p-Aminohippurate transport in airways: competitive inhibition.

PubMed

Cloutier, M M; Guernsey, L

1992-05-01

p-Aminohippurate (PAH) transport in canine tracheal epithelium occurs by a HCO3- -PAH exchange process that is located on the luminal membrane and is inhibited by stilbene derivatives. The effects of increasing concentrations of other organic anions, including probenecid (10-250 microM), dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP; 10-1,000 microM), phenol red (10-250 microM), and urate (25-500 microM), and the organic cation tetraethylammonium bromide (TEA; 250 microM) on PAH transport were examined in canine tracheal epithelium mounted in Ussing chambers. Neither phenol red, urate, nor TEA had any effect on electrophysiological properties or unidirectional or net PAH fluxes. In contrast, beginning at 10 microM, both probenecid and cAMP produced significant decreases in unidirectional and net PAH absorption without change in unidirectional PAH secretion. The initial change in net PAH absorption occurred in the absence of any change in electrophysiological properties. Higher concentrations of both probenecid and cAMP produced further decreases in net PAH absorption and significant changes in electrophysiological properties. Probenecid and cAMP increased the apparent Michaelis constant for PAH absorption without affecting maximum transport rate. The inhibitory constant for probenecid was 1.01 +/- 0.06 x 10(-4) M (mean +/- SE) and for cAMP was 5.18 +/- 0.20 x 10(-4) M. We conclude that PAH transport in canine tracheal epithelium demonstrates competitive inhibition by other organic anions and substrate specificity. We also conclude that the affinity of the exchange transport system is higher for probenecid than for PAH and cAMP.

Inhibition of muscarinic receptor-induced inositol phospholipid hydrolysis by caffeine, beta-adrenoceptors and protein kinase C in intestinal smooth muscle.

PubMed Central

Prestwich, S A; Bolton, T B

1995-01-01

1. The effects of caffeine, isoprenaline, dibutyryl cyclic AMP, isobutylmethylxanthine (IBMX), 12-O-tetradecanoylphorbol-13-acetate (TPA) or 1-oleoyl-2-acetylglycerol (OAG), (protein kinase C (PKC) activators), 2-methoxy verapamil (D600), thapsigargin and ryanodine on muscarinic acetylcholine receptor (AChR)-stimulated inositol phospholipid hydrolysis were studied in smooth muscle fragments from the longitudinal layer of the small intestine of the guinea-pig. 2. Incubation of the fragments with the muscarinic agonist, carbachol (CCh) (100 microM) resulted in rapid increases in the levels of all the inositol phosphate isomers with maximal increases in the [3H]-inositol (1,4,5) trisphosphate ([3H]-Ins(1,4,5)P3) isomer occurring 10 s following incubation. 3. The beta-adrenoceptor agonist, isoprenaline (10 microM) and dibutyryl cyclic AMP (10 microM), a membrane permeant analogue of cyclic AMP both reduced the CCh stimulation, but not the basal levels of [3H]-inositol phosphates. This inhibition by dibutyryl cyclic AMP was enhanced in the presence of the phosphodiesterase inhibitor, IBMX. CCh inhibited the isoprenaline-induced increases in the levels of cyclic AMP and this was via a pertussi toxin (PTX)-sensitive G-protein mechanism. 4. TPA (1 microM) and OAG (100 microM) a 1,2-diacylglycerol (DAG) analogue both reduced the CCh-induced increases in [3H]-inositol phosphates levels but neither affected basal values nor the basal levels of cyclic AMP. 5. D600 (10 microM), which blocks voltage-dependent Ca2+ channels, also reduced the CCh-stimulated levels of [3H]-inositol phosphates suggesting that some of the agonist-induced increases are due to a potentiating effect of Ca2+ entering the cell. 6. Caffeine (0.5-30 mM) significantly inhibited both the basal and CCh-induced increases in all the [3H]-inositol phosphate isomers. Its inhibitory action was not due to increases in cyclic AMP since caffeine had no effect on the levels of cyclic AMP at concentrations up to 30 mM. 7. Incubation with thapsigargin (1 microM) and ryanodine (10 microM) had no effect on either basal or CCh-induced inositol phospholipid hydrolysis or cyclic AMP levels. 8. The results indicate a reciprocal inhibition by beta-adrenoceptors and muscarinic AChRs of their effects on cyclic AMP and inositol phosphate levels respectively. Ca2+ entering the cell (but not the action of ryanodine or thapsigargin) potentiates while caffeine inhibits muscarinic AChR-induced rises in inositol phosphate levels. Diacylglycerols may exert a negative feedback inhibition on inositol phosphate production. PMID:7537591

Cannabinoids reduce cAMP levels in the striatum of freely moving rats: an in vivo microdialysis study.

PubMed

Wade, Mark R; Tzavara, Eleni T; Nomikos, George G

2004-04-16

The cannabinoid receptor subtype 1 (CB1R) is a member of the G(i)-protein-coupled receptor family and cannabinoid signaling is largely dependent on the suppression of adenylyl cyclase-catalyzed cAMP production. In cell lines transfected with the CB1R or in native tissue preparations, treatment with cannabinoid agonists reduces both basal and forskolin-stimulated cAMP synthesis. We measured extracellular cAMP concentrations in the striatum of freely moving rats utilizing microdialysis to determine if changes in cAMP concentrations in response to CB1R agonists can be monitored in vivo. Striatal infusion of the CB1R agonist WIN55,212-2 (100 microM or 1 mM), dose-dependently decreased basal and forskolin-stimulated extracellular cAMP. These effects were reversed by co-infusion of the CB1R antagonist SR141716A (30 microM), which alone had no effect up to the highest concentration tested (300 microM). These data indicate that changes in extracellular cAMP concentrations in response to CB1R stimulation can be monitored in vivo allowing the study of cannabinoid signaling in the whole animal.

Optical transition radiation used in the diagnostic of low energy and low current electron beams in particle accelerators.

PubMed

Silva, T F; Bonini, A L; Lima, R R; Maidana, N L; Malafronte, A A; Pascholati, P R; Vanin, V R; Martins, M N

2012-09-01

Optical transition radiation (OTR) plays an important role in beam diagnostics for high energy particle accelerators. Its linear intensity with beam current is a great advantage as compared to fluorescent screens, which are subject to saturation. Moreover, the measurement of the angular distribution of the emitted radiation enables the determination of many beam parameters in a single observation point. However, few works deals with the application of OTR to monitor low energy beams. In this work we describe the design of an OTR based beam monitor used to measure the transverse beam charge distribution of the 1.9-MeV electron beam of the linac injector of the IFUSP microtron using a standard vision machine camera. The average beam current in pulsed operation mode is of the order of tens of nano-Amps. Low energy and low beam current make OTR observation difficult. To improve sensitivity, the beam incidence angle on the target was chosen to maximize the photon flux in the camera field-of-view. Measurements that assess OTR observation (linearity with beam current, polarization, and spectrum shape) are presented, as well as a typical 1.9-MeV electron beam charge distribution obtained from OTR. Some aspects of emittance measurement using this device are also discussed.

Apical ammonium inhibition of cAMP-stimulated secretion in T84 cells is bicarbonate dependent.

PubMed

Worrell, Roger T; Best, Alison; Crawford, Oscar R; Xu, Jie; Soleimani, Manoocher; Matthews, Jeffrey B

2005-10-01

Normal human colonic luminal (NH(4)(+)) concentration ([NH(4)(+)]) ranges from approximately 10 to 100 mM. However, the nature of the effects of NH(4)(+) on transport, as well as NH(4)(+) transport itself, in colonic epithelium is poorly understood. We elucidate here the effects of apical NH(4)(+) on cAMP-stimulated Cl(-) secretion in colonic T84 cells. In HEPES-buffered solutions, 10 mM apical NH(4)(+) had no significant effect on cAMP-stimulated current. In contrast, 10 mM apical NH(4)(+) reduced current within 5 min to 61 +/- 4% in the presence of 25 mM HCO(3)(-). Current inhibition was not simply due to an increase in extracellular K(+)-like cations, in that the current magnitude was 95 +/- 5% with 10 mM apical K(+) and 46 +/- 3% with 10 mM apical NH(4)(+) relative to that with 5 mM apical K(+). We previously demonstrated that inhibition of Cl(-) secretion by basolateral NH(4)(+) occurs in HCO(3)(-)-free conditions and exhibits anomalous mole fraction behavior. In contrast, apical NH(4)(+) inhibition of current in HCO(3)(-) buffer did not show anomalous mole fraction behavior and followed the absolute [NH(4)(+)] in K(+)-NH(4)(+) mixtures, where K(+) concentration + [NH(4)(+)] = 10 mM. The apical NH(4)(+) inhibitory effect was not prevented by 100 microM methazolamide, suggesting no role for apical carbonic anhydrase. However, apical NH(4)(+) inhibition of current was prevented by 10 min of pretreatment of the apical surface with 500 microM DIDS, 100 microM 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS), or 25 microM niflumic acid, suggesting a role for NH(4)(+) action through an apical anion exchanger. mRNA and protein for the apical anion exchangers SLC26A3 [downregulated in adenoma (DRA)] and SLC26A6 [putative anion transporter (PAT1)] were detected in T84 cells by RT-PCR and Northern and Western blots. DRA and PAT1 appear to associate with CFTR in the apical membrane. We conclude that the HCO(3)(-) dependence of apical NH(4)(+) inhibition of secretion is due to the action of NH(4)(+) on an apical anion exchanger.

Concept of a tunable source of coherent THz radiation driven by a plasma modulated electron beam

NASA Astrophysics Data System (ADS)

Zhang, H.; Konoplev, I. V.; Doucas, G.; Smith, J.

2018-04-01

We have carried out numerical studies which consider the modulation of a picosecond long relativistic electron beam in a plasma channel and the generation of a micro-bunched train. The subsequent propagation of the micro-bunched beam in the vacuum area was also investigated. The same numerical model was then used to simulate the radiation arising from the interaction of the micro-bunched beam with a metallic grating. The dependence of the radiation spectrum on the parameters of the micro-bunched beam has been studied and the tunability of the radiation by the variation of the micro-bunch spacing has been demonstrated. The micro-bunch spacing can be changed easily by altering the plasma density without changing the beam energy or current. Using the results of these studies, we develop a conceptual design of a tunable source of coherent terahertz (THz) radiation driven by a plasma modulated beam. Such a source would be a potential and useful alternative to conventional vacuum THz tubes and THz free-electron laser sources.

Induction of dopamine biosynthesis by l-DOPA in PC12 cells: implications of L-DOPA influx and cyclic AMP.

