobic or oxidative stress growth conditions. PMID:23003323

Liposomal Bupivacaine Mixture Has Similar Pain Relief and Significantly Fewer Complications at Less Cost Compared to Indwelling Interscalene Catheter in Total Shoulder Arthroplasty.

PubMed

Weller, William J; Azzam, Michael G; Smith, Richard A; Azar, Frederick M; Throckmorton, Thomas W

2017-11-01

The efficacy and costs of indwelling interscalene catheter (ISC) and liposomal bupivacaine (LBC), with and without adjunctive medications, in patients with primary shoulder arthroplasty are a source of current debate. In 214 arthroplasties, 156 patients had ISC and 58 had LBC injections that were mixed with morphine, ketorolac, and 0.5% bupivacaine with epinephrine. Charts were reviewed for visual analog scale pain scores, oral morphine equivalent (OME) usage, major complications, and costs. Visual analog scale scores were not significantly different at 24 hours or at 2, 6, and 12 weeks. Average OME consumption at 24 hours was significantly more with LBC, but was not significantly different at 12 weeks. Relative risk of a major complication was nearly 4 times higher with ISC than with LBC. The average cost for the LBC mixture was $289.04, and for ISC, including equipment and anesthesia fees, was $1559.42. The intraoperative LBC mixture provided equivalent pain relief with significantly fewer major complications and at markedly lower cost than ISC. LBC required almost twice as much OME to attain the same level of pain relief at 24 hours, but there was no significant difference in the cumulative amount of outpatient narcotic use. Copyright © 2017 Elsevier Inc. All rights reserved.

Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients with Intestinal Failure.

PubMed

Hong, Sung Noh; Dunn, James C Y; Stelzner, Matthias; Martín, Martín G

2017-02-01

Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure. Organoids have demonstrated the capacity to proliferate indefinitely and differentiate into the various cellular lineages of the gut. Genome-editing techniques, including the overexpression of the corrected form of the defective gene, or the use of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to selectively correct the monogenic disease-causing variant within the stem cell, make autologous ISC transplantation a feasible approach. However, numerous techniques still need to be further optimized, including more robust ex vivo ISC expansion, native ISC ablation, and engraftment protocols. Large-animal models can to be used to develop such techniques and protocols and to establish the safety of autologous ISC transplantation because outcomes in such models can be extrapolated more readily to humans. Stem Cells Translational Medicine 2017;6:666-676. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Ion transport in proximal colon of the rat. Sodium depletion stimulates neutral sodium chloride absorption.

PubMed Central

Foster, E S; Budinger, M E; Hayslett, J P; Binder, H J

1986-01-01

The model of sodium and chloride transport proposed for the colon is based on studies performed in the distal segment and tacitly assumes that ion transport is similar throughout the colon. In rat distal colon, neutral sodium-chloride absorption accounts for the major fraction of overall sodium absorption and aldosterone stimulates electrogenic, amiloride-sensitive sodium absorption. Since we have demonstrated qualitative differences in potassium transport in proximal and distal segments of rat colon, unidirectional 22Na and 36Cl fluxes were performed under short-circuit conditions across isolated proximal colon of control and sodium-depleted rats with secondary hyperaldosteronism. In the control group, net sodium absorption (JNanet) (7.4 +/- 0.5 mu eq/h . cm2) was greater than Isc (1.4 +/- 0.1 mu eq/h . cm2), and JClnet was 0 in Ringer solution. Residual flux (JR) was -5.2 +/- 0.5 mu eq/h . cm2 consistent with hydrogen ion secretion suggesting that neutral sodium absorption may represent sodium-hydrogen exchange. 1 mM mucosal amiloride, which inhibits sodium-hydrogen exchange in other epithelia, produced comparable decreases in JNanet and JR (4.1 +/- 0.6 and 3.2 +/- 0.6 mu eq/h . cm2, respectively) without a parallel fall in Isc. Sodium depletion stimulated JNanet, JClnet, and Isc by 7.0 +/- 1.4, 6.3 +/- 1.9, and 0.8 +/- 0.2 mu eq/h . cm2, respectively, and 1 mM amiloride markedly inhibited JNanet and JClnet by 6.0 +/- 1.1 and 4.0 +/- 1.6 mu eq/h . cm2, respectively, with only a minimal reduction in Isc. Conclusions: the predominant neutral sodium-absorptive mechanism in proximal colon is sodium-hydrogen exchange. Sodium depletion stimulates electroneutral chloride-dependent sodium absorption (most likely as a result of increasing sodium-hydrogen and chloride-bicarbonate exchanges), not electrogenic chloride-independent sodium transport. The model of ion transport in the proximal colon is distinct from that of the distal colon. PMID:2418060

A new method for drug transport studies on pig nasal mucosa using a horizontal Ussing chamber.

PubMed

Osth, Karin; Gråsjö, Johan; Björk, Erik

2002-05-01

The horizontal Ussing chamber method described here allows performance of transport studies on pig nasal respiratory mucosa under conditions simulating reality in that it mimics the air-mucosa interface. The transport of testosterone and mannitol through pig nasal mucosa in the horizontal Ussing chamber was investigated using both liquid and air mucosal interfaces. There were no significant differences in either the bioelectrical parameters (transmucosal electrical resistance, R, potential difference, PD, and short circuit current, I(sc)) or the apparent permeability (P(app)) of the mucosa to testosterone or mannitol between the liquid and air interface experiments. The histological study showed that the epithelial cell layer tolerates exposure to the air interface well. The P(app) equation was developed to correct for substance binding to the wall of the receiver chamber. The mean values +/- SD of R, PD, and I(sc) for the mucosae in the study were 75.0 +/- 28.0 Omegacm(2), (-4.53) +/- 3.46 mV and 58.6 +/- 28.8 microA/cm(2), respectively. The corrected P(app) for testosterone with and without the mucosal air interface were 9.82. 10(-6) +/- 11.41. 10(-6) cm/s and 32.24. 10(-6) +/- 31.12. 10(-6) cm/s, respectively. The P(app) values for mannitol with and without the air interface were 2.26. 10(-6) +/- 1.42. 10(-6) cm/s and 3.12. 10(-6) +/- 1.72. 10(-6) cm/s, respectively. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association

Chinese mitten crab (Eriocheir sinensis) iron-sulphur cluster assembly protein 2 (EsIscA2) is differentially regulated after immune and oxidative stress challenges.

PubMed

Zhang, Peng; Liu, Yu; Wang, Min; Dong, Miren; Liu, Zhaoqun; Jia, Zhihao; Wang, Weilin; Zhang, Anguo; Wang, Lingling; Song, Linsheng

2018-07-01

Iron-sulphur clusters (ISCs), one of the oldest and most versatile cofactors of proteins, are involved in catalysis reactions, electron transport reactions, regulation processes as well as sensing of ambient conditions. Iron-sulphur cluster assembly protein (IscA) is a scaffold protein member of ISC formation system, which plays a significant role in the assembly and maturation process of ISC proteins. In the present study, the cDNA sequence of iron-sulphur cluster assembly protein 2 (designated as EsIscA2) was cloned from Eriocheir sinensis. The open reading frame (ORF) of EsIscA2 was of 507 bp, encoding a peptide of 168 amino acids with a typically conserved Fe-S domain. A tetrameric form was predicated by the SWISS-MODEL prediction algorithm, and three conserved cysteine residues (Cys-93, Cys-158, Cys-160) from each IscA monomer were predicted to form a 'cysteine pocket'. The deduced amino acid sequence of EsIscA2 shared over 50% similarity with that of other IscAs. EsIscA2 was clustered with IscA2 proteins from invertebrates and vertebrates, indicating that the protein was highly conservative in the evolution. rEsIscA2 exhibited a high iron binding affinity in the concentration ranging from 2 to 200 μM. EsIscA2 transcripts were detected in all the tested tissues including gonad, hemocytes, gill, muscle, heart, hepatopancreas and eyestalk, and EsIscA2 protein was detected in the mitochondria of hemocytes. The highest mRNA expression level of EsIscA2 was detected in muscle and hepatopancreas, which was about 34.66-fold (p < 0.05) and 27.07-fold (p < 0.05) of that in hemocytes, respectively. After Aeromonas hydrophila and lipopolysaccharide (LPS) stimulations, the mRNA expression of EsIscA2 in hemocytes was down-regulated and reached the lowest level at 24 h (0.31-fold, p < 0.05) and 48 h (0.29-fold, p < 0.05) compared to control group, respectively. And the expression of EsIscA2 mRNA in hepatopancreas was repressed from 6 h to 48 h post stimulation (p < 0.05). When the primary cultured crab hemocytes were incubated with different concentrations of H 2 O 2 for 15 min, the expression level of EsIscA2 mRNA was significantly repressed to the 0.34-0.44-fold of that in the control group. After A. hydrophila stimulation, the mRNA expression of EsGrx2 was up-regulated at 3 h (3.22-fold compared to control group, p < 0.05) and reached the peak at 12 h (4.88-fold, p < 0.05). All these results suggested that EsIscA2 had iron-binding capabilities as observed in IscA proteins from other organisms, supporting the role of EsIscA2 as a mitochondrial iron donor for ISC synthesis in Chinese mitten crab. Its differential mRNA expression after immune and oxidative stress challenges suggested the adaptations of ISC synthesis rates to these stress conditions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Towards routine determination of focal mechanisms obtained from first motion P-wave arrivals

NASA Astrophysics Data System (ADS)

Lentas, K.

2018-03-01

The Bulletin of the International Seismological Centre (ISC) contains information on earthquake mechanisms collected from many different sources including national and global agencies, resulting in a satisfactory coverage over a wide magnitude range (M ˜2-9). Nevertheless, there are still a vast number of earthquakes with no reported source mechanisms especially for magnitudes up to 5. This study investigates the possibility of calculating earthquake focal mechanisms in a routine and systematic way based on P-wave first motion polarities. Any available parametric data in the ISC database is being used, as well as auto-picked polarities from waveform data up to teleseismic epicentral distances (90°) for stations that are not reported to the ISC. The determination of the earthquake mechanisms is carried out with a modified version of the HASH algorithm that is compatible with a wide range of epicentral distances and takes into account the ellipsoids defined by the ISC location errors, and the Earth's structure uncertainties. Initially, benchmark tests for a set of ISC reviewed earthquakes (mb > 4.5) are carried out and the HASH mechanism classification scheme is used to define the mechanism quality. Focal mechanisms of quality A, B and C with an azimuthal gap up to 90° compare well to the benchmark mechanisms. Nevertheless, the majority of the obtained mechanisms fall into class D as a result of limited polarity data from stations in local/regional epicentral distances. Specifically, the computation of the minimum rotation angle between the obtained mechanisms and the benchmarks, reveals that 41 per cent of the examined earthquakes show rotation angles up to 35°. Finally, the current technique is applied to a small set of earthquakes from the reviewed ISC bulletin where 62 earthquakes, with no previously reported source mechanisms, are successfully obtained.

Investigating the Effect of Titanium Dioxide (TiO2) Pollution on the Performance of the Mono-crystalline Solar Module

NASA Astrophysics Data System (ADS)

Ahmed Darwish, Zeki; Sopian, K.; Kazem, Hussein A.; Alghoul, M. A.; Alawadhi, Hussain

2017-11-01

This paper presents a study of titanium oxide TiO2 as one of the components of dust pollution affecting the PV performance. This pollutant can be found in various quantities in different locations around the world. The production of energy by different types of photovoltaic systems is very sensitive and depends on various environmental factors. Dust is one of the main contributing factors, yet the type of the dust is often neglected when studying the behaviour of the solar panel. In this experimental work we have studied the performance of the monocrystalline solar module as affected by the density of TiO2. The reduction of the PV module power caused by titanium dioxide under various mass densities was investigated. The results showed that the TiO2 has a significant effect on the PV output power. The dust density varied between 0-125 g.m-2. The corresponding reduction of the PV output power increased from 0 to 86.7%. This is based on various influencing parameters such as: short circuit current (Isc), maximum current (Im), open circuit voltage (Voc), maximum voltage (Vm), maximum power (Pm) and efficiency (E). Two functions are proposed as a mathematical model in order to explain this behaviour, namely the exponential and Fourier functions. The coefficients of all general models are valid for this type of dust with a density value ranging from 0-125 g.m-2.

Effect of indium on photovoltaic property of n-ZnO/p-Si heterojunction device prepared using solution-synthesized ZnO nanowire film

NASA Astrophysics Data System (ADS)

Kathalingam, Adaikalam; Kim, Hyun-Seok; Park, Hyung-Moo; Valanarasu, Santiyagu; Mahalingam, Thaiyan

2015-01-01

Preparation of n-ZnO/p-Si heterostructures using solution-synthesized ZnO nanowire films and their photovoltaic characterization is reported. The solution-grown ZnO nanowire film is characterized using scanning electron microscope, electron dispersive x-ray, and optical absorption studies. Electrical and photovoltaic properties of the fabricated heterostructures are studied using e-beam-evaporated aluminum as metal contacts. In order to use transparent contact and to simultaneously collect the photogenerated carriers, sandwich-type solar cells were fabricated using ZnO nanorod films grown on p-silicon and indium tin oxide (ITO) coated glass as ITO/n-ZnO NR/p-Si. The electrical properties of these structures are analyzed from current-voltage (I-V) characteristics. ZnO nanowire film thickness-dependent photovoltaic properties are also studied. Indium metal was also deposited over the ZnO nanowires and its effects on the photovoltaic response of the devices were studied. The results demonstrated that all the samples exhibit a strong rectifying behavior indicating the diode nature of the devices. The sandwich-type ITO/n-ZnO NR/p-Si solar cells exhibit improved photovoltaic performance over the Al-metal-coated n-ZnO/p-Si structures. The indium deposition is found to show enhancement in photovoltaic behavior with a maximum open-circuit voltage (Voc) of 0.3 V and short-circuit current (Isc) of 70×10-6 A under ultraviolet light excitation.

The photovoltaic impact of atomic layer deposited TiO2 interfacial layer on Si-based photodiodes

NASA Astrophysics Data System (ADS)

Karabulut, Abdulkerim; Orak, İkram; Türüt, Abdulmecit

2018-06-01

In present work, photocurrent, current-voltage (I-V) and capacitance/conductance-voltage-frequency (C/G-V-f) measurements were analyzed for the photodiode and diode parameters of Al/TiO2/p-Si structure. The TiO2 thin film structure was deposited on p-Si by using atomic layer deposition technique (ALD) and its thickness was about 10 nm. The surface morphology of TiO2 coated on p-Si structure was observed via atomic force microscope (AFM). Barrier height (Φb) and ideality factor (n) values of device were found to be 0.80 eV, 0.70 eV, 0.56 eV and 1.04, 2.24, 10.27 under dark, 10 and 100 mW/cm2, respectively. Some photodiodes parameters such as fill factor (FF), power efficiency (%η), open circuit voltage (Voc), short circuit current (Isc) were obtained from I-V measurement under different light intensity. FF and η were accounted 49.2, 39,0 and 0.05, 0.45 under 10 and 100 mW/cm2 light power intensity, respectively. C-2-V graph was plotted from C-V-f measurements and zero bias voltage (V0), donor concentration (Nd), Fermi energy (EF), barrier height (Φb) and maximum electric field (Em) were determined from C-2-V data for different frequencies. The electrical and photocurrent values demonstrated that it can be used for photodiode, photo detector and photo sensing applications.

In vivo [Fe-S] cluster acquisition by IscR and NsrR, two stress regulators in Escherichia coli.

PubMed

Vinella, Daniel; Loiseau, Laurent; Ollagnier de Choudens, Sandrine; Fontecave, Marc; Barras, Frédéric

2013-02-01

The multi-proteins Isc and Suf systems catalyse the biogenesis of [Fe-S] proteins. Here we investigate how NsrR and IscR, transcriptional regulators that sense NO and [Fe-S] homeostasis, acquire their [Fe-S] clusters under both normal and iron limitation conditions. Clusters directed at the apo-NsrR and apo-IscR proteins are built on either of the two scaffolds, IscU or SufB. However, differences arise in [Fe-S] delivery steps. In the case of NsrR, scaffolds deliver clusters to either one of the two ATCs, IscA and SufA, and, subsequently, to the 'non-Isc non-Suf' ATC, ErpA. Nevertheless, a high level of SufA can bypass the requirement for ErpA. In the case of IscR, several routes occur. One does not include assistance of any ATC. Others implicate ATCs IscA or ErpA, but, surprisingly, SufA was totally absent from any IscR maturation pathways. Both IscR and NsrR have the intrinsic capacity to sense iron limitation. However, NsrR appeared to be efficiently matured by Isc and Suf, thereby preventing NsrR to act as a physiologically relevant iron sensor. This work emphasizes that different maturation pathways arise as a function of the apo-target considered, possibly in relation with the type of cluster, [2Fe-2S] versus [4Fe-4S], it binds. © 2013 Blackwell Publishing Ltd.

A Sulfurtransferase Is Essential for Activity of Formate Dehydrogenases in Escherichia coli*

PubMed Central

Thomé, Rémi; Gust, Alexander; Toci, René; Mendel, Ralf; Bittner, Florian; Magalon, Axel; Walburger, Anne

2012-01-01

l-Cysteine desulfurases provide sulfur to several metabolic pathways in the form of persulfides on specific cysteine residues of an acceptor protein for the eventual incorporation of sulfur into an end product. IscS is one of the three Escherichia coli l-cysteine desulfurases. It interacts with FdhD, a protein essential for the activity of formate dehydrogenases (FDHs), which are iron/molybdenum/selenium-containing enzymes. Here, we address the role played by this interaction in the activity of FDH-H (FdhF) in E. coli. The interaction of IscS with FdhD results in a sulfur transfer between IscS and FdhD in the form of persulfides. Substitution of the strictly conserved residue Cys-121 of FdhD impairs both sulfur transfer from IscS to FdhD and FdhF activity. Furthermore, inactive FdhF produced in the absence of FdhD contains both metal centers, albeit the molybdenum cofactor is at a reduced level. Finally, FdhF activity is sulfur-dependent, as it shows reversible sensitivity to cyanide treatment. Conclusively, FdhD is a sulfurtransferase between IscS and FdhF and is thereby essential to yield FDH activity. PMID:22194618

Controlled expression of nif and isc iron-sulfur protein maturation components reveals target specificity and limited functional replacement between the two systems.

PubMed

Dos Santos, Patricia C; Johnson, Deborah C; Ragle, Brook E; Unciuleac, Mihaela-Carmen; Dean, Dennis R

2007-04-01

The nitrogen-fixing organism Azotobacter vinelandii contains at least two systems that catalyze formation of [Fe-S] clusters. One of these systems is encoded by nif genes, whose products supply [Fe-S] clusters required for maturation of nitrogenase. The other system is encoded by isc genes, whose products are required for maturation of [Fe-S] proteins that participate in general metabolic processes. The two systems are similar in that they include an enzyme for the mobilization of sulfur (NifS or IscS) and an assembly scaffold (NifU or IscU) upon which [Fe-S] clusters are formed. Normal cellular levels of the Nif system, which supplies [Fe-S] clusters for the maturation of nitrogenase, cannot also supply [Fe-S] clusters for the maturation of other cellular [Fe-S] proteins. Conversely, when produced at the normal physiological levels, the Isc system cannot supply [Fe-S] clusters for the maturation of nitrogenase. In the present work we found that such target specificity for IscU can be overcome by elevated production of NifU. We also found that NifU, when expressed at normal levels, is able to partially replace the function of IscU if cells are cultured under low-oxygen-availability conditions. In contrast to the situation with IscU, we could not establish conditions in which the function of IscS could be replaced by NifS. We also found that elevated expression of the Isc components, as a result of deletion of the regulatory iscR gene, improved the capacity for nitrogen-fixing growth of strains deficient in either NifU or NifS.

The Inertial Stellar Compass (ISC): A Multifunction, Low Power, Attitude Determination Technology Breakthrough

NASA Technical Reports Server (NTRS)

Bauer, Frank H. (Technical Monitor); Dennehy, Neil; Gambino, Joel; Maynard, Andrew; Brady, T.; Buckley, S.; Zinchuk, J.

2003-01-01

The Inertial Stellar Compass (ISC) is a miniature, low power, stellar inertial attitude determination system with an accuracy of better than 0.1 degree (1 sigma) in three axes. The ISC consumes only 3.5 Watts of power and is contained in a 2.5 kg package. With its embedded on-board processor, the ISC provides attitude quaternion information and has Lost-in-Space (LIS) initialization capability. The attitude accuracy and LIS capability are provided by combining a wide field of view Active Pixel Sensor (APS) star camera and Micro- ElectroMechanical System (MEMS) inertial sensor information in an integrated sensor system. The performance and small form factor make the ISC a useful sensor for a wide range of missions. In particular, the ISC represents an enabling, fully integrated, micro-satellite attitude determination system. Other applications include using the ISC as a single sensor solution for attitude determination on medium performance spacecraft and as a bolt on independent safe-hold sensor or coarse acquisition sensor for many other spacecraft. NASA's New Millennium Program (NMP) has selected the ISC technology for a Space Technology 6 (ST6) flight validation experiment scheduled for 2004. NMP missions, such a s ST6, are intended to validate advanced technologies that have not flown in space in order to reduce the risk associated with their infusion into future NASA missions. This paper describes the design, operation, and performance of the ISC and outlines the technology validation plan. A number of mission applications for the ISC technology are highlighted, both for the baseline ST6 ISC configuration and more ambitious applications where ISC hardware and software modifications would be required. These applications demonstrate the wide range of Space and Earth Science missions that would benefit from infusion of the ISC technology.

Impact of diet-induced obesity on intestinal stem cells: hyperproliferation but impaired intrinsic function that requires insulin/IGF1.

PubMed

Mah, Amanda T; Van Landeghem, Laurianne; Gavin, Hannah E; Magness, Scott T; Lund, P Kay

2014-09-01

Nutrient intake regulates intestinal epithelial mass and crypt proliferation. Recent findings in model organisms and rodents indicate nutrient restriction impacts intestinal stem cells (ISC). Little is known about the impact of diet-induced obesity (DIO), a model of excess nutrient intake on ISC. We used a Sox9-EGFP reporter mouse to test the hypothesis that an adaptive response to DIO or associated hyperinsulinemia involves expansion and hyperproliferation of ISC. The Sox9-EGFP reporter mouse allows study and isolation of ISC, progenitors, and differentiated lineages based on different Sox9-EGFP expression levels. Sox9-EGFP mice were fed a high-fat diet for 20 weeks to induce DIO and compared with littermates fed low-fat rodent chow. Histology, fluorescence activated cell sorting, and mRNA analyses measured impact of DIO on jejunal crypt-villus morphometry, numbers, and proliferation of different Sox9-EGFP cell populations and gene expression. An in vitro culture assay directly assessed functional capacity of isolated ISC. DIO mice exhibited significant increases in body weight, plasma glucose, insulin, and insulin-like growth factor 1 (IGF1) levels and intestinal Igf1 mRNA. DIO mice had increased villus height and crypt density but decreased intestinal length and decreased numbers of Paneth and goblet cells. In vivo, DIO resulted in a selective expansion of Sox9-EGFP(Low) ISC and percentage of ISC in S-phase. ISC expansion significantly correlated with plasma insulin levels. In vitro, isolated ISC from DIO mice formed fewer enteroids in standard 3D Matrigel culture compared to controls, indicating impaired ISC function. This decreased enteroid formation in isolated ISC from DIO mice was rescued by exogenous insulin, IGF1, or both. We conclude that DIO induces specific increases in ISC and ISC hyperproliferation in vivo. However, isolated ISC from DIO mice have impaired intrinsic survival and growth in vitro that can be rescued by exogenous insulin or IGF1.

Interaction of the iron–sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichia coli

PubMed Central

Hoff, Kevin G.; Silberg, Jonathan J.; Vickery, Larry E.

2000-01-01

The iscU gene in bacteria is located in a gene cluster encoding proteins implicated in iron–sulfur cluster assembly and an hsc70-type (heat shock cognate) molecular chaperone system, iscSUA-hscBA. To investigate possible interactions between these systems, we have overproduced and purified the IscU protein from Escherichia coli and have studied its interactions with the hscA and hscB gene products Hsc66 and Hsc20. IscU and its iron–sulfur complex (IscU–Fe/S) stimulated the basal steady-state ATPase activity of Hsc66 weakly in the absence of Hsc20 but, in the presence of Hsc20, increased the ATPase activity up to 480-fold. Hsc20 also decreased the apparent Km for IscU stimulation of Hsc66 ATPase activity, and surface plasmon resonance studies revealed that Hsc20 enhances binding of IscU to Hsc66. Surface plasmon resonance and isothermal titration calorimetry further showed that IscU and Hsc20 form a complex, and Hsc20 may thereby aid in the targeting of IscU to Hsc66. These results establish a direct and specific role for the Hsc66/Hsc20 chaperone system in functioning with isc gene components for the assembly of iron–sulfur cluster proteins. PMID:10869428

Hsc66 substrate specificity is directed toward a discrete region of the iron-sulfur cluster template protein IscU.

PubMed

Hoff, Kevin G; Ta, Dennis T; Tapley, Tim L; Silberg, Jonathan J; Vickery, Larry E

2002-07-26

Hsc66 and Hsc20 comprise a specialized chaperone system important for the assembly of iron-sulfur clusters in Escherchia coli. Only a single substrate, the Fe/S template protein IscU, has been identified for the Hsc66/Hsc20 system, but the mechanism by which Hsc66 selectively binds IscU is unknown. We have investigated Hsc66 substrate specificity using phage display and a peptide array of IscU. Screening of a heptameric peptide phage display library revealed that Hsc66 prefers peptides with a centrally located Pro-Pro motif. Using a cellulose-bound peptide array of IscU we determined that Hsc66 interacts specifically with a region (residues 99-103, LPPVK) that is invariant among all IscU family members. A synthetic peptide (ELPPVKIHC) corresponding to IscU residues 98-106 behaves in a similar manner to native IscU, stimulating the ATPase activity of Hsc66 with similar affinity as IscU, preventing Hsc66 suppression of bovine rhodanese aggregation, and interacting with the peptide-binding domain of Hsc66. Unlike native IscU, however, the synthetic peptide is not bound by Hsc20 and does not synergistically stimulate Hsc66 ATPase activity with Hsc20. Our results indicate that Hsc66 and Hsc20 recognize distinct regions of IscU and further suggest that Hsc66 will not bind LPPVK motifs with high affinity in vivo unless they are in the context of native IscU and can be directed to Hsc66 by Hsc20.

Analysis of the interaction of an electron beam with a solar cell. III - The effect of spacial variations of the number density of recombination centers on SEM measurements

NASA Technical Reports Server (NTRS)

Von Roos, O.

1979-01-01

By means of an exactly soluble model the short circuit current generated by a scanning electron microscope in a P-N junction has been determined in cases where the trap density is inhomogeneous. The diffusion length for minority carriers becomes then dependent on the spacial coordinates. It is shown that in this case the dependence of the Isc on characteristic parameters as cell thickness, distance of the beam excitation spot from ohmic contacts, etc., becomes very intricate. This fact precludes the determination of the local diffusion length in the usual manner. Although the model is somewhat simplified in order to make it amenable to exact solutions, it is nevertheless realistic enough to lead to the conclusion that SEM measurements of bulk transport parameters in inhomogeneous semiconductor material are impractical since they may lead to serious errors in the interpretation of the data by customary means.

Histamine stimulates chloride secretion in omeprazole-inhibited frog gastric mucosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGreevy, J.; Barton, R.; Housinger, T.

1986-03-05

Omeprazole (OME) stops hydrogen ion (H) secretion in the histamine (HIST)-stimulated gastric mucosa while the chloride (Cl) which had accompanied the H continues to be pumped into the lumen. This finding suggests that the Cl pump is independent of the H/K ATP-ase driven H pump. To test this hypothesis, 16 Ussing-chambered frog mucosas were exposed to OME prior to HIST stimulation. If the Cl pump is independent, HIST should stimulate Cl secretion in the OME-inhibited mucosa. A 1 hr control (CON) interval preceded exposure to OME (10/sup -4/M) in the nutrient solution. Potential difference (PD), short-circuit current (Isc), resistance (R),more » H flux (J/sup H/) and Cl flux (J/sup Cl/ with /sup 36/Cl) were measured every 15 min. After 1 hr of OME exposure, HIST (10/sup -5/M) was added to the nutrient solution. The findings demonstrate that HIST stimulates Cl secretion in the OME-inhibited bullfrog gastric mucosa.« less

The Role of SufS Is Restricted to Fe-S Cluster Biosynthesis in Escherichia coli.

PubMed

Bühning, Martin; Valleriani, Angelo; Leimkühler, Silke

2017-04-11

In Escherichia coli, two different systems that are important for the coordinate formation of Fe-S clusters have been identified, namely, the ISC and SUF systems. The ISC system is the housekeeping Fe-S machinery, which provides Fe-S clusters for numerous cellular proteins. The IscS protein of this system was additionally revealed to be the primary sulfur donor for several sulfur-containing molecules with important biological functions, among which are the molybdenum cofactor (Moco) and thiolated nucleosides in tRNA. Here, we show that deletion of central components of the ISC system in addition to IscS leads to an overall decrease in Fe-S cluster enzyme and molybdoenzyme activity in addition to a decrease in the number of Fe-S-dependent thiomodifications of tRNA, based on the fact that some proteins involved in Moco biosynthesis and tRNA thiolation are Fe-S-dependent. Complementation of the ISC deficient strains with the suf operon restored the activity of Fe-S-containing proteins, including the MoaA protein, which is involved in the conversion of 5'GTP to cyclic pyranopterin monophosphate in the fist step of Moco biosynthesis. While both systems share a high degree of similarity, we show that the function of their respective l-cysteine desulfurase IscS or SufS is specific for each cellular pathway. It is revealed that SufS cannot play the role of IscS in sulfur transfer for the formation of 2-thiouridine, 4-thiouridine, or the dithiolene group of molybdopterin, being unable to interact with TusA or ThiI. The results demonstrate that the role of the SUF system is exclusively restricted to Fe-S cluster assembly in the cell.

Effect of individual SCFA on the epithelial barrier of sheep rumen under physiological and acidotic luminal pH conditions.

PubMed

Greco, Gabriele; Hagen, Franziska; Meißner, Svenja; Shen, Zanming; Lu, Zhongyan; Amasheh, Salah; Aschenbach, Jörg R

2018-02-15

The objective of this study was to investigate whether individual short-chain fatty acids (SCFA) have a different potential to either regulate the formation of the ruminal epithelial barrier (REB) at physiological pH or to damage the REB at acidotic ruminal pH. Ruminal epithelia of sheep were incubated in Ussing chambers on their mucosal side in buffered solutions (pH 6.1 or 5.1) containing no SCFA (control), 30 mM of either acetate, propionate or butyrate, or 100 mM acetate. Epithelial conductance (Gt), short-circuit current (Isc), and fluorescein flux rates were measured over 7 h. Thereafter, mRNA and protein abundance, as well as localization of the tight junction proteins claudin (Cldn)-1, -4, -7, and occludin were analyzed. At pH 6.1, butyrate increased Gt and decreased Isc, with additional decreases in claudin-7 mRNA and protein abundance (each P < 0.05) and disappearance of Cldn-7 immunosignals from the stratum corneum. By contrast, the mRNA abundance of Cldn-1 and/or Cldn-4 were upregulated by 30 mM propionate, 30 mM butyrate, or 100 mM acetate (P < 0.05), however, without coordinated changes in protein abundance. At luminal pH 5.1, neither Gt, Isc, nor TJ protein abundance was altered in the absence of SCFA; only fluorescein flux rates were slightly increased (P < 0.05) and fluorescein signals were no longer restricted to the stratum corneum. The presence of acetate, propionate, or butyrate at pH 5.1 increased fluorescein flux rates and Gt, and decreased Isc (each P < 0.05). Protein abundance of Cldn-1 was decreased in all SCFA treatments but 30 mM butyrate; abundance of Cldn -4 and -7 was decreased in all SCFA treatments but 30 mM acetate; and abundance of occludin was decreased in all SCFA treatments but 30 mM propionate (each P < 0.05). Immunofluorescence staining of SCFA-treated tissues at pH 5.1 showed disappearance of Cldn-7, discontinuous pattern for Cldn-4 and blurring of occludin and Cldn-1 signals in tight junction complexes. The fluorescein dye appeared to freely diffuse into deeper cell layers. The strongest increase in Gt and consistent decreases in the abundance and immunosignals of tight junction proteins were observed with 100 mM acetate at pH 5.1. We conclude that SCFA may contribute differently to the REB formation at luminal pH 6.1 with possible detrimental effects of butyrate at 30 mM concentration. At luminal pH 5.1, all SCFA elicited REB damage with concentration appearing more critical than SCFA species.

Electrical parameters and water permeability properties of monolayers formed by T84 cells cultured on permeable supports.

PubMed

Ozu, M; Toriano, R; Capurro, C; Parisi, M

2005-01-01

T84 is an established cell line expressing an enterocyte phenotype whose permeability properties have been widely explored. Osmotic permeability (POSM), hydraulic permeability (PHYDR) and transport-associated net water fluxes (JW-transp), as well as short-circuit current (ISC), transepithelial resistance (RT), and potential difference (deltaVT) were measured in T84 monolayers with the following results: POSM 1.3 +/- 0.1 cm.s-1 x 10-3; PHYDR 0.27 +/- 0.02 cm.s-1; RT 2426 +/- 109 omega.cm2, and deltaVT 1.31 +/- 0.38 mV. The effect of 50 microM 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DCEBIO), a "net Cl- secretory agent", on T84 cells was also studied. We confirm the reported important increase in ISC induced by DCEBIO which was associated here with a modest secretory deltaJW-transp. The present results were compared with those reported using the same experimental approach applied to established cell lines originating from intestinal and renal epithelial cells (Caco-2, LLC-PK1 and RCCD-1). No clear association between PHYDR and RT could be demonstrated and high PHYDR values were observed in an electrically tight epithelium, supporting the view that a "water leaky" barrier is not necessarily an "electrically leaky" one. Furthermore, the modest secretory deltaJW-transp was not consistent with previous results obtained with RCCD-1 cells stimulated with vasopressin (absorptive fluxes) or with T84 cells secreting water under the action of Escherichia coli heat stable enterotoxin. We conclude that, while the presence of aquaporins is necessary to dissipate an external osmotic gradient, coupling between water and ion transport cannot be explained by a simple and common underlying mechanism.

Novel aspects of cholinergic regulation of colonic ion transport

PubMed Central

Bader, Sandra; Diener, Martin

2015-01-01

Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (Isc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on Isc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport – up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors – is more complex than previously assumed. PMID:26236483

Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model

PubMed Central

Weber, Nina C.; van der Sluijs, Koen; Hackl, Florian; Hotz, Lorenz; Dahan, Albert; Hollmann, Markus W.; Berger, Marc M.

2014-01-01

We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (IV) bolus injection had no effect. The aim of the present study was to characterize whether continuous IV infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of IV S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered IV over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by IV lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by IV S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by IV S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of IV S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport. PMID:25386677

Bradykinin regulates human colonic ion transport in vitro

PubMed Central

Baird, A W; Skelly, M M; O'Donoghue, D P; Barrett, K E; Keely, S J

2008-01-01

Background and purpose: Kinins are acknowledged as important regulators of intestinal function during inflammation; however, their effects on human intestinal ion transport have not been reported. Here, we used muscle-stripped human colonic tissue and cultured T84-cell monolayers to study bradykinin (BK) actions on human intestinal ion transport. Experimental approach: Ion transport was measured as changes in short-circuit current (Isc) across colonic epithelia mounted in Ussing chambers. Key results: In intact tissue, there was a distinct polarity to BK-elicited Isc responses. Whereas basolateral BK stimulated sustained responses (EC50=0.5±0.1 μM), those to apical BK were more rapid and transient (EC50=4.1±1.2 nM). In T84 cells, responses to both apical and basolateral BK were similar to those seen upon apical addition to intact tissues. Cross-desensitization between apical and basolateral domains was not observed. BK-induced responses were largely due to Cl− secretion as shown by their sensitivity to bumetanide and removal of Cl− from the bathing solution. Studies using selective agonists and antagonists indicate responses to BK are mediated by B2 receptors. Finally, responses to basolateral BK in intact tissues were inhibited by tetrodotoxin (1 μM), atropine (1 μM), capsaicin (100 μM) and piroxicam (10 μM). BK-stimulated prostaglandin (PG)E2 release from colonic tissue. Conclusions: BK stimulates human colonic Cl− secretion by activation of apical and basolateral B2 receptors. Responses to apical BK reflect a direct action on epithelial cells, whereas those to basolateral BK are amplified by stimulation of enteric nerves and PG synthesis. PMID:18604228

Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation

PubMed Central

Gareau, Mélanie G; Jury, Jennifer; MacQueen, Glenda; Sherman, Philip M; Perdue, Mary H

2007-01-01

Background We previously showed that neonatal maternal separation (MS) of rat pups causes immediate and long‐term changes in intestinal physiology. Aim To examine if administration of probiotics affects MS‐induced gut dysfunction. Methods MS pups were separated from the dam for 3 h/day from days 4 to 19; non‐separated (NS) pups served as controls. Twice per day during the separation period, 108 probiotic organisms (two strains of Lactobacillus species) were administered to MS and NS pups; vehicle‐treated pups received saline. Studies were conducted on day 20, when blood was collected for corticosterone measurement as an indication of hypothalamus–pituitary–adrenal (HPA) axis activity, and colonic function was studied in tissues mounted in Ussing chambers. Ion transport was indicated by baseline and stimulated short‐circuit current (Isc); macromolecular permeability was measured by flux of horseradish peroxidase (HRP) across colonic tissues; and bacterial adherence/penetration into the mucosa was quantified by culturing tissues in selective media. Colonic function and host defence were also evaluated at day 60. Results Isc and HRP flux were significantly higher in the colon of MS versus NS pups. There was increased adhesion/penetration of total bacteria in MS pups, but a significant reduction in Lactobacillus species. Probiotic administration ameliorated the MS‐induced gut functional abnormalities and bacterial adhesion/penetration at both day 20 and 60, and reduced the elevated corticosterone levels at day 20. Conclusions The results indicate that altered enteric flora are responsible for colonic pathophysiology. Probiotics improve gut dysfunction induced by MS, at least in part by normalisation of HPA axis activity. PMID:17339238

Investigations of nerve populations influencing ion transport that can be stimulated electrically, by serotonin and by a nicotinic agonist.

PubMed

Keast, J R; Furness, J B; Costa, M

1985-11-01

It is known that the majority of the mucosal nerve fibres in the guinea-pig small intestine arise from submucous ganglia. There are a number of neurochemically distinct populations of nerve cells in these ganglia, approximately half of them being cholinergic. In these studies we have stimulated isolated preparations of mucosa and submucosa with electrical field stimulation (EFS), 5-hydroxytryptamine (5-HT) and the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) and monitored changes in ion transport. Segments of intestine were dissected free of external muscle and myenteric plexus and mounted in Ussing chambers. Short-circuit current (Isc) was measured as an indication of net ion transport across the tissue. EFS consisted of passing bipolar rectangular stimulus pulses through two platinum wires, one placed on each of the mucosal and submucosal sides of the tissue. EFS, 5-HT and DMPP each caused a transient increase in Isc. Tetrodotoxin (TTX) abolished all of the EFS response and the majority of the response observed with 5-HT or DMPP, suggesting that the action of these stimuli on the mucosa is primarily nerve-mediated. The TTX-sensitive responses to 5-HT (greater than 5 X 10(-7) M) and DMPP consisted of two components, appearing with different latencies. The response to EFS also consisted of two components. Hyoscine abolished the first component of each of these responses and significantly reduced the amplitude of the second, by 40% (for EFS and 5-HT) and 84% (for DMPP). At lower 5-HT concentrations, only the later component was seen, and this was unaffected by hyoscine.(ABSTRACT TRUNCATED AT 250 WORDS)

Synergistic action of cyclic adenosine monophosphate- and calcium-mediated chloride secretion in a colonic epithelial cell line.

PubMed Central

Cartwright, C A; McRoberts, J A; Mandel, K G; Dharmsathaphorn, K

1985-01-01

Vasoactive intestinal polypeptide (VIP) and the calcium ionophore A23187 caused dose-dependent changes in the potential difference and the short circuit current (Isc) across confluent T84 cell monolayers mounted in modified Ussing chambers. Both VIP and A23187 stimulated net chloride secretion without altering sodium transport. Net chloride secretion accounted for the increase in Isc. When A23187 was tested in combination with VIP, net chloride secretion was significantly greater than predicted from the calculated sum of their individual responses indicating a synergistic effect. VIP increased cellular cyclic AMP (cAMP) production in a dose-dependent manner, whereas A23187 had no effect on cellular cAMP. We then determined whether VIP and A23187 activated different transport pathways. Earlier studies suggest that VIP activates a basolaterally localized, barium-sensitive potassium channel as well as an apically localized chloride conductance pathway. In this study, stimulation of basolateral membrane potassium efflux by A23187 was documented by preloading the monolayers with 86Rb+. Stimulation of potassium efflux by A23187 was additive to the VIP-stimulated potassium efflux. By itself, 0.3 microM A23187 did not alter transepithelial chloride permeability, and its stimulation of basolateral membrane potassium efflux caused only a relatively small amount of chloride secretion. However, in the presence of an increased transepithelial chloride permeability induced by VIP, the effectiveness of A23187 on chloride secretion was greatly augmented. Our studies suggest that cAMP and calcium each activate basolateral potassium channels, but cAMP also activates an apically localized chloride channel. Synergism results from cooperative interaction of potassium channels and the chloride channel. PMID:2997291

Effects of butyrate on active sodium and chloride transport in rat and rabbit distal colon

PubMed Central

Vidyasagar, S; Ramakrishna, B S

2002-01-01

Short chain fatty acids, particularly butyrate, stimulate electroneutral NaCl absorption from the colon. Their effect in colonic epithelia lacking basal electroneutral NaCl absorption is unknown. Butyrate is also reported to inhibit active Cl− secretion in the colon. The present studies were undertaken to investigate the inter-relationships between the effects of butyrate on active Na+ and Cl− transport in the colon. Studies were carried out in rabbit distal colon (known to have predominant electrogenic Na+ absorption), rat distal colon (characterised by electroneutral Na+ absorption), and hyperaldosteronaemic rat distal colon (characterised by electrogenic Na+ absorption). The effect of cholera toxin (CT) was also noted. Potential difference, short-circuit current (ISC) and fluxes of Na+ and Cl− were measured in stripped mucosa under voltage-clamp conditions. Butyrate stimulated electroneutral Na+ and Cl− absorption in distal colon of normal and salt-depleted rats, and stimulated Na+ absorption in rabbit distal colon. Amiloride (10−4m) or CT did not inhibit this process. In rabbit distal colon, stimulation of Na+ absorption by butyrate was not dependent on the presence of Cl− in the medium. Butyrate significantly decreased conductance, decreased flux of sodium from serosa to mucosa (particularly in rabbit distal colon), and decreased ISC. Net Cl− secretion, induced by CT, was completely inhibited by butyrate. Stimulation of Na+ absorption was independent of exposure to CT. Bumetanide reversed net Cl− secretion to net absorption, but did not alter Na+ or Cl− fluxes in tissues exposed to butyrate. Thus butyrate stimulates active Na+ absorption in colonic epithelia, with or without expression of basal Na+-H+ exchange. Independently, butyrate inhibits active Cl− secretion induced by cAMP in these epithelia. PMID:11850510

Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone.

PubMed

Moeser, Adam J; Nighot, Prashant K; Engelke, Kory J; Ueno, Ryuji; Blikslager, Anthony T

2007-02-01

Previous studies utilizing an ex vivo porcine model of intestinal ischemic injury demonstrated that prostaglandin (PG)E(2) stimulates repair of mucosal barrier function via a mechanism involving Cl(-) secretion and reductions in paracellular permeability. Further experiments revealed that the signaling mechanism for PGE(2)-induced mucosal recovery was mediated via type-2 Cl(-) channels (ClC-2). Therefore, the objective of the present study was to directly investigate the role of ClC-2 in mucosal repair by evaluating mucosal recovery in ischemia-injured intestinal mucosa treated with the selective ClC-2 agonist lubiprostone. Ischemia-injured porcine ileal mucosa was mounted in Ussing chambers, and short-circuit current (I(sc)) and transepithelial electrical resistance (TER) were measured in response to lubiprostone. Application of 0.01-1 microM lubiprostone to ischemia-injured mucosa induced concentration-dependent increases in TER, with 1 microM lubiprostone stimulating a twofold increase in TER (DeltaTER = 26 Omega.cm(2); P < 0.01). However, lubiprostone (1 microM) stimulated higher elevations in TER despite lower I(sc) responses compared with the nonselective secretory agonist PGE(2) (1 microM). Furthermore, lubiprostone significantly (P < 0.05) reduced mucosal-to-serosal fluxes of (3)H-labeled mannitol to levels comparable to those of normal control tissues and restored occludin localization to tight junctions. Activation of ClC-2 with the selective agonist lubiprostone stimulated elevations in TER and reductions in mannitol flux in ischemia-injured intestine associated with structural changes in tight junctions. Prostones such as lubiprostone may provide a selective and novel pharmacological mechanism of accelerating recovery of acutely injured intestine compared with the nonselective action of prostaglandins such as PGE(2).

Loss of Ca2+-mediated ion transport during colitis correlates with reduced ion transport responses to a Ca2+-activated K+ channel opener

PubMed Central

Hirota, Christina L; McKay, Derek M

2009-01-01

Background and purpose: Epithelial surface hydration is critical for proper gut function. However, colonic tissues from individuals with inflammatory bowel disease or animals with colitis are hyporesponsive to Cl− secretagogues. The Cl− secretory responses to the muscarinic receptor agonist bethanechol are virtually absent in colons of mice with dextran sodium sulphate (DSS)-induced colitis. Our aim was to define the mechanism underlying this cholinergic hyporesponsiveness. Experimental approach: Colitis was induced by 4% DSS water, given orally. Epithelial ion transport was measured in Ussing chambers. Colonic crypts were isolated and processed for mRNA expression via RT-PCR and protein expression via immunoblotting and immunolocalization. Key results: Expression of muscarinic M3 receptors in colonic epithelium was not decreased during colitis. Short-circuit current (ISC) responses to other Ca2+-dependent secretagogues (histamine, thapsigargin, cyclopiazonic acid and calcium ionophore) were either absent or severely attenuated in colonic tissue from DSS-treated mice. mRNA levels of several ion transport molecules (a Ca2+-regulated Cl− channel, the intermediate-conductance Ca2+-activated K+ channel, the cystic fibrosis transmembrane conductance regulator, the Na+/K+-ATPase pump or the Na+/K+/2Cl− co-transporter) were not reduced in colonic crypts from DSS-treated mice. However, protein expression of Na+/K+-ATPase α1 subunits was decreased twofold during colitis. Activation of Ca2+-activated K+ channels increased ISC significantly less in DSS colons compared with control, as did the protein kinase C activator, phorbol 12-myristate 13-acetate. Conclusions and implications: Decreased Na+/K+-ATPase expression probably contributes to overall epithelial hyporesponsiveness during colitis, while dysfunctional K+ channels may account, at least partially, for lack of epithelial secretory responses to Ca2+-mediated secretagogues. PMID:19298254

Mercury toxicity in the shark (Squalus acanthias) rectal gland: apical CFTR chloride channels are inhibited by mercuric chloride.

PubMed

Ratner, Martha A; Decker, Sarah E; Aller, Stephen G; Weber, Gerhard; Forrest, John N

2006-03-01

In the shark rectal gland, basolateral membrane proteins have been suggested as targets for mercury. To examine the membrane polarity of mercury toxicity, we performed experiments in three preparations: isolated perfused rectal glands, primary monolayer cultures of rectal gland epithelial cells, and Xenopus oocytes expressing the shark cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. In perfused rectal glands we observed: (1) a dose-dependent inhibition by mercury of forskolin/3-isobutyl-1-methylxanthine (IBMX)-stimulated chloride secretion; (2) inhibition was maximal when mercury was added before stimulation with forskolin/IBMX; (3) dithiothrietol (DTT) and glutathione (GSH) completely prevented inhibition of chloride secretion. Short-circuit current (Isc) measurements in monolayers of rectal gland epithelial cells were performed to examine the membrane polarity of this effect. Mercuric chloride inhibited Isc more potently when applied to the solution bathing the apical vs. the basolateral membrane (23 +/- 5% and 68 +/- 5% inhibition at 1 and 10 microM HgCl2 in the apical solution vs. 2 +/- 0.9% and 14 +/- 5% in the basolateral solution). This inhibition was prevented by pre-treatment with apical DTT or GSH; however, only the permeant reducing agent DTT reversed mercury inhibition when added after exposure. When the shark rectal gland CFTR channel was expressed in Xenopus oocytes and chloride conductance was measured by two-electrode voltage clamping, we found that 1 microM HgCl2 inhibited forskolin/IBMX conductance by 69.2 +/- 2.0%. We conclude that in the shark rectal gland, mercury inhibits chloride secretion by interacting with the apical membrane and that CFTR is the likely site of this action. Copyright 2006 Wiley-Liss, Inc.

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

PubMed

Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-06-01

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

HscA and HscB stimulate [2Fe-2S] cluster transfer from IscU to apo-ferredoxin in an ATP-dependent reaction†

PubMed Central

Chandramouli, Kala; Johnson, Michael K.

2008-01-01

The role of the Azotobacter vinelandii HscA/HscB co-chaperone system in ISC-mediated iron-sulfur cluster biogenesis has been investigated in vitro by using CD and EPR spectrometry to monitor the effect of HscA, HscB, MgATP, and MgADP on the time course of cluster transfer from [2Fe-2S]IscU to apo-Isc ferredoxin. CD spectra indicate that both HscB and HscA interact with [2Fe-2S] IscU and the rate of cluster transfer was stimulated more than 20-fold in the presence stoichiometric HscA and HscB and excess MgATP. No stimulation was observed in the absence of either HscB or MgATP and cluster transfer was found to be an ATP-dependent reaction based on concomitant phosphate production and the enhanced rates of cluster transfer in the presence of KCl which is known to stimulated HscA ATPase activity. The results demonstrate a role of the ISC HscA/HscB co-chaperone system in facilitating efficient [2Fe-2S] cluster transfer from the IscU scaffold protein to acceptor proteins and that [2Fe-2S] cluster transfer from IscU is an ATP-dependent process. The data are consistent with the proposed regulation of the HscA ATPase cycle by HscB and IscU (Silberg, J. J., Tapley, T. L., Hoff, K. G., and Vickery, L. E. (2004) J. Biol. Chem. 279, 53924-53931), and mechanistic proposals for coupling of the HscA ATPase cycle with cluster transfer from [2Fe-2S]IscU to apo-IscFdx are discussed. PMID:16964969

HscA and HscB stimulate [2Fe-2S] cluster transfer from IscU to apoferredoxin in an ATP-dependent reaction.

PubMed

Chandramouli, Kala; Johnson, Michael K

2006-09-19

The role of the Azotobacter vinelandii HscA/HscB cochaperone system in ISC-mediated iron-sulfur cluster biogenesis has been investigated in vitro by using CD and EPR spectrometry to monitor the effect of HscA, HscB, MgATP, and MgADP on the time course of cluster transfer from [2Fe-2S]IscU to apo-Isc ferredoxin. CD spectra indicate that both HscB and HscA interact with [2Fe-2S]IscU and the rate of cluster transfer was stimulated more than 20-fold in the presence stoichiometric HscA and HscB and excess MgATP. No stimulation was observed in the absence of either HscB or MgATP, and cluster transfer was found to be an ATP-dependent reaction based on concomitant phosphate production and the enhanced rates of cluster transfer in the presence of KCl which is known to stimulate HscA ATPase activity. The results demonstrate a role of the ISC HscA/HscB cochaperone system in facilitating efficient [2Fe-2S] cluster transfer from the IscU scaffold protein to acceptor proteins and that [2Fe-2S] cluster transfer from IscU is an ATP-dependent process. The data are consistent with the proposed regulation of the HscA ATPase cycle by HscB and IscU [Silberg, J. J., Tapley, T. L., Hoff, K. G., and Vickery, L. E. (2004) J. Biol. Chem. 279, 53924-53931], and mechanistic proposals for coupling of the HscA ATPase cycle with cluster transfer from [2Fe-2S]IscU to apo-IscFdx are discussed.

The Sulfur Carrier Protein TusA Has a Pleiotropic Role in Escherichia coli That Also Affects Molybdenum Cofactor Biosynthesis*

PubMed Central

Dahl, Jan-Ulrik; Radon, Christin; Bühning, Martin; Nimtz, Manfred; Leichert, Lars I.; Denis, Yann; Jourlin-Castelli, Cécile; Iobbi-Nivol, Chantal; Méjean, Vincent; Leimkühler, Silke

2013-01-01

The Escherichia coli l-cysteine desulfurase IscS mobilizes sulfur from l-cysteine for the synthesis of several biomolecules such as iron-sulfur (FeS) clusters, molybdopterin, thiamin, lipoic acid, biotin, and the thiolation of tRNAs. The sulfur transfer from IscS to various biomolecules is mediated by different interaction partners (e.g. TusA for thiomodification of tRNAs, IscU for FeS cluster biogenesis, and ThiI for thiamine biosynthesis/tRNA thiolation), which bind at different sites of IscS. Transcriptomic and proteomic studies of a ΔtusA strain showed that the expression of genes of the moaABCDE operon coding for proteins involved in molybdenum cofactor biosynthesis is increased under aerobic and anaerobic conditions. Additionally, under anaerobic conditions the expression of genes encoding hydrogenase 3 and several molybdoenzymes such as nitrate reductase were also increased. On the contrary, the activity of all molydoenzymes analyzed was significantly reduced in the ΔtusA mutant. Characterization of the ΔtusA strain under aerobic conditions showed an overall low molybdopterin content and an accumulation of cyclic pyranopterin monophosphate. Under anaerobic conditions the activity of nitrate reductase was reduced by only 50%, showing that TusA is not essential for molybdenum cofactor biosynthesis. We present a model in which we propose that the direction of sulfur transfer for each sulfur-containing biomolecule is regulated by the availability of the interaction partner of IscS. We propose that in the absence of TusA, more IscS is available for FeS cluster biosynthesis and that the overproduction of FeS clusters leads to a modified expression of several genes. PMID:23281480

Regulation of the HscA ATPase reaction cycle by the co-chaperone HscB and the iron-sulfur cluster assembly protein IscU.

PubMed

Silberg, Jonathan J; Tapley, Tim L; Hoff, Kevin G; Vickery, Larry E

2004-12-24

The ATPase activity of HscA, a specialized hsp70 molecular chaperone from Escherichia coli, is regulated by the iron-sulfur cluster assembly protein IscU and the J-type co-chaperone HscB. IscU behaves as a substrate for HscA, and HscB enhances the binding of IscU to HscA. To better understand the mechanism by which HscB and IscU regulate HscA, we examined binding of HscB to the different conformational states of HscA and the effects of HscB and IscU on the kinetics of the individual steps of the HscA ATPase reaction cycle. Affinity sensor studies revealed that whereas IscU binds both ADP (R-state) and ATP (T-state) HscA complexes, HscB interacts only with an ATP-bound state. Studies of ATPase activity under single-turnover and rapid mixing conditions showed that both IscU and HscB interact with the low peptide affinity T-state of HscA (HscA++.ATP) and that both modestly accelerate (3-10-fold) the rate-determining steps in the HscA reaction cycle, k(hyd) and k(T-->R). When present together, IscU and HscB synergistically stimulate both k(hyd) (approximately = 500-fold) and k(T-->R) (approximately = 60-fold), leading to enhanced formation of the HscA.ADP-IscU complex (substrate capture). Following ADP/ATP exchange, IscU also stimulates k(R-->T) (approximately = 50-fold) and thereby accelerates the rate at which the low peptide affinity HscA++.ATP T-state is regenerated. Because HscA nucleotide exchange is fast, the overall rate of the chaperone cycle in vivo will be determined by the availability of the IscU-HscB substrate-co-chaperone complex.

Apc inactivation, but not obesity, synergizes with Pten deficiency to drive intestinal stem cell-derived tumorigenesis.

PubMed

Tabrizian, Tahmineh; Wang, Donghai; Guan, Fangxia; Hu, Zunju; Beck, Amanda P; Delahaye, Fabien; Huffman, Derek M

2017-06-01

Obesity is a major risk factor for colorectal cancer and can accelerate Lgr5+ intestinal stem cell (ISC)-derived tumorigenesis after the inactivation of Apc However, whether non-canonical pathways involving PI3K-Akt signaling in ISCs can lead to tumor formation, and if this can be further exacerbated by obesity is unknown. Despite the synergy between Pten and Apc inactivation in epithelial cells on intestinal tumor formation, their combined role in Lgr5+-ISCs, which are the most rapidly dividing ISC population in the intestine, is unknown. Lgr5+-GFP mice were provided low-fat diet (LFD) or high-fat diet (HFD) for 8 months, and the transcriptome was evaluated in Lgr5+-ISCs. For tumor studies, Lgr5+-GFP and Lgr5+-GFP- Pten flox/flox mice were tamoxifen treated to inactivate Pten in ISCs and provided LFD or HFD until 14-15 months of age. Finally, various combinations of Lgr5+-ISC-specific, Apc- and Pten -deleted mice were generated and evaluated for histopathology and survival. HFD did not overtly alter Akt signaling in ISCs, but did increase other metabolic pathways. Pten deficiency, but not HFD, increased BrdU-positive cells in the small intestine ( P  < 0.05). However, combining Pten and Apc deficiency synergistically increased proliferative markers, tumor pathology and mortality, in a dose-dependent fashion ( P  < 0.05). In summary, we show that HFD alone fails to drive Akt signaling in ISCs and that Pten deficiency is dispensable as a tumor suppressor in Lgr5+-ISCs. However, combining Pten and Apc deficiency in ISCs synergistically increases proliferation, tumor formation and mortality. Thus, aberrant Wnt/β-catenin, rather than PI3K-Akt signaling, is requisite for obesity to drive Lgr5+ ISC-derived tumorigenesis. © 2017 Society for Endocrinology.

Interaction of frataxin, an iron binding protein, with IscU of Fe-S clusters biogenesis pathway and its upregulation in AmpB resistant Leishmania donovani.

PubMed

Zaidi, Amir; Singh, Krishn Pratap; Anwar, Shadab; Suman, Shashi S; Equbal, Asif; Singh, Kuljit; Dikhit, Manas R; Bimal, Sanjeeva; Pandey, Krishna; Das, Pradeep; Ali, Vahab

2015-08-01

Leishmania donovani is a unicellular protozoon parasite that causes visceral leishmaniasis (VL), which is a fatal disease if left untreated. Certain Fe-S proteins of the TCA cycle and respiratory chain have been found in the Leishmania parasite but the precise mechanisms for their biogenesis and the maturation of Fe-S clusters remains unknown. Fe-S clusters are ubiquitous cofactors of proteins that perform critical cellular functions. The clusters are biosynthesized by the mitochondrial Iron-Sulphur Cluster (ISC) machinery with core protein components that include the catalytic cysteine desulphurase IscS, the scaffold proteins IscU and IscA, and frataxin as an iron carrier/donor. However, no information regarding frataxin, its regulation, or its role in drug resistance is available for the Leishmania parasite. In this study, we characterized Ld-frataxin to investigate its role in the ISC machinery of L. donovani. We expressed and purified the recombinant Ld-frataxin protein and observed its interaction with Ld-IscU by co-purification and pull-down assay. Furthermore, we observed that the cysteine desulphurase activity of the purified Ld-IscS protein was stimulated in the presence of Ld-frataxin and Ld-IscU, particularly in the presence of iron; neither Ld-frataxin nor Ld-IscU alone had significant effects on Ld-IscS activity. Interestingly, RT-PCR and western blotting showed that Ld-frataxin is upregulated in AmpB-resistant isolates compared to sensitive strains, which may support higher Fe-S protein activity in AmpB-resistant L. donovani. Additionally, Ld-frataxin was localized in the mitochondria, as revealed by digitonin fractionation and indirect immunofluorescence. Thus, our results suggest the role of Ld-frataxin as an iron binding/carrier protein for Fe-S cluster biogenesis that physically interacts with other core components of the ISC machinery within the mitochondria. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The unique contribution of the IDC Reviewed Event Bulletin to global seismicity catalogues

NASA Astrophysics Data System (ADS)

Koch, Karl; Kebede, Fekadu

2010-05-01

For monitoring the Comprehensive Nuclear-Test-Ban Treaty (CTBT) the International Monitoring System (IMS) network is currently being established that will eventually consists of 241 seismic, hydroacoustic and infrasound stations. The final result of processing and analysis of seismological and other waveform technology data from these stations is the Reviewed Event Bulletin (REB), which has been issued by the International Data Center (IDC) under provisional operation since February 2000 on a daily basis, except for a total of 28 days. The nearly 300,000 events produced since then correspond to more than 25,000 events per year. As an accompanying effort to the bulletin production at the IDC, quality assurance work has been carried out for the REB for the years from 2000 to 2008 through comparisons to similar bulletins of global seismicity, issued by the ISC and the National Earthquake Information Center (NEIC) of the United States Geological Survey. The comparisons with the NEIC bulletin concentrate on a timely identification of larger events that were either missed during interactive analysis at the IDC or which have been significantly mislocated. For the scope of this study the comparisons with the ISC bulletin are the focus, as this bulletin provides the most complete reference to global seismicity, even though it becomes available only after about two years of event occurrence. In our quality assessments we aimed at evaluating the consistency of event locations for common events, i.e. found in both the REB and the ISC bulletin having been relocated by ISC; the degree and the geospatial location of the events only produced in the REB and verified not being bogus, and those ISC relocated events not contained in the REB and which were missed during IDC analysis. Even though the seismic component of the IMS network with its maximum 170 seismometer stations is a sparse teleseismic network, locations differences of less than 1° (0.5° ) are observed, on average, for about 94% (85%) of the common events, as obtained from the ISC bulletin comparisons for the years 2000 to 2006. On the other hand, only 0.25% of such events were located more than 5° apart by the IDC and the ISC. The number of events of significant magnitude missed by the IDC is small and related predominantly to lack of sufficient number of observed arrivals to define an event. The unique contribution of the REB to global seismicity catalogues is expressed by the significant number of REB events that are solely reported in the ISC bulletin. Over the most recent years 2004-2006 the REB and ISC bulletin include about 20,000 common events which were reprocessed by the ISC. This compares to a steadily rising number of solely contributed REB events from more than 5,000 events in 2004 to nearly 7,500 events in 2006, i.e. a quarter to a third events more. These unique IDC events are mainly in remote and oceanic areas. A more important aspect, however, is the number of unique IDC events at depth. Below a depth of about 300 km there are nearly any ISC events not detected by the IMS network, while the number of events at larger depths and only detected by the IMS is significant. As conclusion it is found that the IDC REB is a valuable source for studies of deep seismicity occurring within the global subduction zones.

Origin of photovoltaic effect in superconducting YBa2Cu3O6.96 ceramics

PubMed Central

Yang, F.; Han, M. Y.; Chang, F. G.

2015-01-01

We report remarkable photovoltaic effect in YBa2Cu3O6.96 (YBCO) ceramic between 50 and 300 K induced by blue-laser illumination, which is directly related to the superconductivity of YBCO and the YBCO-metallic electrode interface. There is a polarity reversal for the open circuit voltage Voc and short circuit current Isc when YBCO undergoes a transition from superconducting to resistive state. We show that there exists an electrical potential across the superconductor-normal metal interface, which provides the separation force for the photo-induced electron-hole pairs. This interface potential directs from YBCO to the metal electrode when YBCO is superconducting and switches to the opposite direction when YBCO becomes nonsuperconducting. The origin of the potential may be readily associated with the proximity effect at metal-superconductor interface when YBCO is superconducting and its value is estimated to be ~10–8 mV at 50 K with a laser intensity of 502 mW/cm2. Combination of a p-type material YBCO at normal state with an n-type material Ag-paste forms a quasi-pn junction which is responsible for the photovoltaic behavior of YBCO ceramics at high temperatures. Our findings may pave the way to new applications of photon-electronic devices and shed further light on the proximity effect at the superconductor-metal interface. PMID:26099727

Performance of non-compartmentalized enzymatic biofuel cell based on buckypaper cathode and ferrocene-containing redox polymer anode

NASA Astrophysics Data System (ADS)

Bunte, Christine; Hussein, Laith; Urban, Gerald A.

2014-02-01

Novel single compartment Glucose/O2 biofuel cells (BFCs) were developed using immobilized enzymes and the mediated electron transfer (MET) approach. The bioanode was prepared through a ferrocene-containing redox polymer crosslinked in the presence of a biocatalyst on a glassy carbon support. Here, the redox polymer can physically entrap the enzyme and prevent it from leaching. Additionally it provides a biocompatible microenvironment and thus could extend the life time of enzyme. On the other side, the mediated biocathode was prepared based on bilirubin oxidase and 2,2‧-azinobis(3-ethylbenzothiazoline-6-sulfonate) diammonium salt (ABTS2-) system which has been physically entrapped in Nafion matrix and then adsorbed directly on a highly porous, conductive and functionalized buckypaper (fBP). Both electrodes were characterized physically and electrochemically. Employing these electrodes, the resulting BFC generates an open circuit voltage (Voc) of approximately 0.550 V and a peak power density of 26 μW cm-2 at 0.2 V at 37 °C in quiescent O2-saturated physiological buffer containing 5 mM glucose. The cell sustains a load up to 225 μA cm-2. Moreover, a high short circuit current (Isc) of 300 μA cm-2 is approached. This BFC can operate in mild conditions without using any toxic materials which makes it attractive for implantable devices.

Photoelectrochemical Cell of Hybrid Regioregular POLY(3-HEXYLTHIOPHENE-2,5-DIYL) and Molybdenum Disulfide Film

NASA Astrophysics Data System (ADS)

Abdelmola, Fatmaelzahraa M.; Ram, Manoj K.; Takshi, Arash; Stafanakos, Elias; Kumar, Ashok; Goswami, D. Yogi

The photoelectrochemical cell attracts attention worldwide due to conversion of optical energy into electricity, production of hydrogen through water splitting and use in photodetector and photo-sensor applications. We have been working on the photochemical cell based on regioregular polyhexylthiophenes hybrid-structured films for photoelectrochemical and photovoltaic applications. This paper discusses the hybrid film studies on regioregular poly(3-hexylthiophene-2,5-diyl) (P3HT) with 2D molybdenum disulfide (MoS2) for photoelectrochemical cell. The hybrid P3HT/MoS2 films deposited over indium tin oxide (ITO)-coated glass plate or n-type silicon substrates were characterized using FTIR, UV/vis, electrochemical and scanning electron microscopy (SEM) techniques. The optical measurements showed a higher absorption magnitude with low reflection properties of P3HT/MoS2 hybrid films revealing a superior photocurrent compared to both P3HT and MoS2 films. The P3HT/MoS2 hybrid-based photoelectrochemical cell yielded a short-circuit current (Isc) of 183.16μAṡcm-2, open-circuit voltage (Voc) of 0.92V, fill factor (FF) of 25% and power conversion efficiency (η) of 0.18% under the light intensity of 242Wṡm-2. The estimated power conversion efficiency and fill factor are comparable to organic-based photovoltaic devices.

Porous polymer composite membrane based nanogenerator: A realization of self-powered wireless green energy source for smart electronics applications

NASA Astrophysics Data System (ADS)

Ghosh, Sujoy Kumar; Sinha, Tridib Kumar; Mahanty, Biswajit; Jana, Santanu; Mandal, Dipankar

2016-11-01

An efficient, flexible and unvaryingly porous polymer composite membrane based nanogenerator (PPCNG) without any electrical poling treatment has been realised as wireless green energy source to power up smart electronic gadgets. Owing to self-polarized piezo- and ferro-electretic phenomenon of in situ platinum nanoparticles (Pt-NPs) doped porous poly(vinylidenefluoride-co-hexafluoropropylene)-membrane, a simple, inexpensive and scalable PPCNG fabrication is highlighted. The molecular orientations of the -CH2/-CF2 dipoles that cause self-polarization phenomenon has been realized by angular dependent near edge X-ray absorption fine structure spectroscopy. The square-like hysteresis loop with giant remnant polarization, Pr ˜ 68 μC/cm2 and exceptionally high piezoelectric charge coefficient, d33 ˜ - 836 pC/N promises a best suited ferro- and piezo-electretic membrane. The PPCNG exhibits a high electrical throughput such as, ranging from 2.7 V to 23 V of open-circuit voltage (Voc) and 2.9 μA to 24.7 μA of short-circuit current (Isc) under 0.5 MPa to 4.3 MPa of imparted stress amplitude by periodic human finger motion. The harvested mechanical and subsequent electrical energy by PPCNG is shown to transfer wirelessly via visible and infrared transmitter-receiver systems, where 17% and 49% of wireless power transfer efficiency, respectively, has been realized to power up several consumer electronics.

Use of titanium dioxide nanoparticles biosynthesized by Bacillus mycoides in quantum dot sensitized solar cells

PubMed Central

2014-01-01

Background One of the major challenges of nanotechnology during the last decade has been the development of new procedures to synthesize nanoparticles. In this context, biosynthetic methods have taken hold since they are simple, safe and eco-friendly. Results In this study, we report the biosynthesis of TiO2 nanoparticles by an environmental isolate of Bacillus mycoides, a poorly described Gram-positive bacterium able to form colonies with novel morphologies. This isolate was able to produce TiO2 nanoparticles at 37°C in the presence of titanyl hydroxide. Biosynthesized nanoparticles have anatase polymorphic structure, spherical morphology, polydisperse size (40–60 nm) and an organic shell as determined by UV–vis spectroscopy, TEM, DLS and FTIR, respectively. Also, conversely to chemically produced nanoparticles, biosynthesized TiO2 do not display phototoxicity. In order to design less expensive and greener solar cells, biosynthesized nanoparticles were evaluated in Quantum Dot Sensitized Solar Cells (QDSSCs) and compared with chemically produced TiO2 nanoparticles. Solar cell parameters such as short circuit current density (ISC) and open circuit voltage (VOC) revealed that biosynthesized TiO2 nanoparticles can mobilize electrons in QDSSCs similarly than chemically produced TiO2. Conclusions Our results indicate that bacterial extracellular production of TiO2 nanoparticles at low temperatures represents a novel alternative for the construction of green solar cells. PMID:25027643

Biogenesis of Fe/S proteins and pathogenicity: IscR plays a key role in allowing Erwinia chrysanthemi to adapt to hostile conditions.

PubMed

Rincon-Enriquez, Gabriel; Crété, Patrice; Barras, Frédéric; Py, Béatrice

2008-03-01

The Erwinia chrysanthemi genome is predicted to encode three systems, Nif, Isc and Suf, known to assist Fe/S cluster biogenesis and the CsdAE cysteine desulphurase. Single iscU, hscA and fdx mutants were found sensitive to paraquat and exhibited reduced virulence on both chicory leaves and Arabidopsis thaliana. Depletion of the whole Isc system led to a pleiotropic phenotype, including sensitivity to both paraquat and 2,2'-dipyridyl, auxotrophies for branched-chain amino acids, thiamine, nicotinic acid, and drastic alteration in virulence. IscR was able to suppress all of the phenotypes listed above in a sufC-dependent manner while depletion of the Isc system led to IscR-dependent activation of the suf operon. No virulence defects were found associated with csdA or nifS mutations. Surprisingly, we found that the sufC mutant was virulent against A. thaliana, whereas its virulence had been found altered in Saintpaulia. Collectively, these results lead us to propose that E. chrysanthemi possess the Fe/S biogenesis strategy suited to the physico-chemical conditions encountered in its host upon infection. In this view, the IscR regulator, which controls both Isc and Suf, is predicted to play a major role in the ability of E. chrysanthemi to colonize a wide array of different plants.

Autoregulation of apical membrane Na+ permeability of tight epithelia. Noise analysis with amiloride and CGS 4270

PubMed Central

1985-01-01

Noise analysis of the Na+ channels of the apical membranes of frog skin bathed symmetrically in a Cl-HCO3 Ringer solution was done with amiloride and CGS 4270. Tissues were studied in their control states and after inhibition of transepithelial Na+ transport (Isc) by addition of quinine or quinidine to the apical solution. A critical examination of the amiloride-induced noise indicated that the single channel Na+ currents (iNa) were decreased by quinine and quinidine, probably because of depolarization of apical membrane voltage. Despite considerable statistical uncertainty in the methods of estimation of the Na+ channel density with amiloride-induced noise (NA, see text), the striking observation was a large increase of NA with amiloride inhibition of the rate of Na+ entry into the cells. NA was increased to 406% of control, whereas Isc was inhibited to 8.6% of control by 6 microM amiloride. Studies were done also with the Na+ channel blocker CGS 4270. Noise analysis with this compound was advantageous, permitting iCGSNa and NCGS to be measured in individual tissues with a relatively small inhibition of Isc. As with amiloride, inhibition of Isc with CGS 4270 caused large increases of the Na+ channel density (approximately 200% at approximately 35% inhibition of the Isc). Quinine and quinidine caused an approximately 50% increase of Na+ channel density while inhibiting iNa by approximately 60-70%. As inhibition of Na+ entry leads to an increase of Na+ channel density, a mechanism of autoregulation appears to be a major factor in adjusting the apical membrane Na+ permeability of the cells. PMID:2409219

Characterization of the Vibrio vulnificus 1-Cys peroxiredoxin Prx3 and regulation of its expression by the Fe-S cluster regulator IscR in response to oxidative stress and iron starvation.

PubMed

Lim, Jong Gyu; Bang, Ye-Ji; Choi, Sang Ho

2014-12-26

Peroxiredoxins (Prxs) are ubiquitous antioxidant enzymes that reduce toxic peroxides. A new Vibrio vulnificus Prx, named Prx3, was identified and characterized in this study. Biochemical and mutational analyses revealed that Prx3 reduces H2O2, utilizing glutaredoxin 3 (Grx3) and glutathione (GSH) as reductants, and requires only N-terminal peroxidatic cysteine for its catalysis. These results, combined with the monomeric size of Prx3 observed under non-reducing conditions, suggested that Prx3 is a Grx3/GSH-dependent 1-Cys Prx and oxidized without forming intermolecular disulfide bonds. The prx3 mutation impaired growth in the medium containing peroxides and reduced virulence in mice, indicating that Prx3 is essential for survival under oxidative stress and pathogenesis of V. vulnificus. The Fe-S cluster regulator IscR activates prx3 by direct binding to a specific binding sequence centered at -44 from the transcription start site. The binding sequence was homologous to the Type 2 IscR-binding sequence, most likely recognized by the Fe-S clusterless apo-IscR in Escherichia coli. The iscR3CA mutant, chromosomally encoding the apo-locked IscR, exhibited 3-fold higher levels of activation of prx3 than the wild type and accumulated more IscR3CA protein in cells. The IscR-dependent activation of prx3 by aerobic growth and iron starvation was also associated with the increase in cellular levels of IscR protein. Taken together, the results suggested that IscR senses iron starvation as well as reactive oxygen species and shifts to the apo-form, which leads to the increase of cellular IscR and in turn prx3 expression, contributing to the survival and virulence of V. vulnificus during pathogenesis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Improved radial dose function estimation using current version MCNP Monte-Carlo simulation: Model 6711 and ISC3500 125I brachytherapy sources.

PubMed

Duggan, Dennis M

2004-12-01

Improved cross-sections in a new version of the Monte-Carlo N-particle (MCNP) code may eliminate discrepancies between radial dose functions (as defined by American Association of Physicists in Medicine Task Group 43) derived from Monte-Carlo simulations of low-energy photon-emitting brachytherapy sources and those from measurements on the same sources with thermoluminescent dosimeters. This is demonstrated for two 125I brachytherapy seed models, the Implant Sciences Model ISC3500 (I-Plant) and the Amersham Health Model 6711, by simulating their radial dose functions with two versions of MCNP, 4c2 and 5.

Synchronous brain activity across individuals underlies shared psychological perspectives

PubMed Central

Lahnakoski, Juha M.; Glerean, Enrico; Jääskeläinen, Iiro P.; Hyönä, Jukka; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

2014-01-01

For successful communication, we need to understand the external world consistently with others. This task requires sufficiently similar cognitive schemas or psychological perspectives that act as filters to guide the selection, interpretation and storage of sensory information, perceptual objects and events. Here we show that when individuals adopt a similar psychological perspective during natural viewing, their brain activity becomes synchronized in specific brain regions. We measured brain activity with functional magnetic resonance imaging (fMRI) from 33 healthy participants who viewed a 10-min movie twice, assuming once a ‘social’ (detective) and once a ‘non-social’ (interior decorator) perspective to the movie events. Pearson's correlation coefficient was used to derive multisubject voxelwise similarity measures (inter-subject correlations; ISCs) of functional MRI data. We used k-nearest-neighbor and support vector machine classifiers as well as a Mantel test on the ISC matrices to reveal brain areas wherein ISC predicted the participants' current perspective. ISC was stronger in several brain regions—most robustly in the parahippocampal gyrus, posterior parietal cortex and lateral occipital cortex—when the participants viewed the movie with similar rather than different perspectives. Synchronization was not explained by differences in visual sampling of the movies, as estimated by eye gaze. We propose that synchronous brain activity across individuals adopting similar psychological perspectives could be an important neural mechanism supporting shared understanding of the environment. PMID:24936687

Pink1 and Parkin regulate Drosophila intestinal stem cell proliferation during stress and aging.

PubMed

Koehler, Christopher L; Perkins, Guy A; Ellisman, Mark H; Jones, D Leanne

2017-08-07

Intestinal stem cells (ISCs) maintain the midgut epithelium in Drosophila melanogaster Proper cellular turnover and tissue function rely on tightly regulated rates of ISC division and appropriate differentiation of daughter cells. However, aging and epithelial injury cause elevated ISC proliferation and decreased capacity for terminal differentiation of daughter enteroblasts (EBs). The mechanisms causing functional decline of stem cells with age remain elusive; however, recent findings suggest that stem cell metabolism plays an important role in the regulation of stem cell activity. Here, we investigate how alterations in mitochondrial homeostasis modulate stem cell behavior in vivo via RNA interference-mediated knockdown of factors involved in mitochondrial dynamics. ISC/EB-specific knockdown of the mitophagy-related genes Pink1 or Parkin suppresses the age-related loss of tissue homeostasis, despite dramatic changes in mitochondrial ultrastructure and mitochondrial damage in ISCs/EBs. Maintenance of tissue homeostasis upon reduction of Pink1 or Parkin appears to result from reduction of age- and stress-induced ISC proliferation, in part, through induction of ISC senescence. Our results indicate an uncoupling of cellular, tissue, and organismal aging through inhibition of ISC proliferation and provide insight into strategies used by stem cells to maintain tissue homeostasis despite severe damage to organelles. © 2017 Koehler et al.

Dual role of BMP signaling in the regulation of Drosophila intestinal stem cell self-renewal.

PubMed

Tian, Aiguo; Jiang, Jin

2017-10-02

Many adult organs including Drosophila adult midguts rely on resident stem cells to replenish damaged cells during tissue homeostasis and regeneration. Previous studies have shown that, upon injury, intestinal stem cells (ISCs) in the midguts can increase proliferation and lineage differentiation to meet the demand for tissue repair. Our recent study has demonstrated that, in response to certain injury, midguts can expand ISC population size as an additional regenerative mechanism. We found that injury elicited by bleomycin feeding or bacterial infection increased the production of two BMP ligands (Dpp and Gbb) in enterocytes (ECs), leading to elevated BMP signaling in progenitor cells that drove an expansion of ISCs by promoting their symmetric self-renewing division. Interestingly, we also found that BMP signaling in ECs inhibits the production of Dpp and Gbb, and that this negative feedback mechanism is required to reset ISC pool size to the homeostatic state. Our findings suggest that BMP signaling exerts two opposing influences on stem cell activity depending on where it acts: BMP signaling in progenitor cells promotes ISC self-renewal while BMP signaling in ECs restricts ISC self-renewal by preventing excessive production of BMP ligands. Our results further suggest that transient expansion of ISC population in conjunction with increasing ISC proliferation provides a more effective strategy for tissue regeneration.

ISC-GEM: Global Instrumental Earthquake Catalogue (1900-2009), II. Location and seismicity patterns

NASA Astrophysics Data System (ADS)

Bondár, I.; Engdahl, E. Robert; Villaseñor, A.; Harris, James; Storchak, D.

2015-02-01

We present the final results of a two-year project sponsored by the Global Earthquake Model (GEM) Foundation. The ISC-GEM global catalogue consists of some 19 thousand instrumentally recorded, moderate to large earthquakes, spanning 110 years of seismicity. We relocated all events in the catalogue using a two-tier approach. The EHB location methodology (Engdahl et al., 1998) was applied first to obtain improved hypocentres with special focus on the depth determination. The locations were further refined in the next step by fixing the depths to those from the EHB analysis and applying the new International Seismological Centre (ISC) location algorithm (Bondár and Storchak, 2011) that reduces location bias by accounting for correlated travel-time prediction error structure. To facilitate the relocation effort, some one million seismic P and S wave arrival-time data were added to the ISC database for the period between 1904 and 1970, either from original station bulletins in the ISC archive or by digitizing the scanned images of the International Seismological Summary (ISS) bulletin (Villaseñor and Engdahl, 2005, 2007). Although no substantial amount of new phase data were acquired for the modern period (1964-2009), the number of phases used in the location has still increased by three millions, owing to fact that both the EHB and ISC locators use most well-recorded ak135 (Kennett et al., 1995) phases in the location. We show that the relocation effort yielded substantially improved locations, especially in the first half of the 20th century; we demonstrate significant improvements in focal depth estimates in subduction zones and other seismically active regions; and we show that the ISC-GEM catalogue provides an improved view of 110 years of global seismicity of the Earth. The ISC-GEM Global Instrumental Earthquake Catalogue represents the final product of one of the ten global components in the GEM program, and is available to researchers at the ISC (http://www.isc.ac.uk).

Correlation of Disturbed Sleep and Cancer Stress.

PubMed

Vander Wal, Gregory S; Lichstein, Kenneth L; Perkins, Cynthia K

2017-01-01

To illuminate the course of insomnia in the presence of an acute comorbidity, we examined the association between insomnia severity and breast cancer symptom severity over time and determined if this association varies with insomnia history and presleep arousal. Twenty-nine newly diagnosed breast cancer patients, who also exhibited insomnia, completed sleep diary and cancer symptom severity questionnaires every other week (total of 28 days) over 7 weeks, as well as baseline and postobservation measures. Participants were defined as having insomnia prior to cancer (IPC) or insomnia secondary to cancer (ISC) based on precancer sleep status. Insomnia and cancer symptom severity were strongly correlated at baseline but significantly declined over the evaluation period. Among ISC individuals, there was an association between sleep severity and cancer severity at baseline but not 7 weeks later. IPC individuals showed a consistent pattern of no significant association between sleep severity and cancer symptom severity. IPC had higher levels of cognitive presleep arousal than ISC. The current study documented the evolution of the relation between insomnia and breast cancer symptom severity over time and identified factors (premorbid insomnia and presleep hyperarousal) that may influence this association.

Toll-like Receptor 4-mediated Endoplasmic Reticulum Stress in Intestinal Crypts Induces Necrotizing Enterocolitis*

PubMed Central

Afrazi, Amin; Branca, Maria F.; Sodhi, Chhinder P.; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E.; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D.; Ozolek, John A.; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K.; Billiar, Timothy R.; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J.

2014-01-01

The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4ΔIEC-OVER mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4ΔIEC mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development. PMID:24519940

Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis.

PubMed

Afrazi, Amin; Branca, Maria F; Sodhi, Chhinder P; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D; Ozolek, John A; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K; Billiar, Timothy R; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J

2014-04-04

The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4(ΔIEC-OVER) mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4(ΔIEC) mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development.

Predicting Success in ISCS Level II.

ERIC Educational Resources Information Center

McDuffie, Thomas E., Jr.

1979-01-01

Investigates a method to predict best and least suited students for the ISCS instructional approach. Aptitude-treatment interactions associated with ISCS instruction and a set of aptitude, attitude, and skill factors were utilized to make and verify predictions on two dependent variables--achievement and success. (Author/GA)

Intestinal stem cells in the adult Drosophila midgut

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Huaqi, E-mail: Huaqi.Jiang@UTSouthwestern.edu; Edgar, Bruce A., E-mail: b.edgar@dkfz.de; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109

Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights:more » Black-Right-Pointing-Pointer The homeostasis and regeneration of adult fly midguts are mediated by ISCs. Black-Right-Pointing-Pointer Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). Black-Right-Pointing-Pointer EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. Black-Right-Pointing-Pointer Notch signaling regulates ISC self-renewal and differentiation.« less

Controlling Plasmon-Enhanced Fluorescence via Intersystem Crossing in Photoswitchable Molecules.

PubMed

Wang, Mingsong; Hartmann, Gregory; Wu, Zilong; Scarabelli, Leonardo; Rajeeva, Bharath Bangalore; Jarrett, Jeremy W; Perillo, Evan P; Dunn, Andrew K; Liz-Marzán, Luis M; Hwang, Gyeong S; Zheng, Yuebing

2017-10-01

By harnessing photoswitchable intersystem crossing (ISC) in spiropyran (SP) molecules, active control of plasmon-enhanced fluorescence in the hybrid systems of SP molecules and plasmonic nanostructures is achieved. Specifically, SP-derived merocyanine (MC) molecules formed by photochemical ring-opening reaction display efficient ISC due to their zwitterionic character. In contrast, ISC in quinoidal MC molecules formed by thermal ring-opening reaction is negligible. The high ISC rate can improve fluorescence quantum yield of the plasmon-modified spontaneous emission, only when the plasmonic electromagnetic field enhancement is sufficiently high. Along this line, extensive photomodulation of fluorescence is demonstrated by switching the ISC in MC molecules at Au nanoparticle aggregates, where strongly enhanced plasmonic hot spots exist. The ISC-mediated plasmon-enhanced fluorescence represents a new approach toward controlling the spontaneous emission of fluorophores near plasmonic nanostructures, which expands the applications of active molecular plasmonics in information processing, biosensing, and bioimaging. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Performance of mid-wave T2SL detectors with heterojunction barriers

NASA Astrophysics Data System (ADS)

Asplund, Carl; Marcks von Würtemberg, Rickard; Lantz, Dan; Malm, Hedda; Martijn, Henk; Plis, Elena; Gautam, Nutan; Krishna, Sanjay

2013-07-01

A heterojunction T2SL barrier detector which effectively blocks majority carrier leakage over the pn-junction was designed and fabricated for the mid-wave infrared (MWIR) atmospheric transmission window. The layers in the barrier region comprised AlSb, GaSb and InAs, and the thicknesses were selected by using k · P-based energy band modeling to achieve maximum valence band offset, while maintaining close to zero conduction band discontinuity in a way similar to the work of Abdollahi Pour et al. [1] The barrier-structure has a 50% cutoff at 4.75 μm and 40% quantum efficiency and shows a dark current density of 6 × 10-6 A/cm2 at -0.05 V bias and 120 K. This is one order of magnitude lower than for comparable T2SL-structures without the barrier. Further improvement of the (non-surface related) bulk dark current can be expected with optimized doping of the absorber and barrier, and by fine tuning of the barrier layer design. We discuss the effect of barrier doping on dark current based on simulations. A T2SL focal plane array with 320 × 256 pixels, 30 μm pitch and 90% fill factor was processed in house using a conventional homojunction p-i-n photodiode architecture and the ISC9705 readout circuit. High-quality imaging up to 110 K was demonstrated with the substrate fully removed.

Patterns of physical activity and associated factors among teenagers from Barcelona (Spain) in 2012.

PubMed

Ruiz-Trasserra, Alicia; Pérez, Anna; Continente, Xavier; O'Brien, Kerry; Bartroli, Montse; Teixidó-Compaño, Ester; Espelt, Albert

To estimate the prevalence of moderate and vigorous physical activity (MVPA), as defined by the World Health Organisation (WHO), and associated factors among teenagers from Barcelona in 2012. Cross-sectional survey to assess risk factors in a representative sample of secondary school students (aged 13-16 years, International Standard Classification of Education [ISCED] 2, n=2,162; and 17-18 years, ISCED 3, n=1016) in Barcelona. We estimated MVPA prevalence overall, and for each independent variable and each gender. Poisson regression models with robust variance were fit to examine the factors associated with high-level MVPA, and obtained prevalence ratios (PR) and 95% confidence intervals (95%CI). Only 13% of ISCED 2 and 10% of ISCED 3 students met the WHO physical activity recommendations. This percentage was lower among girls at both academic levels. MVPA was lower among ISCED 3 compared to ISCED 2 students, and among students with a lower socioeconomic status. Physical activity was associated with positive self-perception of the health status (e.g., positive self-perception of health status among ISCED 2 compared to ISCED 3 students: PR=1.31 [95%CI: 1.22-1.41] and 1.61 [95%CI: 1.44-1.81] for boys and girls, respectively]. The percentage of teenagers who met WHO MVPA recommendations was low. Strategies are needed to increase MVPA levels, particularly in older girls, and students from low socioeconomic backgrounds. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Handling the Diversity in the Coming Flood of InSAR Data with the InSAR Scientific Computing Environment

NASA Astrophysics Data System (ADS)

Rosen, P. A.; Gurrola, E. M.; Sacco, G. F.; Agram, P. S.; Lavalle, M.; Zebker, H. A.

2014-12-01

The NASA ESTO-developed InSAR Scientific Computing Environment (ISCE) provides acomputing framework for geodetic image processing for InSAR sensors that ismodular, flexible, and extensible, enabling scientists to reduce measurementsdirectly from a diverse array of radar satellites and aircraft to newgeophysical products. ISCE can serve as the core of a centralized processingcenter to bring Level-0 raw radar data up to Level-3 data products, but isadaptable to alternative processing approaches for science users interested innew and different ways to exploit mission data. This is accomplished throughrigorous componentization of processing codes, abstraction and generalization ofdata models, and a xml-based input interface with multi-level prioritizedcontrol of the component configurations depending on the science processingcontext. The proposed NASA-ISRO SAR (NISAR) Mission would deliver data ofunprecedented quantity and quality, making possible global-scale studies inclimate research, natural hazards, and Earth's ecosystems. ISCE is planned tobecome a key element in processing projected NISAR data into higher level dataproducts, enabling a new class of analyses that take greater advantage of thelong time and large spatial scales of these new data than current approaches.NISAR would be but one mission in a constellation of radar satellites in thefuture delivering such data. ISCE has been incorporated into two prototypecloud-based systems that have demonstrated its elasticity to addressing largerdata processing problems in a "production" context and its ability to becontrolled by individual science users on the cloud for large data problems.

Parameter extraction using global particle swarm optimization approach and the influence of polymer processing temperature on the solar cell parameters

NASA Astrophysics Data System (ADS)

Kumar, S.; Singh, A.; Dhar, A.

2017-08-01

The accurate estimation of the photovoltaic parameters is fundamental to gain an insight of the physical processes occurring inside a photovoltaic device and thereby to optimize its design, fabrication processes, and quality. A simulative approach of accurately determining the device parameters is crucial for cell array and module simulation when applied in practical on-field applications. In this work, we have developed a global particle swarm optimization (GPSO) approach to estimate the different solar cell parameters viz., ideality factor (η), short circuit current (Isc), open circuit voltage (Voc), shunt resistant (Rsh), and series resistance (Rs) with wide a search range of over ±100 % for each model parameter. After validating the accurateness and global search power of the proposed approach with synthetic and noisy data, we applied the technique to the extract the PV parameters of ZnO/PCDTBT based hybrid solar cells (HSCs) prepared under different annealing conditions. Further, we examine the variation of extracted model parameters to unveil the physical processes occurring when different annealing temperatures are employed during the device fabrication and establish the role of improved charge transport in polymer films from independent FET measurements. The evolution of surface morphology, optical absorption, and chemical compositional behaviour of PCDTBT co-polymer films as a function of processing temperature has also been captured in the study and correlated with the findings from the PV parameters extracted using GPSO approach.

Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia

PubMed Central

Raju, Sammeta V.; Wang, Guoshun

2012-01-01

Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (ISC) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A2B adenosine receptor (A2BAR), largely abolished the adenosine-stimulated chloride transport, suggesting that A2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections. PMID:22442662

Individualizing In-Service Teacher Preparation for ISCS Teachers.

ERIC Educational Resources Information Center

Snyder, William R.

Described is a program which attempts to prepare teachers in a fashion that approximates the instructional setting which is expected in science classrooms utilizing the Intermediate Science Curriculum Study (ISCS) programs. It is specifically designed to support the in-service preparation of ISCS teachers. It includes two basic categories of…

The NASA Ames Research Center Institutional Scientific Collection: History, Best Practices and Scientific Opportunities

NASA Technical Reports Server (NTRS)

Rask, Jon C.; Chakravarty, Kaushik; French, Alison; Choi, Sungshin; Stewart, Helen

2017-01-01

The NASA Ames Life Sciences Institutional Scientific Collection (ISC), which is composed of the Ames Life Sciences Data Archive (ALSDA) and the Biospecimen Storage Facility (BSF), is managed by the Space Biosciences Division and has been operational since 1993. The ALSDA is responsible for archiving information and animal biospecimens collected from life science spaceflight experiments and matching ground control experiments. Both fixed and frozen spaceflight and ground tissues are stored in the BSF within the ISC. The ALSDA also manages a Biospecimen Sharing Program, performs curation and long-term storage operations, and makes biospecimens available to the scientific community for research purposes via the Life Science Data Archive public website (https:lsda.jsc.nasa.gov). As part of our best practices, a viability testing plan has been developed for the ISC, which will assess the quality of archived samples. We expect that results from the viability testing will catalyze sample use, enable broader science community interest, and improve operational efficiency of the ISC. The current viability test plan focuses on generating disposition recommendations and is based on using ribonucleic acid (RNA) integrity number (RIN) scores as a criteria for measurement of biospecimen viablity for downstream functional analysis. The plan includes (1) sorting and identification of candidate samples, (2) conducting a statiscally-based power analysis to generate representaive cohorts from the population of stored biospecimens, (3) completion of RIN analysis on select samples, and (4) development of disposition recommendations based on the RIN scores. Results of this work will also support NASA open science initiatives and guides development of the NASA Scientific Collections Directive (a policy on best practices for curation of biological collections). Our RIN-based methodology for characterizing the quality of tissues stored in the ISC since the 1980s also creates unique scientific opportunities for temporal assessment across historical missions. Support from the NASA Space Biology Program and the NASA Human Research Program is gratefully acknowledged.

The Synthetic Aperture Radar Science Data Processing Foundry Concept for Earth Science

NASA Astrophysics Data System (ADS)

Rosen, P. A.; Hua, H.; Norton, C. D.; Little, M. M.

2015-12-01

Since 2008, NASA's Earth Science Technology Office and the Advanced Information Systems Technology Program have invested in two technology evolutions to meet the needs of the community of scientists exploiting the rapidly growing database of international synthetic aperture radar (SAR) data. JPL, working with the science community, has developed the InSAR Scientific Computing Environment (ISCE), a next-generation interferometric SAR processing system that is designed to be flexible and extensible. ISCE currently supports many international space borne data sets but has been primarily focused on geodetic science and applications. A second evolutionary path, the Advanced Rapid Imaging and Analysis (ARIA) science data system, uses ISCE as its core science data processing engine and produces automated science and response products, quality assessments and metadata. The success of this two-front effort has been demonstrated in NASA's ability to respond to recent events with useful disaster support. JPL has enabled high-volume and low latency data production by the re-use of the hybrid cloud computing science data system (HySDS) that runs ARIA, leveraging on-premise cloud computing assets that are able to burst onto the Amazon Web Services (AWS) services as needed. Beyond geodetic applications, needs have emerged to process large volumes of time-series SAR data collected for estimation of biomass and its change, in such campaigns as the upcoming AfriSAR field campaign. ESTO is funding JPL to extend the ISCE-ARIA model to a "SAR Science Data Processing Foundry" to on-ramp new data sources and to produce new science data products to meet the needs of science teams and, in general, science community members. An extension of the ISCE-ARIA model to support on-demand processing will permit PIs to leverage this Foundry to produce data products from accepted data sources when they need them. This paper will describe each of the elements of the SAR SDP Foundry and describe their integration into a new conceptual approach to enable more effective use of SAR instruments.

NREL Blows Up Batteries to Make the World Safer

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

Making lithium-ion batteries safer for earthlings and astronauts is something NREL excels at. In this video you’ll meet Matt Keyser, a senior energy storage engineer who is on a mission to improve the thermal performance of batteries for electric vehicles, consumer gadgets, and technology used by NASA in outer space. Matt and his team study battery failure using innovative technologies, such as the award-winning Battery Internal Short Circuit (ISC) Device that can precisely identify weak spots in battery cells. This cutting-edge research helps battery manufacturers develop advanced materials that can deliver superior results. Who benefits from all of this ingenuitymore » rooted in fundamental science? We all do!« less

NMR studies of conformational states of proteins involved in biosynthesis of iron-sulfur clusters

NASA Astrophysics Data System (ADS)

Dai, Ziqi

Iron-sulfur (Fe-S) clusters are the most ancient and ubiquitous cofactors that exist throughout evolution. The most important biosynthetic system of the cluster in both prokaryotes and eukaryotes is the ISC system. Defects in this system can be lethal and have been associated with a number of human diseases. Previous works show that a number of proteins are involved in the [Fe-S] biosynthetic processes and the structural flexibility may play an important role. For example, it was shown that apo-IscU, the scaffold protein, from Escherichia coli populates two functionally important conformational states, one dynamically disordered (D-state) and the other more structured (S-state) (Kim et al., 2009; Kim et al., 2012c). To further investigate the characteristics and transition of the conformational states of proteins involved in this system, I performed extensive NMR studies. Here, I present the findings based on my studies of two important players of the ISC system, IscU and HscB. In this research, I find that a peptidyl-prolyl cis/trans isomerization might account for the slow step in the S-D interconversion of IscU. More specifically, P14 and P101 are trans in the S-state, but become cis in the D-state. In addition, I discover that IscU is very responsive to pH changes, and I postulate that this response is correlated to conserved histidine residues, H10 and H105. Moreover, my thermodynamic analyses reveal that the S-D equilibrium of IscU is also very sensitive to change in temperature, pressure, and amino acid sequence compared to other proteins. In the study, I also discovered a novel state of IscU, the unfolded U-state. I suspect that this state may serve as an intermediate of interconversion between IscU S-/D-states. Finally, I extended the effort to HscB, and find that it may possess more conformational flexibility than expected earlier. I postulate that this flexibility may be the cause of the line-broadening observed during interaction of HscB with IscU (Fuzery et al., 2008; Kim et al., 2009) and HscA.

Comparison of hypocentre parameters of earthquakes in the Aegean region

NASA Astrophysics Data System (ADS)

Özel, Nurcan M.; Shapira, Avi; Harris, James

2007-06-01

The Aegean Sea is one of the more seismically active areas in the Euro-Mediterranean region. The seismic activity in the Aegean Sea is monitored by a number of local agencies that contribute their data to the International Seismological Centre (ISC). Consequently, the ISC Bulletin may serve as a reliable reference for assessing the capabilities of local agencies to monitor moderate and low magnitude earthquakes. We have compared bulletins of the Kandilli Observatory and Earthquake Research Institute (KOERI) and the ISC, for the period 1976-2003 that comprises the most complete data sets for both KOERI and ISC. The selected study area is the East Aegean Sea and West Turkey, bounded by latitude 35-41°N and by longitude 24-29°E. The total number of events known to occur in this area, during 1976-2003 is about 41,638. Seventy-two percent of those earthquakes were located by ISC and 75% were located by KOERI. As expected, epicentre location discrepancy between ISC and KOERI solutions are larger as we move away from the KOERI seismic network. Out of the 22,066 earthquakes located by both ISC and KOERI, only 4% show a difference of 50 km or more. About 140 earthquakes show a discrepancy of more than 100 km. Focal Depth determinations differ mainly in the subduction zone along the Hellenic arc. Less than 2% of the events differ in their focal depth by more than 25 km. Yet, the location solutions of about 30 events differ by more than 100 km. Almost a quarter of the events listed in the ISC Bulletin are missed by KOERI, most of them occurring off the coast of Turkey, in the East Aegean. Based on the frequency-magnitude distributions, the KOERI Bulletin is complete for earthquakes with duration magnitudes Md > 2.7 (both located and assigned magnitudes) where as the threshold magnitude for events with location and magnitude determinations by ISC is mb > 4.0. KOERI magnitudes seem to be poorly correlated with ISC magnitudes suggesting relatively high uncertainty in the magnitude determinations. It is apparent that KOERI, like other agencies in the region, will greatly benefit from a much improved regional cooperation.

The Comparison of the Inquiry Behavior of ISCS and Non-ISCS Science Students as Measured by the Tab Science Test

ERIC Educational Resources Information Center

Stallings, Everett S.; Snyder, William R.