PubMed

Jin, Chun Mei; Yang, Yoo Jung; Huang, Hai Shan; Lim, Sung Cil; Kai, Masaaki; Lee, Myung Koo

2008-09-04

The effects of 3,4-dihydroxyphenylalanine (l-DOPA) on dopamine biosynthesis and cytotoxicity were investigated in PC12 cells. l-DOPA treatment (20-200 microM) increased the levels of dopamine by 226%-504% after 3-6 h of treatment and enhanced the activities of tyrosine hydroxylase (TH) and aromatic l-amino acid decarboxylase (AADC). l-DOPA (20-200 muM) treatment led to a 562%-937% increase in l-DOPA influx at 1 h, which inhibited the activity of TH, but not AADC, during the same period. The extracellular releases of dopamine were also increased by 231%-570% after treatment with 20 and 200 microM l-DOPA for 0.5-3 h. l-DOPA at a concentration of 100-200 microM, but not 20 microM, exerted apoptotic cytotoxicity towards PC12 cells for 24-48 h. l-DOPA (20-200 microM) increased the intracellular cyclic AMP levels by 318%-557% after 0.5-1 h in a concentration-dependent manner. However, the elevated cyclic AMP levels by l-DOPA could not protect against l-DOPA (100-200 microM)-induced cytotoxicity after 24-48 h. In addition, l-DOPA (20-200 microM)-induced increases in cyclic AMP and dopamine were significantly reduced by treatment with SCH23390 (dopamine D(1) receptor antagonist). The increased levels of dopamine by l-DOPA were also reduced by H89 (protein kinase A, PKA, inhibitor) and GF109203X (protein kinase C inhibitor); however, the reduction by GF109203X was not significant. l-DOPA at 20-200 microM stimulated the phosphorylation of PKA and cyclic AMP-response element binding protein and induced the biosynthesis of the TH protein. These results indicate that 20-200 microM l-DOPA induces dopamine biosynthesis by two pathways. One pathway involves l-DOPA directly entering the cells to convert dopamine through AADC activity (l-DOPA decarboxylation). The other pathway involves l-DOPA and/or released dopamine activating TH to enhance dopamine biosynthesis by the dopamine D(1) receptor-cyclic AMP-PKA signaling system (dopamine biosynthesis by TH).

Role of selective cyclic GMP phosphodiesterase inhibition in the myorelaxant actions of M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine.

PubMed Central

Souness, J. E.; Brazdil, R.; Diocee, B. K.; Jordan, R.

1989-01-01

1. The mechanism by which M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine (MIMAX), which have been described as selective cyclic GMP phosphodiesterase (PDE) inhibitors, relax rat aorta was investigated. 2. Three cyclic nucleotide PDEs were identified in the soluble fraction of rat aorta; a Ca2+-insensitive form exhibiting substrate selectivity for cyclic GMP (cGMP PDE), a Ca2+/calmodulin-stimulated form which also preferentially hydrolyzed cyclic GMP (Ca2+ PDE), and a form demonstrating substrate selectivity for cyclic AMP (cAMP PDE). 3. M&B 22,948 and MIMAX inhibited cGMP PDE (Ki = 0.16 microM and 0.43 microM, respectively) and Ca2+ PDE (Ki = 9.9 microM and 0.55 microM, respectively), but exhibited weak activity against cAMP PDE (Ki = 249 microM and 42 microM, respectively). MY-5445 selectivity inhibited cGMP PDE (Ki = 1.3 microM) and vinpocetine selectively inhibited Ca2+ PDE (Ki = 14 microM). 4. M&B 22,948 and MIMAX induced dose-dependent increases in the accumulation of cyclic GMP, but not cyclic AMP, in rat aorta pieces. These effects were greatly reduced by endothelial denudation and by methylene blue (5 microM) which blocks the actions of endothelium-derived relaxant factor. MY-5445 and vinpocetine had no effect on rat aorta cyclic GMP or cyclic AMP accumulation. 5. All four compounds caused dose-related relaxation of 5-hydroxytryptamine (10 microM) contracted, endothelium-intact rat aorta, the effects of M&B 22,948 and MIMAX being greatly reduced by methylene blue (5 microM). Methylene blue also caused 10 fold and 100 fold rightward shifts in the dose-response curves of MY-5445 and vinpocetine, respectively. 6. The results are consistent with the smooth muscle relaxant actions of M&B 22,948 and MIMAX, but not vinpocetine and MY-5445, being mediated through a mechanism involving inhibition of cyclic GMP hydrolysis. PMID:2480168

Micro/nanofabrication of poly({sub L}-lactic acid) using focused ion beam direct etching

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

Oyama, Tomoko Gowa; Nagasawa, Naotsugu; Taguchi, Mitsumasa

2013-10-14

Micro/nanofabrication of biocompatible and biodegradable poly({sub L}-lactic acid) (PLLA) using focused Ga ion beam direct etching was evaluated for future bio-device applications. The fabrication performance was determined with different ion fluences and fluxes (beam currents), and it was found that the etching speed and fabrication accuracy were affected by irradiation-induced heat. Focused ion beam (FIB)-irradiated surfaces were analyzed using micro-area X-ray photoelectron spectroscopy. Owing to reactions such as the physical sputtering of atoms and radiation-induced decomposition, PLLA was gradually carbonized with increasing C=C bonds. Controlled micro/nanostructures of PLLA were fabricated with C=C bond-rich surfaces expected to have good cell attachmentmore » properties.« less

Further investigation into the signal transduction mechanism of the 5-HT4-like receptor in the circular smooth muscle of human colon.

PubMed Central

McLean, P. G.; Coupar, I. M.

1996-01-01

1. The nature of the receptor coupling mechanism of the 5-hydroxytryptamine4 (5-HT4) receptor in the circular smooth muscle of the human colon has been further investigated. 2. 5-HT stimulated cyclic AMP generation and caused a relaxation in a concentration-dependent fashion, with EC50 values of 175.5 and 274.9 nM respectively. DAU 6236 increased cyclic AMP formation and caused a relaxant effect but was a partial agonist relative to 5-HT. 3. The 5-HT4 receptor antagonist, GR 113808, inhibited cyclic AMP formation and relaxation induced by 5-HT with -log Ki values of 9.1 (cyclic AMP) and 8.9 (relaxation) and apparent pA2 values of 9.2 (cyclic AMP) and 9.5 (relaxation). 4. Ondansetron and methysergide failed to inhibit cyclic AMP formation or the relaxation induced by 5-HT. 5. The phosphodiesterase inhibitor, IBMX, produced a concentration-dependent relaxation (EC50 = 30 microM) and at 1 microM it enhanced the 5-HT-induced relaxation producing a leftward shift of the 5-HT concentration-effect curve with a concentration-ratio of 4.1. Rolipram caused a concentration-dependent relaxation (EC50 = 564.8 nM) and at 200 nm caused a leftward shift of the concentration-effect curve to 5-HT with a concentration-ratio of 5.5. 6. Application of the adenylyl cyclase inhibitor, SQ 22536 (0.1 mM), and the protein kinase inhibitors, H7 (100 nM) and H89 (200 nM), inhibited the relaxant effect of 5-HT inducing a rightward shift of the concentration-effect curve with concentration-ratios of 10.1, 2.7 and 4.2 respectively. 7. Forskolin stimulated cyclic AMP production and caused a relaxation. The maximum relaxant effect of forskolin (6 microM, 13.8 +/- 1.9 cm.s) was not significantly different from the maximum relaxant effect of 5-HT (10 microM, 12.7 +/- 4.9 cm.s). However, the cyclic AMP levels stimulated by forskolin (6 microM, 49.3 +/- 6.6 pmol mg-1) were markedly greater than those stimulated by 5-HT (10 microM, 7.6 +/- 2.0 pmol mg-1). 8. In conclusion, these results indicate that the 5-HT4 receptors of the circular smooth muscle of human colon mediate relaxation and inhibition of spontaneous contractions via activation of adenylyl cyclase, formation of cyclic AMP and activation of protein kinase A. PMID:8799582

Further investigation into the signal transduction mechanism of the 5-HT4-like receptor in the circular smooth muscle of human colon.

PubMed

McLean, P G; Coupar, I M

1996-06-01

1. The nature of the receptor coupling mechanism of the 5-hydroxytryptamine4 (5-HT4) receptor in the circular smooth muscle of the human colon has been further investigated. 2. 5-HT stimulated cyclic AMP generation and caused a relaxation in a concentration-dependent fashion, with EC50 values of 175.5 and 274.9 nM respectively. DAU 6236 increased cyclic AMP formation and caused a relaxant effect but was a partial agonist relative to 5-HT. 3. The 5-HT4 receptor antagonist, GR 113808, inhibited cyclic AMP formation and relaxation induced by 5-HT with -log Ki values of 9.1 (cyclic AMP) and 8.9 (relaxation) and apparent pA2 values of 9.2 (cyclic AMP) and 9.5 (relaxation). 4. Ondansetron and methysergide failed to inhibit cyclic AMP formation or the relaxation induced by 5-HT. 5. The phosphodiesterase inhibitor, IBMX, produced a concentration-dependent relaxation (EC50 = 30 microM) and at 1 microM it enhanced the 5-HT-induced relaxation producing a leftward shift of the 5-HT concentration-effect curve with a concentration-ratio of 4.1. Rolipram caused a concentration-dependent relaxation (EC50 = 564.8 nM) and at 200 nm caused a leftward shift of the concentration-effect curve to 5-HT with a concentration-ratio of 5.5. 6. Application of the adenylyl cyclase inhibitor, SQ 22536 (0.1 mM), and the protein kinase inhibitors, H7 (100 nM) and H89 (200 nM), inhibited the relaxant effect of 5-HT inducing a rightward shift of the concentration-effect curve with concentration-ratios of 10.1, 2.7 and 4.2 respectively. 7. Forskolin stimulated cyclic AMP production and caused a relaxation. The maximum relaxant effect of forskolin (6 microM, 13.8 +/- 1.9 cm.s) was not significantly different from the maximum relaxant effect of 5-HT (10 microM, 12.7 +/- 4.9 cm.s). However, the cyclic AMP levels stimulated by forskolin (6 microM, 49.3 +/- 6.6 pmol mg-1) were markedly greater than those stimulated by 5-HT (10 microM, 7.6 +/- 2.0 pmol mg-1). 8. In conclusion, these results indicate that the 5-HT4 receptors of the circular smooth muscle of human colon mediate relaxation and inhibition of spontaneous contractions via activation of adenylyl cyclase, formation of cyclic AMP and activation of protein kinase A.