1977-01-01

Studies of a group of seventh-grade students who were tested for inquiry skills using the TAB Science Test showed no significant differences between those students who had studied the Intermediate Science Curriculum Study (ISCS) and those who studied another curriculum. (MLH)

Protease-activated receptor-2 stimulates intestinal epithelial chloride transport through activation of PLC and selective PKC isoforms.

PubMed

van der Merwe, Jacques Q; Moreau, France; MacNaughton, Wallace K

2009-06-01

Serine proteases play important physiological roles through their activity at G protein-coupled protease-activated receptors (PARs). We examined the roles that specific phospholipase (PL) C and protein kinase (PK) C (PKC) isoforms play in the regulation of PAR(2)-stimulated chloride secretion in intestinal epithelial cells. Confluent SCBN epithelial monolayers were grown on Snapwell supports and mounted in modified Ussing chambers. Short-circuit current (I(sc)) responses to basolateral application of the selective PAR(2) activating peptide, SLIGRL-NH(2), were monitored as a measure of net electrogenic ion transport caused by PAR(2) activation. SLIGRL-NH(2) induced a transient I(sc) response that was significantly reduced by inhibitors of PLC (U73122), phosphoinositol-PLC (ET-18), phosphatidylcholine-PLC (D609), and phosphatidylinositol 3-kinase (PI3K; LY294002). Immunoblot analysis revealed the phosphorylation of both PLCbeta and PLCgamma following PAR(2) activation. Pretreatment of the cells with inhibitors of PKC (GF 109203X), PKCalpha/betaI (Gö6976), and PKCdelta (rottlerin), but not PKCzeta (selective pseudosubstrate inhibitor), also attenuated this response. Cellular fractionation and immunoblot analysis, as well as confocal immunocytochemistry, revealed increases of PKCbetaI, PKCdelta, and PKCepsilon, but not PKCalpha or PKCzeta, in membrane fractions following PAR(2) activation. Pretreatment of the cells with U73122, ET-18, or D609 inhibited PKC activation. Inhibition of PI3K activity only prevented PKCdelta translocation. Immunoblots revealed that PAR(2) activation induced phosphorylation of both cRaf and ERK1/2 via PKCdelta. Inhibition of PKCbetaI and PI3K had only a partial effect on this response. We conclude that basolateral PAR(2)-induced chloride secretion involves activation of PKCbetaI and PKCdelta via a PLC-dependent mechanism resulting in the stimulation of cRaf and ERK1/2 signaling.

CFTR is restricted to a small population of high expresser cells that provide a forskolin-sensitive transepithelial Cl- conductance in the proximal colon of the possum, Trichosurus vulpecula.

PubMed

Fan, Shujun; Harfoot, Natalie; Bartolo, Ray C; Butt, A Grant

2012-04-01

The cystic fibrosis transmembrane conductance regulator (CFTR) is central to anion secretion in both the possum and eutherian small intestine. Here, we investigated its role in the possum proximal colon, which has novel transport properties compared with the eutherian proximal colon. Despite considerable CFTR expression, high doses of the CFTR activator forskolin (EC(50)≈10 μmol l(-1)) were required for a modest, CFTR-dependent increase in short-circuit current (I(sc)) in the proximal colon. Presumably, this is because CFTR is restricted to the apical membrane of a small population of CFTR high expresser (CHE) cells in the surface and upper crypt epithelium. Furthermore, although the forskolin-stimulated I(sc) was dependent on serosal Na(+), Cl(-) and HCO(3)(-), consistent with anion secretion, inhibition of the basolateral Na-K-2Cl(-) (NKCC1) or Na-HCO(3) (pNBCe1) cotransporters did not prevent it. Therefore, although NKCC1 and pNBCe1 are expressed in the colonic epithelium they do not appear to be expressed in CHE cells. At low doses (IC(50)≈1 μmol l(-1)), forskolin also decreased the transepithelial conductance (G(T)) of the colon through inhibition of a 4,4'-diisothiocyano-2,2'-stilbenedisulphonic acid-sensitive anion conductance in the basolateral membrane of the CHE cells. This conductance is arranged in series with CFTR in the CHE cells and, therefore, the CHE cells provide a transepithelial Cl(-) conductance for passive Cl(-) absorption across the epithelium. Inhibition of the basolateral Cl(-) conductance of the CHE cells by forskolin will inhibit Na(+) absorption by restricting the movement of its counter-ion Cl(-), assisting in the conversion of the tissue from an absorptive to a secretory state.

Early nongenomic events in aldosterone action in renal collecting duct cells: PKCalpha activation, mineralocorticoid receptor phosphorylation, and cross-talk with the genomic response.

PubMed

Le Moëllic, Cathy; Ouvrard-Pascaud, Antoine; Capurro, Claudia; Cluzeaud, Francoise; Fay, Michel; Jaisser, Frederic; Farman, Nicolette; Blot-Chabaud, Marcel

2004-05-01

Effects of aldosterone on its target cells have long been considered to be mediated exclusively through the genomic pathway; however, evidence has been provided for rapid effects of the hormone that may involve nongenomic mechanisms. Whether an interaction exists between these two signaling pathways is not yet established. In this study, the authors show that aldosterone triggers both early nongenomic and late genomic increase in sodium transport in the RCCD(2) rat cortical collecting duct cell line. In these cells, the early (up to 2.5 h) aldosterone-induced increase in short-circuit current (Isc) is not blocked by the mineralocorticoid receptor (MR) antagonist RU26752, it does not require mRNA or protein synthesis, and it involves the PKCalpha signaling pathway. In addition, this early response is reproduced by aldosterone-BSA, which acts at the cell surface and presumably does not enter the cells (aldo-BSA is unable to trigger the late response). The authors also show that MR is rapidly phosphorylated on serine and threonine residues by aldosterone or aldosterone-BSA. In contrast, the late (4 to 24 h) aldosterone-induced increase in ion transport occurs through activation of the MR and requires mRNA and protein synthesis. Interestingly, nongenomic and genomic aldosterone actions appear to be interdependent. Blocking the PKCalpha pathway results in the inhibition of the late genomic response to aldosterone, as demonstrated by the suppression of aldosterone-induced increase in MR transactivation activity, alpha1 Na(+)/K(+)/ATPase mRNA, and Isc. These data suggest cross-talk between the nongenomic and genomic responses to aldosterone in renal cells and suggest that the aldosterone-MR mediated increase in mRNA/protein synthesis and ion transport depends, at least in part, upon PKCalpha activation. E-mail: marcel.blot-chabaud@pharmacie.univ-mrs.fr

ISC, a Novel Group of Bacterial and Archaeal DNA Transposons That Encode Cas9 Homologs

PubMed Central

Kapitonov, Vladimir V.; Makarova, Kira S.

2015-01-01

ABSTRACT Bacterial genomes encode numerous homologs of Cas9, the effector protein of the type II CRISPR-Cas systems. The homology region includes the arginine-rich helix and the HNH nuclease domain that is inserted into the RuvC-like nuclease domain. These genes, however, are not linked to cas genes or CRISPR. Here, we show that Cas9 homologs represent a distinct group of nonautonomous transposons, which we denote ISC (insertion sequences Cas9-like). We identify many diverse families of full-length ISC transposons and demonstrate that their terminal sequences (particularly 3′ termini) are similar to those of IS605 superfamily transposons that are mobilized by the Y1 tyrosine transposase encoded by the TnpA gene and often also encode the TnpB protein containing the RuvC-like endonuclease domain. The terminal regions of the ISC and IS605 transposons contain palindromic structures that are likely recognized by the Y1 transposase. The transposons from these two groups are inserted either exactly in the middle or upstream of specific 4-bp target sites, without target site duplication. We also identify autonomous ISC transposons that encode TnpA-like Y1 transposases. Thus, the nonautonomous ISC transposons could be mobilized in trans either by Y1 transposases of other, autonomous ISC transposons or by Y1 transposases of the more abundant IS605 transposons. These findings imply an evolutionary scenario in which the ISC transposons evolved from IS605 family transposons, possibly via insertion of a mobile group II intron encoding the HNH domain, and Cas9 subsequently evolved via immobilization of an ISC transposon. IMPORTANCE Cas9 endonucleases, the effectors of type II CRISPR-Cas systems, represent the new generation of genome-engineering tools. Here, we describe in detail a novel family of transposable elements that encode the likely ancestors of Cas9 and outline the evolutionary scenario connecting different varieties of these transposons and Cas9. PMID:26712934

Acetic acid induces Sch9p-dependent translocation of Isc1p from the endoplasmic reticulum into mitochondria.

PubMed

Rego, António; Cooper, Katrina F; Snider, Justin; Hannun, Yusuf A; Costa, Vítor; Côrte-Real, Manuela; Chaves, Susana R

2018-06-01

Changes in sphingolipid metabolism have been linked to modulation of cell fate in both yeast and mammalian cells. We previously assessed the role of sphingolipids in cell death regulation using a well characterized yeast model of acetic acid-induced regulated cell death, finding that Isc1p, inositol phosphosphingolipid phospholipase C, plays a pro-death role in this process. Indeed, isc1∆ mutants exhibited a higher resistance to acetic acid associated with reduced mitochondrial alterations. Here, we show that Isc1p is regulated by Sch9p under acetic acid stress, since both single and double mutants lacking Isc1p or/and Sch9p have the same resistant phenotype, and SCH9 deletion leads to a higher retention of Isc1p in the endoplasmic reticulum upon acetic acid exposure. We also found that the higher resistance of all mutants correlates with higher levels of endogenous mitochondrial phosphorylated long chain bases (LCBPs), suggesting that changing the sphingolipid balance in favour of LCBPs in mitochondria results in increased survival to acetic acid. In conclusion, our results suggest that Sch9p pathways modulate acetic acid-induced cell death, through the regulation of Isc1p cellular distribution, thus affecting the sphingolipid balance that regulates cell fate. Copyright © 2018 Elsevier B.V. All rights reserved.

The iron-binding CyaY and IscX proteins assist the ISC-catalyzed Fe-S biogenesis in Escherichia coli.

PubMed

Roche, Béatrice; Huguenot, Allison; Barras, Frédéric; Py, Béatrice

2015-02-01

In eukaryotes, frataxin deficiency (FXN) causes severe phenotypes including loss of iron-sulfur (Fe-S) cluster protein activity, accumulation of mitochondrial iron and leads to the neurodegenerative disease Friedreich's ataxia. In contrast, in prokaryotes, deficiency in the FXN homolog, CyaY, was reported not to cause any significant phenotype, questioning both its importance and its actual contribution to Fe-S cluster biogenesis. Because FXN is conserved between eukaryotes and prokaryotes, this surprising discrepancy prompted us to reinvestigate the role of CyaY in Escherichia coli. We report that CyaY (i) potentiates E. coli fitness, (ii) belongs to the ISC pathway catalyzing the maturation of Fe-S cluster-containing proteins and (iii) requires iron-rich conditions for its contribution to be significant. A genetic interaction was discovered between cyaY and iscX, the last gene of the isc operon. Deletion of both genes showed an additive effect on Fe-S cluster protein maturation, which led, among others, to increased resistance to aminoglycosides and increased sensitivity to lambda phage infection. Together, these in vivo results establish the importance of CyaY as a member of the ISC-mediated Fe-S cluster biogenesis pathway in E. coli, like it does in eukaryotes, and validate IscX as a new bona fide Fe-S cluster biogenesis factor. © 2014 John Wiley & Sons Ltd.

Defining a stem cell hierarchy in the intestine: markers, caveats and controversies

PubMed Central

Smith, Nicholas R.; Gallagher, Alexandra C.

2016-01-01

Abstract The past decade has appreciated rapid advance in identifying the once elusive intestinal stem cell (ISC) populations that fuel the continual renewal of the epithelial layer. This advance was largely driven by identification of novel stem cell marker genes, revealing the existence of quiescent, slowly‐ and active‐cycling ISC populations. However, a critical barrier for translating this knowledge to human health and disease remains elucidating the functional interplay between diverse stem cell populations. Currently, the precise hierarchical and regulatory relationships between these ISC populations are under intense scrutiny. The classical theory of a linear hierarchy, where quiescent and slowly‐cycling stem cells self‐renew but replenish an active‐cycling population, is well established in other rapidly renewing tissues such as the haematopoietic system. Efforts to definitively establish a similar stem cell hierarchy within the intestinal epithelium have yielded conflicting results, been difficult to interpret, and suggest non‐conventional alternatives to a linear hierarchy. While these new and potentially paradigm‐shifting discoveries are intriguing, the field will require development of a number of critical tools, including highly specific stem cell marker genes along with more rigorous experimental methodologies, to delineate the complex cellular relationships within this dynamic organ system. PMID:26864260

The sensitivity of motor response to needle nerve stimulation during ultrasound guided interscalene catheter placement.

PubMed

Fredrickson, Michael J

2008-01-01

Neurostimulation during single shot interscalene block has a significant false negative motor response rate. Compared with tangential needle approaches for single shot block, interscalene catheter (ISC) placement commonly involves Tuohy needles inserted longitudinally to the brachial plexus. This study aimed to determine the sensitivity of neurostimulation during ultrasound-guided ISC needle placement, and the feasibility of an ultrasound-guided ISC needle endpoint. One hundred fifty-five consecutive nonstimulating ISCs were placed with the needle tip position confirmed by the sonographic spread of 5 mL dextrose 5%. Catheter advancement was then blind 2 to 3 cm past the needle tip. A 0.8 mA electrical stimulus at 2 Hz was applied throughout. When a satisfactory image was obtained, neurostimulation was ignored and the minimum motor response amplitude noted. If imaging was equivocal, a brief appropriate motor response at 0.8 mA was sought. A sustained response at <0.5 mA was only sought if imaging was suboptimal. Prior to surgery conducted under general anesthesia, 30 mL ropivacaine 0.5% was administered through the ISC. Catheter success was defined as a recovery room numerical rating pain score of

Tissue underlying the intestinal epithelium elicits proliferation of intestinal stem cells following cytotoxic damage

PubMed Central

Seiler, Kristen M; Schenhals, Erica L; von Furstenberg, Richard J; Allena, Bhavya K; Smith, Brian J; Scaria, Denny; Bresler, Michele N; Dekaney, Christopher M; Henning, Susan J

2015-01-01

The goals of this study were to document the proliferative response of intestinal stem cells (ISCs) during regeneration after damage from doxorubicin (DXR) and to characterize the signals responsible for ISC activation. To this end, jejuni from DXR-treated mice were harvested for histology, assessment of ISC numbers and proliferation by flow cytometry, crypt culture, and RNA analyses. Histology showed that crypt depth and width were increased 4 days after DXR. At this time point, flow cytometry on tissue collected 1 hour after EdU administration revealed increased numbers of CD24loUEA− ISCs and increased percentage of ISCs cycling. In culture, crypts harvested from DXR-treated mice were equally proliferative as those of control mice. Addition of subepithelial intestinal tissue (SET) collected 4 days after DXR elicited increased budding (1.4 ± 0.3 vs. 5.1 ± 1.0 buds per enteroid). Microarray analysis of SET collected 4 days after DXR revealed 1,030 differentially expressed transcripts. Cross comparison of Gene Ontology terms considered relevant to ISC activation pointed to 10 candidate genes. Of these the epidermal growth factor (EGF) family member amphiregulin and the BMP antagonist chordin-like 2 were chosen for further study. In crypt culture, amphiregulin alone did not elicit significant budding, but amphiregulin in combination with BMP antagonism showed marked synergism (yielding 6.3 ± 0.5 buds per enteroid). These data suggest a critical role for underlying tissue in regulating ISC behavior after damage, and point to synergism between amphiregulin and chordin-like 2 as factors which may account for activation of ISCs in the regenerative phase. PMID:25693894

Intestinal stem cells remain viable after prolonged tissue storage

PubMed Central

Fuller, Megan K.; Faulk, Denver M.; Sundaram, Nambirajan; Mahe, Maxime M.; Stout, Kara M.; von Furstenberg, Richard J.; Smith, Brian J.; McNaughton, Kirk K.; Shroyer, Noah F.; Helmrath, Michael A.; Henning, Susan J.

2013-01-01

Intestinal stem cells (ISCs) are responsible for renewal of the epithelium both during normal homeostasis and following injury. As such they have significant therapeutic potential. However, it is unknown whether ISCs can survive tissue storage. We hypothesized that, although the majority of epithelial cells may die, ISCs would remain viable for at least 24 h at 4°C. To explore this hypothesis, jejuni of C57Bl6/J or Lgr5-LacZ mice were removed and either processed immediately or placed in phosphate buffered saline (PBS) at 4°C. Delayed isolations of epithelia were performed after 24, 30, or 48 h storage. At the light microscope level, despite extensive apoptosis of villus epithelial cells, small intestinal crypts remained morphologically intact through 30 h and ISCs were identifiable via Lgr5-LacZ positivity. Electron microscopy showed that ISCs retain high integrity through 24 h. When assessed by flow cytometry, ISCs were more resistant to degeneration than the rest of the epithelium, including neighboring Paneth cells, with higher viability across all time points. Culture of isolated crypts showed no loss of capacity to form complex enteroids after 24 h tissue storage, with efficiencies after 7 days of culture remaining above 80%. By 30 h storage, efficiencies declined but budding capability was retained. We conclude that, with delay in isolation, ISCs remain viable and retain their proliferative capacity. In contrast, the remainder of the epithelium, including the Paneth cells, exhibits degeneration and programmed cell death. If these findings are recapitulated with human tissue, storage at 4°C may offer a valuable temporal window for harvest of crypts or ISCs for therapeutic application. PMID:23820734

Stress responsive miR-31 is a major modulator of mouse intestinal stem cells during regeneration and tumorigenesis.

PubMed

Tian, Yuhua; Ma, Xianghui; Lv, Cong; Sheng, Xiaole; Li, Xiang; Zhao, Ran; Song, Yongli; Andl, Thomas; Plikus, Maksim V; Sun, Jinyue; Ren, Fazheng; Shuai, Jianwei; Lengner, Christopher J; Cui, Wei; Yu, Zhengquan

2017-09-05

Intestinal regeneration and tumorigenesis are believed to be driven by intestinal stem cells (ISCs). Elucidating mechanisms underlying ISC activation during regeneration and tumorigenesis can help uncover the underlying principles of intestinal homeostasis and disease including colorectal cancer. Here we show that miR-31 drives ISC proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Furthermore, miR-31 has oncogenic properties, promoting intestinal tumorigenesis. Mechanistically, miR-31 acts to balance input from Wnt, BMP, TGFβ signals to coordinate control of intestinal homeostasis, regeneration and tumorigenesis. We further find that miR-31 is regulated by the STAT3 signaling pathway in response to radiation injury. These findings identify miR-31 as a critical modulator of ISC biology, and a potential therapeutic target for a broad range of intestinal regenerative disorders and cancers.

Techniques and Tools for Estimating Ionospheric Effects in Interferometric and Polarimetric SAR Data

NASA Technical Reports Server (NTRS)

Rosen, P.; Lavalle, M.; Pi, X.; Buckley, S.; Szeliga, W.; Zebker, H.; Gurrola, E.

2011-01-01

The InSAR Scientific Computing Environment (ISCE) is a flexible, extensible software tool designed for the end-to-end processing and analysis of synthetic aperture radar data. ISCE inherits the core of the ROI_PAC interferometric tool, but contains improvements at all levels of the radar processing chain, including a modular and extensible architecture, new focusing approach, better geocoding of the data, handling of multi-polarization data, radiometric calibration, and estimation and correction of ionospheric effects. In this paper we describe the characteristics of ISCE with emphasis on the ionospheric modules. To detect ionospheric anomalies, ISCE implements the Faraday rotation method using quadpolarimetric images, and the split-spectrum technique using interferometric single-, dual- and quad-polarimetric images. The ability to generate co-registered time series of quad-polarimetric images makes ISCE also an ideal tool to be used for polarimetric-interferometric radar applications.

In an Unpredictable and Changing Environment: Intrapreneurial Self-Capital As a Key Resource for Life Satisfaction and Flourishing

PubMed Central

Di Fabio, Annamaria; Palazzeschi, Letizia; Bucci, Ornella

2017-01-01

The twenty-first century is characterized by an unpredictable and challenging work environment, and the Intrapreneurial Self-Capital (ISC) career and life construct can be seen as a core of individual intrapreneurial resources that enables people to cope with ongoing challenges, changes, and transitions founding innovative solutions when confronted with the constraints imposed by such an environment. The ISC is a challenging construct since it can enhance behavior and attitudes through specific training, unlike personality traits, which are considered substantially stable in the literature. Against this background, the present study examined the relationship between ISC and well-being (hedonic well-being and eudaimonic well-being) controlling for the effects of personality traits. The Big Five Questionnaire (BFQ), the Intrapreneurial Self-Capital Scale (ISCS), the Satisfaction With Life Scale (SWLS), and the Flourishing Scale (FS) were administered to 258 Italian workers. Hierarchical regression analyses showed that ISC explained a percentage of incremental variance beyond that explained by personality traits in relation to both life satisfaction and flourishing. These results indicate that ISC is a key resource for hedonic well-being and eudaimonic well-being and that it offers new research and intervention opportunities. PMID:29109692

In an Unpredictable and Changing Environment: Intrapreneurial Self-Capital As a Key Resource for Life Satisfaction and Flourishing.

PubMed

Di Fabio, Annamaria; Palazzeschi, Letizia; Bucci, Ornella

2017-01-01

The twenty-first century is characterized by an unpredictable and challenging work environment, and the Intrapreneurial Self-Capital (ISC) career and life construct can be seen as a core of individual intrapreneurial resources that enables people to cope with ongoing challenges, changes, and transitions founding innovative solutions when confronted with the constraints imposed by such an environment. The ISC is a challenging construct since it can enhance behavior and attitudes through specific training, unlike personality traits, which are considered substantially stable in the literature. Against this background, the present study examined the relationship between ISC and well-being (hedonic well-being and eudaimonic well-being) controlling for the effects of personality traits. The Big Five Questionnaire (BFQ), the Intrapreneurial Self-Capital Scale (ISCS), the Satisfaction With Life Scale (SWLS), and the Flourishing Scale (FS) were administered to 258 Italian workers. Hierarchical regression analyses showed that ISC explained a percentage of incremental variance beyond that explained by personality traits in relation to both life satisfaction and flourishing. These results indicate that ISC is a key resource for hedonic well-being and eudaimonic well-being and that it offers new research and intervention opportunities.

Guest concentration, bias current, and temperature-dependent sign inversion of magneto-electroluminescence in thermally activated delayed fluorescence devices

NASA Astrophysics Data System (ADS)

Deng, Junquan; Jia, Weiyao; Chen, Yingbing; Liu, Dongyu; Hu, Yeqian; Xiong, Zuhong

2017-03-01

Non-emissive triplet excited states in devices that undergo thermally activated delayed fluorescence (TADF) can be up-converted to singlet excited states via reverse intersystem crossing (RISC), which leads to an enhanced electroluminescence efficiency. Exciton-based fluorescence devices always exhibit a positive magneto-electroluminescence (MEL) because intersystem crossing (ISC) can be suppressed effectively by an external magnetic field. Conversely, TADF devices should exhibit a negative MEL because RISC is suppressed by the external magnetic field. Intriguingly, we observed a positive MEL in TADF devices. Moreover, the sign of the MEL was either positive or negative, and depended on experimental conditions, including doping concentration, current density and temperature. The MEL observed from our TADF devices demonstrated that ISC in the host material and RISC in the guest material coexisted. These competing processes were affected by the experimental conditions, which led to the sign change of the MEL. This work gives important insight into the energy transfer processes and the evolution of excited states in TADF devices.

The CTBTO Link to the database of the International Seismological Centre (ISC)

NASA Astrophysics Data System (ADS)

Bondar, I.; Storchak, D. A.; Dando, B.; Harris, J.; Di Giacomo, D.

2011-12-01

The CTBTO Link to the database of the International Seismological Centre (ISC) is a project to provide access to seismological data sets maintained by the ISC using specially designed interactive tools. The Link is open to National Data Centres and to the CTBTO. By means of graphical interfaces and database queries tailored to the needs of the monitoring community, the users are given access to a multitude of products. These include the ISC and ISS bulletins, covering the seismicity of the Earth since 1904; nuclear and chemical explosions; the EHB bulletin; the IASPEI Reference Event list (ground truth database); and the IDC Reviewed Event Bulletin. The searches are divided into three main categories: The Area Based Search (a spatio-temporal search based on the ISC Bulletin), the REB search (a spatio-temporal search based on specific events in the REB) and the IMS Station Based Search (a search for historical patterns in the reports of seismic stations close to a particular IMS seismic station). The outputs are HTML based web-pages with a simplified version of the ISC Bulletin showing the most relevant parameters with access to ISC, GT, EHB and REB Bulletins in IMS1.0 format for single or multiple events. The CTBTO Link offers a tool to view REB events in context within the historical seismicity, look at observations reported by non-IMS networks, and investigate station histories and residual patterns for stations registered in the International Seismographic Station Registry.

The QWIP Focal Plane Assembly for NASA's Landsat Data Continuity Mission

NASA Technical Reports Server (NTRS)

Jhabvala, M; Choi, K.; Reuter, D.; Sundaram, M.; Jhabvala, C; La, Anh; Waczynski, Augustyn; Bundas, Jason

2010-01-01

The Thermal Infrared Sensor (TIRS) is a QWIP based instrument intended to supplement the Operational Land Imager (OLI) for the Landsat Data Continuity Mission (LDCM). The TIRS instrument is a dual channel far infrared imager with the two bands centered at 10.8[mu]m and 12.0[mu]m. The focal plane assembly (FPA) consists of three 640x512 GaAs Quantum Well Infrared Photodetector (QWIP) arrays precisely mounted to a silicon carrier substrate that is mounted on an invar baseplate. The two spectral bands are defined by bandpass filters mounted in close proximity to the detector surfaces. The focal plane operating temperature is 43K. The QWIP arrays are hybridized to Indigo ISC9803 readout integrated circuits (ROICs). Two varieties of QWIP detector arrays are being developed for this project, a corrugated surface structure QWIP and a grating surface structure QWIP. This paper will describe the TIRS system noise equivalent temperature difference sensitivity as it affects the QWIP focal plane performance requirements: spectral response, dark current, conversion efficiency, read noise, temperature stability, pixel uniformity, optical crosstalk and pixel yield. Additional mechanical constraints as well as qualification through Technology Readiness Level 6 (TRL 6) will also be discussed.

The QWIP Focal Plane Assembly for NASA's Landsat Data Continuity Mission

NASA Technical Reports Server (NTRS)

Jhabvala, M.; Reuter, D.; Choi, K.; Sundaram, M.; Jhabvala, C.; La, A.; Waczynski, A.; Bundas, J.

2011-01-01

The Thermal Infrared Sensor (TIRS) is a QWIP based instrument intended to supplement the Operational Land Imager (OLI) for the Landsat Data Continuity Mission (LDCM). The TIRS instrument is a dual channel far infrared imager with the two bands centered at 10.8 m and 12.0 m. The focal plane assembly (FPA) consists of three 640x512 GaAs Quantum Well Infrared Photodetector (QWIP) arrays precisely mounted to a silicon carrier substrate that is mounted on an invar baseplate. The two spectral bands are defined by bandpass filters mounted in close proximity to the detector surfaces. The focal plane operating temperature is 43K. The QWIP arrays are hybridized to Indigo ISC9803 readout integrated circuits (ROICs). Two varieties of QWIP detector arrays are being developed for this project, a corrugated surface structure QWIP and a grating surface structure QWIP. This paper will describe the TIRS system noise equivalent temperature difference sensitivity as it affects the QWIP focal plane performance requirements: spectral response, dark current, conversion efficiency, read noise, temperature stability, pixel uniformity, optical crosstalk and pixel yield. Additional mechanical constraints as well as qualification through Technology Readiness Level 6 (TRL 6) will also be discussed.

Theoretical study on ultrafast intersystem crossing of chromium(III) acetylacetonate

NASA Astrophysics Data System (ADS)

Ando, Hideo; Iuchi, Satoru; Sato, Hirofumi

2012-05-01

In the relaxation process from the 4T2g state of chromium(III) acetylacetonate, CrIII(acac)3, ultrafast intersystem crossing (ISC) competes with vibrational relaxation (VR). This contradicts the conventional cascade model, where ISC rates are slower than VR ones. We hence investigate the relaxation process with quantum chemical calculations and excited-state wavepacket simulations to obtain clues about the origins of the ultrafast ISC. It is found that a potential energy curve of the 4T2g state crosses those of the 2T1g states near the Franck-Condon region and their spin-orbit couplings are strong. Consequently, ultrafast ISC between these states is observed in the wavepacket simulation.

Haemocytes control stem cell activity in the Drosophila intestine.

PubMed

Ayyaz, Arshad; Li, Hongjie; Jasper, Heinrich

2015-06-01

Coordination of stem cell activity with inflammatory responses is critical for regeneration and homeostasis of barrier epithelia. The temporal sequence of cell interactions during injury-induced regeneration is only beginning to be understood. Here we show that intestinal stem cells (ISCs) are regulated by macrophage-like haemocytes during the early phase of regenerative responses of the Drosophila intestinal epithelium. On tissue damage, haemocytes are recruited to the intestine and secrete the BMP homologue DPP, inducing ISC proliferation by activating the type I receptor Saxophone and the Smad homologue SMOX. Activated ISCs then switch their response to DPP by inducing expression of Thickveins, a second type I receptor that has previously been shown to re-establish ISC quiescence by activating MAD. The interaction between haemocytes and ISCs promotes infection resistance, but also contributes to the development of intestinal dysplasia in ageing flies. We propose that similar interactions influence pathologies such as inflammatory bowel disease and colorectal cancer in humans.

Hemocytes control stem cell activity in the Drosophila intestine

PubMed Central

Ayyaz, Arshad; Li, Hongjie; Jasper, Heinrich

2015-01-01

SUMMARY Coordination of stem cell activity with inflammatory responses is critical for regeneration and homeostasis of barrier epithelia. The temporal sequence of cell interactions during injury-induced regeneration is only beginning to be understood. Here we show that intestinal stem cells (ISCs) are regulated by macrophage-like hemocytes during the early phase of regenerative responses of the Drosophila intestinal epithelium. Upon tissue damage, hemocytes are recruited to the intestine and secrete the TGFβ/BMP homologue Dpp, inducing ISC proliferation by activating the Type I receptor Saxophone and the Smad homologue Smox. Activated ISCs then switch their response to Dpp by inducing expression of Thickveins, a second Type I receptor that has previously been shown to re-establish ISC quiescence by activating Mad. The interaction between hemocytes and ISCs promotes infection resistance, but also contributes to the development of intestinal dysplasia in aging flies. We propose that similar interactions influence pathologies like inflammatory bowel disease and colorectal cancer in humans. PMID:26005834

Mapping 2000 2010 Impervious Surface Change in India Using Global Land Survey Landsat Data

NASA Technical Reports Server (NTRS)

Wang, Panshi; Huang, Chengquan; Brown De Colstoun, Eric C.

2017-01-01

Understanding and monitoring the environmental impacts of global urbanization requires better urban datasets. Continuous field impervious surface change (ISC) mapping using Landsat data is an effective way to quantify spatiotemporal dynamics of urbanization. It is well acknowledged that Landsat-based estimation of impervious surface is subject to seasonal and phenological variations. The overall goal of this paper is to map 200-02010 ISC for India using Global Land Survey datasets and training data only available for 2010. To this end, a method was developed that could transfer the regression tree model developed for mapping 2010 impervious surface to 2000 using an iterative training and prediction (ITP) approach An independent validation dataset was also developed using Google Earth imagery. Based on the reference ISC from the validation dataset, the RMSE of predicted ISC was estimated to be 18.4%. At 95% confidence, the total estimated ISC for India between 2000 and 2010 is 2274.62 +/- 7.84 sq km.

Iron binding activity is essential for the function of IscA in iron-sulphur cluster biogenesis

PubMed Central

Landry, Aaron P.; Cheng, Zishuo; Ding, Huangen

2013-01-01

Iron-sulphur cluster biogenesis requires coordinated delivery of iron and sulphur to scaffold proteins, followed by transfer of the assembled clusters from scaffold proteins to target proteins. This complex process is accomplished by a group of dedicated iron-sulphur cluster assembly proteins that are conserved from bacteria to humans. While sulphur in iron-sulphur clusters is provided by L-cysteine via cysteine desulfurase, the iron donor(s) for iron-sulphur cluster assembly remains largely elusive. Here we report that among the primary iron-sulphur cluster assembly proteins, IscA has a unique and strong binding activity for mononuclear iron in vitro and in vivo. Furthermore, the ferric iron centre tightly bound in IscA can be readily extruded by L-cysteine, followed by reduction to ferrous iron for iron-sulphur cluster biogenesis. Substitution of the highly conserved residue tyrosine 40 with phenylalanine (Y40F) in IscA results in a mutant protein that has a diminished iron binding affinity but retains the iron-sulphur cluster binding activity. Genetic complementation studies show that the IscA Y40F mutant is inactive in vivo, suggesting that the iron binding activity is essential for the function of IscA in iron-sulphur cluster biogenesis. PMID:23258274

Updating default depths in the ISC bulletin

NASA Astrophysics Data System (ADS)

Bolton, Maiclaire K.; Storchak, Dmitry A.; Harris, James

2006-09-01

The International Seismological Centre (ISC) publishes the definitive global bulletin of earthquake locations. In the ISC bulletin, we aim to obtain a free depth, but often this is not possible. Subsequently, the first option is to obtain a depth derived from depth phases. If depth phases are not available, we then use the reported depth from a reputable local agency. Finally, as a last resort, we set a default depth. In the past, common depths of 10, 33, or multiples of 50 km have been assigned. Assigning a more meaningful default depth, specific to a seismic region will increase the consistency of earthquake locations within the ISC bulletin and allow the ISC to publish better positions and magnitude estimates. It will also improve the association of reported secondary arrivals to corresponding seismic events. We aim to produce a global set of default depths, based on a typical depth for each area, from well-constrained events in the ISC bulletin or where depth could be constrained using a consistent set of depth phase arrivals provided by a number of different reporters. In certain areas, we must resort to using other assumptions. For these cases, we use a global crustal model (Crust2.0) to set default depths to half the thickness of the crust.

Iron binding activity is essential for the function of IscA in iron-sulphur cluster biogenesis.

PubMed

Landry, Aaron P; Cheng, Zishuo; Ding, Huangen

2013-03-07

Iron-sulphur cluster biogenesis requires coordinated delivery of iron and sulphur to scaffold proteins, followed by transfer of the assembled clusters from scaffold proteins to target proteins. This complex process is accomplished by a group of dedicated iron-sulphur cluster assembly proteins that are conserved from bacteria to humans. While sulphur in iron-sulphur clusters is provided by L-cysteine via cysteine desulfurase, the iron donor(s) for iron-sulphur cluster assembly remains largely elusive. Here we report that among the primary iron-sulphur cluster assembly proteins, IscA has a unique and strong binding activity for mononuclear iron in vitro and in vivo. Furthermore, the ferric iron centre tightly bound in IscA can be readily extruded by l-cysteine, followed by reduction to ferrous iron for iron-sulphur cluster biogenesis. Substitution of the highly conserved residue tyrosine 40 with phenylalanine (Y40F) in IscA results in a mutant protein that has a diminished iron binding affinity but retains the iron-sulphur cluster binding activity. Genetic complementation studies show that the IscA Y40F mutant is inactive in vivo, suggesting that the iron binding activity is essential for the function of IscA in iron-sulphur cluster biogenesis.

Tangled web of interactions among proteins involved in iron–sulfur cluster assembly as unraveled by NMR, SAXS, chemical crosslinking, and functional studies☆

PubMed Central

Kim, Jin Hae; Bothe, Jameson R.; Alderson, T. Reid; Markley, John L.

2014-01-01

Proteins containing iron–sulfur (Fe–S) clusters arose early in evolution and are essential to life. Organisms have evolved machinery consisting of specialized proteins that operate together to assemble Fe–S clusters efficiently so as to minimize cellular exposure to their toxic constituents: iron and sulfide ions. To date, the best studied system is the iron sulfur cluster (isc) operon of Escherichia coli, and the eight ISC proteins it encodes. Our investigations over the past five years have identified two functional conformational states for the scaffold protein (IscU) and have shown that the other ISC proteins that interact with IscU prefer to bind one conformational state or the other. From analyses of the NMR spectroscopy-derived network of interactions of ISC proteins and small-angle X-ray scattering (SAXS), chemical crosslinking experiments, and functional assays, we have constructed working models for Fe–S cluster assembly and delivery. Future work is needed to validate and refine what has been learned about the E. coli system and to extend these findings to the homologous Fe–S cluster biosynthetic machinery of yeast and human mitochondria. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases. PMID:25450980

Intersectoral collaboration for physical activity in Korean Healthy Cities.

PubMed

Kang, Eunjeong

2016-09-01

Intersectoral collaboration (ISC) is important in the health field because the complexity of determinants of health makes it difficult for one institution to resolve all health issues. Promotion of physical activity can especially benefit from a multi-sectoral approach. Despite so much emphasis on its importance in both primary health and health promotion, ISC has been underachieved in the field. This study aimed to examine the characteristics and level of ISC among physical activity programs in Healthy Cities as compared to non-Healthy Cities. I conducted a postal survey where 24 people from Healthy Cities and 72 people from non-Healthy Cities participated. The survey included questions to measure the level of ISC as well as to determine ISC partners and activities. Among the entire 393 physical activity programs, 336 (85.5%) had some kind of collaboration with one or more partners. The percentage having one or more partners was greater in Healthy Cities than in non-Healthy Cities. However, there were no statistical differences between the two groups in terms of the level of ISC within a municipal organization. Collaboration activities of the other departments were mostly supportive, such as providing a venue, recruiting participants and publicizing, and other kinds of administrative support. To strengthen ISC in Korean Healthy Cities, various actions including providing a legal basis, specific and substantive supports, financial incentives, and organizational recognitions will be helpful as well as the development of partnerships with other departments in urban planning, transport, urban design, and communication. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The InSAR Scientific Computing Environment (ISCE): An Earth Science SAR Processing Framework, Toolbox, and Foundry

NASA Astrophysics Data System (ADS)

Agram, P. S.; Gurrola, E. M.; Lavalle, M.; Sacco, G. F.; Rosen, P. A.

2016-12-01

The InSAR Scientific Computing Environment (ISCE) provides both a modular, flexible, and extensible framework for building software components and applications that work together seamlessly as well as a toolbox for processing InSAR data into higher level geodetic image products from a diverse array of radar satellites and aircraft. ISCE easily scales to serve as the SAR processing engine at the core of the NASA JPL Advanced Rapid Imaging and Analysis (ARIA) Center for Natural Hazards as well as a software toolbox for individual scientists working with SAR data. ISCE is planned as the foundational element in processing NISAR data, enabling a new class of analyses that take greater advantage of the long time and large spatial scales of these data. ISCE in ARIA is also a SAR Foundry for development of new processing components and workflows to meet the needs of both large processing centers and individual users. The ISCE framework contains object-oriented Python components layered to construct Python InSAR components that manage legacy Fortran/C InSAR programs. The Python user interface enables both command-line deployment of workflows as well as an interactive "sand box" (the Python interpreter) where scientists can "play" with the data. Recent developments in ISCE include the addition of components to ingest Sentinel-1A SAR data (both stripmap and TOPS-mode) and a new workflow for processing the TOPS-mode data. New components are being developed to exploit polarimetric-SAR data to provide the ecosystem and land-cover/land-use change communities with rigorous and efficient tools to perform multi-temporal, polarimetric and tomographic analyses in order to generate calibrated, geocoded and mosaicked Level-2 and Level-3 products (e.g., maps of above-ground biomass or forest disturbance). ISCE has been downloaded by over 200 users by a license for WinSAR members through the Unavco.org website. Others may apply directly to JPL for a license at download.jpl.nasa.gov.

HYMOSS signal processing for pushbroom spectral imaging

NASA Technical Reports Server (NTRS)

Ludwig, David E.

1991-01-01

The objective of the Pushbroom Spectral Imaging Program was to develop on-focal plane electronics which compensate for detector array non-uniformities. The approach taken was to implement a simple two point calibration algorithm on focal plane which allows for offset and linear gain correction. The key on focal plane features which made this technique feasible was the use of a high quality transimpedance amplifier (TIA) and an analog-to-digital converter for each detector channel. Gain compensation is accomplished by varying the feedback capacitance of the integrate and dump TIA. Offset correction is performed by storing offsets in a special on focal plane offset register and digitally subtracting the offsets from the readout data during the multiplexing operation. A custom integrated circuit was designed, fabricated, and tested on this program which proved that nonuniformity compensated, analog-to-digital converting circuits may be used to read out infrared detectors. Irvine Sensors Corporation (ISC) successfully demonstrated the following innovative on-focal-plane functions that allow for correction of detector non-uniformities. Most of the circuit functions demonstrated on this program are finding their way onto future IC's because of their impact on reduced downstream processing, increased focal plane performance, simplified focal plane control, reduced number of dewar connections, as well as the noise immunity of a digital interface dewar. The potential commercial applications for this integrated circuit are primarily in imaging systems. These imaging systems may be used for: security monitoring systems, manufacturing process monitoring, robotics, and for spectral imaging when used in analytical instrumentation.

HYMOSS signal processing for pushbroom spectral imaging

NASA Astrophysics Data System (ADS)

Ludwig, David E.

1991-06-01

The objective of the Pushbroom Spectral Imaging Program was to develop on-focal plane electronics which compensate for detector array non-uniformities. The approach taken was to implement a simple two point calibration algorithm on focal plane which allows for offset and linear gain correction. The key on focal plane features which made this technique feasible was the use of a high quality transimpedance amplifier (TIA) and an analog-to-digital converter for each detector channel. Gain compensation is accomplished by varying the feedback capacitance of the integrate and dump TIA. Offset correction is performed by storing offsets in a special on focal plane offset register and digitally subtracting the offsets from the readout data during the multiplexing operation. A custom integrated circuit was designed, fabricated, and tested on this program which proved that nonuniformity compensated, analog-to-digital converting circuits may be used to read out infrared detectors. Irvine Sensors Corporation (ISC) successfully demonstrated the following innovative on-focal-plane functions that allow for correction of detector non-uniformities. Most of the circuit functions demonstrated on this program are finding their way onto future IC's because of their impact on reduced downstream processing, increased focal plane performance, simplified focal plane control, reduced number of dewar connections, as well as the noise immunity of a digital interface dewar. The potential commercial applications for this integrated circuit are primarily in imaging systems. These imaging systems may be used for: security monitoring systems, manufacturing process monitoring, robotics, and for spectral imaging when used in analytical instrumentation.

Characterizing continuous urban growth using composited time-series Landsat data

NASA Astrophysics Data System (ADS)

Song, X. P.; Sexton, J. O.; Huang, C.; Feng, M.; Channan, S.; Baker, M. E.; Townshend, J. R.

2014-12-01

Impervious surfaces are land cover features through which water cannot penetrate into the soil. As an indicator of urban land use, impervious surface cover (ISC) is disproportionally important to human beings-although covering only 0.5% of the Earth's terrestrial surface, cities support over 50% the Earth's population. The increasing demand for built-up space by a growing urban population has been driving land use change in urban areas worldwide. An increase in ISC can significantly impact the biophysical characteristics of land surface, such as altering the local surface energy balance, or transforming regional hydrological systems. Remotely sensed data is commonly used as the primary data source for extracting impervious surface information for monitoring urban growth, but current studies often lack the sufficient temporal resolution or thematic detail to reveal the long-term, nonlinear development of impervious surfaces over time. In a previous study (Sexton et al. 2013), we created an annual stack of 30-m percent ISC estimates for the Washington DC-Baltimore metropolitan region from 1984 to 2010 by compositing all available Landsat images in the USGS archive. Here we developed a robust time-series method to detect impervious surface change. The method employs a customized logistic function for every pixel to model the continuous process of urban growth. It quantifies the fractional intensity of ISC change at the sub-pixel level and also characterizes the timing and length (in years) of urban development. The new method detects change based on a sequence of observations before, during and after change and thus is highly resistant to random noises. Our results showed that the DC-Baltimore metropolitan region experienced an accelerated growth pathway from the late 1980s to the late 2000s. The majority of urban and sub-urban development occurred at scales finer than the Landsat resolution (30 m), with a region-wide mean intensity of 46% ISC increase. Our study demonstrates the value of the long-term and fine temporal resolution data offered by the Landsat archive, and also highlights the possible limitations of Landsat's spatial resolution in characterizing continuous urban development.

Parameter variation of the one-diode model of a-Si and a- Si/μc-Si solar cells for modeling light-induced degradation

NASA Astrophysics Data System (ADS)

Weicht, J. A.; Hamelmann, F. U.; Behrens, G.

2014-11-01

For analyzing the long-term behavior of thin film a-Si/μc-Si photovoltaic modules, it is important to observe the light-induced degradation (LID) in dependence of the temperature for the parameters of the one-diode model for solar cells. According to the IEC 61646 standard, the impact of LID on module parameters of these thin film cells is determined at a constant temperature of 50°C with an irradiation of 1000 W/m2 at open circuit conditions. Previous papers examined the LID of thin film a-Si cells with different temperatures and some others are about a-Si/μc-Si. In these previous papers not all parameters of the one-diode model are examined. We observed the serial resistance (Rs), parallel resistance (Rp), short circuit current (Isc), open circuit voltage (Uoc), the maximum power point (MPP: Umpp, Impp and Pmpp) and the diode factor (n). Since the main reason for the LID of silicon-based thin films is the Staebler Wronski effect in the a-Si part of the cell, the temperature dependence of the healing of defects for all parameters of the one-diode model is also taken into account. We are also measuring modules with different kind of transparent conductive oxides: In a-Si thin film solar cells fluorine-doped tin oxide (FTO) is used and for thin film solar cells of a-Si/μc-Si boron- doped zinc oxide is used. In our work we describe an approach for transferring the parameters of a one-diode model for tandem thin film solar cells into the one-diode model for each part of the solar cell. The measurement of degradation and regeneration at higher temperatures is the necessary base for optimization of the different silicon-based thin films in warm hot climate.

IscR Regulates Synthesis of Colonization Factor Antigen I Fimbriae in Response to Iron Starvation in Enterotoxigenic Escherichia coli

PubMed Central

Arnaud-Barbe, Nadège; Poncet, David; Reverchon, Sylvie; Wawrzyniak, Julien; Nasser, William

2015-01-01

ABSTRACT Iron availability functions as an environmental cue for enteropathogenic bacteria, signaling arrival within the human host. As enterotoxigenic Escherichia coli (ETEC) is a major cause of human diarrhea, the effect of iron on ETEC virulence factors was evaluated here. ETEC pathogenicity is directly linked to production of fimbrial colonization factors and secretion of heat-labile enterotoxin (LT) and/or heat-stable enterotoxin (ST). Efficient colonization of the small intestine further requires at least the flagellin binding adhesin EtpA. Under iron starvation, production of the CFA/I fimbriae was increased in the ETEC H10407 prototype strain. In contrast, LT secretion was inhibited. Furthermore, under iron starvation, gene expression of the cfa (CFA/I) and etp (EtpBAC) operons was induced, whereas transcription of toxin genes was either unchanged or repressed. Transcriptional reporter fusion experiments focusing on the cfa operon further showed that iron starvation stimulated cfaA promoter activity in ETEC, indicating that the impact of iron on CFA/I production was mediated by transcriptional regulation. Evaluation of cfaA promoter activity in heterologous E. coli single mutant knockout strains identified IscR as the regulator responsible for inducing cfa fimbrial gene expression in response to iron starvation, and this was confirmed in an ETEC ΔiscR strain. The global iron response regulator, Fur, was not implicated. IscR binding sites were identified in silico within the cfaA promoter and fixation confirmed by DNase I footprinting, indicating that IscR directly binds the promoter region to induce CFA/I. IMPORTANCE Pathogenic enterobacteria modulate expression of virulence genes in response to iron availability. Although the Fur transcription factor represents the global regulator of iron homeostasis in Escherichia coli, we show that several ETEC virulence factors are modulated by iron, with expression of the major fimbriae under the control of the iron-sulfur cluster regulator, IscR. Furthermore, we demonstrate that the apo form of IscR, lacking an Fe-S cluster, is able to directly fix the corresponding promoter region. These results provide further evidence implicating IscR in bacterial virulence and suggest that IscR may represent a more general regulator mediating the iron response in enteropathogens. PMID:26124243

The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation.

PubMed

Martins, Telma S; Pereira, Clara; Canadell, David; Vilaça, Rita; Teixeira, Vítor; Moradas-Ferreira, Pedro; de Nadal, Eulàlia; Posas, Francesc; Costa, Vítor

2018-01-01

Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Levels of control exerted by the Isc iron-sulfur cluster system on biosynthesis of the formate hydrogenlyase complex.

PubMed

Pinske, Constanze; Jaroschinsky, Monique; Sawers, R Gary

2013-06-01

The membrane-associated formate hydrogenlyase (FHL) complex of bacteria like Escherichia coli is responsible for the disproportionation of formic acid into the gaseous products carbon dioxide and dihydrogen. It comprises minimally seven proteins including FdhF and HycE, the catalytic subunits of formate dehydrogenase H and hydrogenase 3, respectively. Four proteins of the FHL complex have iron-sulphur cluster ([Fe-S]) cofactors. Biosynthesis of [Fe-S] is principally catalysed by the Isc or Suf systems and each comprises proteins for assembly and for delivery of [Fe-S]. This study demonstrates that the Isc system is essential for biosynthesis of an active FHL complex. In the absence of the IscU assembly protein no hydrogen production or activity of FHL subcomponents was detected. A deletion of the iscU gene also resulted in reduced intracellular formate levels partially due to impaired synthesis of pyruvate formate-lyase, which is dependent on the [Fe-S]-containing regulator FNR. This caused reduced expression of the formate-inducible fdhF gene. The A-type carrier (ATC) proteins IscA and ErpA probably deliver [Fe-S] to specific apoprotein components of the FHL complex because mutants lacking either protein exhibited strongly reduced hydrogen production. Neither ATC protein could compensate for the lack of the other, suggesting that they had independent roles in [Fe-S] delivery to complex components. Together, the data indicate that the Isc system modulates FHL complex biosynthesis directly by provision of [Fe-S] as well as indirectly by influencing gene expression through the delivery of [Fe-S] to key regulators and enzymes that ultimately control the generation and oxidation of formate.

A-Type Carrier Protein ErpA Is Essential for Formation of an Active Formate-Nitrate Respiratory Pathway in Escherichia coli K-12

PubMed Central

Pinske, Constanze

2012-01-01

A-type carrier (ATC) proteins of the Isc (iron-sulfur cluster) and Suf (sulfur mobilization) iron-sulfur ([Fe-S]) cluster biogenesis pathways are proposed to traffic preformed [Fe-S] clusters to apoprotein targets. In this study, we analyzed the roles of the ATC proteins ErpA, IscA, and SufA in the maturation of the nitrate-inducible, multisubunit anaerobic respiratory enzymes formate dehydrogenase N (Fdh-N) and nitrate reductase (Nar). Mutants lacking SufA had enhanced activities of both enzymes. While both Fdh-N and Nar activities were strongly reduced in an iscA mutant, both enzymes were inactive in an erpA mutant and in a mutant unable to synthesize the [Fe-S] cluster scaffold protein IscU. It could be shown for both Fdh-N and Nar that loss of enzyme activity correlated with absence of the [Fe-S] cluster-containing small subunit. Moreover, a slowly migrating form of the catalytic subunit FdnG of Fdh-N was observed, consistent with impeded twin arginine translocation (TAT)-dependent transport. The highly related Fdh-O enzyme was also inactive in the erpA mutant. Although the Nar enzyme has its catalytic subunit NarG localized in the cytoplasm, it also exhibited aberrant migration in an erpA iscA mutant, suggesting that these modular enzymes lack catalytic integrity due to impaired cofactor biosynthesis. Cross-complementation experiments demonstrated that multicopy IscA could partially compensate for lack of ErpA with respect to Fdh-N activity but not Nar activity. These findings suggest that ErpA and IscA have overlapping roles in assembly of these anaerobic respiratory enzymes but demonstrate that ErpA is essential for the production of active enzymes. PMID:22081393

Mitochondrial Iron-Sulfur Cluster Activity and Cytosolic Iron Regulate Iron Traffic in Saccharomyces cerevisiae.

PubMed

Wofford, Joshua D; Lindahl, Paul A

2015-11-06

An ordinary differential equation-based mathematical model was developed to describe trafficking and regulation of iron in growing fermenting budding yeast. Accordingly, environmental iron enters the cytosol and moves into mitochondria and vacuoles. Dilution caused by increasing cell volume is included. Four sites are regulated, including those in which iron is imported into the cytosol, mitochondria, and vacuoles, and the site at which vacuolar Fe(II) is oxidized to Fe(III). The objective of this study was to determine whether cytosolic iron (Fecyt) and/or a putative sulfur-based product of iron-sulfur cluster (ISC) activity was/were being sensed in regulation. The model assumes that the matrix of healthy mitochondria is anaerobic, and that in ISC mutants, O2 diffuses into the matrix where it reacts with nonheme high spin Fe(II) ions, oxidizing them to nanoparticles and generating reactive oxygen species. This reactivity causes a further decline in ISC/heme biosynthesis, which ultimately gives rise to the diseased state. The ordinary differential equations that define this model were numerically integrated, and concentrations of each component were plotted versus the concentration of iron in the growth medium and versus the rate of ISC/heme biosynthesis. Model parameters were optimized by fitting simulations to literature data. The model variant that assumed that both Fecyt and ISC biosynthesis activity were sensed in regulation mimicked observed behavior best. Such "dual sensing" probably arises in real cells because regulation involves assembly of an ISC on a cytosolic protein using Fecyt and a sulfur species generated in mitochondria during ISC biosynthesis and exported into the cytosol. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Real-Time Kinetic Probes Support Monothiol Glutaredoxins As Intermediate Carriers in Fe-S Cluster Biosynthetic Pathways.

PubMed

Vranish, James N; Das, Deepika; Barondeau, David P

2016-11-18

Iron-sulfur (Fe-S) clusters are protein cofactors that are required for many essential cellular functions. Fe-S clusters are synthesized and inserted into target proteins by an elaborate biosynthetic process. The insensitivity of most Fe-S assembly and transfer assays requires high concentrations for components and places major limits on reaction complexity. Recently, fluorophore labels were shown to be effective at reporting cluster content for Fe-S proteins. Here, the incorporation of this labeling approach allowed the design and interrogation of complex Fe-S cluster biosynthetic reactions that mimic in vivo conditions. A bacterial Fe-S assembly complex, composed of the cysteine desulfurase IscS and scaffold protein IscU, was used to generate [2Fe-2S] clusters for transfer to mixtures of putative intermediate carrier and acceptor proteins. The focus of this study was to test whether the monothiol glutaredoxin, Grx4, functions as an obligate [2Fe-2S] carrier protein in the Fe-S cluster distribution network. Interestingly, [2Fe-2S] clusters generated by the IscS-IscU complex transferred to Grx4 at rates comparable to previous assays using uncomplexed IscU as a cluster source in chaperone-assisted transfer reactions. Further, we provide evidence that [2Fe-2S]-Grx4 delivers clusters to multiple classes of Fe-S targets via direct ligand exchange in a process that is both dynamic and reversible. Global fits of cluster transfer kinetics support a model in which Grx4 outcompetes terminal target proteins for IscU-bound [2Fe-2S] clusters and functions as an intermediate cluster carrier. Overall, these studies demonstrate the power of chemically conjugated fluorophore reporters for unraveling mechanistic details of biological metal cofactor assembly and distribution networks.

Requirement of ATR for maintenance of intestinal stem cells in aging Drosophila.

PubMed

Park, Joung-Sun; Na, Hyun-Jin; Pyo, Jung-Hoon; Jeon, Ho-Jun; Kim, Young-Shin; Yoo, Mi-Ae

2015-05-01

The stem cell genomic stability forms the basis for robust tissue homeostasis, particularly in high-turnover tissues. For the genomic stability, DNA damage response (DDR) is essential. This study was focused on the role of two major DDR-related factors, ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR) kinases, in the maintenance of intestinal stem cells (ISCs) in the adultDrosophila midgut. We explored the role of ATM and ATR, utilizing immunostaining with an anti-pS/TQ antibody as an indicator of ATM/ATR activation, γ-irradiation as a DNA damage inducer, and the UAS/GAL4 system for cell type-specific knockdown of ATM, ATR, or both during adulthood. The results showed that the pS/TQ signals got stronger with age and after oxidative stress. The pS/TQ signals were found to be more dependent on ATR rather than on ATM in ISCs/enteroblasts (EBs). Furthermore, an ISC/EB-specific knockdown of ATR, ATM, or both decreased the number of ISCs and oxidative stress-induced ISC proliferation. The phenotypic changes that were caused by the ATR knockdown were more pronounced than those caused by the ATM knockdown; however, our data indicate that ATR and ATM are both needed for ISC maintenance and proliferation; ATR seems to play a bigger role than does ATM.

Impaired mitochondrial Fe-S cluster biogenesis activates the DNA damage response through different signaling mediators.

PubMed

Pijuan, Jordi; María, Carlos; Herrero, Enrique; Bellí, Gemma

2015-12-15

Fe-S cluster biogenesis machinery is required for multiple DNA metabolism processes. In this work, we show that, in Saccharomyces cerevisiae, defects at different stages of the mitochondrial Fe-S cluster assembly machinery (ISC) result in increased spontaneous mutation rate and hyper-recombination, accompanied by an increment in Rad52-associated DNA repair foci and a higher phosphorylated state of γH2A histone, altogether supporting the presence of constitutive DNA lesions. Furthermore, ISC assembly machinery deficiency elicits a DNA damage response that upregulates ribonucleotide reductase activity by promoting the reduction of Sml1 levels and the cytosolic redistribution of Rnr2 and Rnr4 enzyme subunits. Depending on the impaired stage of the ISC machinery, different signaling pathway mediators contribute to such a response, converging on Dun1. Thus, cells lacking the glutaredoxin Grx5, which are compromised at the core ISC system, show Mec1- and Rad53-independent Dun1 activation, whereas both Mec1 and Chk1 are required when the non-core ISC member Iba57 is absent. Grx5-null cells exhibit a strong dependence on the error-free post-replication repair and the homologous recombination pathways, demonstrating that a DNA damage response needs to be activated upon ISC impairment to preserve cell viability. © 2015. Published by The Company of Biologists Ltd.

Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells.

PubMed

Barriga, Francisco M; Montagni, Elisa; Mana, Miyeko; Mendez-Lago, Maria; Hernando-Momblona, Xavier; Sevillano, Marta; Guillaumet-Adkins, Amy; Rodriguez-Esteban, Gustavo; Buczacki, Simon J A; Gut, Marta; Heyn, Holger; Winton, Douglas J; Yilmaz, Omer H; Attolini, Camille Stephan-Otto; Gut, Ivo; Batlle, Eduard

2017-06-01

Highly proliferative Lgr5+ stem cells maintain the intestinal epithelium and are thought to be largely homogeneous. Although quiescent intestinal stem cell (ISC) populations have been described, the identity and features of such a population remain controversial. Here we report unanticipated heterogeneity within the Lgr5+ ISC pool. We found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5+ ISCs that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5+ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes. During homeostasis, Mex3a+ cells continually shift into the rapidly dividing, self-renewing ISC pool. Chemotherapy and radiation preferentially target rapidly dividing Lgr5+ cells but spare the Mex3a-high/Lgr5+ population, helping to promote regeneration of the intestinal epithelium following toxic insults. Thus, Mex3a defines a reserve-like ISC population within the Lgr5+ compartment. Copyright © 2017 Elsevier Inc. All rights reserved.

Mitochondrial iron-sulfur cluster biogenesis from molecular understanding to clinical disease

PubMed Central

Alfadhel, Majid; Nashabat, Marwan; Ali, Qais Abu; Hundallah, Khalid

2017-01-01

Iron–sulfur clusters (ISCs) are known to play a major role in various protein functions. Located in the mitochondria, cytosol, endoplasmic reticulum and nucleus, they contribute to various core cellular functions. Until recently, only a few human diseases related to mitochondrial ISC biogenesis defects have been described. Such diseases include Friedreich ataxia, combined oxidative phosphorylation deficiency 19, infantile complex II/III deficiency defect, hereditary myopathy with lactic acidosis and mitochondrial muscle myopathy, lipoic acid biosynthesis defects, multiple mitochondrial dysfunctions syndromes and non ketotic hyperglycinemia due to glutaredoxin 5 gene defect. Disorders of mitochondrial import, export and translation, including sideroblastic anemia with ataxia, EVEN-PLUS syndrome and mitochondrial complex I deficiency due to nucleotide-binding protein-like protein gene defect, have also been implicated in ISC biogenesis defects. With advances in next generation sequencing technologies, more disorders related to ISC biogenesis defects are expected to be elucidated. In this article, we aim to shed the light on mitochondrial ISC biogenesis, related proteins and their function, pathophysiology, clinical phenotypes of related disorders, diagnostic approach, and future implications. PMID:28064324

Photoelectric characteristics of CH3NH3PbI3/p-Si heterojunction

NASA Astrophysics Data System (ADS)

Yamei, Wu; Ruixia, Yang; Hanmin, Tian; Shuai, Chen

2016-05-01

Organic-inorganic hybrid perovskite CH3NH3PbI3 film is prepared on p-type silicon substrate using the one-step solution method to form a CH3NH3PbI3/p-Si heterojunction. The film morphology and structure are characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The photoelectric properties of the CH3NH3PbI3/p-Si heterojunction are studied by testing the current-voltage (I-V) with and without illumination and capacitance-voltage (C-V) characteristics. It turns out from the I-V curve without illumination that the CH3NH3PbI3/p-Si heterojunction has a rectifier feature with the rectification ratio over 70 at the bias of ±5 V. Also, there appears a photoelectric conversion phenomenon on this heterojunction with a short circuit current (Isc) of 0.16 μA and an open circuit voltage (Voc) of about 10 mV The high frequency C-V characteristic of the Ag/CH3NH3PbI3/p-Si heterojunction turns out to be similar to that of the metal-insulator-semiconductor (MIS) structure, and a parallel translation of the C-V curve along the forward voltage axis is found. This parallel translation means the existence of defects at the CH3NH3PbI3/p-Si interface and positive fixed charges in the CH3NH3PbI3 layer. The defects at the interface of the CH3NH3PbI3/p-Si heterojunction result in the dramatic decline of the Voc. Besides, the C-V test of CH3NH3PbI3 film shows a non-linear dielectric property and the dielectric value is about 4.64 as calculated. Project supported by the Hebei Province Natural Science Foundation of China (No. F2014202184) and the Tianjin Natural Science Foundation of China (No. 15JCZDJC37800).

Delivery of Iron-Sulfur Clusters to the Hydrogen-Oxidizing [NiFe]-Hydrogenases in Escherichia coli Requires the A-Type Carrier Proteins ErpA and IscA

PubMed Central

Pinske, Constanze; Sawers, R. Gary

2012-01-01

During anaerobic growth Escherichia coli synthesizes two membrane-associated hydrogen-oxidizing [NiFe]-hydrogenases, termed hydrogenase 1 and hydrogenase 2. Each enzyme comprises a catalytic subunit containing the [NiFe] cofactor, an electron-transferring small subunit with a particular complement of [Fe-S] (iron-sulfur) clusters and a membrane-anchor subunit. How the [Fe-S] clusters are delivered to the small subunit of these enzymes is unclear. A-type carrier (ATC) proteins of the Isc (iron-sulfur-cluster) and Suf (sulfur mobilization) [Fe-S] cluster biogenesis pathways are proposed to traffic pre-formed [Fe-S] clusters to apoprotein targets. Mutants that could not synthesize SufA had active hydrogenase 1 and hydrogenase 2 enzymes, thus demonstrating that the Suf machinery is not required for hydrogenase maturation. In contrast, mutants devoid of the IscA, ErpA or IscU proteins of the Isc machinery had no detectable hydrogenase 1 or 2 activities. Lack of activity of both enzymes correlated with the absence of the respective [Fe-S]-cluster-containing small subunit, which was apparently rapidly degraded. During biosynthesis the hydrogenase large subunits receive their [NiFe] cofactor from the Hyp maturation machinery. Subsequent to cofactor insertion a specific C-terminal processing step occurs before association of the large subunit with the small subunit. This processing step is independent of small subunit maturation. Using western blotting experiments it could be shown that although the amount of each hydrogenase large subunit was strongly reduced in the iscA and erpA mutants, some maturation of the large subunit still occurred. Moreover, in contrast to the situation in Isc-proficient strains, these processed large subunits were not membrane-associated. Taken together, our findings demonstrate that both IscA and ErpA are required for [Fe-S] cluster delivery to the small subunits of the hydrogen-oxidizing hydrogenases; however, delivery of the Fe atom to the active site might have different requirements. PMID:22363723

Comparison of vectorial ion transport in primary murine airway and human sinonasal air-liquid interface cultures, models for studies of cystic fibrosis, and other airway diseases.

PubMed

Zhang, Shaoyan; Fortenberry, James A; Cohen, Noam A; Sorscher, Eric J; Woodworth, Bradford A

2009-01-01

The purpose of this study was to compare vectorial ion transport within murine trachea, murine nasal septa, and human sinonasal cultured epithelium. Our hypothesis is that murine septal epithelium, rather than trachea, will more closely mimic the electrophysiology properties of human sinonasal epithelium. Epithelium from murine trachea, murine septa, and human sinonasal tissue were cultured at an air-liquid interface to confluence and full differentiation. A limited number of homozygous dF508 epithelia were also cultured. Monolayers were mounted in modified Ussing chambers to investigate pharmacologic manipulation of ion transport. The change in forskolin-stimulated current (delta-I(SC), expressed as micro-A/cm(2)) in murine septal (n = 19; 16.84 +/- 2.09) and human sinonasal (n = 18; 12.15 +/- 1.93) cultures was significantly increased over murine tracheal cultures (n = 15; 6.75 +/- 1.35; p = 0.035 and 0.0005, respectively). Forskolin-stimulated I(SC) was inhibited by the specific cystic fibrosis transmembrane regulator (CFTR) inhibitor INH-172 (5 microM). No forskolin-stimulated I(SC) was shown in cultures of dF508 homozygous murine septal epithelium (n = 3). Murine septal I(SC) was largely inhibited by amiloride (12.03 +/- 0.66), whereas human sinonasal cultures had a very limited response (0.70 +/- 0.47; p < 0.0001). The contribution of CFTR to stimulated chloride current as measured by INH-172 was highly significantly different between all groups (murine septa, 19.51 +/- 1.28; human sinonasal, 11.12 +/- 1.58; murine trachea, 4.85 +/- 0.49; p < 0.0001). Human sinonasal and murine septal epithelial cultures represent a useful model for studying CFTR activity and may provide significant advantages over lower airway tissues for investigating upper and lower respiratory pathophysiology.

Thermal and elastic properties of solid neon

NASA Astrophysics Data System (ADS)

Acocella, Dominic; Horton, George K.; Cowley, E. Roger

2000-04-01

We apply the improved effective potential Monte Carlo (IEP) and the improved self-consistent (ISC) theories to study the thermal and elastic properties of natural solid Ne. As a first orientation, we use the (12-6) Lennard-Jones (LJ) potential for first-neighbor forces only. The two parameters in the potential are determined from the 0 K lattice spacing and the sublimation energy of the crystal. We also create a realistic interatomic potential for the Ne dimer based on our study of the existing literature. When supplemented by many-body contributions, this potential is also used with ISC and IEP. The results are then compared with the experimental data in the literature. We conclude that our realistic potential which we regard as the best currently available is not significantly superior in accounting for the experimental data to the LJ potential, though both give a decent account of the experimental data.

Solar harvesting by a heterostructured cell with built-in variable width quantum wells

NASA Astrophysics Data System (ADS)

Brooks, W.; Wang, H.; Mil'shtein, S.

2018-02-01

We propose cascaded heterostructured p-i-n solar cells, where inside of the i-region is a set of Quantum Wells (QWs) with variable thicknesses to enhance absorption of different photonic energies and provide quick relaxation for high energy carriers. Our p-i-n heterostructure carries top p-type and bottom n-type 11.3 Å thick AlAs layers, which are doped by acceptors and donor densities up to 1019/cm3. The intrinsic region is divided into 10 segments where each segment carries ten QWs of the same width and the width of the QWs in each subsequent segment gradually increases. The top segment consists of 10 QWs with widths of 56.5Å, followed by a segment with 10 wider QWs with widths of 84.75Å, followed by increasing QW widths until the last segment has 10 QWs with widths of 565Å, bringing the total number of QWs to 100. The QW wall height is controlled by alternating AlAs and GaAs layers, where the AlAs layers are all 11.3Å thick, throughout the entire intrinsic region. Configuration of variable width QWs prescribes sets of energy levels which are suitable for absorption of a wide range of photon energies and will dissipate high electron-hole energies rapidly, reducing the heat load on the solar cell. We expect that the heating of the solar cell will be reduced by 8-11%, enhancing efficiency. The efficiency of the designed solar cell is 43.71%, the Fill Factor is 0.86, the density of short circuit current (ISC) will not exceed 338 A/m2 and the open circuit voltage (VOC) is 1.51V.

A novel high electrode count spike recording array using an 81,920 pixel transimpedance amplifier-based imaging chip.

PubMed

Johnson, Lee J; Cohen, Ethan; Ilg, Doug; Klein, Richard; Skeath, Perry; Scribner, Dean A

2012-04-15

Microelectrode recording arrays of 60-100 electrodes are commonly used to record neuronal biopotentials, and these have aided our understanding of brain function, development and pathology. However, higher density microelectrode recording arrays of larger area are needed to study neuronal function over broader brain regions such as in cerebral cortex or hippocampal slices. Here, we present a novel design of a high electrode count picocurrent imaging array (PIA), based on an 81,920 pixel Indigo ISC9809 readout integrated circuit camera chip. While originally developed for interfacing to infrared photodetector arrays, we have adapted the chip for neuron recording by bonding it to microwire glass resulting in an array with an inter-electrode pixel spacing of 30 μm. In a high density electrode array, the ability to selectively record neural regions at high speed and with good signal to noise ratio are both functionally important. A critical feature of our PIA is that each pixel contains a dedicated low noise transimpedance amplifier (∼0.32 pA rms) which allows recording high signal to noise ratio biocurrents comparable to single electrode voltage amplifier recordings. Using selective sampling of 256 pixel subarray regions, we recorded the extracellular biocurrents of rabbit retinal ganglion cell spikes at sampling rates up to 7.2 kHz. Full array local electroretinogram currents could also be recorded at frame rates up to 100 Hz. A PIA with a full complement of 4 readout circuits would span 1cm and could acquire simultaneous data from selected regions of 1024 electrodes at sampling rates up to 9.3 kHz. Published by Elsevier B.V.

Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of Notch.

PubMed

López-Arribillaga, Erika; Rodilla, Verónica; Pellegrinet, Luca; Guiu, Jordi; Iglesias, Mar; Roman, Angel Carlos; Gutarra, Susana; González, Susana; Muñoz-Cánoves, Pura; Fernández-Salguero, Pedro; Radtke, Freddy; Bigas, Anna; Espinosa, Lluís

2015-01-01

Genetic data indicate that abrogation of Notch-Rbpj or Wnt-β-catenin pathways results in the loss of the intestinal stem cells (ISCs). However, whether the effect of Notch is direct or due to the aberrant differentiation of the transit-amplifying cells into post-mitotic goblet cells is unknown. To address this issue, we have generated composite tamoxifen-inducible intestine-specific genetic mouse models and analyzed the expression of intestinal differentiation markers. Importantly, we found that activation of β-catenin partially rescues the differentiation phenotype of Rbpj deletion mutants, but not the loss of the ISC compartment. Moreover, we identified Bmi1, which is expressed in the ISC and progenitor compartments, as a gene that is co-regulated by Notch and β-catenin. Loss of Bmi1 resulted in reduced proliferation in the ISC compartment accompanied by p16(INK4a) and p19(ARF) (splice variants of Cdkn2a) accumulation, and increased differentiation to the post-mitotic goblet cell lineage that partially mimics Notch loss-of-function defects. Finally, we provide evidence that Bmi1 contributes to ISC self-renewal. © 2015. Published by The Company of Biologists Ltd.

Correlation between Self-Citation and Impact Factor in Iranian English Medical Journals in WoS and ISC: A Comparative Approach.

PubMed

Ghazi Mirsaeid, Seyed Javad; Motamedi, Nadia; Ramezan Ghorbani, Nahid

2015-09-01

In this study, the impact of self-citation (Journal and Author) on impact factor of Iranian English Medical journals in two international citation databases, Web of Science (WoS) and Islamic world science citation center (ISC), were compared by citation analysis. Twelve journals in WoS and 26 journals in ISC databases indexed between the years (2006-2009) were selected and compared. For comparison of self-citation rate in two databases, we used Wilcoxon and Mann-whitney tests. We used Pearson test for correlation of self-citation and IF in WoS, and the Spearman's correlation coefficient for the ISC database. Covariance analysis was used for comparison of two correlation tests. P. value was 0.05 in all of tests. There was no significant difference between self-citation rates in two databases (P>0.05). Findings also showed no significant difference between the correlation of Journal self-citation and impact factor in two databases (P=0.526) however, there was significant difference between the author's self-citation and impact factor in these databases (P<0.001). The impact of Author's self-citation in the Impact Factor of WoS was higher than the ISC.

Teleradiology system using a magneto-optical disk and N-ISDN

NASA Astrophysics Data System (ADS)

Ban, Hideyuki; Osaki, Takanobu; Matsuo, Hitoshi; Okabe, Akifumi; Nakajima, Kotaro; Ohyama, Nagaaki

1997-05-01

We have developed a new teleradiology system that provides a fast response and secure data transmission while using N- ISDN communication and an ISC magneto-optical disk that is specialized for medical use. The system consists of PC-based terminals connected to a N-ISDN line and the ISC disk. The system uses two types of data: the control data needed for various operational functions and the image data. For quick response, only the much smaller quantity of control data is sent through the N-ISDN during the actual conference. The bulk of the image data is sent to each site on duplicate ISC disks before the conference. The displaying and processing of images are executed using the local data on the ISC disk. We used this system for a trial teleconsultation between two hospitals. The response time needed to display a 2-Mbyte image was 4 seconds. The telepointer could be controlled with no noticeable delay by sending only the pointer's coordinates. Also, since the patient images were exchanged via the ISC disks only, unauthorized access to the patient images through the N-ISDN was prevented. Thus, this trial provides a preliminary demonstration of the usefulness of this system for clinical use.

Interleukin-6 Modulates Colonic Transepithelial Ion Transport in the Stress-Sensitive Wistar Kyoto Rat

PubMed Central

O’Malley, Dervla; Dinan, Timothy G.; Cryan, John F.

2012-01-01

Immunological challenge stimulates secretion of the pro-inflammatory cytokine interleukin (IL)-6, resulting in variety of biological responses. In the gastrointestinal tract, IL-6 modulates the excitability of submucosal neurons and stimulates secretion into the colonic lumen. When considered in the context of the functional bowel disorder, irritable bowel syndrome (IBS), where plasma levels of IL-6 are elevated, this may reflect an important molecular mechanism contributing to symptom flares, particularly in the diarrhea-predominant phenotype. In these studies, colonic ion transport, an indicator of absorption and secretion, was assessed in the stress-sensitive Wistar Kyoto (WKY) rat model of IBS. Mucosa-submucosal colonic preparations from WKY and control Sprague Dawley (SD) rats were mounted in Ussing chambers and the basal short circuit current (ISC) was electrophysiologically recorded and compared between the strains. Exposure to IL-6 (1 nM) stimulated a secretory current of greater amplitude in WKY as compared to SD samples. Furthermore, the observed IL-6-mediated potentiation of secretory currents evoked by veratridine and capsaicin in SD rats was blunted in WKY rats. Exposure to IL-6 also stimulated an increase in transepithelial resistance in both SD and WKY colonic tissue. These studies demonstrate that the neuroexcitatory effects of IL-6 on submucosal plexi have functional consequences with alterations in both colonic secretory activity and permeability. The IL-6-induced increase in colonic secretory activity appears to neurally mediated. Thus, local increases in IL-6 levels and subsequent activation of enteric neurons may underlie alterations in absorpto-secretory function in the WKY model of IBS. PMID:23162465

A Matrix Approach to Software Process Definition

NASA Technical Reports Server (NTRS)

Schultz, David; Bachman, Judith; Landis, Linda; Stark, Mike; Godfrey, Sally; Morisio, Maurizio; Powers, Edward I. (Technical Monitor)

2000-01-01

The Software Engineering Laboratory (SEL) is currently engaged in a Methodology and Metrics program for the Information Systems Center (ISC) at Goddard Space Flight Center (GSFC). This paper addresses the Methodology portion of the program. The purpose of the Methodology effort is to assist a software team lead in selecting and tailoring a software development or maintenance process for a specific GSFC project. It is intended that this process will also be compliant with both ISO 9001 and the Software Engineering Institute's Capability Maturity Model (CMM). Under the Methodology program, we have defined four standard ISO-compliant software processes for the ISC, and three tailoring criteria that team leads can use to categorize their projects. The team lead would select a process and appropriate tailoring factors, from which a software process tailored to the specific project could be generated. Our objective in the Methodology program is to present software process information in a structured fashion, to make it easy for a team lead to characterize the type of software engineering to be performed, and to apply tailoring parameters to search for an appropriate software process description. This will enable the team lead to follow a proven, effective software process and also satisfy NASA's requirement for compliance with ISO 9001 and the anticipated requirement for CMM assessment. This work is also intended to support the deployment of sound software processes across the ISC.

Results of a Research Evaluating Quality of Computer Science Education

ERIC Educational Resources Information Center

Záhorec, Ján; Hašková, Alena; Munk, Michal

2012-01-01

The paper presents the results of an international research on a comparative assessment of the current status of computer science education at the secondary level (ISCED 3A) in Slovakia, the Czech Republic, and Belgium. Evaluation was carried out based on 14 specific factors gauging the students' point of view. The authors present qualitative…

Requirement of matrix metalloproteinase-1 for intestinal homeostasis in the adult Drosophila midgut

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Shin-Hae; Park, Joung-Sun; Kim, Young-Shin

Stem cells are tightly regulated by both intrinsic and extrinsic signals as well as the extracellular matrix (ECM) for tissue homeostasis and regenerative capacity. Matrix metalloproteinases (MMPs), proteolytic enzymes, modulate the turnover of numerous substrates, including cytokine precursors, growth factors, and ECM molecules. However, the roles of MMPs in the regulation of adult stem cells are poorly understood. In the present study, we utilize the Drosophila midgut, which is an excellent model system for studying stem cell biology, to show that Mmp1 is involved in the regulation of intestinal stem cells (ISCs). The results showed that Mmp1 is expressed inmore » the adult midgut and that its expression increases with age and with exposure to oxidative stress. Mmp1 knockdown or Timp-overexpressing flies and flies heterozygous for a viable, hypomorphic Mmp1 allele increased ISC proliferation in the gut, as shown by staining with an anti-phospho-histone H3 antibody and BrdU incorporation assays. Reduced Mmp1 levels induced intestinal hyperplasia, and the Mmp1depletion-induced ISC proliferation was rescued by the suppression of the EGFR signaling pathway, suggesting that Mmp1 regulates ISC proliferation through the EGFR signaling pathway. Furthermore, adult gut-specific knockdown and whole-animal heterozygotes of Mmp1 increased additively sensitivity to paraquat-induced oxidative stress and shortened lifespan. Our data suggest that Drosophila Mmp1 is involved in the regulation of ISC proliferation for maintenance of gut homeostasis. -- Highlights: Black-Right-Pointing-Pointer Mmp1 is expressed in the adult midgut. Black-Right-Pointing-Pointer Mmp1 is involved in the regulation of ISC proliferation activity. Black-Right-Pointing-Pointer Mmp1-related ISC proliferation is associated with EGFR signaling. Black-Right-Pointing-Pointer Mmp1 in the gut is required for the intestinal homeostasis and longevity.« less

Conceptualizing and measuring illness self-concept: a comparison with self-esteem and optimism in predicting fibromyalgia adjustment.

PubMed

Morea, Jessica M; Friend, Ronald; Bennett, Robert M

2008-12-01

Illness self-concept (ISC), or the extent to which individuals are consumed by their illness, was theoretically described and evaluated with the Illness Self-Concept Scale (ISCS), a new 23-item scale, to predict adjustment in fibromyalgia. To establish convergent and discriminant validity, illness self-concept was compared to self-esteem and optimism in predicting health status, illness intrusiveness, depression, and life satisfaction. The ISCS demonstrated good reliability (alpha = .94; test-retest r = .80) and was a strong predictor of outcomes, even after controlling for optimism or self-esteem. The ISCS predicted unique variance in health-related outcomes; optimism and self-esteem did not, providing construct validation. Illness self-concept may play a significant role in coping with fibromyalgia and may prove useful in the evaluation of other chronic illnesses. (c) 2008 Wiley Periodicals, Inc.

Investigation of Electrical and Optical Properties of Highly Transparent TCO/Ag/TCO Multilayer.

PubMed

Kim, Sunbo; Lee, Jaehyeong; Dao, Vinh Ai; Ahn, Shihyun; Hussain, Shahzada Qamar; Park, Jinjoo; Jung, Junhee; Lee, Chan; Song, Bong-Shik; Choi, Byoungdeog; Lee, Youn-Jung; Iftiquar, S M; Yi, Junsin

2015-03-01

Transparent conductive oxides (TCOs) have been widely used as transparent electrodes for opto-electronic devices, such as solar cells, flat-panel displays, and light-emitting diodes, because of their unique characteristics of high optical transmittance and low electrical resistivity. Among various TCO materials, zinc oxide based films have recently received much attention because they have advantages over commonly used indium and tin-based oxide films. Most TCO films, however, exhibit valleys of transmittance in the wavelength range of 550-700 nm, lowering the average transmittance in the visible region and decreasing short-circuit current (Isc) of solar cells. A TCO/Ag/TCO multi-layer structure has emerged as an attractive alternative because it provides optical characteristics without the valley of transmittance compared with a 100-nm-thick single-layer TCO. In this article, we report the electrical, optical and surface properties of TCO/Ag/TCO. These multi-layers were deposited at room temperature with various Ag film thicknesses from 5 to 15 nm while the thickness of TCO thin film was fixed at 40 nm. The TCO/Ag/TCO multi-layer with a 10-nm-thick Ag film showed optimum transmittance in the visible (400-800 nm) wavelength region. These multi-layer structures have advantages over TCO layers of the same thickness.

Cortisol receptor blockade and seawater adaptation in the euryhaline teleost Fundulus heteroclitus

USGS Publications Warehouse

Marshall, W.S.; Cozzi, R.R.F.; Pelis, Ryan M.; McCormick, S.D.

2005-01-01

To examine the role of cortisol in seawater osmoregulation in a euryhaline teleost, adult killifish were acclimated to brackish water (10???) and RU486 or vehicle was administered orally in peanut oil daily for five days at low (40 mg.kg-1) or high dose (200 mg.kg-1). Fish were transferred to 1.5 x seawater (45???) or to brackish water (control) and sampled at 24 h and 48 h after transfer, when Cl- secretion is upregulated. At 24 h, opercular membrane Cl- secretion rate, as Isc, was increased only in the high dose RU486 group. Stimulation of membranes by 3-isobutyl-1-methylxanthine and cAMP increased Isc in vehicle treated controls but those from RU486-treated animals were unchanged and membranes from brackish water animals showed a decrease in Isc. At 48 h, Isc increased and transepithelial resistance decreased in vehicle and RU486 groups, compared to brackish water controls. Plasma cortisol increased in all groups transferred to high salinity, compared to brackish water controls. RU486 treated animals had higher cortisol levels compared to vehicle controls. Vehicle treated controls had lower cortisol levels than untreated or RU486 treated animals, higher stimulation of Isc, and lower hematocrit at 24 h, beneficial effects attributed to increased caloric intake from the peanut oil vehicle. Chloride cell density was significantly increased in the high dose RU486 group at 48 hours, yet Isc was unchanged, suggesting a decrease in Cl- secretion per cell. Thus cortisol enhances NaCl secretion capacity in chloride cells, likely via glucocorticoid type receptors. ?? 2005 Wiley-Liss, Inc.

Molecular Preadaptation to Antimony Resistance in Leishmania donovani on the Indian Subcontinent

PubMed Central

Imamura, H.; Zander, D.; D’Haenens, E.; Maes, I.; Domagalska, M. A.; Clos, J.

2018-01-01

ABSTRACT Antimonials (Sb) were used for decades for chemotherapy of visceral leishmaniasis (VL). Now abandoned in the Indian subcontinent (ISC) because of Leishmania donovani resistance, this drug offers a unique model for understanding drug resistance dynamics. In a previous phylogenomic study, we found two distinct populations of L. donovani: the core group (CG) in the Gangetic plains and ISC1 in the Nepalese highlands. Sb resistance was only encountered within the CG, and a series of potential markers were identified. Here, we analyzed the development of resistance to trivalent antimonials (SbIII) upon experimental selection in ISC1 and CG strains. We observed that (i) baseline SbIII susceptibility of parasites was higher in ISC1 than in the CG, (ii) time to SbIII resistance was higher for ISC1 parasites than for CG strains, and (iii) untargeted genomic and metabolomic analyses revealed molecular changes along the selection process: these were more numerous in ISC1 than in the CG. Altogether these observations led to the hypothesis that CG parasites are preadapted to SbIII resistance. This hypothesis was experimentally confirmed by showing that only wild-type CG strains could survive a direct exposure to the maximal concentration of SbIII. The main driver of this preadaptation was shown to be MRPA, a gene involved in SbIII sequestration and amplified in an intrachromosomal amplicon in all CG strains characterized so far. This amplicon emerged around 1850 in the CG, well before the implementation of antimonials for VL chemotherapy, and we discuss here several hypotheses of selective pressure that could have accompanied its emergence. IMPORTANCE The “antibiotic resistance crisis” is a major challenge for scientists and medical professionals. This steady rise in drug-resistant pathogens also extends to parasitic diseases, with antimony being the first anti-Leishmania drug that fell in the Indian subcontinent (ISC). Leishmaniasis is a major but neglected infectious disease with limited therapeutic options. Therefore, understanding how parasites became resistant to antimonials is of commanding importance. In this study, we experimentally characterized the dynamics of this resistance acquisition and show for the first time that some Leishmania populations of the ISC were preadapted to antimony resistance, likely driven by environmental factors or by drugs used in the 19th century. PMID:29669889

Baselining the New GSFC Information Systems Center: The Foundation for Verifiable Software Process Improvement

NASA Technical Reports Server (NTRS)

Parra, A.; Schultz, D.; Boger, J.; Condon, S.; Webby, R.; Morisio, M.; Yakimovich, D.; Carver, J.; Stark, M.; Basili, V.;

Time domain reshuffling for OFDM based indoor visible light communication systems.

PubMed

You, Xiaodi; Chen, Jian; Yu, Changyuan; Zheng, Huanhuan

2017-05-15

For orthogonal frequency division multiplexing (OFDM) based indoor visible light communication (VLC) systems, partial non-ideal transmission conditions such as insufficient guard intervals and a dispersive channel can result in severe inter-symbol crosstalk (ISC). By deriving from the inverse Fourier transform, we present a novel time domain reshuffling (TDR) concept for both DC-biased optical (DCO-) and asymmetrically clipped optical (ACO-) OFDM VLC systems. By using only simple operations in the frequency domain, potential high peaks can be relocated within each OFDM symbol to alleviate ISC. To simplify the system, we also propose an effective unified design of the TDR schemes for both DCO- and ACO-OFDM. Based on Monte-Carlo simulations, we demonstrate the statistical distribution of the signal high peak values and the complementary cumulative distribution function of the peak-to-average power ratio under different cases for comparison. Simulation results indicate improved bit error rate (BER) performance by adopting TDR to counteract ISC deterioration. For example, for binary phase shift keying at a BER of 10 -3 , the signal to noise ratio gains are ~1.6 dB and ~6.6 dB for DCO- and ACO-OFDM, respectively, with ISC of 1/64. We also show a reliable transmission by adopting TDR for rectangle 8-quadrature amplitude modulation with ISC of < 1/64.

Correlation between Self-Citation and Impact Factor in Iranian English Medical Journals in WoS and ISC: A Comparative Approach

PubMed Central

GHAZI MIRSAEID, Seyed Javad; MOTAMEDI, Nadia; RAMEZAN GHORBANI, Nahid

2015-01-01

Background: In this study, the impact of self-citation (Journal and Author) on impact factor of Iranian English Medical journals in two international citation databases, Web of Science (WoS) and Islamic world science citation center (ISC), were compared by citation analysis. Methods: Twelve journals in WoS and 26 journals in ISC databases indexed between the years (2006–2009) were selected and compared. For comparison of self-citation rate in two databases, we used Wilcoxon and Mann-whitney tests. We used Pearson test for correlation of self-citation and IF in WoS, and the Spearman’s correlation coefficient for the ISC database. Covariance analysis was used for comparison of two correlation tests. P. value was 0.05 in all of tests. Results: There was no significant difference between self-citation rates in two databases (P>0.05). Findings also showed no significant difference between the correlation of Journal self-citation and impact factor in two databases (P=0.526) however, there was significant difference between the author’s self-citation and impact factor in these databases (P<0.001). Conclusion: The impact of Author’s self-citation in the Impact Factor of WoS was higher than the ISC. PMID:26587498

Novel high-resolution VGA QWIP detector

NASA Astrophysics Data System (ADS)

Kataria, H.; Asplund, C.; Lindberg, A.; Smuk, S.; Alverbro, J.; Evans, D.; Sehlin, S.; Becanovic, S.; Tinghag, P.; Höglund, L.; Sjöström, F.; Costard, E.

2017-02-01

Continuing with its legacy of producing high performance infrared detectors, IRnova introduces its high resolution LWIR IDDCA (Integrated Detector Dewar Cooler assembly) based on QWIP (quantum well infrared photodetector) technology. The Focal Plane Array (FPA) has 640×512 pixels, with small (15μm) pixel pitch, and is based on the FLIRIndigo ISC0403 Readout Integrated Circuit (ROIC). The QWIP epitaxial structures are grown by metal-organic vapor phase epitaxy (MOVPE) at IRnova. Detector stability and response uniformity inherent to III/V based material will be demonstrated in terms of high performing detectors. Results showing low NETD at high frame rate will be presented. This makes it one of the first 15μm pitch QWIP based LWIR IDDCA commercially available on the market. High operability and stability of our other QWIP based products will also be shared.

pH-induced conformational change of IscU at low pH correlates with protonation/deprotonation of two conserved histidine residues.

PubMed

Dai, Ziqi; Kim, Jin Hae; Tonelli, Marco; Ali, Ibrahim K; Markley, John L

2014-08-19

IscU, the scaffold protein for the major iron-sulfur cluster biosynthesis pathway in microorganisms and mitochondria (ISC pathway), plays important roles in the formation of [2Fe-2S] and [4Fe-4S] clusters and their delivery to acceptor apo-proteins. Our laboratory has shown that IscU populates two distinct, functionally relevant conformational states, a more structured state (S) and a more dynamic state (D), that differ by cis/trans isomerizations about two peptidyl-prolyl peptide bonds [Kim, J. H., Tonelli, M., and Markley, J. L. (2012) Proc. Natl. Acad. Sci. U.S.A., 109, 454-459. Dai Z., Tonelli, M., and Markley, J. L. (2012) Biochemistry, 51, 9595-9602. Cai, K., Frederick, R. O., Kim, J. H., Reinen, N. M., Tonelli, M., and Markley, J. L. (2013) J. Biol. Chem., 288, 28755-28770]. Here, we report our findings on the pH dependence of the D ⇄ S equilibrium for Escherichia coli IscU in which the D-state is stabilized at low and high pH values. We show that the lower limb of the pH dependence curve results from differences in the pKa values of two conserved histidine residues (His10 and His105) in the two states. The net proton affinity of His10 is about 50 times higher and that of His105 is 13 times higher in the D-state than in the S-state. The origin of the high limb of the D ⇄ S pH dependence remains to be determined. These results show that changes in proton inventory need to be taken into account in the steps in iron-sulfur cluster assembly and transfer that involve transitions of IscU between its S- and D-states.

Expanding the Telepresence Paradigm to the UNOLS Fleet

NASA Astrophysics Data System (ADS)

Coleman, D.; Scowcroft, G.

2014-12-01

The Inner Space Center (ISC) at the University of Rhode Island Graduate School of Oceanography (URI-GSO) has been at the forefront of developing the tools, techniques, and protocols for telepresence-enabled ocean science exploration and education programs. Working primarily with the Ocean Exploration Trust's E/V Nautilus and the NOAA Ship Okeanos Explorer, the ISC facility and staff have supported dozens of research cruises with significant shore-based support, while delivering related educational programming across the globe. Through a partnership with the University National Oceanographic Laboratory System (UNOLS), the ISC is broadening its reach and capabilities to serve vessels in the U.S. academic research fleet, managed by UNOLS. The ISC has developed and used a portable shipboard "mobile telepresence unit" (MTU) on several UNOLS ships to support projects led by ocean scientists that employed the telepresence paradigm as part of their research and outreach programs. Utilizing the ISC facilities provides opportunities for effective, successful broader impact activities and shore-based remote science connectivity. With new UNOLS ships coming online, including the R/V Sikuliaq, the R/V Neil Armstrong, and the R/V Sally Ride, in addition to future Regional Class Research Vessels (RCRVs), telepresence capability has become a technical requirement for a variety of reasons. Older vessels are being retrofit with this forward-looking technology, and URI's research vessel, the R/V Endeavor, has been recently configured with technology to support telepresence operations. This presentation will provide an overview of the future of telepresence technology, its use in ocean science research and education, and advantages for using this capability to support broader impact activities. In addition, ISC successes, challenges, and lessons learned in employing telepresence technologies and methodologies onboard the academic research fleet will be discussed.

Multivariate selection and intersexual genetic constraints in a wild bird population.

PubMed

Poissant, J; Morrissey, M B; Gosler, A G; Slate, J; Sheldon, B C

2016-10-01

When selection differs between the sexes for traits that are genetically correlated between the sexes, there is potential for the effect of selection in one sex to be altered by indirect selection in the other sex, a situation commonly referred to as intralocus sexual conflict (ISC). While potentially common, ISC has rarely been studied in wild populations. Here, we studied ISC over a set of morphological traits (wing length, tarsus length, bill depth and bill length) in a wild population of great tits (Parus major) from Wytham Woods, UK. Specifically, we quantified the microevolutionary impacts of ISC by combining intra- and intersex additive genetic (co)variances and sex-specific selection estimates in a multivariate framework. Large genetic correlations between homologous male and female traits combined with evidence for sex-specific multivariate survival selection suggested that ISC could play an appreciable role in the evolution of this population. Together, multivariate sex-specific selection and additive genetic (co)variance for the traits considered accounted for additive genetic variance in fitness that was uncorrelated between the sexes (cross-sex genetic correlation = -0.003, 95% CI = -0.83, 0.83). Gender load, defined as the reduction in a population's rate of adaptation due to sex-specific effects, was estimated at 50% (95% CI = 13%, 86%). This study provides novel insights into the evolution of sexual dimorphism in wild populations and illustrates how quantitative genetics and selection analyses can be combined in a multivariate framework to quantify the microevolutionary impacts of ISC. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Cadmium uptake capacity of an indigenous cyanobacterial strain, Nostoc entophytum ISC32: new insight into metal uptake in microgravity-simulating conditions.

PubMed

Alidoust, Leila; Soltani, Neda; Modiri, Sima; Haghighi, Omid; Azarivand, Aisan; Khajeh, Khosro; Shahbani Zahiri, Hossein; Vali, Hojatollah; Akbari Noghabi, Kambiz

2016-02-01

Among nine cyanobacterial strains isolated from oil-contaminated regions in southern Iran, an isolate with maximum cadmium uptake capacity was selected and identified on the basis of analysis of morphological criteria and 16S rRNA gene sequence similarity as Nostoc entophytum (with 99% similarity). The isolate was tentatively designated N. entophytum ISC32. The phylogenetic affiliation of the isolates was determined on the basis of their 16S rRNA gene sequence. The maximum amount of Cd(II) adsorbed by strain ISC32 was 302.91 mg g(-1) from an initial exposure to a solution with a Cd(II) concentration of 150 mg l(-1). The cadmium uptake by metabolically active cells of cyanobacterial strain N. entophytum ISC32, retained in a clinostat for 6 days to simulate microgravity conditions, was examined and compared with that of ground control samples. N. entophytum ISC32 under the influence of microgravity was able to take up cadmium at amounts up to 29% higher than those of controls. The activity of antioxidant enzymes including catalase and peroxidase was increased in strain ISC32 exposed to microgravity conditions in a clinostat for 6 days, as catalase activity of the cells was more than three times higher than that of controls. The activity of the peroxidase enzyme increased by 36% compared with that of the controls. Membrane lipid peroxidation was also increased in the cells retained under microgravity conditions, up to 2.89-fold higher than in non-treated cells. Images obtained using scanning electron microscopy showed that cyanobacterial cells form continuous filaments which are drawn at certain levels, while the cells placed in a clinostat appeared as round-shaped, accumulated together and distorted to some extent.

Theoretical kinetics of O + C 2H 4

DOE PAGES

Li, Xiaohu; Jasper, Ahren W.; Zádor, Judit; ...

2016-06-01

The reaction of atomic oxygen with ethylene is a fundamental oxidation step in combustion and is prototypical of reactions in which oxygen adds to double bonds. For 3O+C 2H 4 and for this class of reactions generally, decomposition of the initial adduct via spin-allowed reaction channels on the triplet surface competes with intersystem crossing (ISC) and a set of spin-forbidden reaction channels on the ground-state singlet surface. The two surfaces share some bimolecular products but feature different intermediates, pathways, and transition states. In addition, the overall product branching is therefore a sensitive function of the ISC rate. The 3O+C 2Hmore » 4 reaction has been extensively studied, but previous experimental work has not provided detailed branching information at elevated temperatures, while previous theoretical studies have employed empirical treatments of ISC. Here we predict the kinetics of 3O+C 2H 4 using an ab initio transition state theory based master equation (AITSTME) approach that includes an a priori description of ISC. Specifically, the ISC rate is calculated using Landau–Zener statistical theory, consideration of the four lowest-energy electronic states, and a direct classical trajectory study of the product branching immediately after ISC. The present theoretical results are largely in good agreement with existing low-temperature experimental kinetics and molecular beam studies. Good agreement is also found with past theoretical work, with the notable exception of the predicted product branching at elevated temperatures. Above ~1000 K, we predict CH 2CHO+H and CH 2+CH 2O as the major products, which differs from the room temperature preference for CH 3+HCO (which is assumed to remain at higher temperatures in some models) and from the prediction of a previous detailed master equation study.« less

Intrafibrillar-silicified collagen scaffolds enhance the osteogenic capacity of human dental pulp stem cells.

PubMed

Niu, Li-na; Sun, Jia-qi; Li, Qi-hong; Jiao, Kai; Shen, Li-juan; Wu, Dan; Tay, Franklin; Chen, Ji-hua

2014-07-01

The present study investigated the effects of intrafibrillar-silicified collagen scaffolds (ISCS) on the osteogenic differentiation of human dental pulp stem cells (hDPSCs) in vitro and in vivo. The hDPSCs were co-cultured with ISCS or nonsilicified collagen scaffolds (NCS) in control medium (CM) or osteogenic differentiation medium (ODM). Cell cycle and cell apoptosis were analyzed with flow cytometry to measure the viability of hDPSCs. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to evaluate the expression levels of osteogenic marker genes and proteins of hDPSCs. Alkaline phosphatase (ALP) staining and alizarin red S assay were used to evaluate the ALP activity of hDPSCs and their calcium deposition potential. In addition, hDPSCs and scaffolds were implanted subcutaneously in nude mice for 8 weeks. Harvested tissues were immunohistochemically stained for osteocalcin (OCN) expression from hDPSCs, and stained with alizarin red S for examination of their calcium deposition in vivo. The ISCS had no adverse effect on hDPSCs, promoted their proliferation, and significantly up-regulated the expression of osteogenesis-related genes and proteins. The hDPSCs co-cultured with ISCS in ODM exhibited the highest ALP activity and calcium deposition in vitro. The ISCS promoted the OCN expression and calcium deposition of hDPSCs after ectopic transplantation in vivo. Intrafibrillar-silicified collagen scaffolds significantly promoted the proliferation, osteogenic differentiation and mineralization of hDPSCs, when compared with NCS. This study demonstrates combining the use of hDPSCs and ISCS to promote bone-like tissue formation is a promising approach for clinical bone repair and regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Remote Ischemic Preconditioning Enhances the Expression of Genes Encoding Antioxidant Enzymes and Endoplasmic Reticulum Stress-Related Proteins in Rat Skeletal Muscle.