Verrucotoxin, a stonefish venom, modulates calcium channel activity in guinea-pig ventricular myocytes.

PubMed

Yazawa, K; Wang, J-W; Hao, L-Y; Onoue, Y; Kameyama, M

2007-08-01

Stonefish (Synanceia genus) are commonly found in shallow waters of the Pacific and Indian Oceans. The venom of stonefish is stored in the dorsal fine spines and contains a proteinaceous toxin, verrucotoxin (VTX). The stings produced by the spines induce intense pain, respiratory weakness, damage to the cardiovascular system, convulsions and paralysis, sometimes leading to death. Although there are many studies on VTX, the mechanism(s) underlying the VTX-mediated cardiotoxicity is not yet fully understood. The aim of this study was to investigate the modulation of ion channels in cardiac tissue by VTX. The effects of VTX on changes in the voltage or current in guinea-pig ventricular myocytes were investigated using a patch clamp method. VTX (10 microg ml(-1)) prolonged the action potential duration by 2.5-fold. VTX increased L-type Ca(2+) currents (I (Ca(L))) in a concentration-dependent manner with a EC(50) value of 7 microg ml(-1) and a maximum increase of 3.1-fold. The non-selective beta-adrenoceptor antagonist, propranolol (1 microM) and the selective beta(1)-adrenoceptor antagonist, CGP20712A (10 microM) each abolished the effect of VTX (100 microg ml(-1)) on I (Ca(L)). Furthermore, the protein kinase A (PKA) antagonists H-89 (10 microM) and Rp-8-Br-cAMPS (30 microM) inhibited the effect of VTX on I (Ca(L)). VTX modulates Ca(2+) channel activity through the beta-adrenoceptor-cAMP-PKA pathway.

The Protein Micro-Crystallography Beamlines for Targeted Protein Research Program

NASA Astrophysics Data System (ADS)

Hirata, Kunio; Yamamoto, Masaki; Matsugaki, Naohiro; Wakatsuki, Soichi

In order to collect proper diffraction data from outstanding micro-crystals, a brand-new data collection system should be designed to provide high signal-to noise ratio in diffraction images. SPring-8 and KEK-PF are currently developing two micro-beam beamlines for Targeted Proteins Research Program by MEXT of Japan. The program aims to reveal the structure and function of proteins that are difficult to solve but have great importance in both academic research and industrial application. At SPring-8, a new 1-micron beam beamline for protein micro-crystallography, RIKEN Targeted Proteins Beamline (BL32XU), is developed. At KEK-PF a new low energy micro-beam beamline, BL-1A, is dedicated for SAD micro-crystallography. The two beamlines will start operation in the end of 2010. The present status of the research and development for protein micro-crystallography will be presented.

Size-dependent nonlinear bending of micro/nano-beams made of nanoporous biomaterials including a refined truncated cube cell

NASA Astrophysics Data System (ADS)

Sahmani, S.; Aghdam, M. M.

2017-12-01

Morphology and pore size plays an essential role in the mechanical properties as well as the associated biological capability of a porous structure made of biomaterials. The objective of the current study is to predict the Young's modulus and Poisson's ratio of nanoporous biomaterials including refined truncated cube cells based on a hyperbolic shear deformable beam model. Analytical relationships for the mechanical properties of nanoporous biomaterials are given as a function of the refined cell's dimensions. After that, the size dependency in the nonlinear bending behavior of micro/nano-beams made of such nanoporous biomaterials is analyzed using the nonlocal strain gradient elasticity theory. It is assumed that the micro/nano-beam has one movable end under axial compression in conjunction with a uniform distributed lateral load. The Galerkin method together with an improved perturbation technique is employed to propose explicit analytical expression for nonlocal strain gradient load-deflection curves of the micro/nano-beams made of nanoporous biomaterials subjected to uniform transverse distributed load. It is found that through increment of the pore size, the micro/nano-beam will undergo much more deflection corresponding to a specific distributed load due to the reduction in the stiffness of nanoporous biomaterial. This pattern is more prominent for lower value of applied axial compressive load at the free end of micro/nano-beam.

High Energy Density Physics and Exotic Acceleration Schemes

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

Cowan, T.; /General Atomics, San Diego; Colby, E.

2005-09-27

The High Energy Density and Exotic Acceleration working group took as our goal to reach beyond the community of plasma accelerator research with its applications to high energy physics, to promote exchange with other disciplines which are challenged by related and demanding beam physics issues. The scope of the group was to cover particle acceleration and beam transport that, unlike other groups at AAC, are not mediated by plasmas or by electromagnetic structures. At this Workshop, we saw an impressive advancement from years past in the area of Vacuum Acceleration, for example with the LEAP experiment at Stanford. And wemore » saw an influx of exciting new beam physics topics involving particle propagation inside of solid-density plasmas or at extremely high charge density, particularly in the areas of laser acceleration of ions, and extreme beams for fusion energy research, including Heavy-ion Inertial Fusion beam physics. One example of the importance and extreme nature of beam physics in HED research is the requirement in the Fast Ignitor scheme of inertial fusion to heat a compressed DT fusion pellet to keV temperatures by injection of laser-driven electron or ion beams of giga-Amp current. Even in modest experiments presently being performed on the laser-acceleration of ions from solids, mega-amp currents of MeV electrons must be transported through solid foils, requiring almost complete return current neutralization, and giving rise to a wide variety of beam-plasma instabilities. As keynote talks our group promoted Ion Acceleration (plenary talk by A. MacKinnon), which historically has grown out of inertial fusion research, and HIF Accelerator Research (invited talk by A. Friedman), which will require impressive advancements in space-charge-limited ion beam physics and in understanding the generation and transport of neutralized ion beams. A unifying aspect of High Energy Density applications was the physics of particle beams inside of solids, which is proving to be a very important field for diverse applications such as muon cooling, fusion energy research, and ultra-bright particle and radiation generation with high intensity lasers. We had several talks on these and other subjects, and many joint sessions with the Computational group, the EM Structures group, and the Beam Generation group. We summarize our groups' work in the following categories: vacuum acceleration schemes; ion acceleration; particle transport in solids; and applications to high energy density phenomena.« less

OPC-13013, a cyclic nucleotide phosphodiesterase type III, inhibitor, inhibits cell proliferation and transdifferentiation of cultured rat hepatic stellate cells.

PubMed

Shimizu, E; Kobayashi, Y; Oki, Y; Kawasaki, T; Yoshimi, T; Nakamura, H

1999-01-01

Activated hepatic stellate cells (HSC; lipocytes; Ito cells) proliferate and are responsible for extracellular matrix synthesis during hepatic fibrogenesis. During activation, HSC undergo transdifferentiation into myofibroblasts expressing alpha-smooth muscle actin (alpha-SMA). Adenosine 3', 5'-cyclic monophosphate (cyclic AMP) is an ubiquitous intracellular signaling molecule, and is upregulated by the activation of adenylate cyclase and downregulated via hydrolysis by cyclic nucleotide phosphodiesterases (PDEs). Recently, increased intracellular cyclic AMP has been shown to inhibit HSC activation. The aim of the current study was to determine the effects of inhibition of PDEs on cell proliferation and transdifferentiation in cultured rat HSC. Cell proliferation was determined by [3H]thymidine incorporation, and Western blot analysis was performed for detection of alpha-SMA, a phenotypic marker of transdifferentiation into myofibroblast. When the cells were exposed to 3-isobutyl-1-methylxanthine (IBMX; 50-1000 microM), a nonselective PDE inhibitor, serum-stimulated [3H]thymidine incorporation was suppressed in a dose-dependent manner with a maximum inhibition of 66% at a concentration of 500 microM OPC-13013 (1-60 microM), a selective PDE III isoenzyme inhibitor, induced a dose-dependent inhibitory effect on serum-stimulated DNA synthesis that reached a maximum inhibition of 95% at a concentration of 60 microM, while neither 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MMX), a PDE I isoenzyme inhibitor, nor Ro-20-1724, a PDE IV isoenzyme inhibitor, had an inhibitory effect. Western blot analysis revealed that IBMX or OPC-13013 decreased alpha-SMA expression, while other selective PDE isoenzyme inhibitors did not have a suppressive effect. IBMX, OPC-13013 or Ro-20-1724, but not 8-MMX augmented forskolin-induced increase in intracellular cyclic AMP levels although cyclic AMP levels were not affected by treatment with any of these PDE inhibitors alone. These data indicate that inhibition of PDEs, especially PDE III isoenzyme, can produce an inhibitory effect on HSC activation. The PDE III isoenzyme may contribute to the regulation of HSC activation during fibrogenesis. In addition, OPC-13013 may have the potential to inhibit initiation and progression of hepatic fibrosis by interfering with HSC activation.

Sensitivity of 30-cm mercury bombardment ion thruster characteristics to accelerator grid design

NASA Technical Reports Server (NTRS)

Rawlin, V. K.

1978-01-01

The design of ion optics for bombardment thrusters strongly influences overall performance and lifetime. The operation of a 30 cm thruster with accelerator grid open area fractions ranging from 43 to 24 percent, was evaluated and compared with experimental and theoretical results. Ion optics properties measured included the beam current extraction capability, the minimum accelerator grid voltage to prevent backstreaming, ion beamlet diameter as a function of radial position on the grid and accelerator grid hole diameter, and the high energy, high angle ion beam edge location. Discharge chamber properties evaluated were propellant utilization efficiency, minimum discharge power per beam amp, and minimum discharge voltage.

Study on the steady operating state of a micro-pulse electron gun.

PubMed

Kui, Zhou; Xiangyang, Lu; Shengwen, Quan; Jifei, Zhao; Xing, Luo; Ziqin, Yang

2014-09-01

Micro-pulse electron gun (MPG) employs the basic concept of multipacting to produce high-current and short-pulse electron beams from a radio-frequency (RF) cavity. The concept of MPG has been proposed for more than two decades. However, the unstable operating state of MPG vastly obstructs its practical applications. This paper presents a study on the steady operating state of a micro-pulse electron gun with theory and experiments. The requirements for the steady operating state are proposed through the analysis of the interaction between the RF cavity and the beam load. Accordingly, a MPG cavity with the frequency of 2856 MHz has been designed, constructed, and tested. Some primary experiments have been finished. Both the unstable and stable operating states of the MPG have been observed. The stable output beam current has been detected at about 3.8 mA. Further experimental study is under way now.

[Activation of the alternative oxidase of Yarrowia lipolytica by adenosine 5'-monophosphate].