PubMed

Park, Ui Jun; Kim, Hyoung Tae; Cho, Won Hyun; Park, Jae Hyoung; Jung, Hye Ra; Kim, Min Young

2016-12-01

Ischemic preconditioning (IPC), including remote IPC (rIPC) and direct IPC (dIPC), is a promising method to decrease ischemia-reperfusion (IR) injury. This study tested the effect of both rIPC and dIPC on the genes for antioxidant enzymes and endoplasmic reticulum (ER) stress-related proteins. Twenty rats were randomly divided into the control and study groups. In the control group (n=10), the right hind limb was sham-operated. The left hind limb (IscR) of the control group underwent IR injury without IPC. In the study group (n=10), the right hind limb received IR injury after 3 cycles of rIPC. The IscR received IR injury after 3 cycles of dIPC. Gene expression was analyzed by Quantitative real-time polymerase chain reaction from the anterior tibialis muscle. The expression of the antioxidant enzyme genes including glutathione peroxidase (GPx), superoxide dismutase (SOD) 1 and catalase (CAT) were significantly reduced in IscR compared with sham treatment. In comparison with IscR, rIPC enhanced the expression of GPx, SOD2, and CAT genes. dIPC enhanced the expression of SOD2 and CAT genes. The expression of SOD2 genes was consistently higher in rIPC than in dIPC, but the difference was only significant for SOD2. The expression of genes for ER stress-related proteins tended to be reduced in IscR in comparison with sham treatment. However, the difference was only significant for C/EBP homologous protein (CHOP). In comparison with IscR, rIPC significantly up-regulated activating transcription factor 4 and CHOP, whereas dIPC up-regulated CHOP. Both rIPC and dIPC enhanced expression of genes for antioxidant enzymes and ER stress-related proteins.

ISCED Handbook: United Kingdom (England and Wales).

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France). Div. of Statistics on Education.

The International Standard Classification of Education (ISCED) has been designed as an instrument suitable for assembling, compiling, and presenting statistics of education both within individual countries and internationally. It is expected to facilitate international compilation and comparison of education statistics as such, and also their use…

Revealing the spin–vibronic coupling mechanism of thermally activated delayed fluorescence

PubMed Central

Etherington, Marc K.; Gibson, Jamie; Higginbotham, Heather F.; Penfold, Thomas J.; Monkman, Andrew P.

2016-01-01

Knowing the underlying photophysics of thermally activated delayed fluorescence (TADF) allows proper design of high efficiency organic light-emitting diodes. We have proposed a model to describe reverse intersystem crossing (rISC) in donor–acceptor charge transfer molecules, where spin–orbit coupling between singlet and triplet states is mediated by one of the local triplet states of the donor (or acceptor). This second order, vibronically coupled mechanism describes the basic photophysics of TADF. Through a series of measurements, whereby the energy ordering of the charge transfer (CT) excited states and the local triplet are tuned in and out of resonance, we show that TADF reaches a maximum at the resonance point, substantiating our model of rISC. Moreover, using photoinduced absorption, we show how the populations of both singlet and triplet CT states and the local triplet state change in and out of resonance. Our vibronic coupling rISC model is used to predict this behaviour and describes how rISC and TADF are affected by external perturbation. PMID:27901046

Drosophila Sulf1 is required for the termination of intestinal stem cell division during regeneration.

PubMed

Takemura, Masahiko; Nakato, Hiroshi

2017-01-15

Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here, we show that a specific modification of heparan sulfate is crucial for regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1 resulted in increased ISC division during normal homeostasis, which was caused by upregulation of mitogenic signaling including the JAK-STAT, EGFR and Hedgehog pathways. Using a regeneration model, we found that ISCs failed to properly halt division at the termination stage in Sulf1 mutants, showing that Sulf1 is required for terminating ISC division at the end of regeneration. We propose that post-transcriptional regulation of mitogen signaling by heparan sulfate structural modifications provides a new regulatory step for precise temporal control of stem cell activity during regeneration. © 2017. Published by The Company of Biologists Ltd.

Revealing the spin-vibronic coupling mechanism of thermally activated delayed fluorescence

NASA Astrophysics Data System (ADS)

Etherington, Marc K.; Gibson, Jamie; Higginbotham, Heather F.; Penfold, Thomas J.; Monkman, Andrew P.

2016-11-01

Knowing the underlying photophysics of thermally activated delayed fluorescence (TADF) allows proper design of high efficiency organic light-emitting diodes. We have proposed a model to describe reverse intersystem crossing (rISC) in donor-acceptor charge transfer molecules, where spin-orbit coupling between singlet and triplet states is mediated by one of the local triplet states of the donor (or acceptor). This second order, vibronically coupled mechanism describes the basic photophysics of TADF. Through a series of measurements, whereby the energy ordering of the charge transfer (CT) excited states and the local triplet are tuned in and out of resonance, we show that TADF reaches a maximum at the resonance point, substantiating our model of rISC. Moreover, using photoinduced absorption, we show how the populations of both singlet and triplet CT states and the local triplet state change in and out of resonance. Our vibronic coupling rISC model is used to predict this behaviour and describes how rISC and TADF are affected by external perturbation.

Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent

PubMed Central

Imamura, Hideo; Downing, Tim; Van den Broeck, Frederik; Sanders, Mandy J; Rijal, Suman; Sundar, Shyam; Mannaert, An; Vanaerschot, Manu; Berg, Maya; De Muylder, Géraldine; Dumetz, Franck; Cuypers, Bart; Maes, Ilse; Domagalska, Malgorzata; Decuypere, Saskia; Rai, Keshav; Uranw, Surendra; Bhattarai, Narayan Raj; Khanal, Basudha; Prajapati, Vijay Kumar; Sharma, Smriti; Stark, Olivia; Schönian, Gabriele; De Koning, Harry P; Settimo, Luca; Vanhollebeke, Benoit; Roy, Syamal; Ostyn, Bart; Boelaert, Marleen; Maes, Louis; Berriman, Matthew; Dujardin, Jean-Claude; Cotton, James A

2016-01-01

Leishmania donovani causes visceral leishmaniasis (VL), the second most deadly vector-borne parasitic disease. A recent epidemic in the Indian subcontinent (ISC) caused up to 80% of global VL and over 30,000 deaths per year. Resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. Here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of L. donovani from the ISC. We identify independent radiations that have emerged since a bottleneck coincident with 1960s DDT spraying campaigns. A genetically distinct population frequently resistant to antimonials has a two base-pair insertion in the aquaglyceroporin gene LdAQP1 that prevents the transport of trivalent antimonials. We find evidence of genetic exchange between ISC populations, and show that the mutation in LdAQP1 has spread by recombination. Our results reveal the complexity of L. donovani evolution in the ISC in response to drug treatment. DOI: http://dx.doi.org/10.7554/eLife.12613.001 PMID:27003289

Drosophila Sulf1 is required for the termination of intestinal stem cell division during regeneration

PubMed Central

2017-01-01

ABSTRACT Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here, we show that a specific modification of heparan sulfate is crucial for regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1 resulted in increased ISC division during normal homeostasis, which was caused by upregulation of mitogenic signaling including the JAK-STAT, EGFR and Hedgehog pathways. Using a regeneration model, we found that ISCs failed to properly halt division at the termination stage in Sulf1 mutants, showing that Sulf1 is required for terminating ISC division at the end of regeneration. We propose that post-transcriptional regulation of mitogen signaling by heparan sulfate structural modifications provides a new regulatory step for precise temporal control of stem cell activity during regeneration. PMID:27888216

Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent.

PubMed

Imamura, Hideo; Downing, Tim; Van den Broeck, Frederik; Sanders, Mandy J; Rijal, Suman; Sundar, Shyam; Mannaert, An; Vanaerschot, Manu; Berg, Maya; De Muylder, Géraldine; Dumetz, Franck; Cuypers, Bart; Maes, Ilse; Domagalska, Malgorzata; Decuypere, Saskia; Rai, Keshav; Uranw, Surendra; Bhattarai, Narayan Raj; Khanal, Basudha; Prajapati, Vijay Kumar; Sharma, Smriti; Stark, Olivia; Schönian, Gabriele; De Koning, Harry P; Settimo, Luca; Vanhollebeke, Benoit; Roy, Syamal; Ostyn, Bart; Boelaert, Marleen; Maes, Louis; Berriman, Matthew; Dujardin, Jean-Claude; Cotton, James A

2016-03-22

Leishmania donovani causes visceral leishmaniasis (VL), the second most deadly vector-borne parasitic disease. A recent epidemic in the Indian subcontinent (ISC) caused up to 80% of global VL and over 30,000 deaths per year. Resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. Here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of L. donovani from the ISC. We identify independent radiations that have emerged since a bottleneck coincident with 1960s DDT spraying campaigns. A genetically distinct population frequently resistant to antimonials has a two base-pair insertion in the aquaglyceroporin gene LdAQP1 that prevents the transport of trivalent antimonials. We find evidence of genetic exchange between ISC populations, and show that the mutation in LdAQP1 has spread by recombination. Our results reveal the complexity of L. donovani evolution in the ISC in response to drug treatment.

CAI Programs and Macros for Formative Curriculum Evaluation.

ERIC Educational Resources Information Center

Dasenbrock, David; Teates, Thomas

This technical memo is designed for persons who are interested in research with and development of curriculum material. Detailed information regarding computer programs, and program documentation used in the development and evaluation of ISCS curriculum materials is provided. The memo includes supplemental information to ISCS Technical Report I…

The Impact of the Perceived Value of Critical-Thinking Skills

ERIC Educational Resources Information Center

Denial, A.

2012-01-01

From 2003-2007 at the New England College of Optometry, the Integrative Seminar Course (ISC) was used to facilitate students' learning of clinical reasoning. To examine students' perceptions and experiences regarding their learning, an end-of-year Likert-style survey was administered to 96 first-year students after completion of the ISC. Analysis…

Evaluation of the Integrated Services Pilot Program from Western Australia

ERIC Educational Resources Information Center

Hancock, Peter; Cooper, Trudi; Bahn, Susanne

2009-01-01

Independent evaluation of refugee-focused programs in developed nations is increasingly a mandatory requirement of funding bodies and government agencies. This paper presents an evaluation of the Integrated Services Centre (ISC) Pilot Project that was conducted in Australia in 2007 and early 2008. The purpose of the ISC program was to provide…

The Discrepancy-Induced Source Comprehension (D-ISC) Model: Basic Assumptions and Preliminary Evidence

ERIC Educational Resources Information Center

Braasch, Jason L. G.; Bråten, Ivar

2017-01-01

Despite the importance of source attention and evaluation for learning from texts, little is known about the particular conditions that encourage sourcing during reading. In this article, basic assumptions of the discrepancy-induced source comprehension (D-ISC) model are presented, which describes the moment-by-moment cognitive processes that…

Respiratory chain supercomplexes associate with the cysteine desulfurase complex of the iron–sulfur cluster assembly machinery

PubMed Central

Böttinger, Lena; Mårtensson, Christoph U.; Song, Jiyao; Zufall, Nicole; Wiedemann, Nils; Becker, Thomas

2018-01-01

Mitochondria are the powerhouses of eukaryotic cells. The activity of the respiratory chain complexes generates a proton gradient across the inner membrane, which is used by the F1FO-ATP synthase to produce ATP for cellular metabolism. In baker’s yeast, Saccharomyces cerevisiae, the cytochrome bc1 complex (complex III) and cytochrome c oxidase (complex IV) associate in respiratory chain supercomplexes. Iron–sulfur clusters (ISC) form reactive centers of respiratory chain complexes. The assembly of ISC occurs in the mitochondrial matrix and is essential for cell viability. The cysteine desulfurase Nfs1 provides sulfur for ISC assembly and forms with partner proteins the ISC-biogenesis desulfurase complex (ISD complex). Here, we report an unexpected interaction of the active ISD complex with the cytochrome bc1 complex and cytochrome c oxidase. The individual deletion of complex III or complex IV blocks the association of the ISD complex with respiratory chain components. We conclude that the ISD complex binds selectively to respiratory chain supercomplexes. We propose that this molecular link contributes to coordination of iron–sulfur cluster formation with respiratory activity. PMID:29386296

Triazatruxene: A Rigid Central Donor Unit for a D-A3 Thermally Activated Delayed Fluorescence Material Exhibiting Sub-Microsecond Reverse Intersystem Crossing and Unity Quantum Yield via Multiple Singlet-Triplet State Pairs.

PubMed

Dos Santos, Paloma L; Ward, Jonathan S; Congrave, Daniel G; Batsanov, Andrei S; Eng, Julien; Stacey, Jessica E; Penfold, Thomas J; Monkman, Andrew P; Bryce, Martin R

2018-06-01

By inverting the common structural motif of thermally activated delayed fluorescence materials to a rigid donor core and multiple peripheral acceptors, reverse intersystem crossing (rISC) rates are demonstrated in an organic material that enables utilization of triplet excited states at faster rates than Ir-based phosphorescent materials. A combination of the inverted structure and multiple donor-acceptor interactions yields up to 30 vibronically coupled singlet and triplet states within 0.2 eV that are involved in rISC. This gives a significant enhancement to the rISC rate, leading to delayed fluorescence decay times as low as 103.9 ns. This new material also has an emission quantum yield ≈1 and a very small singlet-triplet gap. This work shows that it is possible to achieve both high photoluminescence quantum yield and fast rISC in the same molecule. Green organic light-emitting diode devices with external quantum efficiency >30% are demonstrated at 76 cd m -2 .

Evolution of Fe/S cluster biogenesis in the anaerobic parasite Blastocystis

PubMed Central

Tsaousis, Anastasios D.; Ollagnier de Choudens, Sandrine; Gentekaki, Eleni; Long, Shaojun; Gaston, Daniel; Stechmann, Alexandra; Vinella, Daniel; Py, Béatrice; Fontecave, Marc; Barras, Frédéric; Lukeš, Julius; Roger, Andrew J.

2012-01-01

Iron/sulfur cluster (ISC)-containing proteins are essential components of cells. In most eukaryotes, Fe/S clusters are synthesized by the mitochondrial ISC machinery, the cytosolic iron/sulfur assembly system, and, in photosynthetic species, a plastid sulfur-mobilization (SUF) system. Here we show that the anaerobic human protozoan parasite Blastocystis, in addition to possessing ISC and iron/sulfur assembly systems, expresses a fused version of the SufC and SufB proteins of prokaryotes that it has acquired by lateral transfer from an archaeon related to the Methanomicrobiales, an important lineage represented in the human gastrointestinal tract microbiome. Although components of the Blastocystis ISC system function within its anaerobic mitochondrion-related organelles and can functionally replace homologues in Trypanosoma brucei, its SufCB protein has similar biochemical properties to its prokaryotic homologues, functions within the parasite’s cytosol, and is up-regulated under oxygen stress. Blastocystis is unique among eukaryotic pathogens in having adapted to its parasitic lifestyle by acquiring a SUF system from nonpathogenic Archaea to synthesize Fe/S clusters under oxygen stress. PMID:22699510

Depletion of FAP+ cells reduces immunosuppressive cells and improves metabolism and functions CD8+T cells within tumors

PubMed Central

Zhang, Ying; Ertl, Hildegund C.J.

2016-01-01

The tumor stroma, which is essential to support growth and metastasis of malignant cells, provides targets for active immunotherapy of cancer. Previous studies have shown that depleting fibroblast activation protein (FAP)-expressing stromal cells reduces tumor progression and concomitantly increases tumor antigen (TA)-specific T cell responses. However the underlying pathways remain ill defined. Here we identify that immunosuppressive cells (ISCs) from tumor-bearing mice impose metabolic stress on CD8+T cells, which is associated with increased expression of the co-inhibitor PD-1. In two mouse melanoma models, depleting FAP+ stroma cells from the tumor microenvironment (TME) upon vaccination with an adenoviral-vector reduces frequencies and functions of ISCs. This is associated with changes in the cytokine/chemokine milieu in the TME and decreased activity of STAT6 signaling within ISCs. Decreases in ISCs upon FAP+stromal cell depletion is associated with reduced metabolic stress of vaccine-induced tumor infiltrating CD8+T cells and their delayed progression towards functional exhaustion, resulting in prolonged survival of tumor-bearing mice. PMID:26943036

Depletion of FAP+ cells reduces immunosuppressive cells and improves metabolism and functions CD8+T cells within tumors.

PubMed

Zhang, Ying; Ertl, Hildegund C J

2016-04-26

The tumor stroma, which is essential to support growth and metastasis of malignant cells, provides targets for active immunotherapy of cancer. Previous studies have shown that depleting fibroblast activation protein (FAP)-expressing stromal cells reduces tumor progression and concomitantly increases tumor antigen (TA)-specific T cell responses. However the underlying pathways remain ill defined. Here we identify that immunosuppressive cells (ISCs) from tumor-bearing mice impose metabolic stress on CD8+T cells, which is associated with increased expression of the co-inhibitor PD-1. In two mouse melanoma models, depleting FAP+ stroma cells from the tumor microenvironment (TME) upon vaccination with an adenoviral-vector reduces frequencies and functions of ISCs. This is associated with changes in the cytokine/chemokine milieu in the TME and decreased activity of STAT6 signaling within ISCs. Decreases in ISCs upon FAP+stromal cell depletion is associated with reduced metabolic stress of vaccine-induced tumor infiltrating CD8+T cells and their delayed progression towards functional exhaustion, resulting in prolonged survival of tumor-bearing mice.

Materials, properties, and applications of nitrogen-doped organic semiconductors

NASA Astrophysics Data System (ADS)

Chan, Calvin Kar-Fai

As organic semiconducting materials draw increasing attention for many promising applications, including efficient organic light-emitting diodes (OLEDs), large-area organic photovoltaic (OPV) cells, and flexible organic thin-film transistors (OTFTs), chemical doping of organic materials is emerging as an important technique for overcoming performance deficiencies and material limitations of intrinsic organic films. Although p-doping has been amply demonstrated, molecular n-type doping has been difficult to study because of the inherent instability of easily oxidized n-dopants. In this work, the facile use of two low ionization energy (IE) small molecules that are suitable for n-doping a wide range of organic electronic materials is demonstrated. Cobaltocene (CoCp2) and its derivative, decamethylcobaltocene ( CoCp*2 ), were found to have fairly low IEs for organic compounds. Co-deposition of the n-dopants with different host molecules results in pronounced shifts of the Fermi-level towards unoccupied molecular states, indicating a significant increase in electron concentration. The Fermi-level shifts, measured with ultra-violet photoemission spectroscopy (UPS), are correlated with excess carrier densities using a model based on Fermi-Dirac (F-D) statistics and a Gaussian distributed density of states. The calculated electron densities suggest full dopant ionization at low concentrations, and diminished efficiency at high donor concentrations. The concentration of incorporated dopants is examined by chemical composition analysis of doped films using X-ray photoemission spectroscopy (XPS). Atomic concentration depth profiling determined by Rutherford backscattering (RBS) suggests that the incorporation of CoCp2 and CoCp*2 is well-controlled and the dopants are minimally diffusive. Organic films n-doped using CoCp2 and CoCp*2 show several orders of magnitude increase in current density resulting from both enhanced electron injection and increased electron conductivity in the bulk. Increases in the bulk conductivity suggest both improved electron mobility and higher electron concentrations. These findings are applied with previous work on p-doping to fabricate organic p-i-n homojunction devices that exhibit strong rectification and large built-in potentials. Heterojunction OPVs using undoped CuPc and n-doped C60 display significant increases in open-circuit voltage (Voc), short-circuit current (Isc), fill-factor (FF), and efficiency.

The enteric microbiota regulates jejunal Paneth cell number and function without impacting intestinal stem cells.

PubMed

Schoenborn, Alexi A; von Furstenberg, Richard J; Valsaraj, Smrithi; Hussain, Farah S; Stein, Molly; Shanahan, Michael T; Henning, Susan J; Gulati, Ajay S

2018-06-08

Paneth cells (PCs) are epithelial cells found in the small intestine, next to intestinal stem cells (ISCs) at the base of the crypts. PCs secrete antimicrobial peptides (AMPs) that regulate the commensal gut microbiota. In contrast, little is known regarding how the enteric microbiota reciprocally influences PC function. In this study, we sought to characterize the impact of the enteric microbiota on PC biology in the mouse small intestine. This was done by first enumerating jejunal PCs in germ-free (GF) versus conventionally-raised (CR) mice. We next evaluated the possible functional consequences of altered PC biology in these experimental groups by assessing epithelial proliferation, ISC numbers, and the production of AMPs. We found that PC numbers were significantly increased in CR versus GF mice; however, there were no differences in ISC numbers or cycling activity between groups. Of the AMPs assessed, only Reg3γ transcript expression was significantly increased in CR mice. Intriguingly, this increase was abrogated in cultured CR versus GF enteroids, and could not be re-induced with various bacterial ligands. Our findings demonstrate the enteric microbiota regulates PC function by increasing PC numbers and inducing Reg3γ expression, though the latter effect may not involve direct interactions between bacteria and the intestinal epithelium. In contrast, the enteric microbiota does not appear to regulate jejunal ISC census and proliferation. These are critical findings for investigators using GF mice and the enteroid system to study PC and ISC biology.

Cysteine desulfurase IscS2 plays a role in oxygen resistance in Clostridium difficile.

PubMed

Giordano, Nicole; Hastie, Jessica L; Smith, Ashley D; Foss, Elissa D; Gutierrez-Munoz, Daniela F; Carlson, Paul E

2018-06-04

Clostridium difficile is an anaerobic, spore-forming bacterium capable of colonizing the gastrointestinal tract of humans following disruption of the normal microbiota, typically from antibiotic therapy for an unrelated infection. With approximately 500,000 confirmed infections leading to 29,000 deaths per year in the United States, C. difficile infection (CDI) is an urgent public health threat. We previously determined C. difficile survives in up to 3% oxygen. Low levels of oxygen are present in the intestinal tract with the higher concentrations being associated with the epithelial cell surface. Additionally, antibiotic treatment, the greatest risk factor for CDI, increases intestinal oxygen concentration. Therefore, we hypothesized that the C. difficile genome encodes mechanisms for survival during oxidative stress. Previous data have shown that cysteine desulfurases involved in iron-sulfur cluster assembly are involved in protecting bacteria from oxidative stress. In this study, deletion of a putative cysteine desulfurase ( Cd 630_12790/IscS2) involved in the iron sulfur cluster (Isc) system caused a severe growth defect in the presence of 2% oxygen. Additionally, this mutant delayed colonization in a conventional mouse model of CDI, and failed to colonize in a germ-free model, which has higher intestinal oxygen levels. These data imply an undefined role for this cysteine desulfurase in protecting C. difficile from low levels of oxygen in the gut. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Triple negative breast cancer initiating cell subsets differ in functional and molecular characteristics and in γ-secretase inhibitor drug responses

PubMed Central

Azzam, Diana J; Zhao, Dekuang; Sun, Jun; Minn, Andy J; Ranganathan, Prathibha; Drews-Elger, Katherine; Han, Xiaoqing; Picon-Ruiz, Manuel; Gilbert, Candace A; Wander, Seth A; Capobianco, Anthony J; El-Ashry, Dorraya; Slingerland, Joyce M

2013-01-01

Increasing evidence suggests that stem-like cells mediate cancer therapy resistance and metastasis. Breast tumour-initiating stem cells (T-ISC) are known to be enriched in CD44+CD24neg/low cells. Here, we identify two T-ISC subsets within this population in triple negative breast cancer (TNBC) lines and dissociated primary breast cancer cultures: CD44+CD24low+ subpopulation generates CD44+CD24neg progeny with reduced sphere formation and tumourigenicity. CD44+CD24low+ populations contain subsets of ALDH1+ and ESA+ cells, yield more frequent spheres and/or T-ISC in limiting dilution assays, preferentially express metastatic gene signatures and show greater motility, invasion and, in the MDA-MB-231 model, metastatic potential. CD44+CD24low+ but not CD44+CD24neg express activated Notch1 intracellular domain (N1-ICD) and Notch target genes. We show N1-ICD transactivates SOX2 to increase sphere formation, ALDH1+ and CD44+CD24low+cells. Gamma secretase inhibitors (GSI) reduced sphere formation and xenograft growth from CD44+CD24low+ cells, but CD44+CD24neg were resistant. While GSI hold promise for targeting T-ISC, stem cell heterogeneity as observed herein, could limit GSI efficacy. These data suggest a breast T-ISC hierarchy in which distinct pathways drive developmentally related subpopulations with different anti-cancer drug responsiveness. PMID:23982961

pH-Induced Conformational Change of IscU at Low pH Correlates with Protonation/Deprotonation of Two Conserved Histidine Residues

PubMed Central

2015-01-01

IscU, the scaffold protein for the major iron–sulfur cluster biosynthesis pathway in microorganisms and mitochondria (ISC pathway), plays important roles in the formation of [2Fe–2S] and [4Fe–4S] clusters and their delivery to acceptor apo-proteins. Our laboratory has shown that IscU populates two distinct, functionally relevant conformational states, a more structured state (S) and a more dynamic state (D), that differ by cis/trans isomerizations about two peptidyl-prolyl peptide bonds [Kim, J. H., Tonelli, M., and Markley, J. L. (2012) Proc. Natl. Acad. Sci. U.S.A., 109, 454–459. Dai Z., Tonelli, M., and Markley, J. L. (2012) Biochemistry, 51, 9595–9602. Cai, K., Frederick, R. O., Kim, J. H., Reinen, N. M., Tonelli, M., and Markley, J. L. (2013) J. Biol. Chem., 288, 28755–28770]. Here, we report our findings on the pH dependence of the D ⇄ S equilibrium for Escherichia coli IscU in which the D-state is stabilized at low and high pH values. We show that the lower limb of the pH dependence curve results from differences in the pKa values of two conserved histidine residues (His10 and His105) in the two states. The net proton affinity of His10 is about 50 times higher and that of His105 is 13 times higher in the D-state than in the S-state. The origin of the high limb of the D ⇄ S pH dependence remains to be determined. These results show that changes in proton inventory need to be taken into account in the steps in iron–sulfur cluster assembly and transfer that involve transitions of IscU between its S- and D-states. PMID:25055301

Prophylactic urethral stenting with Memokath® 028SW in prostate cancer patients undergoing prostate 125I seed implants: phase I/II study

PubMed Central

Chao, Samuel T.; Angermeier, Kenneth; Klein, Eric A.; Reddy, Chandana A.; Ulchaker, James C.; Stephenson, Andrew; Campbell, Steven

2011-01-01

Purpose To study the feasibility/toxicity of urethral stenting with the Memokath® 028SW stent in patients undergoing prostate implant (PI) for prostate adenocarcinoma. Material and methods An Investigational Device Exemption from the Food and Drug Administration (FDA) and institutional review board (IRB) approval were obtained. Twenty patients enrolled. Baseline American Urological Association (AUA) score was obtained prior to PI. Follow-up information was obtained with weekly phone calls for the first 12 weeks and biweekly calls for the next 12 weeks to assess toxicity and AUA score. Removal of the stent was planned at six months after PI, or earlier due to excessive toxicity/patient request. Results Median age was 66.5 years. The median prostate volume was 39 cc (range: 10-90). The median baseline AUA score was 7.5 (range: 1-21). Three patients required intermittent self-catheterization (ISC) within 3 days after PI. No patients required ISC beyond day 3 after PI. The median duration of ISC was 1 day (range: 1-2). AUA scores returned to baseline values 6 weeks after PI. The week 6 AUA score was 10 (range: 4-16). Seven patients (35%) underwent early removal because of patient preference. The reasons were: incontinence (n = 3), discomfort (n = 2), hematuria (n = 1), and obstructive symptoms (n = 1). The median time of stent removal in these patients was 13.9 weeks (range: 0.9-21.4). Thirteen patients (65%) had ISC and/or urinary catheterization post stent removal. Median time for ISC use was 10 days (range: 1-90). Conclusions Urethral stenting with Memokath® in patients undergoing PI was feasible, but resulted in relatively high rate of urinary incontinence and discomfort. Given the adverse effects experienced by patients of this study, further studies should focus only on patients with highest risk of urinary obstruction from PI or those with obstruction needing ISC. PMID:27877196

Spectroscopic and functional characterization of iron-bound forms of Azotobacter vinelandii (Nif)IscA.

PubMed

Mapolelo, Daphne T; Zhang, Bo; Naik, Sunil G; Huynh, Boi Hanh; Johnson, Michael K

2012-10-16

The ability of Azotobacter vinelandii(Nif)IscA to bind Fe has been investigated to assess the role of Fe-bound forms in NIF-specific Fe-S cluster biogenesis. (Nif)IscA is shown to bind one Fe(III) or one Fe(II) per homodimer and the spectroscopic and redox properties of both the Fe(III)- and Fe(II)-bound forms have been characterized using the UV-visible absorption, circular dichroism, and variable-temperature magnetic circular dichroism, electron paramagnetic resonance, Mössbauer and resonance Raman spectroscopies. The results reveal a rhombic intermediate-spin (S = 3/2) Fe(III) center (E/D = 0.33, D = 3.5 ± 1.5 cm(-1)) that is most likely 5-coordinate with two or three cysteinate ligands and a rhombic high spin (S = 2) Fe(II) center (E/D = 0.28, D = 7.6 cm(-1)) with properties similar to reduced rubredoxins or rubredoxin variants with three cysteinate and one or two oxygenic ligands. Iron-bound (Nif)IscA undergoes reversible redox cycling between the Fe(III)/Fe(II) forms with a midpoint potential of +36 ± 15 mV at pH 7.8 (versus NHE). l-Cysteine is effective in mediating release of free Fe(II) from both the Fe(II)- and Fe(III)-bound forms of (Nif)IscA. Fe(III)-bound (Nif)IscA was also shown to be a competent iron source for in vitro NifS-mediated [2Fe-2S] cluster assembly on the N-terminal domain of NifU, but the reaction occurs via cysteine-mediated release of free Fe(II) rather than direct iron transfer. The proposed roles of A-type proteins in storing Fe under aerobic growth conditions and serving as iron donors for cluster assembly on U-type scaffold proteins or maturation of biological [4Fe-4S] centers are discussed in light of these results.

Urbanization and nutrient retention in freshwater riparian wetlands

USGS Publications Warehouse

Hogan, D.M.; Walbridge, M.R.

2007-01-01

Urbanization can degrade water quality and alter watershed hydrology, with profound effects on the structure and function of both riparian wetlands (RWs) and aquatic ecosystems downstream. We used freshwater RWs in Fairfax County, Virginia, USA, as a model system to examine: (1) the effects of increasing urbanization (indexed by the percentage of impervious surface cover [%ISC] in the surrounding watershed) on nitrogen (N) and phosphorus (P) concentrations in surface soils and plant tissues, soil P saturation, and soil iron (Fe) chemistry; and (2) relationships between RW soil and plant nutrient chemistries vs. the physical and biotic integrity of adjacent streams. Soil total P and NaOH-extractable P (representing P bound to aluminum [Al] and Fe hydrous oxides) varied significantly but nonlinearly with %ISC (r2 = 0.69 and 0.57, respectively); a similar pattern was found for soil P saturation but not for soil total N. Relationships were best described by second-order polynomial equations. Riparian wetlands appear to receive greater P loads in moderately (8.6-13.3% ISC) than in highly (25.1-29.1% ISC) urbanized watersheds. These observations are consistent with alterations in watershed hydrology that occur with increasing urbanization, directing water and nutrient flows away from natural RWs. Significant increases in total and crystalline soil Fe (r 2 = 0.57 and 0.53, respectively) and decreases in relative soil Fe crystallinity with increasing %ISC suggest the mobilization and deposition of terrestrial sediments in RWs, likely due to construction activities in the surrounding watershed. Increases in RW plant tissue nutrient concentrations and %ISC in the surrounding watershed were negatively correlated with standard indices of the physical and biotic integrity of adjacent streams. In combination, these data suggest that nutrient and sediment inputs associated with urbanization and storm-water management are important variables that affect wetland ecosystem services, such as water quality improvement, in urbanizing landscapes. ?? 2007 by the Ecological Society of America.

Dysfunction in the mitochondrial Fe-S assembly machinery leads to formation of the chemoresistant truncated VDAC1 isoform without HIF-1α activation

PubMed Central

Ferecatu, Ioana; Canal, Frédéric; Fabbri, Lucilla; Mazure, Nathalie M.; Bouton, Cécile

2018-01-01

Biogenesis of iron-sulfur clusters (ISC) is essential to almost all forms of life and involves complex protein machineries. This process is initiated within the mitochondrial matrix by the ISC assembly machinery. Cohort and case report studies have linked mutations in ISC assembly machinery to severe mitochondrial diseases. The voltage-dependent anion channel (VDAC) located within the mitochondrial outer membrane regulates both cell metabolism and apoptosis. Recently, the C-terminal truncation of the VDAC1 isoform, termed VDAC1-ΔC, has been observed in chemoresistant late-stage tumor cells grown under hypoxic conditions with activation of the hypoxia-response nuclear factor HIF-1α. These cells harbored atypical enlarged mitochondria. Here, we show for the first time that depletion of several proteins of the mitochondrial ISC machinery in normoxia leads to a similar enlarged mitochondria phenotype associated with accumulation of VDAC1-ΔC. This truncated form of VDAC1 accumulates in the absence of HIF-1α and HIF-2α activations and confers cell resistance to drug-induced apoptosis. Furthermore, we show that when hypoxia and siRNA knock-down of the ISC machinery core components are coupled, the cell phenotype is further accentuated, with greater accumulation of VDAC1-ΔC. Interestingly, we show that hypoxia promotes the downregulation of several proteins (ISCU, NFS1, FXN) involved in the early steps of mitochondrial Fe-S cluster biogenesis. Finally, we have identified the mitochondria-associated membrane (MAM) localized Fe-S protein CISD2 as a link between ISC machinery downregulation and accumulation of anti-apoptotic VDAC1-ΔC. Our results are the first to associate dysfunction in Fe-S cluster biogenesis with cleavage of VDAC1, a form which has previously been shown to promote tumor resistance to chemotherapy, and raise new perspectives for targets in cancer therapy. PMID:29596470

Radiotherapy supporting system based on the image database using IS&C magneto-optical disk

NASA Astrophysics Data System (ADS)

Ando, Yutaka; Tsukamoto, Nobuhiro; Kunieda, Etsuo; Kubo, Atsushi

1994-05-01

Since radiation oncologists make the treatment plan by prior experience, information about previous cases is helpful in planning the radiation treatment. We have developed an supporting system for the radiation therapy. The case-based reasoning method was implemented in order to search old treatments and images of past cases. This system evaluates similarities between the current case and all stored cases (case base). The portal images of the similar cases can be retrieved for reference images, as well as treatment records which show examples of the radiation treatment. By this system radiotherapists can easily make suitable plans of the radiation therapy. This system is useful to prevent inaccurate plannings due to preconceptions and/or lack of knowledge. Images were stored into magneto-optical disks and the demographic data is recorded to the hard disk which is equipped in the personal computer. Images can be displayed quickly on the radiotherapist's demands. The radiation oncologist can refer past cases which are recorded in the case base and decide the radiation treatment of the current case. The file and data format of magneto-optical disk is the IS&C format. This format provides the interchangeability and reproducibility of the medical information which includes images and other demographic data.

From Cell to Module: Fabrication and Long-term Stability of Dye-sensitized Solar Cells

NASA Astrophysics Data System (ADS)

Nursam, N. M.; Hidayat, J.; Muliani, L.; Anggraeni, P. N.; Retnaningsih, L.; Idayanti, N.

2017-07-01

Dye-sensitized solar cell (DSSC), which has been firstly developed by Graetzel et al back in 1991, has attracted a considerable interest since its discovery. However, two of the main challenges that the DSSC technology will have to overcome towards commercialization involve device scale-up and long-term stability. In our group, the fabrication technology of DSSC has been developed from laboratory to module scale over the past few years, nevertheless, the long-term stability has still became a major concern. In this contribution, the long-term DSSC performance in relation to their scale-up from cell to module is investigated. The photoelectrode of the DSSCs were fabricated using nanocrystalline titanium dioxide materials that were subsequently sensitized using ruthenium-based dye. Additionally, TiCl4 pre- and post-treatment were carried out to enhance the overall device efficiency. When fabricated as cells, the DSSC prototypes showed relatively stable performance during repeated tests over three months. In order to increase the output power of the solar cells, the DSSCs were then connected in a Z-type series connection to obtain sub-module panels. The DSSC sub-modules exhibit poor stability, particularly as indicated by the significant decrease in the short circuit current (ISC ). Herein, the effect of photoelectrode and sealant materials as well as module design are investigated, highlighting their profound influence upon the DSSC efficiency and long-term stability.

Outdoor Performance Analysis of a Photovoltaic Thermal (PVT) Collector with Jet Impingement and Compound Parabolic Concentrator (CPC)

PubMed Central

Jaaz, Ahed Hameed; Hasan, Husam Abdulrasool; Sopian, Kamaruzzaman; Kadhum, Abdul Amir H.; Gaaz, Tayser Sumer

2017-01-01

This paper discusses the effect of jet impingement of water on a photovoltaic thermal (PVT) collector and compound parabolic concentrators (CPC) on electrical efficiency, thermal efficiency and power production of a PVT system. A prototype of a PVT solar water collector installed with a jet impingement and CPC has been designed, fabricated and experimentally investigated. The efficiency of the system can be improved by using jet impingement of water to decrease the temperature of the solar cells. The electrical efficiency and power output are directly correlated with the mass flow rate. The results show that electrical efficiency was improved by 7% when using CPC and jet impingement cooling in a PVT solar collector at 1:00 p.m. (solar irradiance of 1050 W/m2 and an ambient temperature of 33.5 °C). It can also be seen that the power output improved by 36% when using jet impingement cooling with CPC, and 20% without CPC in the photovoltaic (PV) module at 1:30 p.m. The short-circuit current ISC of the PV module experienced an improvement of ~28% when using jet impingement cooling with CPC, and 11.7% without CPC. The output of the PV module was enhanced by 31% when using jet impingement cooling with CPC, and 16% without CPC. PMID:28763048

International Standard Classification of Education (ISCED) Three Stage Classification System: 1973; Part 2 - Definitions.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France).

The seven levels of education, as classified numerically by International Standard Classification of Education (ISCED), are defined along with courses, programs, and fields of education listed under each level. Also contained is an alphabetical subject index indicating appropriate code numbers. For related documents see TM003535 and TM003536. (RC)

TEDS-M 2008 User Guide for the International Database

ERIC Educational Resources Information Center

Brese, Falk, Ed.

2012-01-01

The Teacher Education Study in Mathematics or TEDS-M is a study conducted under the aegis of the International Association for the Evaluation of Educational Achievement (IEA). The lead research center for the study is the International Study Center at Michigan State University (ISC/MSU). The ISC/MSU worked from 2006 to 2011 with the International…

EEG in the classroom: Synchronised neural recordings during video presentation

PubMed Central

Poulsen, Andreas Trier; Kamronn, Simon; Dmochowski, Jacek; Parra, Lucas C.; Hansen, Lars Kai

2017-01-01

We performed simultaneous recordings of electroencephalography (EEG) from multiple students in a classroom, and measured the inter-subject correlation (ISC) of activity evoked by a common video stimulus. The neural reliability, as quantified by ISC, has been linked to engagement and attentional modulation in earlier studies that used high-grade equipment in laboratory settings. Here we reproduce many of the results from these studies using portable low-cost equipment, focusing on the robustness of using ISC for subjects experiencing naturalistic stimuli. The present data shows that stimulus-evoked neural responses, known to be modulated by attention, can be tracked for groups of students with synchronized EEG acquisition. This is a step towards real-time inference of engagement in the classroom. PMID:28266588

EEG in the classroom: Synchronised neural recordings during video presentation

NASA Astrophysics Data System (ADS)

Poulsen, Andreas Trier; Kamronn, Simon; Dmochowski, Jacek; Parra, Lucas C.; Hansen, Lars Kai

2017-03-01

We performed simultaneous recordings of electroencephalography (EEG) from multiple students in a classroom, and measured the inter-subject correlation (ISC) of activity evoked by a common video stimulus. The neural reliability, as quantified by ISC, has been linked to engagement and attentional modulation in earlier studies that used high-grade equipment in laboratory settings. Here we reproduce many of the results from these studies using portable low-cost equipment, focusing on the robustness of using ISC for subjects experiencing naturalistic stimuli. The present data shows that stimulus-evoked neural responses, known to be modulated by attention, can be tracked for groups of students with synchronized EEG acquisition. This is a step towards real-time inference of engagement in the classroom.

Adjustable direct current and pulsed circuit fault current limiter

DOEpatents

Boenig, Heinrich J.; Schillig, Josef B.

2003-09-23

A fault current limiting system for direct current circuits and for pulsed power circuit. In the circuits, a current source biases a diode that is in series with the circuits' transmission line. If fault current in a circuit exceeds current from the current source biasing the diode open, the diode will cease conducting and route the fault current through the current source and an inductor. This limits the rate of rise and the peak value of the fault current.

Of spotted owls, old growth, and new policies: a history since the Interagency Scientific Committee report.

Treesearch

Bruce G. Marcot; Jack Ward Thomas

1997-01-01

This paper tracks the recent history of planning, management, and litigation regarding northern spotted owls and their habitat on Federal public lands since the 1989 Interagency Scientific Committee to Address the Conservation of the Northern Spotted Owl (ISC). The ISC report and subsequent plans sparked many economic analyses, appeals, lawsuits, forest management...

Deficiency in DNA damage response of enterocytes accelerates intestinal stem cell aging in Drosophila.

PubMed

Park, Joung-Sun; Jeon, Ho-Jun; Pyo, Jung-Hoon; Kim, Young-Shin; Yoo, Mi-Ae

2018-03-07

Stem cell dysfunction is closely linked to tissue and organismal aging and age-related diseases, and heavily influenced by the niche cells' environment. The DNA damage response (DDR) is a key pathway for tissue degeneration and organismal aging; however, the precise protective role of DDR in stem cell/niche aging is unclear. The Drosophila midgut is an excellent model to study the biology of stem cell/niche aging because of its easy genetic manipulation and its short lifespan. Here, we showed that deficiency of DDR in Drosophila enterocytes (ECs) accelerates intestinal stem cell (ISC) aging. We generated flies with knockdown of Mre11 , Rad50 , Nbs1 , ATM , ATR , Chk1 , and Chk2 , which decrease the DDR system in ECs. EC-specific DDR depletion induced EC death, accelerated the aging of ISCs, as evidenced by ISC hyperproliferation, DNA damage accumulation, and increased centrosome amplification, and affected the adult fly's survival. Our data indicated a distinct effect of DDR depletion in stem or niche cells on tissue-resident stem cell proliferation. Our findings provide evidence of the essential role of DDR in protecting EC against ISC aging, thus providing a better understanding of the molecular mechanisms of stem cell/niche aging.

Midgut epithelium in molting silkworm: A fine balance among cell growth, differentiation, and survival.

PubMed

Franzetti, Eleonora; Casartelli, Morena; D'Antona, Paola; Montali, Aurora; Romanelli, Davide; Cappellozza, Silvia; Caccia, Silvia; Grimaldi, Annalisa; de Eguileor, Magda; Tettamanti, Gianluca

2016-07-01

The midgut of insects has attracted great attention as a system for studying intestinal stem cells (ISCs) as well as cell death-related processes, such as apoptosis and autophagy. Among insects, Lepidoptera represent a good model to analyze these cells and processes. In particular, larva-larva molting is an interesting developmental phase since the larva must deal with nutrient starvation and its organs are subjected to rearrangements due to proliferation and differentiation events. Several studies have analyzed ISCs in vitro and characterized key factors involved in their division and differentiation during molt. However, in vivo studies performed during larva-larva transition on these cells, and on the whole midgut epithelium, are fragmentary. In the present study, we analyzed the larval midgut epithelium of the silkworm, Bombyx mori, during larva-larva molting, focusing our attention on ISCs. Moreover, we investigated the metabolic changes that occur in the epithelium and evaluated the intervention of autophagy. Our data on ISCs proliferation and differentiation, autophagy activation, and metabolic and functional activities of the midgut cells shed light on the complexity of this organ during the molting phase. Copyright © 2016 Elsevier Ltd. All rights reserved.

30 CFR 75.900 - Low- and medium-voltage circuits serving three-phase alternating current equipment; circuit...

Code of Federal Regulations, 2011 CFR

2011-07-01

...-phase alternating current equipment; circuit breakers. 75.900 Section 75.900 Mineral Resources MINE... Low- and medium-voltage circuits serving three-phase alternating current equipment; circuit breakers. [Statutory Provisions] Low- and medium-voltage power circuits serving three-phase alternating current...

Current limiter circuit system

DOEpatents

Witcher, Joseph Brandon; Bredemann, Michael V.

2017-09-05

An apparatus comprising a steady state sensing circuit, a switching circuit, and a detection circuit. The steady state sensing circuit is connected to a first, a second and a third node. The first node is connected to a first device, the second node is connected to a second device, and the steady state sensing circuit causes a scaled current to flow at the third node. The scaled current is proportional to a voltage difference between the first and second node. The switching circuit limits an amount of current that flows between the first and second device. The detection circuit is connected to the third node and the switching circuit. The detection circuit monitors the scaled current at the third node and controls the switching circuit to limit the amount of the current that flows between the first and second device when the scaled current is greater than a desired level.

International Solar Cycle Studies (ISCS), "Solar Energy Flux Study: from the interior to the outer layer" — Working Group 1 report

NASA Astrophysics Data System (ADS)

Pap, Judit; Fröhlich, Claus

The purpose of this report is to describe the research activities and plans of Working Group 1: "Solar Energy Flux Study: From the Interior to the Outer Layer" of the International Solar Cycle Study (ISCS), which is an international research organization operating under the auspices of the Scientific Committee on Solar-Terrestrial Physics (SCOSTEP). As part of the report, we also summarize the status of the measurements and results on the solar energy flux variations. The main objective of ISCS's Working Group 1 is to coordinate and support comprehensive international research of the variations in the solar energy flux during the rising portion and maximum of solar cycle 23. The research activities of ISCS's Working Group 1 will concentrate on the following tasks: (1) to measure and study the variations in the solar radiative and mass output and solar activity indices during the solar activity cycle, (2) to understand why the solar radiative and mass output and the solar activity indices vary during the solar cycle, and (3) to study the role of solar variability in solar-terrestrial changes and its contribution to global change. ISCS WG1 "Solar Energy Flux Study: From the Interior to the Outer Layer" has been divided into three panels: •| Panel 1: Variations in Total and Spectral Irradiance from Infrared to Far UV. Panel leaders: Martin Anklin of the Physikalisch-Meteorologishes Observatorium Davos, Switzerland (total irradiance), Gerard Thuillier of the Service d'Aeronomie-CNRS, Verrieres, France (visible and infrared), and Linton Floyd of the Naval Research Laboratory, Washington, DC, USA (ultraviolet). •| Panel 2: Variations in EUV, X-ray and Particle Fluxes. Panel leaders: Gerhard Schmidtke of Fraunhofer IPM, Freiburg, Germany and W. Kent Tobiska of FDC/Jet Propulsion Laboratory, Pasadena, CA, USA (EUV/XUV), and David Winningham of the Southwest Research Institute, San Antonio, TX, USA (particles). •| Panel 3: Solar Indices, Cosmogenic Isotopes, Solar-Stellar Relations. Panel leaders: Gary Chapman of the San Fernando Observatory, CSUN, Northridge, CA, USA (solar indices), Juerg Beer of Institute for Environmental Science and Technology, Dübendorf, Switzerland (cosmogenic isotopes), and Sallie Baliunas of the Harvard Smithsonian Center for Astrophysics, Cambridge, MA, USA (solar-stellar relations). The first two panels concentrate on solar energy flux measurements, whereas the third panel concentrates on solar indices and alternative ways to model and predict irradiance variations at various wavelengths and their terrestrial/climate effects. Working Group 1 of ISCS has supported and adopted the "Thermospheric-Ionospheric Geospheric Research (TIGER)" program as part of ISCS/WG1/Panel 2. The main objectives of TIGER are to measure, model, and interpret solar EUV/UV and particle fluxes and to study and model their effect on the Earth's thermosphere and ionosphere (see details by Schmidtke et al., 2001, this volume). This approach links ISCS/WG1 activities directly with studies of our space environment.

Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal.

PubMed

Yan, Kelley S; Janda, Claudia Y; Chang, Junlei; Zheng, Grace X Y; Larkin, Kathryn A; Luca, Vincent C; Chia, Luis A; Mah, Amanda T; Han, Arnold; Terry, Jessica M; Ootani, Akifumi; Roelf, Kelly; Lee, Mark; Yuan, Jenny; Li, Xiao; Bolen, Christopher R; Wilhelmy, Julie; Davies, Paige S; Ueno, Hiroo; von Furstenberg, Richard J; Belgrader, Phillip; Ziraldo, Solongo B; Ordonez, Heather; Henning, Susan J; Wong, Melissa H; Snyder, Michael P; Weissman, Irving L; Hsueh, Aaron J; Mikkelsen, Tarjei S; Garcia, K Christopher; Kuo, Calvin J

2017-05-11

The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands. For example, individual mutations in Wnt ligands have not revealed homeostatic phenotypes in the intestinal epithelium-an archetypal canonical, Wnt pathway-dependent, rapidly self-renewing tissue, the regeneration of which is fueled by proliferative crypt Lgr5 + intestinal stem cells (ISCs). R-spondin ligands (RSPO1-RSPO4) engage distinct LGR4-LGR6, RNF43 and ZNRF3 receptor classes, markedly potentiate canonical Wnt/β-catenin signalling, and induce intestinal organoid growth in vitro and Lgr5 + ISCs in vivo. However, the interchangeability, functional cooperation and relative contributions of Wnt versus RSPO ligands to in vivo canonical Wnt signalling and ISC biology remain unknown. Here we identify the functional roles of Wnt and RSPO ligands in the intestinal crypt stem-cell niche. We show that the default fate of Lgr5 + ISCs is to differentiate, unless both RSPO and Wnt ligands are present. However, gain-of-function studies using RSPO ligands and a new non-lipidated Wnt analogue reveal that these ligands have qualitatively distinct, non-interchangeable roles in ISCs. Wnt proteins are unable to induce Lgr5 + ISC self-renewal, but instead confer a basal competency by maintaining RSPO receptor expression that enables RSPO ligands to actively drive and specify the extent of stem-cell expansion. This functionally non-equivalent yet cooperative interaction between Wnt and RSPO ligands establishes a molecular precedent for regulation of mammalian stem cells by distinct priming and self-renewal factors, with broad implications for precise control of tissue regeneration.

Ten-year survival and complication rates of lithium-disilicate (Empress 2) tooth-supported crowns, implant-supported crowns, and fixed dental prostheses.