PubMed

Medentsev, A G; Arinbasarova, A Iu; Smirnova, N M; Akimenko, V K

2004-01-01

The study of the effect of nucleoside phosphates on the activity of cyanide-resistant oxidase in the mitochondria and the submitochondrial particles of Yarrowia lipolytica showed that adenosine monophosphate (5'-AMP, AMP) did not stimulate the respiration of the intact mitochondria. The incubation of the mitochondria at room temperature (25 degrees C) for 3-5 h or their treatment with ultrasound, phospholipase A, and detergent Triton X-100 at a low temperature inactivated the cyanide-resistant alternative oxidase. The inactivated alternative oxidase could be reactivated by AMP. The reactivating effect of AMP was enhanced by azolectin. Some other nucleoside phosphates also showed reactivating ability in the following descending order. AMP = GMP > GDP > GTP > XMP > IMP. The apparent reaction rate constant Km for AMP upon the reactivation of the alternative oxidase of mitochondria treated with Triton X-100 or incubated at 25 degrees C was 12.5 and 20 microM, respectively. The Km for AMP upon the reactivation of the alternative oxidase of submitochondrial particles was 15 microM. During the incubation of yeast cells under conditions promoting the development of alternative oxidase, the content of adenine nucleotides (AMP, ADP, and ATP) in the cells and their respiration tended to decrease. The subsequent addition of cyanide to the cells activated their respiration, diminished the intracellular content of ATP three times, and augmented the content of AMP five times. These data suggest that the stimulation of cell respiration by cyanide may be due to the activation of alternative oxidase by AMP.

Tests of a low-pressure switch protected by a saturating inductor

NASA Astrophysics Data System (ADS)

Lauer, E. J.; Birx, D. L.

1981-10-01

A triggered low-pressure switch was tested switching a charged capacitor across a damping resistor simulating a transformer. A series saturating inductor protected the switch from electron beam anode damage. The capacitor was 15 micro F and charge voltages up to 50 kV were used. The time to current maximum was 5 to 8 micro S. The current terminated at about 50 micro S and voltage could be reapplied at about 100 micro S.

Latest developments on the Dutch 1MW free electron maser

NASA Astrophysics Data System (ADS)

Caplan, M.; Verhoeven, A. G. A.; Urbanus, W.

1999-05-01

The FOM Institute (Rijnhuizen, Netherlands), as part of their fusion technology program, has undertaken the development of a Free Electron Maser with the goal of producing 1MW long pulse to CW microwave output in the range 130 GHz-250GHz with wall plug efficiencies of 60%. This project has been carried out as a collaborative effort with Institute of Applied Physics, Nizhny Novgorod Russia, Kurchatov Institute, Moscow Russia, Lawrence Livermore Laboratory, U.S.A and CPI, U.S.A. The key design features of this FEM consists first of a conventional DC acceleration system at high voltage (2MV) which supplies only the unwanted beam interception current and a depressed collector system at 250kV which provides the main beam power. Low body current interception (<25mA) is ensured by using robust inline beam focussing, a low emittance electron gun with halo suppression and periodic magnet side array focussing in the wiggler. The second key feature is use of a low-loss step corrugated waveguide circuit for broad band CW power handling and beam/RF separation. Finally, the required interaction efficiency and mode control is provided by a two stage stepped wiggler. The FEM has been constructed and recently undergone initial short pulse (<10 usec) testing in an inverted mode with the depressed collector absent. Results to date have demonstrated 98.8% beam transmission (over 5 Meters) at currents as high as 8.4 Amps, with 200GHz microwave output at 700kW. There has been good agreement between theory and experiment at the beam current levels tested so far. Details of the most recent experimental results will be presented, in particular the output frequency characteristics with detailed comparisons to theory. The immediate future plans are to operate the system at the design value of 12 Amps with at least 1MW output. The system will then be reconfigured with a 3 stage depressed collector to demonstrate, in the next year, long pulse operation (100 msec) and high wall plug efficiency. Long term future plans call for upgrading the FEM to 2MW and extrapolations up to 5MW are shown to be theoretically possible.

Dibutyryl cyclic AMP induces differentiation of human neuroblastoma SH-SY5Y cells into a noradrenergic phenotype.

PubMed

Kume, Toshiaki; Kawato, Yuka; Osakada, Fumitaka; Izumi, Yasuhiko; Katsuki, Hiroshi; Nakagawa, Takayuki; Kaneko, Shuji; Niidome, Tetsuhiro; Takada-Takatori, Yuki; Akaike, Akinori

2008-10-10

Dibutyryl cyclic AMP (dbcAMP) and retinoic acid (RA) have been demonstrated to be the inducers of morphological differentiation in SH-SY5Y cells, a human catecholaminergic neuroblastoma cell line. However, it remains unclear whether morphologically differentiated SH-SY5Y cells by these compounds acquire catecholaminergic properties. We focused on the alteration of tyrosine hydroxylase (TH) expression and intracellular content of noradrenaline (NA) as the indicators of functional differentiation. Three days treatment with dbcAMP (1mM) and RA (10microM) induced morphological changes and an increase of TH-positive cells using immunocytochemical analysis in SH-SY5Y cells. The percentage of TH-expressing cells in dbcAMP (1mM) treatment was larger than that in RA (10microM) treatment. In addition, dbcAMP increased intracellular NA content, whereas RA did not. The dbcAMP-induced increase in TH-expressing cells is partially inhibited by KT5720, a protein kinase A (PKA) inhibitor. We also investigated the effect of butyrate on SH-SY5Y cells, because dbcAMP is enzymatically degraded by intracellular esterase, thereby resulting in the formation of butyrate. Butyrate induced the increase of NA content at lower concentrations than dbcAMP, although the increase in TH-expressing cells by butyrate was smaller than that by dbcAMP. The dbcAMP (1mM)- and butyrate (0.3mM)-induced increase in NA content was completely suppressed by alpha-methyl-p-tyrosine (1mM), an inhibitor of TH. These results suggest that dbcAMP induces differentiation into the noradrenergic phenotype through both PKA activation and butyrate.

Trains of electron micro-bunches in plasma wake-field acceleration

NASA Astrophysics Data System (ADS)

Lécz, Zsolt; Andreev, Alexander; Konoplev, Ivan; Seryi, Andrei; Smith, Jonathan

2018-07-01

Plasma-based charged particle accelerators have been intensively investigated in the past three decades due to their capability to open up new horizons in accelerator science and particle physics yielding electric field accelerating gradient more than three orders of magnitudes higher than in conventional devices. At the current stage the most advanced and reliable mechanism for accelerating electrons is based on the propagation of an intense laser pulse or a relativistic electron beam in a low density gaseous target. In this paper we concentrate on the electron beam-driven plasma wake-field acceleration and demonstrate using 3D PiC simulations that a train of electron micro-bunches with ∼10 fs period can be generated behind the driving beam propagating in a density down-ramp. We will discuss the conditions and properties of the micro-bunches generated aiming at understanding and study of multi-bunch mechanism of injection. It is show that the periodicity and duration of micro-bunches can be controlled by adjusting the plasma density gradient and driving beam charge.

Beta-Adrenergic Receptor Population is Up-Regulated in Chicken Skeletal Muscle Cells Treated with Forskolin

NASA Technical Reports Server (NTRS)

Bridge, K. Y.; Young, R. B.; Vaughn, J. R.

1998-01-01

Skeletal muscle hypertrophy is promoted by in vivo administration of beta-adrenergic receptor (betaAR) agonists. These compounds presumably exert their physiological action through the betaAR, and alterations in the population of betaAR could potentially change the ability of the cell to respond to the betaAR agonists. Since the intracellular chemical signal generated by the betaAR is cyclic AMP (cAMP), experiments were initiated in primary chicken muscle cell cultures to determine if artificial elevation of intracellular cAMP by treatment with forskolin would alter the population of functional betaAR expressed on the surface of muscle cells. Chicken skeletal muscle cells after 7 days in culture were employed for the experiments because muscle cells have attained a steady state with respect to muscle protein metabolism at this stage. Cells were treated with 0-10 microM forskolin for a total of three days. At the end of the 1, 2, and 3 day treatment intervals, the concentration of cAMP and the betaAR population were measured. Receptor population was measured in intact muscle cell cultures as the difference between total binding of [H-3]CGP-12177 and non-specific binding of [H-3]CGP-12177 in the presence of 1 microM propranolol. Intracellular cAMP concentration was measured by radioimmunoassay. The concentration of cAMP in forskolin-treated cells increased up to 10-fold in a dose dependent manner. Increasing concentrations of forskolin also led to an increase in betaAR population, with a maximum increase of approximately 50% at 10 microM. This increase in PAR population was apparent after only 1 day of treatment, and the pattern of increase was maintained for all 3 days of the treatment period. Thus, increasing the intracellular concentration of cAMP leads to up-regulation of betaAR population. The effect of forskolin on the quantity and apparent synthesis rate of the heavy chain of myosin (mhc) were also investigated. A maximum increase of 50% in the quantity of mhc was observed at 0.2 microM forskolin, but higher concentrations of forskolin reduced the quantity of mhc back to control levels.

Current state of a dual behaviour of antimicrobial peptides-Therapeutic agents and promising delivery vectors.

PubMed

Piotrowska, Urszula; Sobczak, Marcin; Oledzka, Ewa

2017-12-01

Micro-organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties. In contrast to conventional antibiotics, which have very defined and specific molecular targets, host cationic peptides show varying, complex and very rapid mechanisms of actions that make it difficult to form an effective antimicrobial defence. Importantly, AMPs display their antimicrobial activity at micromolar concentrations or less. To do this, many peptide-based drugs are commercially available for the treatment of numerous diseases, such as hepatitis C, myeloma, skin infections and diabetes. Herein, we present an overview of the general mechanism of AMPs action, along with recent developments regarding carriers of AMPs and their potential applications in medical fields. © 2017 John Wiley & Sons A/S.

TSH-induced cyclic AMP production in an ovine thyroid cell line: OVNIS 5H.

PubMed

Fayet, G; Aouani, A; Hovsépian, S

1986-01-06

The TSH-induced cyclic AMP response was studied using a 3-year-old ovine thyroid cell line TSH-independent for growth: OVNIS 5H. The kinetics of cyclic AMP production was followed both in cell layers and in cell culture media, with or without phosphodiesterase inhibitor. It is noteworthy that following the first wave in cyclic AMP obtained within minutes, we observed later a sustained exponential increase in cyclic AMP during the 5 days following TSH stimulation. A bioassay of TSH was derived allowing measurement of 1 microU/ml TSH from a crude bTSH preparation.

The 80 kV electrostatic wire septum for AmPS

NASA Astrophysics Data System (ADS)

Vanderlinden, A.; Bijleveld, J. H. M.; Rookhuizen, H. Boer; Bruinsma, P. J. T.; Heine, E.; Lassing, P.; Prins, E.

The characteristics of the wire septum for the Amsterdam Pulse Stretcher (AmPS) are summarized. In the extraction process of the AmPS the extracted beam is intercepted from the circulating beam by the 1 m long electrostatic wire septum. For a bending angle of 4.4 mrad, the maximum anode voltage is 80 kV. The system developed consists of a wire spacing of 0.65 mm between tungsten wires of 50 micrometers diameter. Stainless steel spring wires, bent in a half cylindrical carrier, stretch the septum wires two by two. Prototype tests were successful up to an anode voltage of 120 kV.

Leishmania major: effect of protein kinase A and phosphodiesterase activity on infectivity and proliferation of promastigotes.

PubMed

Malki-Feldman, Laura; Jaffe, Charles L

2009-09-01

Effect of modulators on protein kinase A (PKA) activity, promastigote growth and their ability to infect peritoneal macrophages was monitored. PKA inhibitors reduced [Protein Kinase Inhibitor (PKI) - 56%; H89 - 54.5%] kemptide phosphorylation by Leishmania major promastigote lysates, while activators increased phosphorylation (8-CPT-cAMP - 88%; Sp-cAMPS-AM - 152%). Activation was specifically inhibited by PKI. Phosphodiesterase inhibitors also increased kemptide phosphorylation (dipyridamole - 171%; rolipram - 106%; and 3-isobutyl-1-methyl-xanthine - 154%). Parasite proliferation was significantly retarded (200 nM H89; 100 microM myristoylated-PKI) or completely inhibited (500 nM H89) by culturing with PKA inhibitors. Incubation with dipyridamole or Sp-cAMPS-AM also inhibited proliferation. Brief treatment (2h) with either H89, myristoylated-PKI, dipyridamole or Sp-cAMPS-AM reduced initial macrophage infection at days 1 and 2 (>40%) and on day 3 (>78% only for 100 microM myr-PKI). Characterization of leishmanial cAMP mediated signal transduction pathways will serve as the basis for the new drug design.

Study on the steady operating state of a micro-pulse electron gun

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

Kui, Zhou; Xing, Luo; Institute of Applied Electronics, Chinese Academy of Engineering Physics, Mianyang 621900

Micro-pulse electron gun (MPG) employs the basic concept of multipacting to produce high-current and short-pulse electron beams from a radio-frequency (RF) cavity. The concept of MPG has been proposed for more than two decades. However, the unstable operating state of MPG vastly obstructs its practical applications. This paper presents a study on the steady operating state of a micro-pulse electron gun with theory and experiments. The requirements for the steady operating state are proposed through the analysis of the interaction between the RF cavity and the beam load. Accordingly, a MPG cavity with the frequency of 2856 MHz has been designed,more » constructed, and tested. Some primary experiments have been finished. Both the unstable and stable operating states of the MPG have been observed. The stable output beam current has been detected at about 3.8 mA. Further experimental study is under way now.« less

Protection from AMP 579 can be added to that from either cariporide or ischemic preconditioning in ischemic rabbit heart.

PubMed

Xu, Zhelong; Jiao, Zhe; Cohen, Michael V; Downey, James M

2002-10-01

AMP 579, an adenosine A /A receptor agonist, is cardioprotective when administered at reperfusion. Pretreatment with the Na /H exchanger inhibitor cariporide or ischemic preconditioning (PC) also limits infarct size. To gain insight into the mechanism of AMP 579 we investigated whether its protection could be added to that from either cariporide or PC. rabbit hearts were subjected to 45 min of regional ischemia followed by 3 h of reperfusion. Infarct size in the control group was 55.8 +/- 3.9% of the risk zone. PC significantly reduced infarct size to 26.0 +/- 6.7% (p<0.05). AMP 579 (30 micro g/kg) given just before reperfusion followed by 3 micro g/kg/min infusion for 70 min also limited infarct size (32.1 +/- 1.8%,) but the combination of AMP 579 and PC showed a significantly greater limitation of infarct size (5.5 +/- 2.7%, p < 0.05). Because cariporide pretreatment was so protective (8.5 +/- 3.7% infarction), we had to increase the ischemic insult to 60 min to test for any additive effect of the combination of AMP 579 + cariporide. Infarct size in the untreated group was 66.0 +/- 4.9% of the risk zone. Cariporide (0.5 mg/kg) 5 min prior to ischemia significantly reduced infarct size to 41.5 +/- 7.7%. When cariporide pre-treatment was combined with AMP 579 at reperfusion, infarction was further limited (14.2 +/- 4.5%). Because AMP 579's protection can be added to that of either cariporide or PC, AMP 579's mechanism of protection probably differs from either of them. The combination of AMP 579 + cariporide was particularly efficacious and could be useful in the surgical setting.

Stable, sensitive, fluorescence-based method for detecting cAMP.

PubMed

Hesley, Jayne; Daijo, Janet; Ferguson, Anne T

2002-09-01

cAMP is a universal secondary messenger that connects changes in the extracellular environment, as detected by cell surface receptors, to transcriptional changes in the nucleus. Since cAMP-mediated signal transduction plays a role in critical cell functions and human diseases, monitoring its activity can aid in understanding these responses and the process of drug discovery. This report examines the performance of a fluorescence-based competitive immunoassay in 384-well microplate format. Using purified cAMP as a competitor the estimated detection limit was determined to be 0.1 nM and Z'-factor was greater than 0.83, which indicates that the assay is of high quality and one of the most sensitive assays currently on the market. Of note, the results obtained were similar whether the reaction was allowed to proceed for 10 min or up to 60 min. Next, HEK 293 cells were treated with the promiscuous adenylate cyclase activator, forskolin, and the beta-adrenoceptor agonist, isoproterenol. The resultant average EC50 values were 11 microM and 123 nM, respectively, which correspond to those found in the literature. Together, these results demonstrate that this assay is afast, accurate, non-radioactive method that is ideal for high-throughput screening.

Biconcave micro-optofluidic lens with low-refractive-index liquids.

PubMed

Song, Chaolong; Nguyen, Nam-Trung; Asundi, Anand Krishna; Low, Cassandra Lee-Ngo

2009-12-01

One of the current problems of micro-optofluidics is the choice of a suitable liquid with a high refractive index (RI). We report the use of a low-RI liquid in a biconcave liquid-core liquid-cladding lens for focusing light. For the characterization of the lens, a telescope system was constructed from polydimethylsiloxane lenses to collimate and expand a light beam emitted from an optical fiber. The tunable optofluidic biconcave lens focuses the parallel beam. Fluorescent dye diluted in an index-matching liquid was used for the visualization of the light rays in a beam-tracing chamber. The focused beam is tuned by adjusting the flow rate ratio between core and cladding streams.

Sweet taste transduction in hamster: role of protein kinases.

PubMed

Varkevisser, B; Kinnamon, S C

2000-05-01

Two different second-messenger pathways have been implicated in sweet taste transduction: sugars produce cyclic AMP (cAMP), whereas synthetic sweeteners stimulate production of inositol 1,4, 5-tris-phosphate (IP(3)) and diacylglycerol (DAG). Both sugars and sweeteners depolarize taste cells by blocking the same resting K(+) conductance, but the intermediate steps in the transduction pathways have not been examined. In this study, the loose-patch recording technique was used to examine the role of protein kinases and other downstream regulatory proteins in the two sweet transduction pathways. Bursts of action currents were elicited from approximately 35% of fungiform taste buds in response to sucrose (200 mM) or NC-00274-01 (NC-01, 200 microM), a synthetic sweetener. To determine whether protein kinase C (PKC) plays a role in sweet transduction, taste buds were stimulated with the PKC activator PDBu (10 microM). In all sweet-responsive taste buds tested (n = 11), PDBu elicited burst of action currents. In contrast, PDBu elicited responses in only 4 of 19 sweet-unresponsive taste buds. Inhibition of PKC by bisindolylmaleimide I (0.15 microM) resulted in inhibition of the NC-01 response by approximately 75%, whereas the response to sucrose either increased or remained unchanged. These data suggest that activation of PKC is required for the transduction of synthetic sweeteners. To determine whether protein kinase A (PKA) is required for the transduction of sugars, sweet responses were examined in the presence of the membrane-permeant PKA inhibitor H-89 (10 and 19 microM). Surprisingly, H-89 did not decrease responses to either sucrose or NC-01. Instead, responses to both compounds were increased in the presence of the inhibitor. These data suggest that PKA is not required for the transduction of sugars, but may play a modulatory role in both pathways, such as adaptation of the response. We also examined whether Ca(2+)-calmodulin dependent cAMP phosphodiesterase (CaM-PDE) plays a role in sweet taste transduction, by examining responses to sucrose and synthetic sweeteners in the presence of the CaM-PDE inhibitor W-7 (100 microM). Inhibition resulted in an increase in the response to sucrose, whereas the response to NC-01 remained unchanged. These data suggest that the pathways for sugars and sweeteners are negatively coupled; the Ca(2+) that is released from intracellular stores during stimulation with synthetic sweeteners may inhibit the response to sucrose by activation of CaM-PDE.

Mathematical model of the current density for the 30-cm engineering model thruster

NASA Technical Reports Server (NTRS)

Cuffel, R. F.

1975-01-01

Mathematical models are presented for both the singly and doubly charged ion current densities downstream of the 30-cm engineering model thruster with 0.5% compensated dished grids. These models are based on the experimental measurements of Vahrenkamp at a 2-amp ion beam operating condition. The cylindrically symmetric beam of constant velocity ions is modeled with continuous radial source and focusing functions across 'plane' grids with similar angular distribution functions. A computer program is used to evaluate the double integral for current densities in the near field and to obtain a far field approximation beyond 10 grid radii. The utility of the model is demonstrated for (1) calculating the directed thrust and (2) determining the impingement levels on various spacecraft surfaces from a two-axis gimballed, 2 x 3 thruster array.

Prostaglandins mediate the stimulatory effects of endothelin-1 on cAMP accumulation and inositol-1,4,5-trisphosphate production and contraction in cat iris sphincter.