PubMed

Teichmann, Maren; Göckler, Fabian; Weber, Volker; Yildirim, Murat; Wolfart, Stefan; Edelhoff, Daniel

2017-01-01

To prospectively evaluate the clinical long-term outcome of tooth-supported crowns (SCs), implant-supported crowns (ISCs), and fixed dental prostheses (FDPs) made of a lithium-disilicate glass-ceramic framework material (IPS Empress 2). Between 1997 and 1999, a total of 184 restorations (106 SCs, 32 ISCs, 33 FDPs, and 13 diverse restorations) were placed in 73 patients. Kaplan-Meier estimation was applied for survival and chipping-free rates. Inter-group comparison of both rates was realized by a log rank test and a 2×2 contingency table. Also, SCs and FDPs were compared regarding adhesive vs. conventional cementation, and anterior vs. posterior positioning, for impact on survival. Due to 14 dropouts (34 restorations) and reasonable exclusion of 19 other restorations, the final dataset included: i) 87 SCs [37 patients, mean observation time 11.4 (±3.8)years]; ii) 17 ISCs [12 patients, mean observation time 13.3 (±2.3)years; and iii) 27 FDPs [19 patients, mean observation time 8.9 (±5.4)years]. The 10-year survival rate/chipping-free rate for SCs were 86.1%/83.4%, for ISCs 93.8%/94.1%, and for FDPs were 51.9%/90.8%. Both ISCs and SCs had a significantly higher survival than FDPs (ISCs vs. FDPs: both tests p=0.001; SCs vs. FDPs: p=0.001 and p=0.005). Differences in the chipping-free rates did not reach significance. Also, neither the cementation mode nor positioning of the restoration had an impact on survival. SCs had a slightly lower outcome than can generally be expected from single crowns. In contrast, ICSs had a favorable outcome and the FDPs predominantly failed. The practitioner's choice of dental materials is based (at best) on long-term experience. The present 10-year results are based on comprehensive data analyses and show the high potential of lithium-disilicate as a reliable material, especially for single-unit restoration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Overview and First Results of an In-situ Stimulation Experiment in Switzerland

NASA Astrophysics Data System (ADS)

Amann, F.; Gischig, V.; Doetsch, J.; Jalali, M.; Valley, B.; Evans, K. F.; Krietsch, H.; Dutler, N.; Villiger, L.

2017-12-01

A decameter-scale in-situ stimulation and circulation (ISC) experiment is currently being conducted at the Grimsel Test Site in Switzerland with the objective of improving our understanding of key seismo-hydro-mechanical coupled processes associated with high pressure fluid injections in a moderately fractured crystalline rock mass. The ISC experiment activities aim to support the development of EGS technology by 1) advancing the understanding of fundamental processes that occur within the rock mass in response to relatively large-volume fluid injections at high pressures, 2) improving the ability to estimate and model induced seismic hazard and risks, 3) assessing the potential of different injection protocols to keep seismic event magnitudes below an acceptable threshold, 4) developing novel monitoring and imaging techniques for pressure, temperature, stress, strain and displacement as well as geophysical methods such as ground penetration radar, passive and active seismic and 5) generating a high-quality benchmark datasets that facilitates the development and validation of numerical modelling tools. The ISC experiment includes six fault slip and five hydraulic fracturing experiments at an intermediate scale (i.e. 20*20*20m) at 480m depth, which allows high resolution monitoring of the evolution of pore pressure in the stimulated fault zone and the surrounding rock matrix, fault dislocations including shear and dilation, and micro-seismicity in an exceptionally well characterized structural setting. In February 2017 we performed the fault-slip experiments on interconnected faults. Subsequently an intense phase of post-stimulation hydraulic characterization was performed. In Mai 2017 we performed hydraulic fracturing tests within test intervals that were free of natural fractures. In this contribution we give an overview and show first results of the above mentioned stimulation tests.

Resting-state sensorimotor rhythm (SMR) power predicts the ability to up-regulate SMR in an EEG-instrumental conditioning paradigm.

PubMed

Reichert, Johanna Louise; Kober, Silvia Erika; Neuper, Christa; Wood, Guilherme

2015-11-01

Instrumental conditioning of EEG activity (EEG-IC) is a promising method for improvement and rehabilitation of cognitive functions. However, it has been found that even healthy adults are not always able to learn how to regulate their brain activity during EEG-IC. In the present study, the role of a neurophysiological predictor of EEG-IC learning performance, the resting-state power of sensorimotor rhythm (rs-SMR, 12-15Hz), was investigated. Eyes-open and eyes-closed rs-SMR power was assessed before N=28 healthy adults underwent 10 training sessions of instrumental SMR conditioning (ISC), in which participants should learn to voluntarily increase their SMR power by means of audio-visual feedback. A control group of N=19 participants received gamma (40-43Hz) or sham EEG-IC. N=19 of the ISC participants could be classified as "responders" as they were able to increase SMR power during training sessions, while N=9 participants ("non-responders") were not able to increase SMR power. Rs-SMR power in responders before start of ISC was higher in widespread parieto-occipital areas than in non-responders. A discriminant analysis indicated that eyes-open rs-SMR power in a central brain region specifically predicted later ISC performance, but not an increase of SMR in the control group. Together, these findings indicate that rs-SMR power is a specific and easy-to-measure predictor of later ISC learning performance. The assessment of factors that influence the ability to regulate brain activity is of high relevance, as it could be used to avoid potentially frustrating and expensive EEG-IC training sessions for participants who have a low chance of success. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Triplet photosensitizers: from molecular design to applications.

PubMed

Zhao, Jianzhang; Wu, Wanhua; Sun, Jifu; Guo, Song

2013-06-21

Triplet photosensitizers (PSs) are compounds that can be efficiently excited to the triplet excited state which subsequently act as catalysts in photochemical reactions. The name is originally derived from compounds that were used to transfer the triplet energy to other compounds that have only a small intrinsic triplet state yield. Triplet PSs are not only used for triplet energy transfer, but also for photocatalytic organic reactions, photodynamic therapy (PDT), photoinduced hydrogen production from water and triplet-triplet annihilation (TTA) upconversion. A good PS should exhibit strong absorption of the excitation light, a high yield of intersystem crossing (ISC) for efficient production of the triplet state, and a long triplet lifetime to allow for the reaction with a reactant molecule. Most transition metal complexes show efficient ISC, but small molar absorption coefficients in the visible spectral region and short-lived triplet excited states, which make them unsuitable as triplet PSs. One obstacle to the development of new triplet PSs is the difficulty in predicting the ISC of chromophores, especially of organic compounds without any heavy atoms. This review article summarizes some molecular design rationales for triplet PSs, based on the molecular structural factors that facilitate ISC. The design of transition metal complexes with large molar absorption coefficients in the visible spectral region and long-lived triplet excited states is presented. A new method of using a spin converter to construct heavy atom-free organic triplet PSs is discussed, with which ISC becomes predictable, C60 being an example. To enhance the performance of triplet PSs, energy funneling based triplet PSs are proposed, which show broadband absorption in the visible region. Applications of triplet PSs in photocatalytic organic reactions, hydrogen production, triplet-triplet annihilation upconversion and luminescent oxygen sensing are briefly introduced.

Malfunctioning of the iron-sulfur cluster assembly machinery in Saccharomyces cerevisiae produces oxidative stress via an iron-dependent mechanism, causing dysfunction in respiratory complexes.

PubMed

Gomez, Mauricio; Pérez-Gallardo, Rocío V; Sánchez, Luis A; Díaz-Pérez, Alma L; Cortés-Rojo, Christian; Meza Carmen, Victor; Saavedra-Molina, Alfredo; Lara-Romero, Javier; Jiménez-Sandoval, Sergio; Rodríguez, Francisco; Rodríguez-Zavala, José S; Campos-García, Jesús

2014-01-01

Biogenesis and recycling of iron-sulfur (Fe-S) clusters play important roles in the iron homeostasis mechanisms involved in mitochondrial function. In Saccharomyces cerevisiae, the Fe-S clusters are assembled into apoproteins by the iron-sulfur cluster machinery (ISC). The aim of the present study was to determine the effects of ISC gene deletion and consequent iron release under oxidative stress conditions on mitochondrial functionality in S. cerevisiae. Reactive oxygen species (ROS) generation, caused by H2O2, menadione, or ethanol, was associated with a loss of iron homeostasis and exacerbated by ISC system dysfunction. ISC mutants showed increased free Fe2+ content, exacerbated by ROS-inducers, causing an increase in ROS, which was decreased by the addition of an iron chelator. Our study suggests that the increment in free Fe2+ associated with ROS generation may have originated from mitochondria, probably Fe-S cluster proteins, under both normal and oxidative stress conditions, suggesting that Fe-S cluster anabolism is affected. Raman spectroscopy analysis and immunoblotting indicated that in mitochondria from SSQ1 and ISA1 mutants, the content of [Fe-S] centers was decreased, as was formation of Rieske protein-dependent supercomplex III2IV2, but this was not observed in the iron-deficient ATX1 and MRS4 mutants. In addition, the activity of complexes II and IV from the electron transport chain (ETC) was impaired or totally abolished in SSQ1 and ISA1 mutants. These results confirm that the ISC system plays important roles in iron homeostasis, ROS stress, and in assembly of supercomplexes III2IV2 and III2IV1, thus affecting the functionality of the respiratory chain.

ISC1-dependent metabolic adaptation reveals an indispensable role for mitochondria in induction of nuclear genes during the diauxic shift in Saccharomyces cerevisiae.

PubMed

Kitagaki, Hiroshi; Cowart, L Ashley; Matmati, Nabil; Montefusco, David; Gandy, Jason; de Avalos, Silvia Vaena; Novgorodov, Sergei A; Zheng, Jim; Obeid, Lina M; Hannun, Yusuf A

2009-04-17

Growth of Saccharomyces cerevisiae following glucose depletion (the diauxic shift) depends on a profound metabolic adaptation accompanied by a global reprogramming of gene expression. In this study, we provide evidence for a heretofore unsuspected role for Isc1p in mediating this reprogramming. Initial studies revealed that yeast cells deleted in ISC1, the gene encoding inositol sphingolipid phospholipase C, which resides in mitochondria in the post-diauxic phase, showed defective aerobic respiration in the post-diauxic phase but retained normal intrinsic mitochondrial functions, including intact mitochondrial DNA, normal oxygen consumption, and normal mitochondrial polarization. Microarray analysis revealed that the Deltaisc1 strain failed to up-regulate genes required for nonfermentable carbon source metabolism during the diauxic shift, thus suggesting a mechanism for the defective supply of respiratory substrates into mitochondria in the post-diauxic phase. This defect in regulating nuclear gene induction in response to a defect in a mitochondrial enzyme raised the possibility that mitochondria may initiate diauxic shift-associated regulation of nucleus-encoded genes. This was established by demonstrating that in respiratory-deficient petite cells these genes failed to be up-regulated across the diauxic shift in a manner similar to the Deltaisc1 strain. Isc1p- and mitochondrial function-dependent genes significantly overlapped with Adr1p-, Snf1p-, and Cat8p-dependent genes, suggesting some functional link among these factors. However, the retrograde response was not activated in Deltaisc1, suggesting that the response of Deltaisc1 cannot be simply attributed to mitochondrial dysfunction. These results suggest a novel role for Isc1p in allowing the reprogramming of gene expression during the transition from anaerobic to aerobic metabolism.

Estimating the Uncertainty and Predictive Capabilities of Three-Dimensional Earth Models (Postprint)

DTIC Science & Technology

2012-03-22

www.isc.ac.uk). This global database includes more than 7,000 events whose epicentral location accuracy is known to at least 5 km. GT events with...region, which illustrates the difficulty of validating a model with travel times alone. However, the IASPEI REL database is currently the highest...S (right) paths in the IASPEI REL ground-truth database . Stations are represented by purple triangles and events by gray circles. Note the sparse

Connecting ground water influxes with fish species diversity in an urbanized watershed

USGS Publications Warehouse

Steffy, L.Y.; McGinty, A.L.; Welty, C.; Kilham, S.S.

2004-01-01

Valley Creek watershed is a small stream system that feeds the Schuylkill River near Philadelphia, Pennsylvania. The watershed is highly urbanized, including over 17 percent impervious surface cover (ISC) by area. Imperviousness in a watershed has been linked to fish community structure and integrity. Generally, above 10 to 12 percent ISC there is marked decline in fish assemblages with fish being absent above 25 percent ISC. This study quantifies the importance of ground water in maintaining fish species diversity in subbasins with over 30 percent ISC. Valley Creek contains an atypical fish assemblage in that the majority of the fish are warm-water species, and the stream supports naturally reproducing brown trout, which were introduced and stocked from the early 1900s to 1985. Fish communities were quantified at 13 stations throughout the watershed, and Simpson's species diversity index was calculated. One hundred and nine springs were located, and their flow rates measured. A cross covariance analysis between Simpson's species diversity index and spring flow rates upstream of fish stations was performed to quantify the spatial correlation between these two variables. The correlation was found to be highest at lag distances up to about 400 m and drop off significantly beyond lag distances of about 800 m.

Prosthetic restoration in the single-tooth gap: patient preferences and analysis of the WTP index.

PubMed

Augusti, Davide; Augusti, Gabriele; Re, Dino

2014-11-01

The objective of this study was to evaluate the preference of a patients' population, according to the index of willingness to pay (WTP), against two treatments to restore a single-tooth gap: the implant-supported crown (ISC) and the 3-unit fixed partial denture prosthesis (FPDP) on natural teeth. Willingness to pay values were recorded on 107 subjects by asking the WTP from a starting bid of €2000 modifiable through monetary increases or decreases (€100). Data were collected through an individually delivered questionnaire. The characteristics of the population and choices made, the median values and WTP associations with socio-demographic parameters (Mann-Whitney and Kruskal-Wallis tests), correlations between variables (chi-square test in contingency tables) and significant parameters for predicting WTP values obtained in a multiple linear regression model were revealed. The 64% of patients expressed a preference for ISC, while the remaining 36% of the population chose the FPDP. The current therapeutic choice and those carried out in the past were generally in agreement (>70% of cases, P = 0.0001); a relationship was discovered between the anterior and posterior area to the same method of rehabilitation (101 of 107 cases, 94.4%). The WTP median values for ISC were of €3000 and of €2500 in the anterior and posterior areas, respectively. The smallest amount of money has been allocated for FPDP in posterior region (median of €1500). The "importance of oral care" for the patient was a significant predictor, in the regression model analysis, for the estimation of both anterior (P = 0.0003) and posterior (P < 0.0001) WTP values. The "previous therapy" variable reached and was just close to significance in anterior (P = 0.0367) and posterior (P = 0.0511) analyses, respectively. Within the limitations of this study, most of the population (64%) surveyed indicated the ISC as a therapeutic solution for the replacement of a single missing tooth, showing a higher WTP index in the anterior area. Among investigated socio-demographic variables, the importance assigned by the patient to oral care appeared to influence WTP values of the rehabilitation, regardless the location of the single gap in the mouth. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Three-phase short circuit calculation method based on pre-computed surface for doubly fed induction generator

NASA Astrophysics Data System (ADS)

Ma, J.; Liu, Q.

2018-02-01

This paper presents an improved short circuit calculation method, based on pre-computed surface to determine the short circuit current of a distribution system with multiple doubly fed induction generators (DFIGs). The short circuit current, injected into power grid by DFIG, is determined by low voltage ride through (LVRT) control and protection under grid fault. However, the existing methods are difficult to calculate the short circuit current of DFIG in engineering practice due to its complexity. A short circuit calculation method, based on pre-computed surface, was proposed by developing the surface of short circuit current changing with the calculating impedance and the open circuit voltage. And the short circuit currents were derived by taking into account the rotor excitation and crowbar activation time. Finally, the pre-computed surfaces of short circuit current at different time were established, and the procedure of DFIG short circuit calculation considering its LVRT was designed. The correctness of proposed method was verified by simulation.

Performance of the QWIP Focal Plane Arrays for NASA's Landsat Data Continuity Mission

NASA Technical Reports Server (NTRS)

Jhabvala, M.; Choi, K.; Waczynski, A.; La, A.; Sundaram, M.; Costard, E.; Jhabvala, C.; Kan, E.; Kahle, D.; Foltz, R.;

Fast-Response electric drives of Mechanical Engineering objects

NASA Astrophysics Data System (ADS)

Doykina, L. A.; Bukhanov, S. S.; Gryzlov, A. A.

2018-03-01

The article gives a solution to the problem of increasing the speed in the electrical drives of machine-building enterprises due to the application of a structure with ISC control. In this case, it is possible to get rid of the speed sensors. It is noted that in this case no circulating pulsations are applied to the input of the control system, caused by a non-identical interface between the sensor and the shaft of the operating mechanism. For detailed modeling, a mathematical model of an electric drive with distributed parameters was proposed. The calculation of such system was carried out by the finite element method. Taking into account the distributed characteristic of the system parameters allowed one to take into account the discrete nature of the electric machine’s work. The simulation results showed that the response time in the control circuit is estimated at a time constant of 0.0015, which is about twice as fast as in traditional vector control schemes.

Physical security and IT convergence: Managing the cyber-related risks.

PubMed

McCreight, Tim; Leece, Doug

The convergence of physical security devices into the corporate network is increasing, due to the perceived economic benefits and efficiencies gained from using one enterprise network. Bringing these two networks together is not without risk. Physical devices like closed circuit television cameras (CCTV), card access readers, and heating, ventilation and air conditioning controllers (HVAC) are typically not secured to the standards we expect for corporate computer networks. These devices can pose significant risks to the corporate network by creating new avenues to exploit vulnerabilities in less-than-secure implementations of physical systems. The ASIS Information Technology Security Council (ITSC) developed a white paper describing steps organisations can take to reduce the risks this convergence can pose, and presented these concepts at the 2015 ASIS/ISC2 Congress in Anaheim, California. 1 This paper expands upon the six characteristics described by ITSC, and provides business continuity planners with information on how to apply these recommendations to physical security devices that use the corporate network.

30 CFR 75.900 - Low- and medium-voltage circuits serving three-phase alternating current equipment; circuit...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Low- and medium-voltage circuits serving three... STANDARDS-UNDERGROUND COAL MINES Underground Low- and Medium-Voltage Alternating Current Circuits § 75.900 Low- and medium-voltage circuits serving three-phase alternating current equipment; circuit breakers...

30 CFR 77.900 - Low- and medium-voltage circuits serving portable or mobile three-phase alternating current...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Low- and medium-voltage circuits serving... Medium-Voltage Alternating Current Circuits § 77.900 Low- and medium-voltage circuits serving portable or mobile three-phase alternating current equipment; circuit breakers. Low- and medium-voltage circuits...

30 CFR 75.900 - Low- and medium-voltage circuits serving three-phase alternating current equipment; circuit...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Low- and medium-voltage circuits serving three... STANDARDS-UNDERGROUND COAL MINES Underground Low- and Medium-Voltage Alternating Current Circuits § 75.900 Low- and medium-voltage circuits serving three-phase alternating current equipment; circuit breakers...

30 CFR 75.900 - Low- and medium-voltage circuits serving three-phase alternating current equipment; circuit...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Low- and medium-voltage circuits serving three... STANDARDS-UNDERGROUND COAL MINES Underground Low- and Medium-Voltage Alternating Current Circuits § 75.900 Low- and medium-voltage circuits serving three-phase alternating current equipment; circuit breakers...

30 CFR 77.900 - Low- and medium-voltage circuits serving portable or mobile three-phase alternating current...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Low- and medium-voltage circuits serving... Medium-Voltage Alternating Current Circuits § 77.900 Low- and medium-voltage circuits serving portable or mobile three-phase alternating current equipment; circuit breakers. Low- and medium-voltage circuits...

30 CFR 77.900 - Low- and medium-voltage circuits serving portable or mobile three-phase alternating current...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Low- and medium-voltage circuits serving... Medium-Voltage Alternating Current Circuits § 77.900 Low- and medium-voltage circuits serving portable or mobile three-phase alternating current equipment; circuit breakers. Low- and medium-voltage circuits...

ORAL DELIVERY OF L-ARGININE STIMULATES PROSTAGLANDIN-DEPENDENT SECRETORY DIARRHEA IN C. PARVUM INFECTED NEONATAL PIGLETS

PubMed Central

Gookin, Jody L.; Foster, Derek M.; Coccaro, Maria R.; Stauffer, Stephen H.

2008-01-01

Objectives To determine if oral supplementation with L-arginine could augment nitric oxide (NO) synthesis and promote epithelial defense in neonatal piglets infected with C. parvum. Methods Neonatal piglets were fed a liquid milk replacer and on day 3 of age infected or not with 108 C. parvum oocysts and the milk replacer supplemented with L-arginine or L-alanine. Milk consumption, body weight, fecal consistency, and oocyst excretion were recorded daily. On day 3 post-infection, piglets were euthanized, and serum concentration of NO metabolites and histological severity of villous atrophy and epithelial infection were quantified. Sheets of ileal mucosa were mounted in Ussing chambers for measurement of barrier function (transepithelial resistance (TER) and permeability) and short-circuit current (Isc; an indirect measurement of Cl− secretion in this tissue). Results C. parvum infected piglets had large numbers of epithelial parasites, villous atrophy, decreased barrier function, severe watery diarrhea, and failure to gain weight. L-arginine promoted synthesis of NO by infected piglets which was unaccompanied by improvement in severity of infection but rather promoted epithelial chloride secretion and diarrhea. Epithelial secretion by infected mucosa from L-arginine supplemented piglets was fully inhibited by the cyclooxygenase inhibitor indomethacin, indicating that prostaglandin synthesis was responsible for this effect. Conclusions Results of these studies demonstrate that provision of additional NO substrate in the form of L-arginine incites prostaglandin-dependent secretory diarrhea and does not promote epithelial defense or barrier function of C. parvum infected neonatal ileum. PMID:18223372

Pelican: SCD's 640 × 512/15 μm pitch InSb detector

NASA Astrophysics Data System (ADS)

Oiknine Schlesinger, J.; Calahorra, Z.; Uri, E.; Shick, O.; Fishman, T.; Shtrichman, I.; Sinbar, E.; Nahum, V.; Kahanov, E.; Shlomovich, B.; Hasson, S.; Fishler, N.; Chen, D.; Markovitz, T.

2007-04-01

Over the last decade, SCD has developed and manufactured high quality InSb Focal Plane Arrays (FPAs), that are currently used in different applications worldwide. SCD's production line includes InSb FPAs with mid format (320x256 elements), and large format (640x512 elements), all available in various packaging configurations, including fully integrated Detector-Dewar-Cooler Assemblies (DDCA). Many of SCD's products are fully customized for customers' needs, and are optimized for each application with respect to the weight, power, size, and performance. In 2006, SCD has added to its broad InSb product portfolio the new "Pelican" detector family. All Pelican detectors include a large format 640×512 InSb FPA with 15μm pitch, which is based on the FLIR/Indigo ISC0403 Readout Integrated Circuit (ROIC). Due to its small size, the Pelican FPA fits in any mid format Dewar, enabling upgrading of mid format systems with higher spatial resolution due to its good MTF. This work presents the high performance of Pelican products. As achieved in all SCD's InSb DDC's, the Pelican detectors demonstrate high uniformity and correctability (residual non uniformity less than 0.05% std/DR) and remarkable operability (typically better than 99.9%). The Pelican FPA can be integrated in various DDCA configurations as per application needs, such as light weight, low power and compact form for hand held imagers, or a rigid configuration for environmentally demanding operating and storage conditions.

Public release of the ISC-GEM Global Instrumental Earthquake Catalogue (1900-2009)

USGS Publications Warehouse

Storchak, Dmitry A.; Di Giacomo, Domenico; Bondára, István; Engdahl, E. Robert; Harris, James; Lee, William H.K.; Villaseñor, Antonio; Bormann, Peter

2013-01-01

The International Seismological Centre–Global Earthquake Model (ISC–GEM) Global Instrumental Earthquake Catalogue (1900–2009) is the result of a special effort to substantially extend and improve currently existing global catalogs to serve the requirements of specific user groups who assess and model seismic hazard and risk. The data from the ISC–GEM Catalogue would be used worldwide yet will prove absolutely essential in those regions where a high seismicity level strongly correlates with a high population density.

Quantifying team cooperation through intrinsic multi-scale measures: respiratory and cardiac synchronization in choir singers and surgical teams.

PubMed

Hemakom, Apit; Powezka, Katarzyna; Goverdovsky, Valentin; Jaffer, Usman; Mandic, Danilo P

2017-12-01

A highly localized data-association measure, termed intrinsic synchrosqueezing transform (ISC), is proposed for the analysis of coupled nonlinear and non-stationary multivariate signals. This is achieved based on a combination of noise-assisted multivariate empirical mode decomposition and short-time Fourier transform-based univariate and multivariate synchrosqueezing transforms. It is shown that the ISC outperforms six other combinations of algorithms in estimating degrees of synchrony in synthetic linear and nonlinear bivariate signals. Its advantage is further illustrated in the precise identification of the synchronized respiratory and heart rate variability frequencies among a subset of bass singers of a professional choir, where it distinctly exhibits better performance than the continuous wavelet transform-based ISC. We also introduce an extension to the intrinsic phase synchrony (IPS) measure, referred to as nested intrinsic phase synchrony (N-IPS), for the empirical quantification of physically meaningful and straightforward-to-interpret trends in phase synchrony. The N-IPS is employed to reveal physically meaningful variations in the levels of cooperation in choir singing and performing a surgical procedure. Both the proposed techniques successfully reveal degrees of synchronization of the physiological signals in two different aspects: (i) precise localization of synchrony in time and frequency (ISC), and (ii) large-scale analysis for the empirical quantification of physically meaningful trends in synchrony (N-IPS).

Do family order and neighbor intervention against intimate partner violence protect children from abuse? Findings from Kathmandu.

PubMed

Emery, Clifton R; Thapa, Sirjana; Do, Mi Hyang; Chan, Ko Ling

2015-03-01

Drawing on previous research on intimate partner violence, child maltreatment, and informal social control, we hypothesized relationships between child abuse severity and (1) protective informal social control of intimate partner violence (ISC_IPV) by neighbors, (2) intimate terrorism, (3) family order, and (4) the power of mothers in intimate relationships. In what we believe may be a first study of physical child abuse by parents in Nepal, we used a three stage cluster approach to draw a random sample of 300 families in Kathmandu. Random effects regression models were used to test the study hypotheses. The analyses found support for hypotheses one and two, but with an important caveat. Although observed (actual) protective ISC_IPV had the hypothesized negative association with child abuse severity, in one of our models perceived protective ISC_IPV was positively associated with child abuse severity. The models clarify that the overall direction of protective ISC_IPV appears to be negative (protective), but the positive finding is important to consider for both research and practice. A significant relationship between family order and child abuse severity was found, but the direction was negative rather than positive as in hypothesis three. Implications for neighborhood research and typological research on IPV and child maltreatment are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evolution and Cellular Function of Monothiol Glutaredoxins: Involvement in Iron-Sulphur Cluster Assembly

PubMed Central

Vilella, Felipe; Alves, Rui; Rodríguez-Manzaneque, María Teresa; Bellí, Gemma; Swaminathan, Swarna; Sunnerhagen, Per

2004-01-01

A number of bacterial species, mostly proteobacteria, possess monothiol glutaredoxins homologous to the Saccharomyces cerevisiae mitochondrial protein Grx5, which is involved in iron–sulphur cluster synthesis. Phylogenetic profiling is used to predict that bacterial monothiol glutaredoxins also participate in the iron–sulphur cluster (ISC) assembly machinery, because their phylogenetic profiles are similar to the profiles of the bacterial homologues of yeast ISC proteins. High evolutionary co-occurrence is observed between the Grx5 homologues and the homologues of the Yah1 ferredoxin, the scaffold proteins Isa1 and Isa2, the frataxin protein Yfh1 and the Nfu1 protein. This suggests that a specific functional interaction exists between these ISC machinery proteins. Physical interaction analyses using low-definition protein docking predict the formation of strong and specific complexes between Grx5 and several components of the yeast ISC machinery. Two-hybrid analysis has confirmed the in vivo interaction between Grx5 and Isa1. Sequence comparison techniques and cladistics indicate that the other two monothiol glutaredoxins of S. cerevisiae, Grx3 and Grx4, have evolved from the fusion of a thioredoxin gene with a monothiol glutaredoxin gene early in the eukaryotic lineage, leading to differential functional specialization. While bacteria do not contain these chimaeric glutaredoxins, in many eukaryotic species Grx5 and Grx3/4-type monothiol glutaredoxins coexist in the cell. PMID:18629168

CIRCUITS FOR CURRENT MEASUREMENTS

DOEpatents

Cox, R.J.

1958-11-01

Circuits are presented for measurement of a logarithmic scale of current flowing in a high impedance. In one form of the invention the disclosed circuit is in combination with an ionization chamber to measure lonization current. The particular circuit arrangement lncludes a vacuum tube having at least one grid, an ionization chamber connected in series with a high voltage source and the grid of the vacuum tube, and a d-c amplifier feedback circuit. As the ionization chamber current passes between the grid and cathode of the tube, the feedback circuit acts to stabilize the anode current, and the feedback voltage is a measure of the logaritbm of the ionization current.

Faster Hall-Effect Current-Measuring Circuit

NASA Technical Reports Server (NTRS)

Sullender, Craig C.; Johnson, Daniel D.; Walker, Daniel D.

1993-01-01

Current-measuring circuit operates on Hall-effect-sensing and magnetic-field-nulling principles similar to those described in article, "Nulling Hall-Effect Current-Measuring Circuit" (LEW-15023), but simpler and responds faster. Designed without feedback loop, and analog pulse-width-modulated output indicates measured current. Circuit measures current at frequency higher than bandwidth of its Hall-effect sensor.

Hospitalizations associated with malignant neoplasia and in situ carcinoma in the anus and penis in men and women during a 5-year period (2009-2013) in Spain: An epidemiological study.

PubMed

López, Noelia; Gil-de-Miguel, Ángel; Pascual-García, Raquel; Gil-Prieto, Ruth

2017-10-03

Approximately 40,000 new cases of anal cancer and 26,000 new cases of penile cancer occurred in 2012 worldwide. Human Papillomavirus (HPV) infection is responsible for 88.3% and 33.0% of these cancers, respectively. The aim of this study was to describe the hospital burden associated with malignant neoplasm (MN) and in situ carcinoma (ISC) in the anus and penis in Spain from 2009 to 2013. This observational, retrospective study used discharge information obtained from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos, provided by the Ministry of Health. We found 3,668 hospitalizations due to MN and ISC in the anus for both genders, and more than 55% of these hospitalizations occurred in men and were associated with a lower median age of hospitalization (p < 0.001), higher average length of hospital stay (ALOS) (p = 0.0032), higher hospitalization costs (p < 0.001) and higher hospitalization rate (2.141 per 100,000 males aged > 14 y old and 1.604 per 100,000 women aged > 14 y old, p < 0.001) than in women. During the same period, 4,156 hospitalizations due to MN and ISC of the penis were registered. The hospitalization rate was 4.320 per 100,000 males aged > 14 y old. The hospitalization rate due to MN and ISC in the anus in males increased significantly during this period (p = 0.048). Our study provides relevant information about the hospital burden of anal and penile MN and ISC in Spain. This information could be useful for cost effectiveness analysis of universal HPV vaccination and for future HPV vaccination impact monitoring in Spain, and for other countries of similar socioeconomic status.

Crystal structure of IscA, an iron-sulfur cluster assembly protein from Escherichia coli.

PubMed

Cupp-Vickery, Jill R; Silberg, Jonathan J; Ta, Dennis T; Vickery, Larry E

2004-04-16

IscA, an 11 kDa member of the hesB family of proteins, binds iron and [2Fe-2S] clusters, and participates in the biosynthesis of iron-sulfur proteins. We report the crystal structure of the apo-protein form of IscA from Escherichia coli to a resolution of 2.3A. The crystals belong to the space group P3(2)21 and have unit cell dimensions a=b=66.104 A, c=150.167 A (alpha=beta=90 degrees, gamma=120 degrees ). The structure was solved using single-wavelength anomalous dispersion (SAD) phasing of a selenomethionyl derivative, and the IscA model was refined to R=21.4% (Rfree=25.4%). IscA exists as an (alpha1alpha2)2 homotetramer with the (alpha1alpha2) dimer comprising the asymmetric unit. Cys35, implicated in Fe-S cluster assembly, is located in a central cavity formed at the tetramer interface with the gamma-sulfur atoms of residues from the alpha1 and alpha2' monomers (and alpha1'alpha2) positioned close to one another (approximately equal 7 A). C-terminal residues 99-107 are disordered, and the exact positions of Cys99 and Cys101 could not be determined. However, computer modeling of C-terminal residues in the tetramer suggests that Cys99 and Cys101 in the alpha1 monomer and those of the alpha1' monomer (or alpha2 and alpha2') are positioned sufficiently close to coordinate [2Fe-2S] clusters between the two dimers, whereas this is not possible within the (alpha1alpha2) or (alpha1'alpha2') dimer. This symmetrical arrangement allows for binding of two [2Fe-2S] clusters on opposite sides of the tetramer. Modeling further reveals that Cys101 is positioned sufficiently close to Cys35 to allow Cys35 to participate in cluster assembly, formation, or transfer.

ISCE: A Modular, Reusable Library for Scalable SAR/InSAR Processing

NASA Astrophysics Data System (ADS)

Agram, P. S.; Lavalle, M.; Gurrola, E. M.; Sacco, G. F.; Rosen, P. A.

2016-12-01

Traditional community SAR/InSAR processing software tools have primarily focused on differential interferometry and Solid Earth applications. The InSAR Scientific Computing Environment (ISCE) was specifically designed to support the Earth Sciences user community as well as large scale operational processing tasks, thanks to its two-layered (Python+C/Fortran) architecture and modular framework. ISCE is freely distributed as a source tarball, allowing advanced users to modify and extend it for their research purposes and developing exploratory applications, while providing a relatively simple user interface for novice users to perform routine data analysis efficiently. Modular design of the ISCE library also enables easier development of applications to address the needs of Ecosystems, Cryosphere and Disaster Response communities in addition to the traditional Solid Earth applications. In this talk, we would like to emphasize the broader purview of the ISCE library and some of its unique features that sets it apart from other freely available community software like GMTSAR and DORIS, including: Support for multiple geometry regimes - Native Doppler (ALOS-1) as well Zero Doppler (ESA missions) systems. Support for data acquired by airborne platforms - e.g, JPL's UAVSAR and AirMOSS, DLR's F-SAR. Radiometric Terrain Correction - Auxiliary output layers from the geometry modules include projection angles, incidence angles, shadow-layover masks. Dense pixel offsets - Parallelized amplitude cross correlation for cryosphere / ionospheric correction applications. Rubber sheeting - Pixel-by-pixel offsets fields for resampling slave imagery for geometric co-registration/ ionospheric corrections. Preliminary Tandem-X processing support - Bistatic geometry modules. Extensibility to support other non-Solid Earth missions - Modules can be directly adopted for use with other SAR missions, e.g., SWOT. Preliminary support for multi-dimensional data products- multi-polarization, multi-frequency, multi-temporal, multi-baseline stacks via the PLANT and GIAnT toolboxes. Rapid prototyping - Geometry manipulation functionality at the python level allows users to prototype and test processing modules at the interpreter level before optimal implementation in C/C++/Fortran.

Gate drive latching circuit for an auxiliary resonant commutation circuit

NASA Technical Reports Server (NTRS)

Delgado, Eladio Clemente (Inventor); Kheraluwala, Mustansir Hussainy (Inventor)

1999-01-01

A gate drive latching circuit for an auxiliary resonant commutation circuit for a power switching inverter includes a current monitor circuit providing a current signal to a pair of analog comparators to implement latching of one of a pair of auxiliary switching devices which are used to provide commutation current for commutating switching inverters in the circuit. Each of the pair of comparators feeds a latching circuit which responds to an active one of the comparators for latching the associated gate drive circuit for one of the pair of auxiliary commutating switches. An initial firing signal is applied to each of the commutating switches to gate each into conduction and the resulting current is monitored to determine current direction and therefore the one of the switches which is carrying current. The comparator provides a latching signal to the one of the auxiliary power switches which is actually conducting current and latches that particular power switch into an on state for the duration of current through the device. The latching circuit is so designed that the only time one of the auxiliary switching devices can be latched on is during the duration of an initial firing command signal.

30 CFR 77.900 - Low- and medium-voltage circuits serving portable or mobile three-phase alternating current...

Code of Federal Regulations, 2011 CFR

2011-07-01

... portable or mobile three-phase alternating current equipment; circuit breakers. 77.900 Section 77.900... mobile three-phase alternating current equipment; circuit breakers. Low- and medium-voltage circuits supplying power to portable or mobile three-phase alternating current equipment shall be protected by...

Another Nulling Hall-Effect Current-Measuring Circuit

NASA Technical Reports Server (NTRS)

Thibodeau, Phillip E.; Sullender, Craig C.

1993-01-01

Lightweight, low-power circuit provides noncontact measurement of alternating or direct current of many ampheres in main conductor. Advantages of circuit over other nulling Hall-effect current-measuring circuits is stability and accuracy increased by putting both analog-to-digital and digital-to-analog converters in nulling feedback loop. Converters and rest of circuit designed for operation at sampling rate of 100 kHz, but rate changed to alter time or frequency response of circuit.

Ultrafast intersystem-crossing in platinum containing π-conjugated polymers with tunable spin-orbit coupling.

PubMed

Sheng, C-X; Singh, S; Gambetta, A; Drori, T; Tong, M; Tretiak, S; Vardeny, Z V

2013-01-01

The development of efficient organic light-emitting diodes (OLED) and organic photovoltaic cells requires control over the dynamics of spin sensitive excitations. Embedding heavy metal atoms in π-conjugated polymer chains enhances the spin-orbit coupling (SOC), and thus facilitates intersystem crossing (ISC) from the singlet to triplet manifolds. Here we use various nonlinear optical spectroscopies such as two-photon absorption and electroabsorption in conjunction with electronic structure calculations, for studying the energies, emission bands and ultrafast dynamics of spin photoexcitations in two newly synthesized π-conjugated polymers that contain intrachain platinum (Pt) atoms separated by one (Pt-1) or three (Pt-3) organic spacer units. The controllable SOC in these polymers leads to a record ISC time of <~1 ps in Pt-1 and ~6 ps in Pt-3. The tunable ultrafast ISC rate modulates the intensity ratio of the phosphorescence and fluorescence emission bands, with potential applications for white OLEDs.

Mex3a marks slow-proliferating multilineage progenitors of the intestinal epithelium

PubMed Central

Barriga, Francisco M.; Montagni, Elisa; Mana, Miyeko; Guillaumet-Adkins, Amy; Hernando-Momblona, Xavier; Sevillano, Marta; Rodriguez-Esteban, Gustavo; Mendez-Lago, Maria; Buczacki, Simon J. A.; Gut, Ivo; Gut, Marta; Winton, Douglas J.; Yilmaz, Omer; Stephan-Otto, Camille; Hein, Holger; Batlle, Eduard

2017-01-01

SUMMARY The intestinal epithelium is continuously regenerated by highly proliferative Lgr5+ intestinal stem cells (ISCs). The existence of a population of quiescent ISCs has been suggested yet its identity and features remain controversial. Here we describe that the expression of the RNA-binding protein Mex3a labels a subpopulation of Lgr5+ cells that divide less frequently and contribute to regenerate all intestinal lineages with slow kinetics. Single cell transcriptomic analysis revealed two classes of Lgr5-high cells, one of them defined by the Mex3a-expression program and by low levels of proliferation genes. Lineage tracing experiments show that large fraction of Mex3a+ cell population is continuously recalled into the rapidly dividing self-renewing ISC pool in homeostatic conditions. Chemotherapy and radiation target preferentially rapidly dividing Lgr5+ cells but spare the Mex3a-high/Lgr5+ population, which helps sustain the renewal of the intestinal epithelium during treatment. PMID:28285904

LCD denoise and the vector mutual information method in the application of the gear fault diagnosis under different working conditions

NASA Astrophysics Data System (ADS)

Xiangfeng, Zhang; Hong, Jiang

2018-03-01

In this paper, the full vector LCD method is proposed to solve the misjudgment problem caused by the change of the working condition. First, the signal from different working condition is decomposed by LCD, to obtain the Intrinsic Scale Component (ISC)whose instantaneous frequency with physical significance. Then, calculate of the cross correlation coefficient between ISC and the original signal, signal denoising based on the principle of mutual information minimum. At last, calculate the sum of absolute Vector mutual information of the sample under different working condition and the denoised ISC as the characteristics to classify by use of Support vector machine (SVM). The wind turbines vibration platform gear box experiment proves that this method can identify fault characteristics under different working conditions. The advantage of this method is that it reduce dependence of man’s subjective experience, identify fault directly from the original data of vibration signal. It will has high engineering value.

PAF-Myc-Controlled Cell Stemness Is Required for Intestinal Regeneration and Tumorigenesis.

PubMed

Kim, Moon Jong; Xia, Bo; Suh, Han Na; Lee, Sung Ho; Jun, Sohee; Lien, Esther M; Zhang, Jie; Chen, Kaifu; Park, Jae-Il

2018-03-12

The underlying mechanisms of how self-renewing cells are controlled in regenerating tissues and cancer remain ambiguous. PCNA-associated factor (PAF) modulates DNA repair via PCNA. Also, PAF hyperactivates Wnt/β-catenin signaling independently of PCNA interaction. We found that PAF is expressed in intestinal stem and progenitor cells (ISCs and IPCs) and markedly upregulated during intestinal regeneration and tumorigenesis. Whereas PAF is dispensable for intestinal homeostasis, upon radiation injury, genetic ablation of PAF impairs intestinal regeneration along with the severe loss of ISCs and Myc expression. Mechanistically, PAF conditionally occupies and transactivates the c-Myc promoter, which induces the expansion of ISCs/IPCs during intestinal regeneration. In mouse models, PAF knockout inhibits Apc inactivation-driven intestinal tumorigenesis with reduced tumor cell stemness and suppressed Wnt/β-catenin signaling activity, supported by transcriptome profiling. Collectively, our results unveil that the PAF-Myc signaling axis is indispensable for intestinal regeneration and tumorigenesis by positively regulating self-renewing cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Spontaneous activity of cochlear hair cells triggered by fluid secretion mechanism in adjacent support cells

PubMed Central

Wang, Han Chin; Lin, Chun-Chieh; Cheung, Rocky; Zhang-Hooks, YingXin; Agarwal, Amit; Ellis-Davies, Graham; Rock, Jason; Bergles, Dwight E.

2015-01-01

Summary Spontaneous electrical activity of neurons in developing sensory systems promotes their maturation and proper connectivity. In the auditory system, spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from glia-like inner supporting cells (ISCs), facilitating maturation of central pathways before hearing onset. Here, we find that ATP stimulates purinergic autoreceptors in ISCs, triggering Cl− efflux and osmotic cell shrinkage by opening TMEM16A Ca2+-activated Cl− channels. Release of Cl− from ISCs also forces K+ efflux, causing transient depolarization of IHCs near ATP release sites. Genetic deletion of TMEM16A markedly reduces the spontaneous activity of IHCs and spiral ganglion neurons in the developing cochlea, and prevents ATP-dependent shrinkage of supporting cells. These results indicate that support cells in the developing cochlea have adapted a pathway used for fluid secretion in other organs to induce periodic excitation of hair cells. PMID:26627734

The excited-state decay of 1-methyl-2(1H)-pyrimidinone is an activated process.

PubMed

Ryseck, Gerald; Schmierer, Thomas; Haiser, Karin; Schreier, Wolfgang; Zinth, Wolfgang; Gilch, Peter

2011-07-11

The photophysics of 1-methyl-2(1H)-pyrimidinone (1MP) dissolved in water is investigated by steady-state and time-resolved fluorescence, UV/Vis absorption, and IR spectroscopy. In the experiments, excitation light is tuned to the lowest-energy absorption band of 1MP peaking at 302 nm. At room temperature (291 K) its fluorescence lifetime amounts to 450 ps. With increasing temperature this lifetime decreases and equals 160 ps at 338 K. Internal conversion (IC) repopulating the ground state and intersystem crossing (ISC) to a triplet state are the dominant decay channels of the excited singlet state. At room temperature both channels contribute equally to the decay, that is, the quantum yields of IC and ISC are both approximately 0.5. The temperature dependence of UV/Vis transient absorption signals shows that the activation energy of the IC process (2140 cm(-1)) is higher than that of the ISC process (640 cm(-1)). Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Factors determining ethnic differences in the incidence of bacteriologically confirmed genitourinary tuberculosis in south east England.

PubMed

Grange, J M; Yates, M D; Ormerod, L P

1995-01-01

In South East England, genitourinary (GU) tuberculosis is a much less common manifestation of non-respiratory tuberculosis in patients of Indian subcontinent (ISC) ethnic origin than in those of European ethnic origin. When considered in relation to all bacteriologically confirmed cases of tuberculosis, both respiratory and non-respiratory, the ethnic difference in the occurrence of GU tuberculosis is much less evident, while there is a highly significant excess of other forms of non-respiratory tuberculosis among the ethnic ISC patients. Unlike other forms of non-respiratory tuberculosis, GU disease tends to occur in an older age range in the ethnic ISC population and, when stratified for age, the ethnic difference in the occurrence of this form of tuberculosis is not significant while that of lymph node tuberculosis remains significantly high. Thus, after elimination of the confounding factor of age, the occurrence of GU tuberculosis is very similar in the two ethnic groups while other forms of non-respiratory tuberculosis differ considerably.

Magnetically Controlled Variable Transformer

NASA Technical Reports Server (NTRS)

Kleiner, Charles T.

1994-01-01

Improved variable-transformer circuit, output voltage and current of which controlled by use of relatively small current supplied at relatively low power to control windings on its magnetic cores. Transformer circuits of this type called "magnetic amplifiers" because ratio between controlled output power and power driving control current of such circuit large. This ratio - power gain - can be as large as 100 in present circuit. Variable-transformer circuit offers advantages of efficiency, safety, and controllability over some prior variable-transformer circuits.

49 CFR 234.213 - Grounds.

Code of Federal Regulations, 2014 CFR

2014-10-01

...: circuits that include track rail; alternating current power distribution circuits that are grounded in the...) Circuits that include track rail; (2) Alternating current power distribution circuits that are grounded in...

Survival and failure modes: platform-switching for internal and external hexagon cemented fixed dental prostheses.

PubMed

Anchieta, Rodolfo B; Machado, Lucas S; Hirata, Ronaldo; Coelho, Paulo G; Bonfante, Estevam A

2016-10-01

This study evaluated the probability of survival (reliability) of platform-switched fixed dental prostheses (FDPs) cemented on different implant-abutment connection designs. Eighty-four-three-unit FDPs (molar pontic) were cemented on abutments connected to two implants of external or internal hexagon connection. Four groups (n = 21 each) were established: external hexagon connection and regular platform (ERC); external hexagon connection and switched platform (ESC); internal hexagon and regular platform (IRC); and internal hexagon and switched platform (ISC). Prostheses were subjected to step-stress accelerated life testing in water. Weibull curves and probability of survival for a mission of 100,000 cycles at 400 N (two-sided 90% CI) were calculated. The beta values of 0.22, 0.48, 0.50, and 1.25 for groups ERC, ESC, IRC, and ISC, respectively, indicated a limited role of fatigue in damage accumulation, except for group ISC. Survival decreased for both platform-switched groups (ESC: 74%, and ISC: 59%) compared with the regular matching platform counterparts (ERC: 95%, and IRC: 98%). Characteristic strength was higher only for ERC compared with ESC, but not different between internal connections. Failures chiefly involved the abutment screw. Platform switching decreased the probability of survival of FDPs on both external and internal connections. The absence in loss of characteristic strength observed in internal hexagon connections favor their use compared with platform-switched external hexagon connections. © 2016 Eur J Oral Sci.

Local infiltration analgesia versus continuous interscalene brachial plexus block for shoulder replacement pain: a randomized clinical trial.

PubMed

Bjørnholdt, Karen T; Jensen, Jan M; Bendtsen, Thomas F; Søballe, Kjeld; Nikolajsen, Lone

2015-12-01

Shoulder replacement involves significant post-operative pain, which is often managed by continuous interscalene brachial plexus block. Catheter displacement and complications limit the beneficial effect of the block. Local infiltration analgesia (LIA) has provided good results in knee replacement. We aimed to assess the effectiveness of LIA for pain after shoulder replacement. Patients scheduled for primary shoulder replacement under general anaesthesia were randomized to receive either local infiltration analgesia (LIA) (150 ml ropivacaine 0.2 % with epinephrine intra-operatively) or interscalene brachial plexus catheter (ISC) (ropivacaine 0.75 %, 7 ml bolus followed by 48-h 5 ml/h infusion). The primary outcome was opioid consumption during the first 24 post-operative hours. Secondary outcomes were pain ratings, supplementary analgesics, and side effects for 3 days, and complications until 3 months after surgery. Data were analysed for 61 patients (LIA 30, ISC 31). Twenty-four-hour opioid consumption was higher in the LIA group compared with the ISC group: median (IQR) 95 mg (70-150 mg) versus 40 mg (8-76 mg) (P = 0.0001). No significant difference in opioid consumption was found between groups during the following 3 days. The LIA group had higher pain scores at 0, 2, 4, and 8 h. Two patients in the ISC group had long-lasting complications. The LIA technique cannot be recommended for shoulder replacement unless substantially modified. Occurrence of inadequate analgesia and complications following interscalene brachial plexus block prompt further studies into pain management after shoulder replacement.

Development of the Drosophila entero-endocrine lineage and its specification by the Notch signaling pathway

PubMed Central

Takashima, Shigeo; Adams, Katrina L.; Ortiz, Paola A.; Ying, Chong T.; Moridzadeh, Rameen; Younossi-Hartenstein, Amelia; Hartenstein, Volker

2013-01-01

In this paper we have investigated the developmental-genetic steps that shape the entero-endocrine system of Drosophila melanogaster from the embryo to the adult. The process starts in the endoderm of the early embryo where precursors of endocrine cells and enterocytes of the larval midgut, as well as progenitors of the adult midgut, are specified by a Notch signaling-dependent mechanism. In a second step that occurs during the late larval period, enterocytes and endocrine cells of a transient pupal midgut are selected from within the clusters of adult midgut progenitors. As in the embryo, activation of the Notch pathway triggers enterocyte differentiation, and inhibits cells from further proliferation or choosing the endocrine fate. The third step of entero-endocrine cell development takes place at a mid-pupal stage. Before this time point, the epithelial layer destined to become the adult midgut is devoid of endocrine cells. However, precursors of the intestinal midgut stem cells (pISCs) are already present. After an initial phase of symmetric divisions which causes an increase in their own population size, pISCs start to spin off cells that become postmitotic and express the endocrine fate marker, Prospero. Activation of Notch in pISCs forces these cells into an enterocyte fate. Loss of Notch function causes an increase in the proliferatory activity of pISCs, as well as a higher ratio of Prospero-positive cells. PMID:21382366

Nulling Hall-Effect Current-Measuring Circuit

NASA Technical Reports Server (NTRS)

Sullender, Craig C.; Vazquez, Juan M.; Berru, Robert I.