PubMed

Yousufzai, S Y; Ye, Z; Abdel-Latif, A A

1995-12-01

We previously reported that in the iris sphincter smooth muscle, endothelin-1 (ET-1) activates both adenylyl cyclase and the phosphoinositide cascade and that the changes in the levels of cAMP and inositol-1,4,5-trisphosphate (IP3) produced are species specific. In the present study, we examined the mechanism of the ET-1 effects in cat iris sphincter. In general, we found that ET-1 (0.1 microM) increased prostaglandin E2 (PGE2) release by 156%, cAMP accumulation by 310%, IP3 production by 88% and induced contraction; that PGE2 increased cAMP accumulation, IP3 production and contraction; and that the effects of ET-1 are inhibited by indomethacin (Indo), suggesting that arachidonic acid metabolites may mediate the responses to the peptide. Kinetic studies revealed the following: (1) The effect of ET-1 on cAMP accumulation is rapid (within 30 sec), dose dependent (EC50 = 5.8 nM) and completely abolished by Indo (Ki = 0.16 microM), a cyclooxygenase inhibitor, but not by nordihydroguairetic acid, a lipoxygenase inhibitor, implying the involvement of PGs. (2) ET-1 dose-dependently evoked PGe2 release (EC50 = 1.8 nM), IP3 production (EC50 = 4.5 nM) and contraction (EC50 = 5 nM) and that all of these responses were inhibited by Indo. (3) PGE2 increased cAMP accumulation in a dose-dependent manner with an EC50 of 1.5 x 10(-7) M, and PGD2 and PGF2 alpha had little effect on the cyclic nucleotide. (4) PGE2 (1 microM), increased IP3 production by 55% and induced muscle contraction in a dose-dependent manner (EC50 = 40 nM). We conclude from these data that in cat iris sphincter PGs may mediate ET-1-induced cAMP accumulation, IP3 production and smooth muscle contraction.

A stable partitioned FSI algorithm for incompressible flow and deforming beams

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

Li, L., E-mail: lil19@rpi.edu; Henshaw, W.D., E-mail: henshw@rpi.edu; Banks, J.W., E-mail: banksj3@rpi.edu

2016-05-01

An added-mass partitioned (AMP) algorithm is described for solving fluid–structure interaction (FSI) problems coupling incompressible flows with thin elastic structures undergoing finite deformations. The new AMP scheme is fully second-order accurate and stable, without sub-time-step iterations, even for very light structures when added-mass effects are strong. The fluid, governed by the incompressible Navier–Stokes equations, is solved in velocity-pressure form using a fractional-step method; large deformations are treated with a mixed Eulerian-Lagrangian approach on deforming composite grids. The motion of the thin structure is governed by a generalized Euler–Bernoulli beam model, and these equations are solved in a Lagrangian frame usingmore » two approaches, one based on finite differences and the other on finite elements. The key AMP interface condition is a generalized Robin (mixed) condition on the fluid pressure. This condition, which is derived at a continuous level, has no adjustable parameters and is applied at the discrete level to couple the partitioned domain solvers. Special treatment of the AMP condition is required to couple the finite-element beam solver with the finite-difference-based fluid solver, and two coupling approaches are described. A normal-mode stability analysis is performed for a linearized model problem involving a beam separating two fluid domains, and it is shown that the AMP scheme is stable independent of the ratio of the mass of the fluid to that of the structure. A traditional partitioned (TP) scheme using a Dirichlet–Neumann coupling for the same model problem is shown to be unconditionally unstable if the added mass of the fluid is too large. A series of benchmark problems of increasing complexity are considered to illustrate the behavior of the AMP algorithm, and to compare the behavior with that of the TP scheme. The results of all these benchmark problems verify the stability and accuracy of the AMP scheme. Results for one benchmark problem modeling blood flow in a deforming artery are also compared with corresponding results available in the literature.« less

cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes.

PubMed Central

Heuschneider, G; Schwartz, R D

1989-01-01

The effects of the cyclic nucleotide cAMP on gamma-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate inhibited muscimol-induced 36Cl- uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner (IC50 = 1.3 mM). The inhibition was due to a decrease in the maximal effect of muscimol, with no change in potency. Similar effects were observed with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, 8-bromoadenosine 3',5'-cyclic monophosphate, and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the gamma-aminobutyric acid-gated Cl- channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced 36Cl- uptake and generated cAMP with similar potencies (IC50 = 14.3 microM; EC50 = 6.2 microM, respectively). Surprisingly, 1,9-dideoxyforskolin, which does not activate adenylate cyclase, also inhibited the muscimol response, suggesting that forskolin and its lipophilic derivatives may interact with the Cl- channel directly. Indeed, forskolin inhibition of muscimol-induced 36Cl- uptake was extremely rapid (within 5 sec), preceding the accumulation of sufficient levels of cAMP. After 5 min, a slower phase of inhibition was seen, similar to the time course for cAMP accumulation. The data suggest that gamma-aminobutyric acid (GABAA) receptor function in brain can be regulated by cAMP-dependent phosphorylation. PMID:2468163

Assessing the Ability of Ground-Penetrating Radar to Detect Fungal Decay in Douglas-Fir Beams

Treesearch

Christopher Adam Senalik; James Wacker; Xiping Wang; F. Jalinoos

2016-01-01

This paper describes the testing plan and current progress for assessing the efficacy of using ground-penetrating radar (GPR) to detect fungal decay within Douglas-fir beams. Initially, the beams were assessed using a variety of physical, mechanical, and nondestructive evaluation (NDE) test methods including micro-resistance drilling, Janka hardness, ultrasonic...

New data acquisition system for beam loss monitor used in J-PARC main ring

NASA Astrophysics Data System (ADS)

Satou, K.; Toyama, T.; Kamikubota, N.; Yoshida, S.; Matsushita, J.; Wakita, T.; Sugiyama, M.; Morino, T.

2018-04-01

A new data acquisition system has been developed continually as a part of the development of a new beam loss monitor (BLM) system for the J-PARC main ring. This development includes a newly designed front-end isolation amp that uses photo-couplers and a VME-based new analog-to-digital converter (ADC) system. Compared to the old amp, the new amp has a 10 times higher conversion impedance for the input current to the output voltage; this value is 1 M Ω. Moreover, the bandwidth was improved to from DC to 50 kHz, which is about two orders of magnitude greater than the previously used bandwidth. The theoretical estimations made in this study roughly agree with the frequency response obtained for the new system. The new ADC system uses an on-board field-programmable gate array chip for signal processing. By replacing the firmware of this chip, changes pertaining to future accelerator upgrade plans may be introduced into the new ADC system; in addition, the ADC system can be used in other applications. The sampling speed of the system is 1 MS/s, and it exhibits a 95 dBc spurious-free dynamic range and 16.5 effective number of bits. The obtained waveform and integrated charge data are compared with two reference levels in the ADC system. If the data exceeds the reference level, the system generates an alarm to dump the beams. By using the new data acquisition system, it was proved that the new BLM system shows a wide dynamic range of 160 dB. In this study, the details of the new data acquisition system are described.

Trypanocidal and leishmanicidal activities of different antimicrobial peptides (AMPs) isolated from aquatic animals.

PubMed

Löfgren, S E; Miletti, L C; Steindel, M; Bachère, E; Barracco, M A

2008-02-01

Most of the available animal antimicrobial peptides (AMPs) have been tested against bacteria and fungi, but very few against protozoan parasites. In the present study, we investigated the antiparasitic activity of different AMPs isolated from aquatic animals: tachyplesin (Tach, from Tachypleus tridentatus), magainin (Mag, from Xenopus laevis), clavanin (Clav, from Styela clava), penaeidin (Pen, from Litopenaeus vannamei), mytilin (Myt, from Mytilus edulis) and anti-lipopolysaccharide factor (ALF, from Penaeus monodon). The antiparasitic activity was evaluated against the promastigote form of Leishmania braziliensis and epi and trypomastigote forms of Trypanosoma cruzi, through the MTT method. Tach was the most potent peptide, killing completely L. braziliensis and trypomastigote T. cruzi from 12.5microM, whereas Pen and Clav were weakly active against trypomastigotes and Myt against L. braziliensis, only at a high concentration (100microM). Tach and Mag were markedly hemolytic at high concentrations, whereas the other peptides caused only a slight hemolysis (<10% up to 50microM). Our results point to Tach as the only potential candidate for further investigation and potential application as a therapeutic agent.

Pulse charging of lead-acid traction cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1980-01-01

Pulse charging, as a method of rapidly and efficiently charging 300 amp-hour lead-acid traction cells for an electric vehicle application was investigated. A wide range of charge pulse current square waveforms were investigated and the results were compared to constant current charging at the time averaged pulse current values. Representative pulse current waveforms were: (1) positive waveform-peak charge pulse current of 300 amperes (amps), discharge pulse-current of zero amps, and a duty cycle of about 50%; (2) Romanov waveform-peak charge pulse current of 300 amps, peak discharge pulse current of 15 amps, and a duty of 50%; and (3) McCulloch waveform peak charge pulse current of 193 amps, peak discharge pulse current of about 575 amps, and a duty cycle of 94%. Experimental results indicate that on the basis of amp-hour efficiency, pulse charging offered no significant advantage as a method of rapidly charging 300 amp-hour lead-acid traction cells when compared to constant current charging at the time average pulse current value. There were, however, some disadvantages of pulse charging in particular a decrease in charge amp-hour and energy efficiencies and an increase in cell electrolyte temperature. The constant current charge method resulted in the best energy efficiency with no significant sacrifice of charge time or amp-hour output. Whether or not pulse charging offers an advantage over constant current charging with regard to the cell charge/discharge cycle life is unknown at this time.

Shielding properties of the ordinary concrete loaded with micro- and nano-particles against neutron and gamma radiations.

PubMed

Mesbahi, Asghar; Ghiasi, Hosein

2018-06-01

The shielding properties of ordinary concrete doped with some micro and nano scaled materials were studied in the current study. Narrow beam geometry was simulated using MCNPX Monte Carlo code and the mass attenuation coefficient of ordinary concrete doped with PbO 2 , Fe 2 O 3 , WO 3 and H 4 B (Boronium) in both nano and micro scales was calculated for photon and neutron beams. Mono-energetic beams of neutrons (100-3000 keV) and photons (142-1250 keV) were used for calculations. The concrete doped with nano-sized particles showed higher neutron removal cross section (7%) and photon attenuation coefficient (8%) relative to micro-particles. Application of nano-sized material in the composition of new concretes for dual protection against neutrons and photons are recommended. For further studies, the calculation of attenuation coefficients of these nano-concretes against higher energies of neutrons and photons and different particles are suggested. Copyright © 2018 Elsevier Ltd. All rights reserved.

Magnetic plasma confinement for laser ion source.

PubMed

Okamura, M; Adeyemi, A; Kanesue, T; Tamura, J; Kondo, K; Dabrowski, R

2010-02-01

A laser ion source (LIS) can easily provide a high current beam. However, it has been difficult to obtain a longer beam pulse while keeping a high current. On occasion, longer beam pulses are required by certain applications. For example, more than 10 micros of beam pulse is required for injecting highly charged beams to a large sized synchrotron. To extend beam pulse width, a solenoid field was applied at the drift space of the LIS at Brookhaven National Laboratory. The solenoid field suppressed the diverging angle of the expanding plasma and the beam pulse was widened. Also, it was observed that the plasma state was conserved after passing through a few hundred gauss of the 480 mm length solenoid field.

Microfabricated Ion Beam Drivers for Magnetized Target Fusion

NASA Astrophysics Data System (ADS)

Persaud, Arun; Seidl, Peter; Ji, Qing; Ardanuc, Serhan; Miller, Joseph; Lal, Amit; Schenkel, Thomas

2015-11-01

Efficient, low-cost drivers are important for Magnetized Target Fusion (MTF). Ion beams offer a high degree of control to deliver the required mega joules of driver energy for MTF and they can be matched to several types of magnetized fuel targets, including compact toroids and solid targets. We describe an ion beam driver approach based on the MEQALAC concept (Multiple Electrostatic Quadrupole Array Linear Accelerator) with many beamlets in an array of micro-fabricated channels. The channels consist of a lattice of electrostatic quadrupoles (ESQ) for focusing and of radio-frequency (RF) electrodes for ion acceleration. Simulations with particle-in-cell and beam envelope codes predict >10x higher current densities compared to state-of-the-art ion accelerators. This increase results from dividing the total ion beam current up into many beamlets to control space charge forces. Focusing elements can be biased taking advantage of high breakdown electric fields in sub-mm structures formed using MEMS techniques (Micro-Electro-Mechanical Systems). We will present results on ion beam transport and acceleration in MEMS based beamlets. Acknowledgments: This work is supported by the U.S. DOE under Contract No. DE-AC02-05CH11231.

Ultra-short pulse laser micro patterning with highest throughput by utilization of a novel multi-beam processing head

NASA Astrophysics Data System (ADS)

Homburg, Oliver; Jarczynski, Manfred; Mitra, Thomas; Brüning, Stephan

2017-02-01

In the last decade much improvement has been achieved for ultra-short pulse lasers with high repetition rates. This laser technology has vastly matured so that it entered a manifold of industrial applications recently compared to mainly scientific use in the past. Compared to ns-pulse ablation ultra-short pulses in the ps- or even fs regime lead to still colder ablation and further reduced heat-affected zones. This is crucial for micro patterning when structure sizes are getting smaller and requirements are getting stronger at the same time. An additional advantage of ultra-fast processing is its applicability to a large variety of materials, e.g. metals and several high bandgap materials like glass and ceramics. One challenge for ultra-fast micro machining is throughput. The operational capacity of these processes can be maximized by increasing the scan rate or the number of beams - parallel processing. This contribution focuses on process parallelism of ultra-short pulsed lasers with high repetition rate and individually addressable acousto-optical beam modulation. The core of the multi-beam generation is a smooth diffractive beam splitter component with high uniform spots and negligible loss, and a prismatic array compressor to match beam size and pitch. The optical design and the practical realization of an 8 beam processing head in combination with a high average power single mode ultra-short pulsed laser source are presented as well as the currently on-going and promising laboratory research and micro machining results. Finally, an outlook of scaling the processing head to several tens of beams is given.

Investigation of chemical vapour deposition diamond detectors by X-ray micro-beam induced current and X-ray micro-beam induced luminescence techniques

NASA Astrophysics Data System (ADS)

Olivero, P.; Manfredotti, C.; Vittone, E.; Fizzotti, F.; Paolini, C.; Lo Giudice, A.; Barrett, R.; Tucoulou, R.

2004-10-01

Tracking detectors have become an important ingredient in high-energy physics experiments. In order to survive the harsh detection environment of the large hadron collider (LHC), trackers need to have special properties. They must be radiation hard, provide fast collection of charge, be as thin as possible and remove heat from readout electronics. The unique properties of diamond allow it to fulfill these requirements. In this work we present an investigation of the charge transport and luminescence properties of "detector grade" artificial chemical vapour deposition (CVD) diamond devices developed within the CERN RD42 collaboration, performed by means of X-ray micro-beam induced current collection (XBICC) and X-ray micro-beam induced luminescence (XBIL) techniques. XBICC technique allows quantitative estimates of the transport parameters of the material to be evaluated and mapped with micrometric spatial resolution. In particular, the high resolution and sensitivity of the technique has allowed a quantitative study of the inhomogeneity of the charge transport parameter defined as the product of mobility and lifetime for both electron and holes. XBIL represents a technique complementary to ion beam induced luminescence (IBIL), which has already been used by our group, since X-ray energy loss profile in the material is different from that of MeV ions. X-ray induced luminescence maps have been performed simultaneously with induced photocurrent maps, to correlate charge transport and induced luminescence properties of diamond. Simultaneous XBICC and XBIL maps exhibit features of partial complementarity that have been interpreted on the basis of considerations on radiative and non-radiative recombination processes which compete with charge transport efficiency.

Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current

PubMed Central

1992-01-01

The properties of the low threshold Ca current (ICaT) in bullfrog (Rana catesbeiana) isolated atrial cardiomyocytes were studied using the whole-cell recording patch-clamp technique and compared with those of the high threshold Ca current (ICaL). In 91% of atrial cells we observed both ICaT and ICaL when collagenase and trypsin were used to dissociate the cells. But when pronase was used, only 30% of the cells exhibited ICaT. ICaT was never found in ventricular cells. ICaT could be investigated more easily when ICaL was inhibited by Cd ions (50 microM). Its kinetics were unchanged by substituting Ba for Ca, or in the presence of high concentrations of Ba. Both ICaT and ICaL exhibited reduced inactivation after high depolarizing prepulses. ICaT was found to be sensitive to dihydropyridines: 1 microM nifedipine decreased this current while 1 microM BAY K 8644 increased it; this occurred without significant variations in the steady-state inactivation curve. ICaT was more sensitive than ICaL to alpha 1-adrenergic and P2-purinergic stimulations, while ICaL was more sensitive to beta-adrenergic stimulation. Isoproterenol was still able to increase ICaT in the presence of high intracellular cAMP. Both currents were increased by 1 microM ouabain (although ICaL only transiently) and decreased by 10 microM ouabain. It is concluded that the two types of Ca channels can be observed in bullfrog atrial cells and that they are specifically altered by pharmacological agents and neuromediators. This may have implications for cardiac behavior. PMID:1279097

Evaluation of the MicroScan ESBL plus confirmation panel for detection of extended-spectrum beta-lactamases in clinical isolates of oxyimino-cephalosporin-resistant Gram-negative bacteria.

PubMed

Stürenburg, Enno; Lang, Melanie; Horstkotte, Matthias A; Laufs, Rainer; Mack, Dietrich

2004-11-01

We aimed to assess the performance of the MicroScan ESBL plus confirmation panel using a series of 87 oxyimino-cephalosporin-resistant Gram-negative bacilli of various species. Organisms tested included 57 extended-spectrum beta-lactamase (ESBL) strains comprising Enterobacter aerogenes (3), Enterobacter cloacae (10), Escherichia coli (11), Klebsiella pneumoniae (26), Klebsiella oxytoca (3) and Proteus mirabilis (4). Also included were 30 strains resistant to oxyimino cephalosporins but lacking ESBLs, which were characterized with other resistance mechanisms, such as inherent clavulanate susceptibility in Acinetobacter spp. (4), hyperproduction of AmpC enzyme in Citrobacter freundii (2), E. aerogenes (3), E. cloacae (3), E. coli (4), Hafnia alvei (1) and Morganella morganii (1), production of plasmid-mediated AmpC beta-lactamase in K. pneumoniae (3) and E. coli (3) or hyperproduction of K1 enzyme in K. oxytoca (6). The MicroScan MIC-based clavulanate synergy correctly classified 50 of 57 ESBL strains as ESBL-positive and 23 of 30 non-ESBL strains as ESBL-negative (yielding a sensitivity of 88% and a specificity of 76.7%, respectively). False negatives among ESBL producers were highest with Enterobacter spp. due to masking interactions between ESBL and AmpC beta-lactamases. False-positive classifications occurred in two Acinetobacter spp., one E. coli producing plasmid-mediated AmpC beta-lactamase and two K. oxytoca hyperproducing their chromosomal K1 beta-lactamase. The MicroScan clavulanate synergy test proved to be a valuable tool for ESBL confirmation. However, this test has limitations in detecting ESBLs in Enterobacter spp. and in discriminating ESBL-related resistance from the K1 enzyme and from inherent clavulanate susceptibility in Acinetobacter spp.

Increase in Ca2+ current by sustained cAMP levels enhances proliferation rate in GH3 cells.

PubMed

Rodrigues, Andréia Laura; Brescia, Marcella; Koschinski, Andreas; Moreira, Thaís Helena; Cameron, Ryan T; Baillie, George; Beirão, Paulo S L; Zaccolo, Manuela; Cruz, Jader S

2018-01-01

Ca 2+ and cAMP are important intracellular modulators. In order to generate intracellular signals with various amplitudes, as well as different temporal and spatial properties, a tightly and precise control of these modulators in intracellular compartments is necessary. The aim of this study was to evaluate the effects of elevated and sustained cAMP levels on voltage-dependent Ca 2+ currents and proliferation in pituitary tumor GH3 cells. Effect of long-term exposure to forskolin and dibutyryl-cyclic AMP (dbcAMP) on Ca 2+ current density and cell proliferation rate were determined by using the whole-cell patch-clamp technique and real time cell monitoring system. The cAMP levels were assayed, after exposing transfected GH3 cells with the EPAC-1 cAMP sensor to forskolin and dbcAMP, by FRET analysis. Sustained forskolin treatment (24 and 48h) induced a significant increase in total Ca 2+ current density in GH3 cells. Accordingly, dibutyryl-cAMP incubation (dbcAMP) also elicited increase in Ca 2+ current density. However, the maximum effect of dbcAMP occurred only after 72h incubation, whereas forskolin showed maximal effect at 48h. FRET-experiments confirmed that the time-course to elevate intracellular cAMP was distinct between forskolin and dbcAMP. Mibefradil inhibited the fast inactivating current component selectively, indicating the recruitment of T-type Ca 2+ channels. A significant increase on cell proliferation rate, which could be related to the elevated and sustained intracellular levels of cAMP was observed. We conclude that maintaining high levels of intracellular cAMP will cause an increase in Ca 2+ current density and this phenomenon impacts proliferation rate in GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Stimulation of secretion by the T84 colonic epithelial cell line with dietary flavonols.