1993-01-01

Circuit measures electrical current via combination of Hall-effect-sensing and magnetic-field-nulling techniques. Known current generated by feedback circuit adjusted until it causes cancellation or near cancellation of magnetic field produced in toroidal ferrite core by current measured. Remaining magnetic field measured by Hall-effect sensor. Circuit puts out analog signal and digital signal proportional to current measured. Accuracy of measurement does not depend on linearity of sensing components.

Short-circuit current and ionic fluxes in the isolated colonic mucosa of Bufo arenarum.

PubMed

Lew, V L

1970-03-01

1. The unidirectional fluxes of (22)Na, (36)Cl and [(14)C]bicarbonate ions were measured in paired portions of the isolated and short-circuited colonic mucosa of Bufo arenarum, separated from its muscular layer. Pharmacological effects as well as effects of changes in the composition of the nutrient solutions on the electrical parameters of membrane activity (potential difference, short-circuit current and total membrane resistance) are described.2. The net fluxes of both Cl and bicarbonate ions were not significantly different from zero in the absence of electrochemical gradients across the membrane.3. The net Na flux from mucosa to serosa represented a variable proportion of the short-circuit current ranging from 62 to 100%.4. The proportion of membranes with high discrepancies between net Na flux and short-circuit current decreased with the duration of captivity of the toads.5. When Na was entirely replaced by choline in the mucosal bathing solution, the short-circuit current dropped by a variable amount within the range of 64 to 98% of its control values in different membranes. This effect was completely reversible. Similar changes in the serosal solution had no effect.6. The short-circuit current and potential difference were very sensitive to the serosal concentration of bicarbonate ions. In different membranes, 60-100% of the short-circuit current was reversibly abolished by bathing the serosal surface with a bicarbonate-free solution. The mucosal bicarbonate level had no effect on either the potential difference or the short-circuit current. 5 mM bicarbonate in the serosal solution restored at least 50% of the short-circuit control value and full recovery was attained by concentrations near 30 mM bicarbonate.7. Anoxia brought the potential difference and short-circuit current reversibly down to zero in about 50 min.8. Ouabain reduced the short-circuit current up to 80% in about 40 min when present in the serosal solution at a concentration of 10(-4)M. At this or lower concentrations the ouabain effect was reversible. Above this level ouabain produced 100% inhibition in 3-4 hr, but this was no longer reversible. Ouabain had no effect on the short-circuit current either when applied to the mucosal surface or in the absence of Na from the mucosal solution.9. Diamox produced a variable inhibition of the short-circuit current of up to 30% only at concentrations above 10 mM.10. Possible mechanisms are discussed for the appearance of the non-Na component of the short-circuit current. A theory concerning its nature is proposed.

Focal plane infrared readout circuit with automatic background suppression

NASA Technical Reports Server (NTRS)

Pain, Bedabrata (Inventor); Yang, Guang (Inventor); Sun, Chao (Inventor); Shaw, Timothy J. (Inventor); Wrigley, Chris J. (Inventor)

2002-01-01

A circuit for reading out a signal from an infrared detector includes a current-mode background-signal subtracting circuit having a current memory which can be enabled to sample and store a dark level signal from the infrared detector during a calibration phase. The signal stored by the current memory is subtracted from a signal received from the infrared detector during an imaging phase. The circuit also includes a buffered direct injection input circuit and a differential voltage readout section. By performing most of the background signal estimation and subtraction in a current mode, a low gain can be provided by the buffered direct injection input circuit to keep the gain of the background signal relatively small, while a higher gain is provided by the differential voltage readout circuit. An array of such readout circuits can be used in an imager having an array of infrared detectors. The readout circuits can provide a high effective handling capacity.

InSAR Scientific Computing Environment

NASA Astrophysics Data System (ADS)

Gurrola, E. M.; Rosen, P. A.; Sacco, G.; Zebker, H. A.; Simons, M.; Sandwell, D. T.

2010-12-01

The InSAR Scientific Computing Environment (ISCE) is a software development effort in its second year within the NASA Advanced Information Systems and Technology program. The ISCE will provide a new computing environment for geodetic image processing for InSAR sensors that will enable scientists to reduce measurements directly from radar satellites and aircraft to new geophysical products without first requiring them to develop detailed expertise in radar processing methods. The environment can serve as the core of a centralized processing center to bring Level-0 raw radar data up to Level-3 data products, but is adaptable to alternative processing approaches for science users interested in new and different ways to exploit mission data. The NRC Decadal Survey-recommended DESDynI mission will deliver data of unprecedented quantity and quality, making possible global-scale studies in climate research, natural hazards, and Earth's ecosystem. The InSAR Scientific Computing Environment is planned to become a key element in processing DESDynI data into higher level data products and it is expected to enable a new class of analyses that take greater advantage of the long time and large spatial scales of these new data, than current approaches. At the core of ISCE is both legacy processing software from the JPL/Caltech ROI_PAC repeat-pass interferometry package as well as a new InSAR processing package containing more efficient and more accurate processing algorithms being developed at Stanford for this project that is based on experience gained in developing processors for missions such as SRTM and UAVSAR. Around the core InSAR processing programs we are building object-oriented wrappers to enable their incorporation into a more modern, flexible, extensible software package that is informed by modern programming methods, including rigorous componentization of processing codes, abstraction and generalization of data models, and a robust, intuitive user interface with graduated exposure to the levels of sophistication, allowing novices to apply it readily for common tasks and experienced users to mine data with great facility and flexibility. The environment is designed to easily allow user contributions, enabling an open source community to extend the framework into the indefinite future. In this paper we briefly describe both the legacy and the new core processing algorithms and their integration into the new computing environment. We describe the ISCE component and application architecture and the features that permit the desired flexibility, extensibility and ease-of-use. We summarize the state of progress of the environment and the plans for completion of the environment and for its future introduction into the radar processing community.

Superconducting dc Current Limiting Vacuum Circuit Breaker

NASA Astrophysics Data System (ADS)

Alferov, D. F.; Akhmetgareev, M. R.; Budovskii, A. I.; Bunin, R. A.; Voloshin, I. F.; Degtyarenko, P. N.; Yevsin, D. V.; Ivanov, V. P.; Sidorov, V. A.; Fisher, L. M.; Tshai, E. V.

Acircuitofadc superconductingfault current limiter witha direct current circuit-breaker fora nominal current 300A is proposed. It includes the 2G high temperature superconducting (HTS) tapes and the high-speed dc vacuum circuit breaker.Thetestresultsof current-limitingcapacityandrecoverytimeof superconductivityafter currentfaultatvoltage upto3 kV are presented.

Time course of salinity adaptation in a strongly euryhaline estuarine teleost, fundulus heteroclitus: A multivariable approach

USGS Publications Warehouse

Marshall, W.S.; Emberley, T.R.; Singer, T.D.; Bryson, S.E.; McCormick, S.D.

1999-01-01

Freshwater-adapted killifish (Fundulus heteroclitus) were transferred directly from soft fresh water to full-strength sea water for periods of 1h, 3h, 8h and 1, 2, 7, 14 and 30 days. Controls were transferred to fresh water for 24 h. Measured variables included: blood [Na+], osmolality, glucose and cortisol levels, basal and stimulated rates of ion transport and permeability of in vitro opercular epithelium, gill Na+/K+-ATPase and citrate synthase activity and chloride cell ultrastructure. These data were compared with previously published killifish cystic fibrosis transmembrane conductance regulator (kfCFTR) expression in the gills measured over a similar time course. Plasma cortisol levels peaked at 1 h, coincident with a rise in plasma [Na+]. At 8 h after transfer to sea water, a time at which previous work has shown kfCFTR expression to be elevated, blood osmolality and [Na+] were high, and cortisol levels and opercular membrane short-circuit current (I(SC); a measure of Cl- secretion rate) were low. The 24h group, which showed the highest level of kfCFTR expression, had the highest plasma [Na+] and osmolality, elevated plasma cortisol levels, significantly lower opercular membrane resistance, an increased opercular membrane ion secretion rate and collapsed tubule inclusions in mitochondria-rich cells, but no change in gill Na+/K+-ATPase and citrate synthase activity or plasma glucose levels. Apparently, killifish have a rapid (<1h) cortisol response to salinity coupled to subsequent (8-48 h) expression of kfCFTR anion channel proteins in existing mitochondria-rich cells that convert transport from ion uptake to ion secretion.

Overload protection system for power inverter

NASA Technical Reports Server (NTRS)

Nagano, S. (Inventor)

1977-01-01

An overload protection system for a power inverter utilized a first circuit for monitoring current to the load from the power inverter to detect an overload and a control circuit to shut off the power inverter, when an overload condition was detected. At the same time, a monitoring current inverter was turned on to deliver current to the load at a very low power level. A second circuit monitored current to the load, from the monitoring current inverter, to hold the power inverter off through the control circuit, until the overload condition was cleared so that the control circuit may be deactivated in order for the power inverter to be restored after the monitoring current inverter is turned off completely.

30 CFR 18.51 - Electrical protection of circuits and equipment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the junction with the main circuit when the branch-circuit conductor(s) has a current carrying... same duty. (1) If the overcurrent-protective device in a direct-current circuit does not open both... preventing the possibility of reversing connections which would result in changing the circuit interrupter to...

30 CFR 18.51 - Electrical protection of circuits and equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the junction with the main circuit when the branch-circuit conductor(s) has a current carrying... same duty. (1) If the overcurrent-protective device in a direct-current circuit does not open both... preventing the possibility of reversing connections which would result in changing the circuit interrupter to...

Device, system and method for a sensing electrical circuit

NASA Technical Reports Server (NTRS)

Vranish, John M. (Inventor)

2009-01-01

The invention relates to a driven ground electrical circuit. A driven ground is a current-measuring ground termination to an electrical circuit with the current measured as a vector with amplification. The driven ground module may include an electric potential source V.sub.S driving an electric current through an impedance (load Z) to a driven ground. Voltage from the source V.sub.S excites the minus terminal of an operational amplifier inside the driven ground which, in turn, may react by generating an equal and opposite voltage to drive the net potential to approximately zero (effectively ground). A driven ground may also be a means of passing information via the current passing through one grounded circuit to another electronic circuit as input. It may ground one circuit, amplify the information carried in its current and pass this information on as input to the next circuit.

Driver circuit for solid state light sources

DOEpatents

Palmer, Fred; Denvir, Kerry; Allen, Steven

2016-02-16

A driver circuit for a light source including one or more solid state light sources, a luminaire including the same, and a method of so driving the solid state light sources are provided. The driver circuit includes a rectifier circuit that receives an alternating current (AC) input voltage and provides a rectified AC voltage. The driver circuit also includes a switching converter circuit coupled to the light source. The switching converter circuit provides a direct current (DC) output to the light source in response to the rectified AC voltage. The driver circuit also includes a mixing circuit, coupled to the light source, to switch current through at least one solid state light source of the light source in response to each of a plurality of consecutive half-waves of the rectified AC voltage.

Antibody and Cytokine Responses of Koalas (Phascolarctos cinereus) Vaccinated with Recombinant Chlamydial Major Outer Membrane Protein (MOMP) with Two Different Adjuvants

PubMed Central

Khan, Shahneaz Ali; Desclozeaux, Marion; Waugh, Courtney; Hanger, Jon; Loader, Jo; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

2016-01-01

Developing a vaccine against Chlamydia is key to combating widespread mortalities and morbidities associated with this infection in koalas (Phascolarctos cinereus). In previous studies, we have shown that two or three doses of a Recombinant Major Outer Membrane Protein (rMOMP) antigen-based vaccine, combined with immune stimulating complex (ISC) adjuvant, results in strong cellular and humoral immune responses in koalas. We have also separately evaluated a single dose vaccine, utilising a tri-adjuvant formula that comprises polyphosphazine based poly I: C and host defense peptides, with the same antigen. This formulation also produced strong cellular and humoral immune responses in captive koalas. In this current study, we directly compared the host immune responses of two sub-groups of wild Chlamydia negative koalas in one population vaccinated with the rMOMP protein antigen and adjuvanted with either the ISC or tri-adjuvant formula. Overall, both adjuvants produced strong Chlamydia-specific cellular (IFN-γ and IL-17A) responses in circulating PBMCs as well as MOMP-specific and functional, in vitro neutralising antibodies. While the immune responses were similar, there were adjuvant-specific immune differences between the two adjuvants, particularly in relation to the specificity of the MOMP epitope antibody responses. PMID:27219467

Short-circuit current and ionic fluxes in the isolated colonic mucosa of Bufo arenarum

PubMed Central

Lew, V. L.

1970-01-01

1. The unidirectional fluxes of 22Na, 36Cl and [14C]bicarbonate ions were measured in paired portions of the isolated and short-circuited colonic mucosa of Bufo arenarum, separated from its muscular layer. Pharmacological effects as well as effects of changes in the composition of the nutrient solutions on the electrical parameters of membrane activity (potential difference, short-circuit current and total membrane resistance) are described. 2. The net fluxes of both Cl and bicarbonate ions were not significantly different from zero in the absence of electrochemical gradients across the membrane. 3. The net Na flux from mucosa to serosa represented a variable proportion of the short-circuit current ranging from 62 to 100%. 4. The proportion of membranes with high discrepancies between net Na flux and short-circuit current decreased with the duration of captivity of the toads. 5. When Na was entirely replaced by choline in the mucosal bathing solution, the short-circuit current dropped by a variable amount within the range of 64 to 98% of its control values in different membranes. This effect was completely reversible. Similar changes in the serosal solution had no effect. 6. The short-circuit current and potential difference were very sensitive to the serosal concentration of bicarbonate ions. In different membranes, 60-100% of the short-circuit current was reversibly abolished by bathing the serosal surface with a bicarbonate-free solution. The mucosal bicarbonate level had no effect on either the potential difference or the short-circuit current. 5 mM bicarbonate in the serosal solution restored at least 50% of the short-circuit control value and full recovery was attained by concentrations near 30 mM bicarbonate. 7. Anoxia brought the potential difference and short-circuit current reversibly down to zero in about 50 min. 8. Ouabain reduced the short-circuit current up to 80% in about 40 min when present in the serosal solution at a concentration of 10-4 M. At this or lower concentrations the ouabain effect was reversible. Above this level ouabain produced 100% inhibition in 3-4 hr, but this was no longer reversible. Ouabain had no effect on the short-circuit current either when applied to the mucosal surface or in the absence of Na from the mucosal solution. 9. Diamox produced a variable inhibition of the short-circuit current of up to 30% only at concentrations above 10 mM. 10. Possible mechanisms are discussed for the appearance of the non-Na component of the short-circuit current. A theory concerning its nature is proposed. PMID:5498503

Circuit engineering principles for construction of bipolar large-scale integrated circuit storage devices and very large-scale main memory

NASA Astrophysics Data System (ADS)

Neklyudov, A. A.; Savenkov, V. N.; Sergeyez, A. G.

1984-06-01

Memories are improved by increasing speed or the memory volume on a single chip. The most effective means for increasing speeds in bipolar memories are current control circuits with the lowest extraction times for a specific power consumption (1/4 pJ/bit). The control current circuitry involves multistage current switches and circuits accelerating transient processes in storage elements and links. Circuit principles for the design of bipolar memories with maximum speeds for an assigned minimum of circuit topology are analyzed. Two main classes of storage with current control are considered: the ECL type and super-integrated injection type storage with data capacities of N = 1/4 and N 4/16, respectively. The circuits reduce logic voltage differentials and the volumes of lexical and discharge buses and control circuit buses. The limiting speed is determined by the antiinterference requirements of the memory in storage and extraction modes.

30 CFR 75.900-3 - Testing, examination, and maintenance of circuit breakers; procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... current circuits serving three-phase alternating current equipment and their auxiliary devices shall be... Underground Low- and Medium-Voltage Alternating Current Circuits § 75.900-3 Testing, examination, and...

30 CFR 75.900-3 - Testing, examination, and maintenance of circuit breakers; procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... current circuits serving three-phase alternating current equipment and their auxiliary devices shall be... Underground Low- and Medium-Voltage Alternating Current Circuits § 75.900-3 Testing, examination, and...

Practical applications of current loop signal conditioning

NASA Astrophysics Data System (ADS)

Anderson, Karl F.

1994-10-01

This paper describes a variety of practical application circuits based on the current loop signal conditioning paradigm. Equations defining the circuit response are also provided. The constant current loop is a fundamental signal conditioning circuit concept that can be implemented in a variety of configurations for resistance-based transducers, such as strain gages and resistance temperature devices. The circuit features signal conditioning outputs which are unaffected by extremely large variations in lead wire resistance, direct current frequency response, and inherent linearity with respect to resistance change. Sensitivity of this circuit is double that of a Wheatstone bridge circuit. Electrical output is zero for resistance change equals zero. The same excitation and output sense wires can serve multiple transducers. More application arrangements are possible with constant current loop signal conditioning than with the Wheatstone bridge.

Current loop signal conditioning: Practical applications

NASA Technical Reports Server (NTRS)

Anderson, Karl F.

1995-01-01

This paper describes a variety of practical application circuits based on the current loop signal conditioning paradigm. Equations defining the circuit response are also provided. The constant current loop is a fundamental signal conditioning circuit concept that can be implemented in a variety of configurations for resistance-based transducers, such as strain gages and resistance temperature detectors. The circuit features signal conditioning outputs which are unaffected by extremely large variations in lead wire resistance, direct current frequency response, and inherent linearity with respect to resistance change. Sensitivity of this circuit is double that of a Wheatstone bridge circuit. Electrical output is zero for resistance change equals zero. The same excitation and output sense wires can serve multiple transducers. More application arrangements are possible with constant current loop signal conditioning than with the Wheatstone bridge.

ISC-GEM: Global Instrumental Earthquake Catalogue (1900-2009), I. Data collection from early instrumental seismological bulletins

NASA Astrophysics Data System (ADS)

Di Giacomo, Domenico; Harris, James; Villaseñor, Antonio; Storchak, Dmitry A.; Engdahl, E. Robert; Lee, William H. K.

2015-02-01

In order to produce a new global reference earthquake catalogue based on instrumental data covering the last 100+ years of global earthquakes, we collected, digitized and processed an unprecedented amount of printed early instrumental seismological bulletins with fundamental parametric data for relocating and reassessing the magnitude of earthquakes that occurred in the period between 1904 and 1970. This effort was necessary in order to produce an earthquake catalogue with locations and magnitudes as homogeneous as possible. The parametric data obtained and processed during this work fills a large gap in electronic bulletin data availability. This new dataset complements the data publicly available in the International Seismological Centre (ISC) Bulletin starting in 1964. With respect to the amplitude-period data necessary to re-compute magnitude, we searched through the global collection of printed bulletins stored at the ISC and entered relevant station parametric data into the database. As a result, over 110,000 surface and body-wave amplitude-period pairs for re-computing standard magnitudes MS and mb were added to the ISC database. To facilitate earthquake relocation, different sources have been used to retrieve body-wave arrival times. These were entered into the database using optical character recognition methods (International Seismological Summary, 1918-1959) or manually (e.g., British Association for the Advancement of Science, 1913-1917). In total, ∼1,000,000 phase arrival times were added to the ISC database for large earthquakes that occurred in the time interval 1904-1970. The selection of earthquakes for which data was added depends on time period and magnitude: for the early years of last century (until 1917) only very large earthquakes were selected for processing (M ⩾ 7.5), whereas in the periods 1918-1959 and 1960-2009 the magnitude thresholds are 6.25 and 5.5, respectively. Such a selection was mainly dictated by limitations in time and funding. Although the newly available parametric data is only a subset of the station data available in the printed bulletins, its electronic availability will be important for any future study of earthquakes that occurred during the early instrumental period.

Automatic recloser circuit breaker integrated with GSM technology for power system notification

NASA Astrophysics Data System (ADS)

Lada, M. Y.; Khiar, M. S. A.; Ghani, S. A.; Nawawi, M. R. M.; Rahim, N. H.; Sinar, L. O. M.

2015-05-01

Lightning is one type of transient faults that usually cause the circuit breaker in the distribution board trip due to overload current detection. The instant tripping condition in the circuit breakers clears the fault in the system. Unfortunately most circuit breakers system is manually operated. The power line will be effectively re-energized after the clearing fault process is finished. Auto-reclose circuit is used on the transmission line to carry out the duty of supplying quality electrical power to customers. In this project, an automatic reclose circuit breaker for low voltage usage is designed. The product description is the Auto Reclose Circuit Breaker (ARCB) will trip if the current sensor detects high current which exceeds the rated current for the miniature circuit breaker (MCB) used. Then the fault condition will be cleared automatically and return the power line to normal condition. The Global System for Mobile Communication (GSM) system will send SMS to the person in charge if the tripping occurs. If the over current occurs in three times, the system will fully trip (open circuit) and at the same time will send an SMS to the person in charge. In this project a 1 A is set as the rated current and any current exceeding a 1 A will cause the system to trip or interrupted. This system also provides an additional notification for user such as the emergency light and warning system.

Thermal Fluxes and Temperatures in Small Urban Headwater Streams of the BES LTER: Landscape Forest and Impervious Patches and the Importance of Spatial and Temporal Scales

NASA Astrophysics Data System (ADS)

Kim, H.; Belt, K. T.; Welty, C.; Heisler, G.; Pouyat, R. V.; McGuire, M. P.; Stack, W. P.

2006-05-01

Water and material fluxes from urban landscape patches to small streams are modulated by extensive "engineered" drainage networks. Small urban headwater catchments are different in character and function from their larger receiving streams because of their extensive, direct connections to impervious surface cover (ISC) and their sometimes buried nature. They need to be studied as unique functional hydrologic units if impacts on biota are to be fully understood. As part of the Baltimore Ecosystem Study LTER project, continuous water temperature data are being collected at 2-minute intervals at over twenty small catchments representing various mixtures of forest and ISC. Suburban stream sites with greater ISC generally have higher summer water temperatures. Suburban catchments with most of their channel drainage contained within storm drain pipes show subdued diurnal variation and cool temperatures, but with very large spikes in summer runoff events. Conversely, high ISC urban piped streams have elevated "baseline" temperatures that stand well above all the other monitoring sites. There is a pronounced upstream-downstream effect; nested small headwater catchments experience more frequent, larger temperature spikes related to runoff events than downstream sites. Also, runoff-initiated temperature elevations at small stream sites unexpectedly last much longer than the storm runoff hydrographs. These observations suggest that for small headwater catchments, urban landscapes not only induce an ambient, "heat island" effect on stream temperatures, but also introduce thermal disturbance regimes and fluxes that are not trivial to aquatic biota.

Increased centrosome amplification in aged stem cells of the Drosophila midgut

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Joung-Sun; Pyo, Jung-Hoon; Na, Hyun-Jin

Highlights: • Increased centrosome amplification in ISCs of aged Drosophila midguts. • Increased centrosome amplification in ISCs of oxidative stressed Drosophila midguts. • Increased centrosome amplification in ISCs by overexpression of PVR, EGFR, and AKT. • Supernumerary centrosomes can be responsible for abnormal ISC polyploid cells. • Supernumerary centrosomes can be a useful marker for aging stem cells. - Abstract: Age-related changes in long-lived tissue-resident stem cells may be tightly linked to aging and age-related diseases such as cancer. Centrosomes play key roles in cell proliferation, differentiation and migration. Supernumerary centrosomes are known to be an early event in tumorigenesismore » and senescence. However, the age-related changes of centrosome duplication in tissue-resident stem cells in vivo remain unknown. Here, using anti-γ-tubulin and anti-PH3, we analyzed mitotic intestinal stem cells with supernumerary centrosomes in the adult Drosophila midgut, which may be a versatile model system for stem cell biology. The results showed increased centrosome amplification in intestinal stem cells of aged and oxidatively stressed Drosophila midguts. Increased centrosome amplification was detected by overexpression of PVR, EGFR, and AKT in intestinal stem cells/enteroblasts, known to mimic age-related changes including hyperproliferation of intestinal stem cells and hyperplasia in the midgut. Our data show the first direct evidence for the age-related increase of centrosome amplification in intestinal stem cells and suggest that the Drosophila midgut is an excellent model for studying molecular mechanisms underlying centrosome amplification in aging adult stem cells in vivo.« less

Cellular and subcellular structure of anterior sensory pathways in Phestilla sibogae (Gastropoda, Nudibranchia).

PubMed

Boudko, D Y; Switzer-Dunlap, M; Hadfield, M G

1999-01-05

Two sensory-cell types, subepithelial sensory cells (SSCs) and intraepithelial sensory cells (ISCs), were identified in the anterior sensory organs (ASO: pairs of rhinophores and oral tentacles, and the anterior field formed by the oral plate and cephalic shield) of the nudibranch Phestilla sibogae after filling through anterior nerves with the neuronal tracers biocytin and Lucifer Yellow. A third type of sensory cells, with subepithelial somata and tufts of stiff-cilia (TSCs, presumably rheoreceptors), was identified after uptake of the mitochondrial dye DASPEI. Each sensory-cell type has a specific spatial distribution in the ASO. The highest density of ISCs is in the oral tentacles (approximately 1,200/mm2), SSCs in the middle parts of the rhinophores (>4,000/mm2), and TSCs in the tips of cephalic tentacles (100/mm2). These morphologic data, together with electrophysiologic evidence for greater chemical sensitivity of the rhinophores than the oral tentacles (Murphy and Hadfield [1997] Comp. Biochem. Physiol. 118A:727-735; Boudko et al. [1997] Soc. Neurosci. Abstr. 23:1787), led us to conclude that the two pairs of chemosensory tentacles serve different chemosensory functions in P. sibogae; i.e., ISCs and the oral tentacles serve contact- or short-distance chemoreception, and SSCs and the rhinophores function for long-distance chemoreception or olfaction. If this is true, then the ISC subsystem probably represents an earlier stage in the evolution and adaptations of gastropod chemosensory biology, whereas among the opisthobranchs, the SSC subsystem evolved with the rhinophores from ancestral cephalaspidean opisthobranchs.

Interleaved segment correction achieves higher improvement factors in using genetic algorithm to optimize light focusing through scattering media

NASA Astrophysics Data System (ADS)

Li, Runze; Peng, Tong; Liang, Yansheng; Yang, Yanlong; Yao, Baoli; Yu, Xianghua; Min, Junwei; Lei, Ming; Yan, Shaohui; Zhang, Chunmin; Ye, Tong

2017-10-01

Focusing and imaging through scattering media has been proved possible with high resolution wavefront shaping. A completely scrambled scattering field can be corrected by applying a correction phase mask on a phase only spatial light modulator (SLM) and thereby the focusing quality can be improved. The correction phase is often found by global searching algorithms, among which Genetic Algorithm (GA) stands out for its parallel optimization process and high performance in noisy environment. However, the convergence of GA slows down gradually with the progression of optimization, causing the improvement factor of optimization to reach a plateau eventually. In this report, we propose an interleaved segment correction (ISC) method that can significantly boost the improvement factor with the same number of iterations comparing with the conventional all segment correction method. In the ISC method, all the phase segments are divided into a number of interleaved groups; GA optimization procedures are performed individually and sequentially among each group of segments. The final correction phase mask is formed by applying correction phases of all interleaved groups together on the SLM. The ISC method has been proved significantly useful in practice because of its ability to achieve better improvement factors when noise is present in the system. We have also demonstrated that the imaging quality is improved as better correction phases are found and applied on the SLM. Additionally, the ISC method lowers the demand of dynamic ranges of detection devices. The proposed method holds potential in applications, such as high-resolution imaging in deep tissue.

High accuracy switched-current circuits using an improved dynamic mirror

NASA Technical Reports Server (NTRS)

Zweigle, G.; Fiez, T.

1991-01-01

The switched-current technique, a recently developed circuit approach to analog signal processing, has emerged as an alternative/compliment to the well established switched-capacitor circuit technique. High speed switched-current circuits offer potential cost and power savings over slower switched-capacitor circuits. Accuracy improvements are a primary concern at this stage in the development of the switched-current technique. Use of the dynamic current mirror has produced circuits that are insensitive to transistor matching errors. The dynamic current mirror has been limited by other sources of error including clock-feedthrough and voltage transient errors. In this paper we present an improved switched-current building block using the dynamic current mirror. Utilizing current feedback the errors due to current imbalance in the dynamic current mirror are reduced. Simulations indicate that this feedback can reduce total harmonic distortion by as much as 9 dB. Additionally, we have developed a clock-feedthrough reduction scheme for which simulations reveal a potential 10 dB total harmonic distortion improvement. The clock-feedthrough reduction scheme also significantly reduces offset errors and allows for cancellation with a constant current source. Experimental results confirm the simulated improvements.

Phenotypic Screening for Friedreich Ataxia Using Random shRNA Selection.

PubMed

Cotticelli, M Grazia; Acquaviva, Fabio; Xia, Shujuan; Kaur, Avinash; Wang, Yongping; Wilson, Robert B

2015-10-01

Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardio-degenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the protein frataxin. Frataxin chaperones iron in the mitochondrial matrix and regulates the iron-sulfur cluster (ISC) assembly complex. ISCs are prosthetic groups critical for the function of the Krebs cycle and the mitochondrial electron transport chain. Decreased expression of frataxin is associated with decreased ISC assembly, mitochondrial iron accumulation, and increased oxidative stress, all of which contribute to mitochondrial dysfunction. In media with beta-hydroxybutyrate (BHB) as carbon source, primary FRDA fibroblasts grow poorly and/or lose viability over several days. We screened a random, short-hairpin-RNA (shRNA)-expressing library in primary FRDA fibroblasts and identified two shRNAs that reverse the growth/viability defect in BHB media. One of these two clones increases frataxin expression in primary FRDA fibroblasts, either as a vector-expressed shRNA or as a transfected short-interfering RNA (siRNA). © 2015 Society for Laboratory Automation and Screening.

Differential biofilms characteristics of Shewanella decolorationis microbial fuel cells under open and closed circuit conditions.

PubMed

Yang, Yonggang; Sun, Guoping; Guo, Jun; Xu, Meiying

2011-07-01

Biofilms formation capacities of Shewanella species in microbial fuel cells (MFCs) and their roles in current generation have been documented to be species-dependent. Understandings of the biofilms growth and metabolism are essential to optimize the current generation of MFCs. Shewanella decolorationis S12 was used in both closed-circuit and open-circuit MFCs in this study. The anodic S. decolorationis S12 biofilms could generate fivefold more current than the planktonic cells, playing a dominant role in current generation. Anodic biofilms viability was sustained at 98 ± 1.2% in closed-circuit while biofilms viability in open-circuit decreased to 72 ± 7% within 96 h. The unviable domain in open-circuit MFCs biofilms majorly located at the inner layer of biofilm. The decreased biofilms viability in open-circuit MFCs could be recovered by switching into closed-circuit, indicating that the current-generating anode in MFCs could serve as a favorable electron acceptor and provide sufficient energy to support cell growth and metabolism inside biofilms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dual amplitude pulse generator for radiation detectors

DOEpatents

Hoggan, Jerry M.; Kynaston, Ronnie L.; Johnson, Larry O.

2001-01-01

A pulsing circuit for producing an output signal having a high amplitude pulse and a low amplitude pulse may comprise a current source for providing a high current signal and a low current signal. A gate circuit connected to the current source includes a trigger signal input that is responsive to a first trigger signal and a second trigger signal. The first trigger signal causes the gate circuit to connect the high current signal to a pulse output terminal whereas the second trigger signal causes the gate circuit to connect the low current signal to the pulse output terminal.

Electronic circuit for measuring series connected electrochemical cell voltages

DOEpatents

Ashtiani, Cyrus N.; Stuart, Thomas A.

2000-01-01

An electronic circuit for measuring voltage signals in an energy storage device is disclosed. The electronic circuit includes a plurality of energy storage cells forming the energy storage device. A voltage divider circuit is connected to at least one of the energy storage cells. A current regulating circuit is provided for regulating the current through the voltage divider circuit. A voltage measurement node is associated with the voltage divider circuit for producing a voltage signal which is proportional to the voltage across the energy storage cell.

Method of determining the open circuit voltage of a battery in a closed circuit

DOEpatents

Brown, William E.

1980-01-01

The open circuit voltage of a battery which is connected in a closed circuit is determined without breaking the circuit or causing voltage upsets therein. The closed circuit voltage across the battery and the current flowing through it are determined under normal load and then a fractional change is made in the load and the new current and voltage values determined. The open circuit voltage is then calculated, according to known principles, from the two sets of values.

30 CFR 75.601-3 - Short circuit protection; dual element fuses; current ratings; maximum values.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Trailing Cables § 75.601-3 Short circuit protection; dual element fuses; current ratings; maximum values... circuit protection of trailing cables as provided in § 75.601, however, the current ratings of such...

Research of vibration control based on current mode piezoelectric shunt damping circuit

NASA Astrophysics Data System (ADS)

Liu, Weiwei; Mao, Qibo

2017-12-01

The piezoelectric shunt damping circuit using current mode approach is imposed to control the vibration of a cantilever beam. Firstly, the simulated inductance with large values are designed for the corresponding RL series shunt circuits. Moreover, with an example of cantilever beam, the second natural frequency of the beam is targeted to control for experiment. By adjusting the values of the equivalent inductance and equivalent resistance of the shunt circuit, the optimal damping of the shunt circuit is obtained. Meanwhile, the designed piezoelectric shunt damping circuit stability is experimental verified. Experimental results show that the proposed piezoelectric shunt damping circuit based on current mode circuit has good vibration control performance. However, the control performance will be reduced if equivalent inductance and equivalent resistance values deviate from optimal values.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, E.R.C. da; Filho, B.J.C.

This paper presents a PWM current clamping circuit for improving a series resonant DC link converter. This circuit is capable of reducing current peaks to about 1.2--1.4 times the DC bias current. When desired, resonant transition creates notches in the dc link current, allowing the converter`s switches to synchronize with external PWM strategy. A regulated DC current source may be obtained--by using a conventional rectifier source--to feed a DC load or a current source inverter. Phase plane approach makes ease the understanding the operation, control and design procedure of the circuit. Another topology is derived and its features compared tomore » the first circuit. Simulation results for the simplified circuit and for a three-phase induction motor driven by such inverter will be presented. Moreover, the principle is corroborated by experimental results.« less

Power-Switching Circuit

NASA Technical Reports Server (NTRS)

Praver, Gerald A.; Theisinger, Peter C.; Genofsky, John

1987-01-01

Functions of circuit breakers, meters, and switches combined. Circuit that includes power field-effect transistors (PFET's) provides on/off switching, soft starting, current monitoring, current tripping, and protection against overcurrent for 30-Vdc power supply at normal load currents up to 2 A. Has no moving parts.

Starting Circuit For Erasable Programmable Logic Device

NASA Technical Reports Server (NTRS)

Cole, Steven W.

1990-01-01

Voltage regulator bypassed to supply starting current. Starting or "pullup" circuit supplies large inrush of current required by erasable programmable logic device (EPLD) while being turned on. Operates only during such intervals of high demand for current and has little effect any other time. Performs needed bypass, acting as current-dependent shunt connecting battery or other source of power more nearly directly to EPLD. Input capacitor of regulator removed when starting circuit installed, reducing probability of damage to transistor in event of short circuit in or across load.

The Relationship between the Current Waveform just before the Current Zero and the Interruption Ability in the High-speed VCB

NASA Astrophysics Data System (ADS)

Niwa, Yoshimitsu; Matsuzaki, Jun; Yokokura, Kunio

The high-speed vacuum circuit breaker, which forced the fault current to zero was investigated. The test circuit breaker consisted of a vacuum interrupter and a high frequency current source. The vacuum interrupter, which had the axial magnetic field electrode and the disk shape electrode, was tested. The arcing period of the high-speed vacuum circuit breaker is much shorter than that of conventional circuit breaker. The arc behavior of the test electrodes immediately after the contact separation was observed by a high-speed video camcorder. The relation between the current waveform just before the current zero and the interruption ability by varying the high frequency current source was investigated experimentally. The results demonstrate the interruption ability and the arc behavior of the high-speed vacuum circuit breaker. The high current interruption was made possible by the low current period just before the current zero, although the arcing time is short and the arc is concentrated.

Low phase noise oscillator using two parallel connected amplifiers

NASA Technical Reports Server (NTRS)

Kleinberg, Leonard L.

1987-01-01

A high frequency oscillator is provided by connecting two amplifier circuits in parallel where each amplifier circuit provides the other amplifier circuit with the conditions necessary for oscillation. The inherent noise present in both amplifier circuits causes the quiescent current, and in turn, the generated frequency, to change. The changes in quiescent current cause the transconductance and the load impedance of each amplifier circuit to vary, and this in turn results in opposing changes in the input susceptance of each amplifier circuit. Because the changes in input susceptance oppose each other, the changes in quiescent current also oppose each other. The net result is that frequency stability is enhanced.

Commutation circuit for an HVDC circuit breaker

DOEpatents

Premerlani, William J.

1981-01-01

A commutation circuit for a high voltage DC circuit breaker incorporates a resistor capacitor combination and a charging circuit connected to the main breaker, such that a commutating capacitor is discharged in opposition to the load current to force the current in an arc after breaker opening to zero to facilitate arc interruption. In a particular embodiment, a normally open commutating circuit is connected across the contacts of a main DC circuit breaker to absorb the inductive system energy trapped by breaker opening and to limit recovery voltages to a level tolerable by the commutating circuit components.

Commutation circuit for an HVDC circuit breaker

DOEpatents

Premerlani, W.J.

1981-11-10

A commutation circuit for a high voltage DC circuit breaker incorporates a resistor capacitor combination and a charging circuit connected to the main breaker, such that a commutating capacitor is discharged in opposition to the load current to force the current in an arc after breaker opening to zero to facilitate arc interruption. In a particular embodiment, a normally open commutating circuit is connected across the contacts of a main DC circuit breaker to absorb the inductive system energy trapped by breaker opening and to limit recovery voltages to a level tolerable by the commutating circuit components. 13 figs.

Circuit protects regulated power supply against overload current

NASA Technical Reports Server (NTRS)

Airth, H. B.

1966-01-01

Sensing circuit in which a tunnel diode controls a series regulator transistor protects a low voltage transistorized dc regulator from damage by excessive load currents. When a fault occurs, the faulty circuit is limited to a preset percentage of the current when limiting first occurs.

Design and optimization of LCL-VSC grid-tied converter having short circuit fault current limiting ability

NASA Astrophysics Data System (ADS)

Liu, Mengqi; Liu, Haijun; Wang, Zhikai

2017-01-01

Traditional LCL grid-tied converters haven't the ability to limit the short-circuit fault current and only remove grid-connected converter using the breaker. However, the VSC converters become uncontrollable after the short circuit fault cutting off and the power switches may be damaged if the circuit breaker removes slowly. Compared to the filter function of the LCL passive components in traditional VSC converters, the novel LCL-VSC converter has the ability of limiting the short circuit fault current using the reasonable designed LCL parameters. In this paper the mathematical model of the LCL converter is established and the characteristics of the short circuit fault current generated by the ac side and dc side are analyzed. Thus one design and optimization scheme of the reasonable LCL passive parameter is proposed for the LCL-VSC converter having short circuit fault current limiting ability. In addition to ensuring the LCL passive components filtering the high-frequency harmonic, this scheme also considers the impedance characteristics to limit the fault current of AC and DC short circuit fault respectively flowing through the power switch no more than the maximum allowable operating current, in order to make the LCL converter working continuously. Finally, the 200kW simulation system is set up to prove the validity and feasibility of the theoretical analysis using the proposed design and optimization scheme.

Simple constant-current-regulated power supply

NASA Technical Reports Server (NTRS)

Priebe, D. H. E.; Sturman, J. C.

1977-01-01

Supply incorporates soft-start circuit that slowly ramps current up to set point at turn-on. Supply consists of full-wave rectifier, regulating pass transistor, current feedback circuit, and quad single-supply operational-amplifier circuit providing control. Technique is applicable to any system requiring constant dc current, such as vacuum tube equipment, heaters, or battery charges; it has been used to supply constant current for instrument calibration.

Commutating Permanent-Magnet Motors At Low Speed

NASA Technical Reports Server (NTRS)

Dolland, C.

1985-01-01

Circuit provides forced commutation during starting. Forced commutation circuit diverts current from inverter SCR's and turns SCR's off during commutation intervals. Silicon controlled rectifier in circuit unnecessary when switch S10 replaced by high-current, high-voltage transistor. At present, high-current, low-voltage device must suffice.

30 CFR 75.824 - Electrical protection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... transformer and over-current relay in the neutral grounding resistor circuit. (vi) A single window-type current transformer that encircles all three-phase conductors must be used to activate the ground-fault... current transformer. (vii) A test circuit for the ground-fault device must be provided. The test circuit...

30 CFR 75.824 - Electrical protection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... transformer and over-current relay in the neutral grounding resistor circuit. (vi) A single window-type current transformer that encircles all three-phase conductors must be used to activate the ground-fault... current transformer. (vii) A test circuit for the ground-fault device must be provided. The test circuit...

30 CFR 75.824 - Electrical protection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... transformer and over-current relay in the neutral grounding resistor circuit. (vi) A single window-type current transformer that encircles all three-phase conductors must be used to activate the ground-fault... current transformer. (vii) A test circuit for the ground-fault device must be provided. The test circuit...

30 CFR 75.824 - Electrical protection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... transformer and over-current relay in the neutral grounding resistor circuit. (vi) A single window-type current transformer that encircles all three-phase conductors must be used to activate the ground-fault... current transformer. (vii) A test circuit for the ground-fault device must be provided. The test circuit...

30 CFR 75.824 - Electrical protection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... transformer and over-current relay in the neutral grounding resistor circuit. (vi) A single window-type current transformer that encircles all three-phase conductors must be used to activate the ground-fault... current transformer. (vii) A test circuit for the ground-fault device must be provided. The test circuit...

Influence of controlled encoding and retrieval facilitation on memory performance in patients with different profiles of mild cognitive impairment.

PubMed

Perri, Roberta; Monaco, Marco; Fadda, Lucia; Serra, Laura; Marra, Camillo; Caltagirone, Carlo; Bruni, Amalia C; Curcio, Sabrina; Bozzali, M; Carlesimo, Giovanni A

2015-01-01

Memory tests able to differentiate encoding and retrieval processes from the memoranda storing ones should be used to differentiate patients in a very early phase of AD. In fact, individuals with mild cognitive impairment (MCI) can be characterized by two different memory profiles: a pure amnestic one (with poor learning and retrieval and poor improvement when encoding is assisted and retrieval is facilitated) and a dysexecutive one (with inefficient encoding and/or poor retrieval strategies and improvement with assisted encoding and retrieval). The amnestic profile characterizes subjects affected by medio-temporal atrophy typical of AD. In this study, a Grober-Buschke memory procedure was used to evaluate normal controls and MCI patients with different cognitive profiles: pure amnestic (aMCIsd), amnestic plus other cognitive impairments (aMCImd) and non-amnestic (naMCI). An index of sensitivity of cueing (ISC) measured the advantage passing from free to cued recall. Results showed that both strategic and consolidation abilities were impaired in the aMCIsd and aMCImd groups and were preserved in the naMCI group. aMCImd, however, compensated the memory deficit with assisted encoding and retrieval, but aMCIsd performed very poorly. When MCI subjects were defined according to the ISC value, subjects with poor ISC were primarily in the aMCIsd group and, to a lesser extent, in the aMCImd group and the naMCI group. Finally, patients with a poor ISC showed cerebral atrophy documented in the precocious phase of AD and the retrosplenial cerebral areas seemed to be the most useful areas for identifying patients in the early phase of AD.

MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron-sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells.

PubMed

He, M; Lu, Y; Xu, S; Mao, L; Zhang, L; Duan, W; Liu, C; Pi, H; Zhang, Y; Zhong, M; Yu, Z; Zhou, Z

2014-02-27

The cellular energy metabolism shift, characterized by the inhibition of oxidative phosphorylation (OXPHOS) and enhancement of glycolysis, is involved in nickel-induced neurotoxicity. MicroRNA-210 (miR-210) is regulated by hypoxia-inducible transcription factor-1α (HIF-1α) under hypoxic conditions and controls mitochondrial energy metabolism by repressing the iron-sulfur cluster assembly protein (ISCU1/2). ISCU1/2 facilitates the assembly of iron-sulfur clusters (ISCs), the prosthetic groups that are critical for mitochondrial oxidation-reduction reactions. This study aimed to investigate whether miR-210 modulates alterations in energy metabolism after nickel exposure through suppressing ISCU1/2 and inactivating ISCs-containing metabolic enzymes. We determined that NiCl2 exposure leads to a significant accumulation of HIF-1α, rather than HIF-1β, in Neuro-2a cells. The miR-210 overexpression and ISCU1/2 downregulation was observed in a dose- and time-dependent manner. The gain-of-function and loss-of-dysfunction assays revealed that miR-210 mediated the ISCU1/2 suppression, energy metabolism alterations, and ISC-containing metabolic enzyme inactivation after nickel exposure. In addition, the impact of miR-210 on ISC-containing metabolic enzymes was independent from cellular iron regulation. Overall, these data suggest that repression of miR-210 on ISCU1/2 may contribute to HIF-1α-triggered alterations in energy metabolism after nickel exposure. A better understanding of how nickel impacts cellular energy metabolism may facilitate the elucidation of the mechanisms by which nickel affects the human health.

Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

PubMed

Sureban, Sripathi M; May, Randal; Qu, Dongfeng; Chandrakesan, Parthasarathy; Weygant, Nathaniel; Ali, Naushad; Lightfoot, Stan A; Ding, Kai; Umar, Shahid; Schlosser, Michael J; Houchen, Courtney W

2015-01-01

Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

Early-Time Excited-State Relaxation Dynamics of Iridium Compounds: Distinct Roles of Electron and Hole Transfer.

PubMed

Liu, Xiang-Yang; Zhang, Ya-Hui; Fang, Wei-Hai; Cui, Ganglong

2018-06-28

Excited-state and photophysical properties of Ir-containing complexes have been extensively studied because of their potential applications as organic light-emitting diode emitting materials. However, their early time excited-state relaxation dynamics are less explored computationally. Herein we have employed our recently implemented TDDFT-based generalized surface-hopping dynamics method to simulate excited-state relaxation dynamics of three Ir(III) compounds having distinct ligands. According to our multistate dynamics simulations including five excited singlet states i.e., S n ( n = 1-5) and ten excited triplet states, i.e., T n ( n = 1-10), we have found that the intersystem crossing (ISC) processes from the S n to T n are very efficient and ultrafast in these three Ir(III) compounds. The corresponding ISC rates are estimated to be 65, 81, and 140 fs, which are reasonably close to the experimentally measured ca. 80, 80, and 110 fs. In addition, the internal conversion (IC) processes within respective singlet and triplet manifolds are also ultrafast. These ultrafast IC and ISC processes are caused by large nonadiabatic and spin-orbit couplings, respectively, as well as small energy gaps. Importantly, although these Ir(III) complexes share similar macroscopic phenomena, i.e., ultrafast IC and ISC, their microscopic excited-state relaxation mechanism and dynamics are qualitatively distinct. Specifically, the dynamical behaviors of electron and hole and their roles are variational in modulating the excited-state relaxation dynamics of these Ir(III) compounds. In other words, the electronic properties of the ligands that are coordinated with the central Ir(III) atom play important roles in regulating the microscopic excited-state relaxation dynamics. These gained insights could be useful for rationally designing Ir(III) compounds with excellent photoluminescence.

Acute exercises induce disorders of the gastrointestinal integrity in a murine model.

PubMed

Gutekunst, Katrin; Krüger, Karsten; August, Christian; Diener, Martin; Mooren, Frank-Christoph

2014-03-01

Many endurance athletes complain about gastrointestinal (GI) symptoms. It is assumed that exercise-induced shift of perfusion with consecutive hypoperfusion of the enteral vascular system leads to an increased GI permeability and tissue damage. Therefore, the aim of the study was to investigate permeability, apoptosis, electrogenic ion transport (Isc), and tissue conductance (Gt) of the small intestine in a murine exercise model. After spirometry, male Swiss CD-1 mice were subjected to an intensive treadmill exercise (80% VO2max). Sedentary mice served as controls. The small intestine was removed at several time intervals post-exercise. Apoptotic cells were determined by the TUNEL method, while fluorescein isothiocyanate dextran permeation indicated intestinal permeability. The Gt and Isc measurements were carried out in a modified Ussing chamber. Apoptosis of epithelial cells increased continuously until 24 h post exercise (0.8 ± 0.42 versus 39.2 ± 26.0%; p < 0.05). Compared with the control group the permeability increased 2 h after exercise (0.47 ± 0.07 versus 0.67 ± 0.14 FU/min; p < 0.05). Isc measurements of the ileum were augmented after 24 h (3.33 ± 0.56 versus 5.77 ± 1.16 μEq/h/cm(2); p < 0.05). At this time the Gt increased as well (28.8 ± 3.37 versus 32.5 ± 2.59 mS/cm(2); p < 0.05). In the murine exercise model there is evidence that after intense endurance exercise repair processes occur in small intestinal epithelial cells, which affect permeability, Gt, and Isc. The formation of lamellipodia to close the "leaky" tight junctions caused by apoptosis might be an underlying mechanism.

Mapping cellular Fe-S cluster uptake and exchange reactions - divergent pathways for iron-sulfur cluster delivery to human ferredoxins.

PubMed

Fidai, Insiya; Wachnowsky, Christine; Cowan, J A

2016-12-07

Ferredoxins are protein mediators of biological electron-transfer reactions and typically contain either [2Fe-2S] or [4Fe-4S] clusters. Two ferredoxin homologues have been identified in the human genome, Fdx1 and Fdx2, that share 43% identity and 69% similarity in protein sequence and both bind [2Fe-2S] clusters. Despite the high similarity, the two ferredoxins play very specific roles in distinct physiological pathways and cannot replace each other in function. Both eukaryotic and prokaryotic ferredoxins and homologues have been reported to receive their Fe-S cluster from scaffold/delivery proteins such as IscU, Isa, glutaredoxins, and Nfu. However, the preferred and physiologically relevant pathway for receiving the [2Fe-2S] cluster by ferredoxins is subject to speculation and is not clearly identified. In this work, we report on in vitro UV-visible (UV-vis) circular dichroism studies of [2Fe-2S] cluster transfer to the ferredoxins from a variety of partners. The results reveal rapid and quantitative transfer to both ferredoxins from several donor proteins (IscU, Isa1, Grx2, and Grx3). Transfer from Isa1 to Fdx2 was also observed to be faster than that of IscU to Fdx2, suggesting that Fdx2 could receive its cluster from Isa1 instead of IscU. Several other transfer combinations were also investigated and the results suggest a complex, but kinetically detailed map for cellular cluster trafficking. This is the first step toward building a network map for all of the possible iron-sulfur cluster transfer pathways in the mitochondria and cytosol, providing insights on the most likely cellular pathways and possible redundancies in these pathways.

Inflammation Caused by Praziquantel Treatment Depends on the Location of the Taenia solium Cysticercus in Porcine Neurocysticercosis

PubMed Central

Cangalaya, Carla; Zimic, Mirko; Marzal, Miguel; González, Armando E.; Guerra-Giraldez, Cristina; Mahanty, Siddhartha; Nash, Theodore E.; García, Hector H.

2015-01-01

Background Neurocysticercosis (NCC), infection of the central nervous system by Taenia solium cysticerci, is a pleomorphic disease. Inflammation around cysticerci is the major cause of disease but is variably present. One factor modulating the inflammatory responses may be the location and characteristics of the brain tissue adjacent to cysticerci. We analyzed and compared the inflammatory responses to cysticerci located in the parenchyma to those in the meninges or cysticerci partially in contact with both the parenchyma and the meninges (corticomeningeal). Methodology/Principal Findings Histological specimens of brain cysticerci (n = 196) from 11 pigs naturally infected with Taenia solium cysticerci were used. Four pigs were sacrificed after 2 days and four after 5 days of a single dose of praziquantel; 3 pigs did not receive treatment. All pigs were intravenously injected with Evans Blue to assess disruption of the blood-brain barrier. The degree of inflammation was estimated by use of a histological score (ISC) based on the extent of the inflammation in the pericystic areas as assessed in an image composed of several photomicrographs taken at 40X amplification. Parenchymal cysticerci provoked a significantly greater level of pericystic inflammation (higher ISC) after antiparasitic treatment compared to meningeal and corticomeningeal cysticerci. ISC of meningeal cysticerci was not significantly affected by treatment. In corticomeningeal cysticerci, the increase in ISC score was correlated to the extent of the cysticercus adjacent to the brain parenchyma. Disruption of the blood-brain barrier was associated with treatment only in parenchymal tissue. Significance Inflammatory response to cysticerci located in the meninges was significantly decreased compared to parenchymal cysticerci. The suboptimal inflammatory response to cysticidal drugs may be the reason subarachnoid NCC is generally refractory to treatment compared to parenchymal NCC. PMID:26658257

Theoretical investigation of intersystem crossing in the cyanonitrene molecule, 1NCN → 3NCN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pfeifle, Mark; Georgievskii, Yuri; Jasper, Ahren W.

The NCN diradical is an important intermediate of prompt nitric oxide formation in flames. The mechanism of intersystem crossing (ISC) in the NCN molecule formed via pyrolysis or photolysis of NCN 3 is of relevance to the interpretation of experiments that utilize NCN 3 as a precursor for laboratory studies of NCN kinetics. This mechanism has been investigated by means of multi-reference configuration interaction calculations. From the potential energy surfaces for NCN 3 dissociation, it was inferred that both thermal and photo-chemical decomposition initially lead to NCN in its lowest singlet state,more » $$\\tilde{a}^{-1}$$$Δ_g$$, with a possible contribution from the $$\\tilde{b}^{-1}\\Sigma_g^+$$ state at low photolysis wavelengths. Direct formation of the triplet ground state $$\\tilde{X}^{-3}\\Sigma_g^-$$ is also feasible for the photolytic pathway. Ananalysis of surface crossings between $$\\tilde{a}$$ or $$\\tilde{b}$$ and the triplet ground state $$\\tilde{X}^{-3}\\Sigma_g^-$$ in the absence and presence of a helium atom revealed an ISC channel 1NCN ($$\\tilde{a}$$) → 3NCN($$\\tilde{X}$$) via a strongly bent structure. However, its barrier of 38 kcal mol -1 relative to the singlet minimum turned out to be much too high to explain the fast ISC observed in experiments. A rigid-bender model including Renner-Teller interactions was used to examine the occurrence of mixed-multiplicity rovibrational states-so-called gateway states-that could enhance collision-induced ISC. The results of this study indicate that a gateway mechanism is probably not operative in the case of the $$\\tilde{a}$$/$$\\tilde{X}$$pair of states in NCN.« less

Theoretical investigation of intersystem crossing in the cyanonitrene molecule, 1NCN → 3NCN

DOE PAGES

Pfeifle, Mark; Georgievskii, Yuri; Jasper, Ahren W.; ...

2017-08-28

The NCN diradical is an important intermediate of prompt nitric oxide formation in flames. The mechanism of intersystem crossing (ISC) in the NCN molecule formed via pyrolysis or photolysis of NCN 3 is of relevance to the interpretation of experiments that utilize NCN 3 as a precursor for laboratory studies of NCN kinetics. This mechanism has been investigated by means of multi-reference configuration interaction calculations. From the potential energy surfaces for NCN 3 dissociation, it was inferred that both thermal and photo-chemical decomposition initially lead to NCN in its lowest singlet state,more » $$\\tilde{a}^{-1}$$$Δ_g$$, with a possible contribution from the $$\\tilde{b}^{-1}\\Sigma_g^+$$ state at low photolysis wavelengths. Direct formation of the triplet ground state $$\\tilde{X}^{-3}\\Sigma_g^-$$ is also feasible for the photolytic pathway. Ananalysis of surface crossings between $$\\tilde{a}$$ or $$\\tilde{b}$$ and the triplet ground state $$\\tilde{X}^{-3}\\Sigma_g^-$$ in the absence and presence of a helium atom revealed an ISC channel 1NCN ($$\\tilde{a}$$) → 3NCN($$\\tilde{X}$$) via a strongly bent structure. However, its barrier of 38 kcal mol -1 relative to the singlet minimum turned out to be much too high to explain the fast ISC observed in experiments. A rigid-bender model including Renner-Teller interactions was used to examine the occurrence of mixed-multiplicity rovibrational states-so-called gateway states-that could enhance collision-induced ISC. The results of this study indicate that a gateway mechanism is probably not operative in the case of the $$\\tilde{a}$$/$$\\tilde{X}$$pair of states in NCN.« less

RF lockout circuit for electronic locking system

NASA Astrophysics Data System (ADS)

Becker, Earl M., Jr.; Miller, Allen

1991-02-01

An electronics lockout circuit was invented that includes an antenna adapted to receive radio frequency signals from a transmitter, and a radio frequency detector circuit which converts the radio frequency signals into a first direct current voltage indicative of the relative strength of the field resulting from the radio frequency signals. The first direct current voltage is supplied to a trigger circuit which compares this direct current voltage to an adjustable direct current reference voltage. This provides a second direct current voltage at the output whenever the amplitude of the first direct current voltage exceeds the amplitude of the reference voltage provided by the comparator circuit. This is supplied to a disconnect relay circuit which, upon receiving a signal from the electronic control unit of an electronic combination lock during the time period at which the second direct current voltage is present, isolates the door strike coil of a security door from the electronic control unit. This prevents signals falsely generated by the electronic control unit because of radio frequency signals in the vicinity of the electronic control unit energizing the door strike coil and accidentally opening a security door.

An alternative explanation for the occurrence of short circuit current increases in the small intestine following challenge by bacterial enterotoxins.

PubMed

Lucas, M L

2013-10-01

Secretory diarrhoeal disease due to enterotoxins is thought to arise from the enhancement to pathologically high rates of normally occurring chloride ion and therefore fluid secretion from enterocytes. In support of this concept, many enterotoxins increase intestinal short-circuit current, regarded now as faithfully reflecting the increased chloride ion secretion. Contradicting this assumption, STa reduces absorption but does not cause secretion in vivo although short-circuit current is increased in vitro. There is therefore a mismatch between an assumed enterocyte mediated secretory event that should but does not cause net fluid secretion and an undoubtedly increased short-circuit current. It is proposed here that short-circuit current increases are not themselves secretory events but result from interrupted fluid absorption. A noteworthy feature of compounds that inhibit the increase in short-circuit current is that the majority are vasoactive, neuroactive or both. In general, vasodilator substances increase current. An alternative hypothesis for the origin of short-circuit current increases is that these result from reflex induction of electrogenic fluid absorption. This reflex enhances a compensatory response that is also present at a cellular level. An intestinal reflex is therefore proposed by which decreases in interstitial and intravascular volume or pressure within the intestine initiate an electrogenic fluid absorption mechanism that compensates for the loss of electrically neutral fluid absorption. This hypothesis would explain the apparently complex pharmacology of short-circuit current increases since many depressor substances have receptors in common with enterocytes and enteric nerves. The proposed alternative view of the origin of short-circuit current increases assumes that these do not represent chloride secretion from the enterocytes. This view may therefore aid the successful development of anti-diarrhoeal drugs to overcome a major cause of infant mortality worldwide, if short-circuit current data are being persistently misinterpreted. The putative but testable link between interstitial volume or pressure and fluid absorption also provides support for the alternative view of secretion; namely, that enhanced capillary and epithelial cell tight junctional permeability together with increased intracapillary pressure may cause secretion and not chloride exit from the enterocytes. Copyright © 2013. Published by Elsevier Ltd.

Effect of apical hyperosmotic sodium challenge and amiloride on sodium transport in human bronchial epithelial cells from cystic fibrosis donors.

PubMed

Rasgado-Flores, Hector; Krishna Mandava, Vamsi; Siman, Homayoun; Van Driessche, Willy; Pilewski, Joseph M; Randell, Scott H; Bridges, Robert J

2013-12-01

Hypertonic saline (HS) inhalation therapy benefits cystic fibrosis (CF) patients [Donaldson SH, Bennet WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. N Engl J Med 354: 241-250, 2006; Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; the National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. N Engl J Med 354: 229-240, 2006]. Surprisingly, these benefits are long-lasting and are diminished by the epithelial Na(+) channel blocker amiloride (Donaldson SH, Bennet WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. N Engl J Med 354: 241-250, 2006). Our aim was to explain these effects. Human bronchial epithelial (hBE) cells from CF lungs were grown in inserts and were used in three experimental approaches: 1) Ussing chambers to measure amiloride-sensitive short-circuit currents (INa); 2) continuous perfusion Ussing chambers; and 3) near "thin-film" conditions in which the airway surface of the inserts was exposed to a small volume (30 μl) of isosmotic or HS solution as the inserts were kept in their incubation tray and were subsequently used to measure INa under isosmotic conditions (near thin-film experiments; Tarran R, Boucher RC. Methods Mol Med 70: 479-492, 2002). HS solutions (660 mosmol/kgH2O) were prepared by adding additional NaCl to the isosmotic buffer. The transepithelial short-circuit current (ISC), conductance (GT), and capacitance (CT) were measured by transepithelial impedance analysis (Danahay H, Atherton HC, Jackson AD, Kreindler JL, Poll CT, Bridges RJ. Am J Physiol Lung Cell Mol Physiol 290: L558-L569, 2006; Singh AK, Singh S, Devor DC, Frizzell RA, van Driessche W, Bridges RJ. Methods Mol Med 70: 129-142, 2002). Exposure to apical HS inhibited INa, GT, and CT. The INa inhibition required 60 min of reexposure to the isosmotic solution to recover 75%. The time of exposure to HS required to inhibit INa was <2.5 min. Under near thin-film conditions, apical exposure to HS inhibited INa, but as osmotically driven water moved to the apical surface, the aqueous apical volume increased, leading to an amiloride-insensitive decrease in its osmolality and to recovery of INa that lagged behind the osmotic recovery. Amiloride significantly accelerated the recovery of INa following exposure to HS. Our conclusions are that exposure to HS inhibits hBE INa and that amiloride diminishes this effect.

46 CFR 111.52-3 - Systems below 1500 kilowatts.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-GENERAL REQUIREMENTS Calculation of Short-Circuit Currents § 111.52-3 Systems below 1500 kilowatts. The following short-circuit assumptions must be made for a system with an aggregate generating capacity below... maximum short-circuit current of a direct current system must be assumed to be 10 times the aggregate...

30 CFR 75.825 - Power centers.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., and be designed and installed as follows: (1) Rated for the maximum phase-to-phase voltage of the circuit; (2) Rated for the full-load current of the circuit that is supplied power through the device. (3... current of the circuit or causes the current to be interrupted automatically before the disconnecting...

A device for testing cables

NASA Technical Reports Server (NTRS)

Hayhurst, Arthur Ray (Inventor)

1993-01-01

A device for testing current paths is attachable to a conductor. The device automatically checks the current paths of the conductor for continuity of a center conductor, continuity of a shield, and a short circuit between the shield and the center conductor. The device includes a pair of connectors and a circuit to provide for testing of the conductive paths of a cable to be tested with the circuit paths of the circuit. The circuit paths in the circuit include indicators to simultaneously indicate the results of the testing.

A complete dc characterization of a constant-frequency, clamped-mode, series-resonant converter

NASA Technical Reports Server (NTRS)

Tsai, Fu-Sheng; Lee, Fred C.

1988-01-01

The dc behavior of a clamped-mode series-resonant converter is characterized systematically. Given a circuit operating condition, the converter's mode of operation is determined and various circuit parameters are calculated, such as average inductor current (load current), rms inductor current, peak capacitor voltage, rms switch currents, average diode currents, switch turn-on currents, and switch turn-off currents. Regions of operation are defined, and various circuit characteristics are derived to facilitate the converter design.

Protective Socket For Integrated Circuits

NASA Technical Reports Server (NTRS)

Wilkinson, Chris; Henegar, Greg

1988-01-01

Socket for intergrated circuits (IC's) protects from excessive voltages and currents or from application of voltages and currents in wrong sequence during insertion or removal. Contains built-in switch that opens as IC removed, disconnecting leads from signals and power. Also protects other components on circuit board from transients produced by insertion and removal of IC. Makes unnecessary to turn off power to entire circuit board so other circuits on board continue to function.

The dc power circuits: A compilation

NASA Technical Reports Server (NTRS)

1972-01-01

A compilation of reports concerning power circuits is presented for the dissemination of aerospace information to the general public as part of the NASA Technology Utilization Program. The descriptions for the electronic circuits are grouped as follows: dc power supplies, power converters, current-voltage power supply regulators, overload protection circuits, and dc constant current power supplies.

Module Twelve: Series AC Resistive-Reactive Circuits; Basic Electricity and Electronics Individualized Learning System.

ERIC Educational Resources Information Center

Bureau of Naval Personnel, Washington, DC.

The module covers series circuits which contain both resistive and reactive components and methods of solving these circuits for current, voltage, impedance, and phase angle. The module is divided into six lessons: voltage and impedance in AC (alternating current) series circuits, vector computations, rectangular and polar notation, variational…

Module failure isolation circuit for paralleled inverters. [preventing system failure during power conditioning for spacecraft applications

NASA Technical Reports Server (NTRS)

Nagano, S. (Inventor)

1979-01-01

A module failure isolation circuit is described which senses and averages the collector current of each paralled inverter power transistor and compares the collector current of each power transistor the average collector current of all power transistors to determine when the sensed collector current of a power transistor in any one inverter falls below a predetermined ratio of the average collector current. The module associated with any transistor that fails to maintain a current level above the predetermined radio of the average collector current is then shut off. A separate circuit detects when there is no load, or a light load, to inhibit operation of the isolation circuit during no load or light load conditions.

46 CFR 28.860 - Overcurrent protection and switched circuits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... current carrying conductor must be protected in accordance with its current carrying capacity by a circuit breaker or fuse at the connection to the switchboard or distribution panel bus. (d) Each circuit breaker...

46 CFR 28.860 - Overcurrent protection and switched circuits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... current carrying conductor must be protected in accordance with its current carrying capacity by a circuit breaker or fuse at the connection to the switchboard or distribution panel bus. (d) Each circuit breaker...

30 CFR 77.900-2 - Testing, examination, and maintenance of circuit breakers; record.

Code of Federal Regulations, 2011 CFR

2011-07-01

... protecting low- and medium-voltage circuits serving three-phase alternating current equipment and such record... AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits...

30 CFR 77.900-1 - Testing, examination, and maintenance of circuit breakers; procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... protecting low- and medium-voltage circuits serving portable or mobile three-phase alternating current... AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits...

30 CFR 77.900-2 - Testing, examination, and maintenance of circuit breakers; record.

Code of Federal Regulations, 2010 CFR

2010-07-01

... protecting low- and medium-voltage circuits serving three-phase alternating current equipment and such record... AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits...

30 CFR 77.900-1 - Testing, examination, and maintenance of circuit breakers; procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... protecting low- and medium-voltage circuits serving portable or mobile three-phase alternating current... AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits...

The effects of amiloride and age on oxygen consumption coupled to electrogenic sodium transport in the human sigmoid colon.

PubMed

Carra, Graciela E; Matus, Daniel; Ibáñez, Jorge E; Saraví, Fernando D

2015-01-01

Aerobic metabolism is necessary for ion transport in many transporting epithelia, including the human colonic epithelium. We assessed the effects of the epithelial sodium channel blocker, amiloride, on oxygen consumption and short-circuit current of the human sigmoid epithelium to determine whether these effects were influenced by the age of the subject. Segments of the sigmoid colon were obtained from the safety margin of resections performed in patients of 62-77 years of age. Isolated mucosa preparations were obtained and mounted in airtight Ussing chambers, fit for simultaneous measurement of short-circuit current and oxygen concentration, before and after blocking epithelial sodium channels with amiloride (0.1 mmol/L). Regression analyses were performed to assess the associations between short-circuit current, oxygen consumption, and age of the subject as well as to define the relationship between the decreases in short-circuit current and oxygen consumption after blockade. Epithelial sodium channel blockade caused an 80% reduction in short-circuit current and a 26% reduction in oxygen consumption. Regression analysis indicated that both changes were significantly related (r = 0.884;P = 0.0007). Oxygen consumption decreased by 1 m mol/h/cm2 for each 25 m A/cm2 decrease in short-circuit current. Neither short-circuit current nor oxygen consumption had any significant relationship with the age of the subjects. The decrease in epithelial oxygen consumption caused by amiloride is proportional to the decrease in short-circuit current and independent of the age of the subject.

A laser flash photolysis and quantum chemical study of the fluorinated derivatives of singlet phenylnitrene.

PubMed

Gritsan, N P; Gudmundsdóttir, A D; Tigelaar, D; Zhu, Z; Karney, W L; Hadad, C M; Platz, M S

2001-03-07

Laser flash photolysis (LFP, Nd:YAG laser, 35 ps, 266 nm, 10 mJ or KrF excimer laser, 10 ns, 249 nm, 50 mJ) of 2-fluoro, 4-fluoro, 3,5-difluoro, 2,6-difluoro, and 2,3,4,5,6-pentafluorophenyl azides produces the corresponding singlet nitrenes. The singlet nitrenes were detected by transient absorption spectroscopy, and their spectra are characterized by sharp absorption bands with maxima in the range of 300-365 nm. The kinetics of their decay were analyzed as a function of temperature to yield observed decay rate constants, k(OBS). The observed rate constant in inert solvents is the sum of k(R) + k(ISC) where k(R) is the absolute rate constant of rearrangement of singlet nitrene to an azirine and k(ISC) is the absolute rate constant of nitrene intersystem crossing (ISC). Values of k(R) and k(ISC) were deduced after assuming that k(ISC) is independent of temperature. Barriers to cyclization of 4-fluoro-, 3,5-difluoro-, 2-fluoro-, 2,6-difluoro-, and 2,3,4,5,6-pentafluorophenylnitrene in inert solvents are 5.3 +/- 0.3, 5.5 +/- 0.3, 6.7 +/- 0.3, 8.0 +/- 1.5, and 8.8 +/- 0.4 kcal/mol, respectively. The barrier to cyclization of parent singlet phenylnitrene is 5.6 +/- 0.3 kcal/mol. All of these values are in good quantitative agreement with CASPT2 calculations of the relative barrier heights for the conversion of fluoro-substituted singlet aryl nitrenes to benzazirines (Karney, W. L. and Borden, W. T. J. Am. Chem. Soc. 1997, 119, 3347). A single ortho-fluorine substituent exerts a small but significant bystander effect on remote cyclization that is not steric in origin. The influence of two ortho-fluorine substituents on the cyclization is pronounced. In the case of the singlet 2-fluorophenylnitrene system, evidence is presented that the benzazirine is an intermediate and that the corresponding singlet nitrene and benzazirine interconvert. Ab initio calculations at different levels of theory on a series of benzazirines, their isomeric ketenimines, and the transition states converting the benzazirines to ketenimines were performed. The computational results are in good qualitative and quantitative agreement with the experimental findings.

A High-Resolution View of Global Seismicity

NASA Astrophysics Data System (ADS)

Waldhauser, F.; Schaff, D. P.

2014-12-01

We present high-precision earthquake relocation results from our global-scale re-analysis of the combined seismic archives of parametric data for the years 1964 to present from the International Seismological Centre (ISC), the USGS's Earthquake Data Report (EDR), and selected waveform data from IRIS. We employed iterative, multistep relocation procedures that initially correct for large location errors present in standard global earthquake catalogs, followed by a simultaneous inversion of delay times formed from regional and teleseismic arrival times of first and later arriving phases. An efficient multi-scale double-difference (DD) algorithm is used to solve for relative event locations to the precision of a few km or less, while incorporating information on absolute hypocenter locations from catalogs such as EHB and GEM. We run the computations on both a 40-core cluster geared towards HTC problems (data processing) and a 500-core HPC cluster for data inversion. Currently, we are incorporating waveform correlation delay time measurements available for events in selected regions, but are continuously building up a comprehensive, global correlation database for densely distributed events recorded at stations with a long history of high-quality waveforms. The current global DD catalog includes nearly one million earthquakes, equivalent to approximately 70% of the number of events in the ISC/EDR catalogs initially selected for relocation. The relocations sharpen the view of seismicity in most active regions around the world, in particular along subduction zones where event density is high, but also along mid-ocean ridges where existing hypocenters are especially poorly located. The new data offers the opportunity to investigate earthquake processes and fault structures along entire plate boundaries at the ~km scale, and provides a common framework that facilitates analysis and comparisons of findings across different plate boundary systems.

Pupils' Representations of Electric Current before, during and after Instruction on DC Circuits.

ERIC Educational Resources Information Center

Psillos, D.; And Others

1987-01-01

Reported are compulsory education pupils' representations of electric current in a constructivist approach to introducing direct current (DC) circuits. Suggests that the pupils views can be modelled after an energy framework. Makes suggestions about the content, the apparatus and the experiments used in teaching DC circuits. (CW)

Direct current ballast circuit for metal halide lamp

NASA Technical Reports Server (NTRS)

Lutus, P. (Inventor)

1981-01-01

A direct current ballast circuit for a two electrode metal halide lamp is described. Said direct current ballast circuit includes a low voltage DC input and a high frequency power amplifier and power transformer for developing a high voltage output. The output voltage is rectified by diodes and filtered by inductor and capacitor to provide a regulated DC output through commutating diodes to one terminal of the lamp at the output terminal. A feedback path from the output of the filter capacitor through the bias resistor to power the high frequency circuit which includes the power amplifier and the power transformer for sustaining circuit operations during low voltage transients on the input DC supply is described. A current sensor connected to the output of the lamp through terminal for stabilizing lamp current following breakdown of the lamp is described.

Clime: analyzing and producing climate data in GIS environment

NASA Astrophysics Data System (ADS)

Cattaneo, Luigi; Rillo, Valeria; Mercogliano, Paola

2014-05-01

In the last years, Impacts on Soil and Coasts Division (ISC) of CMCC (Euro-Mediterranean Center on Climate Change) had several collaboration experiences with impact communities, including IS-ENES (FP7-INF) and SafeLand (FP7-ENV) projects, which involved a study of landslide risk in Europe, and is currently active in GEMINA (FIRB) and ORIENTGATE (SEE Transnational Cooperation Programme) research projects. As a result, it has brought research activities about different impact of climate changes as flood and landslide hazards, based on climate simulation obtained from the high resolution regional climate models COSMO CLM, developed at CMCC as member of the consortium CLM Assembly. ISC-Capua also collaborates with local institutions interested in atmospherical climate change and also of their impacts on the soil, such as river basin authorities in the Campania region, ARPA Emilia Romagna and ARPA Calabria. Impact models (e.g. hydraulic or stability models) are usually developed in a GIS environment, since they need an accurate territory description, so Clime has been designed to bridge the usually existing gap between climate data - both observed and simulated - gathered from different sources, and impact communities. The main goal of Clime, special purpose Geographic Information System (GIS) software integrated in ESRI ArcGIS Desktop 10, is to easily evaluate multiple climate features and study climate changes over specific geographical domains with their related effects on environment, including impacts on soil. Developed as an add-in tool, this software has been conceived for research activities of ISC Division in order to provide a substantial contribution during post-processing and validation phase. Therefore, it is possible to analyze and compare multiple datasets (observations, climate simulations, etc.) through processes involving statistical functions, percentiles, trends test and evaluation of extreme events with a flexible system of temporal and spatial filtering, and to represent results as maps, temporal and statistic plots (time series, seasonal cycles, PDFs, scatter plots, Taylor diagrams) or Excel tables; in addition, it features bias correction techniques for climate model results. Summarizing, Clime is able to provide users a simple and fast way to retrieve analysis over simulated climate data and observations within any geographical site of interest (provinces, regions, countries, etc.).

A Current-Mode Common-Mode Feedback Circuit (CMFB) with Rail-to-Rail Operation

NASA Astrophysics Data System (ADS)

Suadet, Apirak; Kasemsuwan, Varakorn

2011-03-01

This paper presents a current-mode common-mode feedback (CMFB) circuit with rail-to-rail operation. The CMFB is a stand-alone circuit, which can be connected to any low voltage transconductor without changing or upsetting the existing circuit. The proposed CMFB employs current mirrors, operating as common-mode detector and current amplifier to enhance the loop gain of the CMFB. The circuit employs positive feedback to enhance the output impedance and gain. The circuit has been designed using a 0.18 μm CMOS technology under 1V supply and analyzed using HSPICE with BSIM3V3 device models. A pseudo-differential amplifier using two common sources and the proposed CMFB shows rail to rail output swing (± 0.7 V) with low common-mode gain (-36 dB) and power dissipation of 390 μW.

Method and apparatus for linear low-frequency feedback in monolithic low-noise charge amplifiers

DOEpatents

DeGeronimo, Gianluigi

2006-02-14

A charge amplifier includes an amplifier, feedback circuit, and cancellation circuit. The feedback circuit includes a capacitor, inverter, and current mirror. The capacitor is coupled across the signal amplifier, the inverter is coupled to the output of the signal amplifier, and the current mirror is coupled to the input of the signal amplifier. The cancellation circuit is coupled to the output of the signal amplifier. A method of charge amplification includes providing a signal amplifier; coupling a first capacitor across the signal amplifier; coupling an inverter to the output of the signal amplifier; coupling a current mirror to the input of the signal amplifier; and coupling a cancellation circuit to the output of the signal amplifier. A front-end system for use with radiation sensors includes a charge amplifier and a current amplifier, shaping amplifier, baseline stabilizer, discriminator, peak detector, timing detector, and logic circuit coupled to the charge amplifier.

L-Cysteine enhances nutrient absorption via a cystathionine-β-synthase-derived H2 S pathway in rodent jejunum.

PubMed

Xiao, Ailin; Li, Jing; Liu, Tianjian; Liu, Zhuxi; Wei, Chuanfei; Xu, Xiaomeng; Li, Qin; Li, Jingxin

2016-05-01

Hydrogen sulphide (H2 S) is generated endogenously from L-cysteine (L-Cys) by the enzymes cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). In addition, L-Cys is commonly used as a precursor in the food and pharmaceutical industries. The aim of the present study is to determine whether L-Cys regulates intestinal nutrient transport. To that end, the presence of CBS and CSE in the jejunum epithelium was assessed by immunohistochemistry, Western blotting and the methylene blue assay. In addition, in vivo L-Cys (100 mg/kg, administered immediately after the glucose load) significantly increased blood glucose levels 30 min after the oral administration of glucose to mice. This effect of L-Cys was completely blocked by amino-oxyacetic acid (AOA; 50 mg/kg; administered at the same time as L-Cys) an inhibitor of CBS. Measurements of the short-circuit current (Isc) in the rat jejunum epithelium revealed that L-Cys (1 mmol/L; 6 min before the administration of L-alanine) enhances Na(+)-coupled L-alanine or glucose transport, and that this effect is inhibited by AOA (1 mmol/L;10 min before the administration of L-Cys), but not D,L-propargylglycine (PAG;1 mmol/L; 10 min before the administration of L-Cys), a CSE inhibitor. Notably, L-Cys-evoked enhancement of nutrient transport was alleviated by glibenclamide (Gli;0.1 mmol/L; 10 min before the administration of L-Cys), a K(+) channel blocker. Together, the data indicate that L-Cys enhances jejunal nutrient transport, suggesting a new approach to future treatment of nutrition-related maladies, including a range of serious health consequences linked to undernutrition. © 2016 John Wiley & Sons Australia, Ltd.

Wet-chemical passivation of atomically flat and structured silicon substrates for solar cell application

NASA Astrophysics Data System (ADS)

Angermann, H.; Rappich, J.; Korte, L.; Sieber, I.; Conrad, E.; Schmidt, M.; Hübener, K.; Polte, J.; Hauschild, J.

2008-04-01

Special sequences of wet-chemical oxidation and etching steps were optimised with respect to the etching behaviour of differently oriented silicon to prepare very smooth silicon interfaces with excellent electronic properties on mono- and poly-crystalline substrates. Surface photovoltage (SPV) and photoluminescence (PL) measurements, atomic force microscopy (AFM) and scanning electron microscopy (SEM) investigations were utilised to develop wet-chemical smoothing procedures for atomically flat and structured surfaces, respectively. Hydrogen-termination as well as passivation by wet-chemical oxides were used to inhibit surface contamination and native oxidation during the technological processing. Compared to conventional pre-treatments, significantly lower micro-roughness and densities of surface states were achieved on mono-crystalline Si(100), on evenly distributed atomic steps, such as on vicinal Si(111), on silicon wafers with randomly distributed upside pyramids, and on poly-crystalline EFG ( Edge-defined Film-fed- Growth) silicon substrates. The recombination loss at a-Si:H/c-Si interfaces prepared on c-Si substrates with randomly distributed upside pyramids was markedly reduced by an optimised wet-chemical smoothing procedure, as determined by PL measurements. For amorphous-crystalline hetero-junction solar cells (ZnO/a-Si:H(n)/c-Si(p)/Al) with textured c-Si substrates the smoothening procedure results in a significant increase of short circuit current Isc, fill factor and efficiency η. The scatter in the cell parameters for measurements on different cells is much narrower, as compared to conventional pre-treatments, indicating more well-defined and reproducible surface conditions prior to a-Si:H emitter deposition and/or a higher stability of the c-Si surface against variations in the a-Si:H deposition conditions.

Cholinergic regulation of epithelial ion transport in the mammalian intestine

PubMed Central

Hirota, C L; McKay, D M

2006-01-01

Acetylcholine (ACh) is critical in controlling epithelial ion transport and hence water movements for gut hydration. Here we review the mechanism of cholinergic control of epithelial ion transport across the mammalian intestine. The cholinergic nervous system affects basal ion flux and can evoke increased active ion transport events. Most studies rely on measuring increases in short-circuit current (ISC = active ion transport) evoked by adding ACh or cholinomimetics to intestinal tissue mounted in Ussing chambers. Despite subtle species and gut regional differences, most data indicate that, under normal circumstances, the effect of ACh on intestinal ion transport is mainly an increase in Cl- secretion due to interaction with epithelial M3 muscarinic ACh receptors (mAChRs) and, to a lesser extent, neuronal M1 mAChRs; however, AChR pharmacology has been plagued by a lack of good receptor subtype-selective compounds. Mice lacking M3 mAChRs display intact cholinergically-mediated intestinal ion transport, suggesting a possible compensatory mechanism. Inflamed tissues often display perturbations in the enteric cholinergic system and reduced intestinal ion transport responses to cholinomimetics. The mechanism(s) underlying this hyporesponsiveness are not fully defined. Inflammation-evoked loss of mAChR-mediated control of epithelial ion transport in the mouse reveals a role for neuronal nicotinic AChRs, representing a hitherto unappreciated braking system to limit ACh-evoked Cl- secretion. We suggest that: i) pharmacological analyses should be supported by the use of more selective compounds and supplemented with molecular biology techniques targeting specific ACh receptors and signalling molecules, and ii) assessment of ion transport in normal tissue must be complemented with investigations of tissues from patients or animals with intestinal disease to reveal control mechanisms that may go undetected by focusing on healthy tissue only. PMID:16981004

Epithelial cell specific properties and genetic complementation in a delta F508 cystic fibrosis nasal polyp cell line.

PubMed

Kunzelmann, K; Lei, D C; Eng, K; Escobar, L C; Koslowsky, T; Gruenert, D C

1995-09-01

Analysis of vectorial ion transport and protein trafficking in transformed cystic fibrosis (CF) epithelial cells has been limited because the cells tend to lose their tight junctions with multiple subcultures. To elucidate ion transport and protein trafficking in CF epithelial cells, a polar cell line with apical and basolateral compartments will facilitate analysis of the efficacy of different gene therapy strategies in a "tight epithelium" in vitro. This study investigates the genotypic and phenotypic properties of a CF nasal polyp epithelial, delta F508 homozygote, cell line that has tight junctions pre-crisis. The cells (sigma CFNPE14o-) were transformed with an origin-of-replication defective SV40 plasmid. They develop transepithelial resistance in Ussing chambers and are defective in cAMP-dependent Cl- transport as measured by efflux of radioactive Cl-, short circuit current (Isc), or whole-cell patch clamp. Stimulation of the cells by bradykinin, histamine, or ATP seems to activate both K(+)- and Ca(+2)-dependent Cl- transport. Measurement of 36Cl- efflux following stimulation with A23187 and ionomycin indicate a Ca(+2)-dependent Cl- transport. Volume regulatory capacity of the cells is indicated by cell swelling conductance. Expression of the CF transmembrane conductance regulator mRNA was indicated by RT-PCR amplification. When cells are grown at 26 degrees C for 48 h there is no indication of cAMP-dependent Cl- as has been previously indicated in heterologous expression systems. Antibodies specific for secretory cell antigens indicate the presence of antigens found in goblet, serous, and mucous cells; in goblet and serous cells; or in goblet and mucous cells; but not antigens found exclusively in mucous or serous cells.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of the rectum in osmoregulation and the potential effect of renoguanylin on SLC26a6 transport activity in the Gulf toadfish (Opsanus beta)

PubMed Central

Takei, Yoshio; Grosell, Martin

2016-01-01

Teleosts living in seawater continually absorb water across the intestine to compensate for branchial water loss to the environment. The present study reveals that the Gulf toadfish (Opsanus beta) rectum plays a comparable role to the posterior intestine in ion and water absorption. However, the posterior intestine appears to rely more on SLC26a6 (a HCO3−/Cl− antiporter) and the rectum appears to rely on NKCC2 (SLC12a1) for the purposes of solute-coupled water absorption. The present study also demonstrates that the rectum responds to renoguanylin (RGN), a member of the guanylin family of peptides that alters the normal osmoregulatory processes of the distal intestine, by inhibited water absorption. RGN decreases rectal water absorption more greatly than in the posterior intestine and leads to net Na+ and Cl− secretion, and a reversal of the absorptive short-circuit current (ISC). It is hypothesized that maintaining a larger fluid volume within the distal segments of intestinal tract facilitates the removal of CaCO3 precipitates and other solids from the intestine. Indeed, the expression of the components of the Cl−-secretory response, apical CFTR, and basolateral NKCC1 (SLC12a2), are upregulated in the rectum of the Gulf toadfish after 96 h in 60 ppt, an exposure that increases CaCO3 precipitate formation relative to 35 ppt. Moreover, the downstream intracellular effects of RGN appear to directly inhibit ion absorption by NKCC2 and anion exchange by SLC26a6. Overall, the present findings elucidate key electrophysiological differences between the posterior intestine and rectum of Gulf toadfish and the potent regulatory role renoguanylin plays in osmoregulation. PMID:27030664

c-Kit mutation reduce intestinal epithelial cell proliferation and migration, but not influence intestinal permeability stimulated by lipopolysaccharide.

PubMed

Xue, Hong; Wang, Feng Yun; Kang, Qian; Tang, Xu Dong

2018-06-20

The proto-oncogene c-kit, as a marker of interstitial cells of Cajal (ICCs) in the gastrointestinal tract, plays an important role in the ICCs. Although limited evidences showed c-kit is present in the colonic epithelium but its roles remain unclear. In the present study, we aimed to investigate the expression, location and function of c-kit in the intestinal epithelium. Immunofluorescence, western blotting, and RT-PCR were performed to detect the expression and location of c-kit in the intestinal mucosa of WT mice. We investigated intestinal epithelial proliferation and migration in vivo by performing 5-Bromodeoxyuridine (BrdU) incorporation and Ki-67 staining in WT and Wads m/m mice. An Ussing chamber with fluorescein-isothiocyanate dextran 4000 was used to detect the transepithelial electric resistance (TER), short circuit current (ISC) and permeability across ex vivo colon segments under control and endotoxaemia conditions. We demonstrated that c-kit was located and expressed in the gut crypt compartment in WT mice, which was demonstrated in the c-kit mutant mice (Wads m/m ). In addition, both the number of proliferating cells and the percentage of the distance migrated were lower in the Wads m/m mice than those in the WT mice. Moreover, the intestinal permeability, TER and tight junction were unaltered in the Wads m/m mice under endotoxic conditions compared with those in both the control condition and the WT mice. Altogether, these observations imply that the expression of c-kit in the colonic epithelium is involved in the proliferation and permeability of the colonic epithelium. Copyright © 2018. Published by Elsevier GmbH.

Multijunction high voltage concentrator solar cells

NASA Technical Reports Server (NTRS)

Valco, G. J.; Kapoor, V. J.; Evans, J. C.; Chai, A.-T.

1981-01-01

The standard integrated circuit technology has been developed to design and fabricate new innovative planar multi-junction solar cell chips for concentrated sunlight applications. This 1 cm x 1 cm cell consisted of several voltage generating regions called unit cells which were internally connected in series within a single chip resulting in high open circuit voltages. Typical open-circuit voltages of 3.6 V and short-circuit currents of 90 ma were obtained at 80 AM1 suns. A dramatic increase in both short circuit current and open circuit voltage with increased light levels was observed.

The excited-state structure, vibrations, lifetimes, and nonradiative dynamics of jet-cooled 1-methylcytosine.

PubMed

Trachsel, Maria A; Wiedmer, Timo; Blaser, Susan; Frey, Hans-Martin; Li, Quansong; Ruiz-Barragan, Sergi; Blancafort, Lluís; Leutwyler, Samuel

2016-10-07

We have investigated the S 0 → S 1 UV vibronic spectrum and time-resolved S 1 state dynamics of jet-cooled amino-keto 1-methylcytosine (1MCyt) using two-color resonant two-photon ionization, UV/UV holeburning and depletion spectroscopies, as well as nanosecond and picosecond time-resolved pump/delayed ionization measurements. The experimental study is complemented with spin-component-scaled second-order coupled-cluster and multistate complete active space second order perturbation ab initio calculations. Above the weak electronic origin of 1MCyt at 31 852 cm -1 about 20 intense vibronic bands are observed. These are interpreted as methyl group torsional transitions coupled to out-of-plane ring vibrations, in agreement with the methyl group rotation and out-of-plane distortions upon 1 ππ ∗ excitation predicted by the calculations. The methyl torsion and ν 1 ' (butterfly) vibrations are strongly coupled, in the S 1 state. The S 0 → S 1 vibronic spectrum breaks off at a vibrational excess energy E exc ∼ 500 cm -1 , indicating that a barrier in front of the ethylene-type S 1 ⇝S 0 conical intersection is exceeded, which is calculated to lie at E exc = 366 cm -1 . The S 1 ⇝S 0 internal conversion rate constant increases from k IC = 2 ⋅ 10 9 s -1 near the S 1 (v = 0) level to 1 ⋅ 10 11 s -1 at E exc = 516 cm -1 . The 1 ππ ∗ state of 1MCyt also relaxes into the lower-lying triplet T 1 ( 3 ππ ∗ ) state by intersystem crossing (ISC); the calculated spin-orbit coupling (SOC) value is 2.4 cm -1 . The ISC rate constant is 10-100 times lower than k IC ; it increases from k ISC = 2 ⋅ 10 8 s -1 near S 1 (v = 0) to k ISC = 2 ⋅ 10 9 s -1 at E exc = 516 cm -1 . The T 1 state energy is determined from the onset of the time-delayed photoionization efficiency curve as 25 600 ± 500 cm -1 . The T 2 ( 3 nπ ∗ ) state lies >1500 cm -1 above S 1 (v = 0), so S 1 ⇝T 2 ISC cannot occur, despite the large SOC parameter of 10.6 cm -1 . An upper limit to the adiabatic ionization energy of 1MCyt is determined as 8.41 ± 0.02 eV. Compared to cytosine, methyl substitution at N1 lowers the adiabatic ionization energy by ≥0.32 eV and leads to a much higher density of vibronic bands in the S 0 → S 1 spectrum. The effect of methylation on the radiationless decay to S 0 and ISC to T 1 is small, as shown by the similar break-off of the spectrum and the similar computed mechanisms.

The excited-state structure, vibrations, lifetimes, and nonradiative dynamics of jet-cooled 1-methylcytosine

NASA Astrophysics Data System (ADS)

Trachsel, Maria A.; Wiedmer, Timo; Blaser, Susan; Frey, Hans-Martin; Li, Quansong; Ruiz-Barragan, Sergi; Blancafort, Lluís; Leutwyler, Samuel

2016-10-01

We have investigated the S0 → S1 UV vibronic spectrum and time-resolved S1 state dynamics of jet-cooled amino-keto 1-methylcytosine (1MCyt) using two-color resonant two-photon ionization, UV/UV holeburning and depletion spectroscopies, as well as nanosecond and picosecond time-resolved pump/delayed ionization measurements. The experimental study is complemented with spin-component-scaled second-order coupled-cluster and multistate complete active space second order perturbation ab initio calculations. Above the weak electronic origin of 1MCyt at 31 852 cm-1 about 20 intense vibronic bands are observed. These are interpreted as methyl group torsional transitions coupled to out-of-plane ring vibrations, in agreement with the methyl group rotation and out-of-plane distortions upon 1ππ∗ excitation predicted by the calculations. The methyl torsion and ν1 ' (butterfly) vibrations are strongly coupled, in the S1 state. The S0 → S1 vibronic spectrum breaks off at a vibrational excess energy Eexc ˜ 500 cm-1, indicating that a barrier in front of the ethylene-type S1⇝S0 conical intersection is exceeded, which is calculated to lie at Eexc = 366 cm-1. The S1⇝S0 internal conversion rate constant increases from kIC = 2 ṡ 109 s-1 near the S1(v = 0) level to 1 ṡ 1011 s-1 at Eexc = 516 cm-1. The 1ππ∗ state of 1MCyt also relaxes into the lower-lying triplet T1 (3ππ∗) state by intersystem crossing (ISC); the calculated spin-orbit coupling (SOC) value is 2.4 cm-1. The ISC rate constant is 10-100 times lower than kIC; it increases from kISC = 2 ṡ 108 s-1 near S1(v = 0) to kISC = 2 ṡ 109 s-1 at Eexc = 516 cm-1. The T1 state energy is determined from the onset of the time-delayed photoionization efficiency curve as 25 600 ± 500 cm-1. The T2 (3nπ∗) state lies >1500 cm-1 above S1(v = 0), so S1⇝T2 ISC cannot occur, despite the large SOC parameter of 10.6 cm-1. An upper limit to the adiabatic ionization energy of 1MCyt is determined as 8.41 ± 0.02 eV. Compared to cytosine, methyl substitution at N1 lowers the adiabatic ionization energy by ≥0.32 eV and leads to a much higher density of vibronic bands in the S0 → S1 spectrum. The effect of methylation on the radiationless decay to S0 and ISC to T1 is small, as shown by the similar break-off of the spectrum and the similar computed mechanisms.

30 CFR 75.900-4 - Testing, examination, and maintenance of circuit breakers; record.

Code of Federal Regulations, 2011 CFR

2011-07-01

... circuits serving three-phase alternating current equipment used in the mine. Such record shall be kept in a... Underground Low- and Medium-Voltage Alternating Current Circuits § 75.900-4 Testing, examination, and...

30 CFR 75.900-4 - Testing, examination, and maintenance of circuit breakers; record.

Code of Federal Regulations, 2010 CFR

2010-07-01

... circuits serving three-phase alternating current equipment used in the mine. Such record shall be kept in a... Underground Low- and Medium-Voltage Alternating Current Circuits § 75.900-4 Testing, examination, and...

46 CFR 111.30-17 - Protection of instrument circuits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... circuit of a current transformer must not be fused, and the circuit from a current transformer to a device that is not in the switchboard must have a high voltage protector to short the transformer during an...

46 CFR 111.30-17 - Protection of instrument circuits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... circuit of a current transformer must not be fused, and the circuit from a current transformer to a device that is not in the switchboard must have a high voltage protector to short the transformer during an...

46 CFR 111.30-17 - Protection of instrument circuits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... circuit of a current transformer must not be fused, and the circuit from a current transformer to a device that is not in the switchboard must have a high voltage protector to short the transformer during an...

46 CFR 111.30-17 - Protection of instrument circuits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... circuit of a current transformer must not be fused, and the circuit from a current transformer to a device that is not in the switchboard must have a high voltage protector to short the transformer during an...

46 CFR 111.30-17 - Protection of instrument circuits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... circuit of a current transformer must not be fused, and the circuit from a current transformer to a device that is not in the switchboard must have a high voltage protector to short the transformer during an...

Automatic method of measuring silicon-controlled-rectifier holding current

NASA Technical Reports Server (NTRS)

Maslowski, E. A.

1972-01-01

Development of automated silicon controlled rectifier circuit for measuring minimum anode current required to maintain rectifiers in conducting state is discussed. Components of circuit are described and principles of operation are explained. Illustration of circuit is provided.

Active shunt capacitance cancelling oscillator circuit

DOEpatents

Wessendorf, Kurt O.

2003-09-23

An oscillator circuit is disclosed which can be used to produce oscillation using a piezoelectric crystal, with a frequency of oscillation being largely independent of any shunt capacitance associated with the crystal (i.e. due to electrodes on the surfaces of the crystal and due to packaging and wiring for the crystal). The oscillator circuit is based on a tuned gain stage which operates the crystal at a frequency, f, near a series resonance frequency, f.sub.S. The oscillator circuit further includes a compensation circuit that supplies all the ac current flow through the shunt resistance associated with the crystal so that this ac current need not be supplied by the tuned gain stage. The compensation circuit uses a current mirror to provide the ac current flow based on the current flow through a reference capacitor that is equivalent to the shunt capacitance associated with the crystal. The oscillator circuit has applications for driving piezoelectric crystals for sensing of viscous, fluid or solid media by detecting a change in the frequency of oscillation of the crystal and a resonator loss which occur from contact of an exposed surface of the crystal by the viscous, fluid or solid media.

Module Five: Relationships of Current, Voltage, and Resistance; Basic Electricity and Electronics Individualized Learning System.

ERIC Educational Resources Information Center

Bureau of Naval Personnel, Washington, DC.

This module covers the relationships between current and voltage; resistance in a series circuit; how to determine the values of current, voltage, resistance, and power in resistive series circuits; the effects of source internal resistance; and an introduction to the troubleshooting of series circuits. This module is divided into five lessons:…

Method and apparatus for current-output peak detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Geronimo, Gianluigi

2017-01-24

A method and apparatus for a current-output peak detector. A current-output peak detector circuit is disclosed and works in two phases. The peak detector circuit includes switches to switch the peak detector circuit from the first phase to the second phase upon detection of the peak voltage of an input voltage signal. The peak detector generates a current output with a high degree of accuracy in the second phase.

Fault tolerant system based on IDDQ testing

NASA Astrophysics Data System (ADS)

Guibane, Badi; Hamdi, Belgacem; Mtibaa, Abdellatif; Bensalem, Brahim

2018-06-01

Offline test is essential to ensure good manufacturing quality. However, for permanent or transient faults that occur during the use of the integrated circuit in an application, an online integrated test is needed as well. This procedure should ensure the detection and possibly the correction or the masking of these faults. This requirement of self-correction is sometimes necessary, especially in critical applications that require high security such as automotive, space or biomedical applications. We propose a fault-tolerant design for analogue and mixed-signal design complementary metal oxide (CMOS) circuits based on the quiescent current supply (IDDQ) testing. A defect can cause an increase in current consumption. IDDQ testing technique is based on the measurement of power supply current to distinguish between functional and failed circuits. The technique has been an effective testing method for detecting physical defects such as gate-oxide shorts, floating gates (open) and bridging defects in CMOS integrated circuits. An architecture called BICS (Built In Current Sensor) is used for monitoring the supply current (IDDQ) of the connected integrated circuit. If the measured current is not within the normal range, a defect is signalled and the system switches connection from the defective to a functional integrated circuit. The fault-tolerant technique is composed essentially by a double mirror built-in current sensor, allowing the detection of abnormal current consumption and blocks allowing the connection to redundant circuits, if a defect occurs. Spices simulations are performed to valid the proposed design.

Device for testing continuity and/or short circuits in a cable

NASA Technical Reports Server (NTRS)

Hayhurst, Arthur R. (Inventor)

1995-01-01

A device for testing current paths is attachable to a conductor. The device automatically checks the current paths of the conductor for continuity of a center conductor, continuity of a shield and a short circuit between the shield and the center conductor. The device includes a pair of connectors and a circuit to provide for testing of the conductive paths of the cable. The pair of connectors electrically connects the conductive paths of a cable to be tested with the circuit paths of the circuit. The circuit paths in the circuit include indicators to simultaneously indicate the results of the testing.

Maximizing the short circuit current of organic solar cells by partial decoupling of electrical and optical properties

NASA Astrophysics Data System (ADS)

Qarony, Wayesh; Hossain, Mohammad I.; Jovanov, Vladislav; Knipp, Dietmar; Tsang, Yuen Hong

2018-03-01

The partial decoupling of electronic and optical properties of organic solar cells allows for realizing solar cells with increased short circuit current and energy conversion efficiency. The proposed device consists of an organic solar cell conformally prepared on the surface of an array of single and double textured pyramids. The device geometry allows for increasing the optical thickness of the organic solar cell, while the electrical thickness is equal to the nominal thickness of the solar cell. By increasing the optical thickness of the solar cell, the short circuit current is distinctly increased. The quantum efficiency and short circuit current are determined using finite-difference time-domain simulations of the 3D solar cell structure. The influence of different solar cell designs on the quantum efficiency and short circuit current is discussed and optimal device dimensions are proposed.