PubMed

Nguyen, T D; Canada, A T; Heintz, G G; Gettys, T W; Cohn, J A

1991-06-15

Flavonols are dietary compounds widely distributed in plants and characterized by a 2-phenyl-benzo(alpha)pyrane nucleus possessing hydroxyl and ketone groups at positions 3 and 4, respectively. Kaempferol, quercetin, and myricetin are flavonols that are further mono-, di-, or trihydroxylated on the phenyl ring, respectively. To test whether these ingested flavonols might exert a direct secretory effect on intestinal epithelial cells, monolayers of the T84 colonocyte cell line were mounted in Ussing chambers and examined for ion transport response. Twenty minutes after addition of 100 microM quercetin to either the serosal or mucosal side, the short-circuit current change was maximal at 16.6 microA/cm2. Kaempferol was less potent than quercetin, while myricetin and glycosylated quercetin (rutin) did not induce secretion. The secretion induced by quercetin did not seem to be mediated by the reactive oxygen species generated by quercetin through auto-oxidation and/or redox cycling (superoxide, hydrogen peroxide, and the hydroxyl radical) because it was neither enhanced by iron, nor inhibited by desferroxamine B or catalase (alone or in combination with superoxide dismutase). Like vasoactive intestinal peptide, quercetin induced a secretory response that was inhibited by barium chloride and bumetanide, and which exhibited synergism with carbachol. Quercetin also stimulated a modest increase in intracellular cAMP levels and the phosphorylation of endogenous protein substrates for cAMP-dependent protein kinase. Thus, quercetin is a potent stimulus of colonocyte secretion that resembles secretagogues which act via a cAMP-mediated signaling pathway.

Movement of gating machinery during the activation of rod cyclic nucleotide-gated channels.

PubMed Central

Brown, R L; Snow, S D; Haley, T L

1998-01-01

In the visual and olfactory systems, cyclic nucleotide-gated (CNG) ion channels convert stimulus-induced changes in the internal concentrations of cGMP and cAMP into changes in membrane potential. Although it is known that significant activation of these channels requires the binding of three or more molecules of ligand, the detailed molecular mechanism remains obscure. We have probed the structural changes that occur during channel activation by using sulfhydryl-reactive methanethiosulfonate (MTS) reagents and N-ethylmaleimide (NEM). When expressed in Xenopus oocytes, the alpha-subunit of the bovine retinal channel forms homomultimeric channels that are activated by cGMP with a K1/2 of approximately 100 microM. Cyclic AMP, on the other hand, is a very poor activator; a saturating concentration elicits only 1% of the maximum current produced by cGMP. Treatment of excised patches with MTS-ethyltrimethylamine (MTSET) or NEM dramatically potentiated the channel's response to both cyclic nucleotides. After MTSET treatment, the dose-response relation for cGMP was shifted by over two orders of magnitude to lower concentrations. The effect on channel activation by cAMP was even more striking. After modification, the channels were fully activated by cAMP with a K1/2 of approximately 60 microM. This potentiation was abolished by conversion of Cys481 to a nonreactive alanine residue. Potentiation occurred more rapidly in the presence of saturating cGMP, indicating that this region of the channel is more accessible when the channel is open. Cys481 is located in a linker region between the transmembrane and cGMP-binding domains of the channel. These results suggest that this region of the channel undergoes significant movement during the activation process and is critical for coupling ligand binding to pore opening. Potentiation, however, is not mediated by the recently reported interaction between the amino- and carboxy-terminal regions of the alpha-subunit. Deletion of the entire amino-terminal domain had little effect on potentiation by MTSET. PMID:9675183

The effects of resonant magnetic perturbations on fast ion confinement in the Mega Amp Spherical Tokamak

NASA Astrophysics Data System (ADS)

McClements, K. G.; Akers, R. J.; Boeglin, W. U.; Cecconello, M.; Keeling, D.; Jones, O. M.; Kirk, A.; Klimek, I.; Perez, R. V.; Shinohara, K.; Tani, K.

2015-07-01

The effects of resonant magnetic perturbations (RMPs) on the confinement of energetic (neutral beam) ions in the Mega Amp Spherical Tokamak (MAST) are assessed experimentally using measurements of neutrons, fusion protons and fast ion Dα (FIDA) light emission. In single null-diverted (SND) MAST pulses with relatively low plasma current (400 kA), the total neutron emission dropped by approximately a factor of two when RMPs with toroidal mode number n = 3 were applied. The measured neutron rate during RMPs was much lower than that calculated using the TRANSP plasma simulation code, even when non-classical (but axisymmetric) ad hoc fast ion transport was taken into account in the latter. Sharp drops in spatially-resolved neutron rates, fusion proton rates and FIDA emission were also observed. First principles-based simulations of RMP-induced fast ion transport in MAST, using the F3D-OFMC code, show similar losses for two alternative representations of the MAST first wall, with and without full orbit effects taken into account; for n = 6 RMPs in a 600 kA plasma, the additional loss of beam power due to the RMPs was found in the simulations to be approximately 11%.

Maintenance of cAMP in non-heart-beating donor lungs reduces ischemia-reperfusion injury.

PubMed

Hoffmann, S C; Bleiweis, M S; Jones, D R; Paik, H C; Ciriaco, P; Egan, T M

2001-06-01

Studies suggest that pulmonary vascular ischemia-reperfusion injury (IRI) can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, assessed by capillary filtration coeficient (Kfc), in lungs retrieved from non-heart-beating donors (NHBDs) and reperfused with the addition of the beta(2)-adrenergic receptor agonist isoproterenol (iso), and rolipram (roli), a phosphodiesterase (type IV) inhibitor. Using an in situ isolated perfused lung model, lungs were retrieved from NHBD rats at varying intervals after death and either ventilated with O(2) or not ventilated. The lungs were reperfused with Earle's solution with or without a combination of iso (10 microM) and roli (2 microM). Kfc, lung viability, and pulmonary hemodynamics were measured. Lung tissue levels of adenine nucleotides and cAMP were measured by HPLC. Combined iso and roli (iso/roli) reperfusion decreased Kfc significantly (p < 0.05) compared with non-iso/roli-reperfused groups after 2 h of postmortem ischemia. Total adenine nucleotide (TAN) levels correlated with Kfc in non-iso/roli-reperfused (r = 0.89) and iso/roli-reperfused (r = 0.97) lungs. cAMP levels correlated with Kfc (r = 0.93) in iso/roli-reperfused lungs. Pharmacologic augmentation of tissue TAN and cAMP levels might ameliorate the increased capillary permeability observed in lungs retrieved from NHBDs.

On the role of calcium ions in the regulation of glycogenolysis in mouse brain cortical slices.

PubMed

Ververken, D; Van Veldhoven, P; Proost, C; Carton, H; De Wulf, H

1982-05-01

Using mouse brain cortical slices, we investigated the relative roles of cyclic AMP and of calcium ions as the intracellular messengers for the activation of glycogen phosphorylase (EC 2.4.1.1; alpha-1,4-glucan:orthophosphate glucosyltransferase) induced by noradrenaline and by depolarization. Activation of phosphorylase by 100 microM noradrenaline is mediated by beta-adrenergic receptors and does not require the copresence of adenosine. The role of the concomitant small increase in cyclic AMP is questioned. Short-term treatment with EGTA or LaCl3 abolishes the noradrenaline activation of phosphorylase, pointing to a critical role of extracellular calcium. Depolarization by 25 mM K+ or 100 microM veratridine produces a rapid and large (fourfold) activation of phosphorylase. Only veratridine increases the cyclic AMP levels; exogenous adenosine deaminase essentially blocks this cyclic AMP accumulation but not the phosphorylase activation. A half-maximal activation of phosphorylase occurs at about 12 mM K+. Addition of EGTA or LaCl3 reduces the effect of both depolarizations to a slight and transient activation of phosphorylase. These results indicate that activation of glycogen phosphorylase by K+ or veratridine occurs by a cyclic AMP-independent and calcium-dependent mechanism. The calcium dependency of brain phosphorylase kinase renders this kinase the prime target enzyme for regulation of glycogenolysis by calcium ions.

Narrow-angle Astrometry with SUSI

NASA Astrophysics Data System (ADS)

Kok, Y.; Ireland, M. J.; Robertson, J. G.; Tuthill, P. G.; Warrington, B. A.; Tango, W. J.

2014-09-01

SUSI (Sydney University Stellar Interferometer) is currently being fitted with a 2nd beam combiner, MUSCA (Micro-arcsecond University of Sydney Companion Astrometry), for the purpose of narrow-angle astrometry. With an aim to achieve ˜10 micro-arcseconds of angular resolution at its best, MUSCA allows SUSI to search for planets around bright binary stars, which are its primary targets. While the first beam combiner, PAVO (Precision Astronomical Visible Observations), is used to track stellar fringes during an observation, MUSCA will be used to measure separations of binary stars. MUSCA is a Michelson interferometer and its setup at SUSI will be described in this poster.

Free electron lasers for transmission of energy in space

NASA Technical Reports Server (NTRS)

Segall, S. B.; Hiddleston, H. R.; Catella, G. C.

1981-01-01

A one-dimensional resonant-particle model of a free electron laser (FEL) is used to calculate laser gain and conversion efficiency of electron energy to photon energy. The optical beam profile for a resonant optical cavity is included in the model as an axial variation of laser intensity. The electron beam profile is matched to the optical beam profile and modeled as an axial variation of current density. Effective energy spread due to beam emittance is included. Accelerators appropriate for a space-based FEL oscillator are reviewed. Constraints on the concentric optical resonator and on systems required for space operation are described. An example is given of a space-based FEL that would produce 1.7 MW of average output power at 0.5 micrometer wavelength with over 50% conversion efficiency of electrical energy to laser energy. It would utilize a 10 m-long amplifier centered in a 200 m-long optical cavity. A 3-amp, 65 meV electrostatic accelerator would provide the electron beam and recover the beam after it passes through the amplifier. Three to five shuttle flights would be needed to place the laser in orbit.

Ion beam modification of zinc white pigment characterized by ex situ and in situ μ-Raman and XPS

NASA Astrophysics Data System (ADS)

Beck, L.; Gutiérrez, P. C.; Miro, S.; Miserque, F.

2017-10-01

Zinc oxide, known as zinc white, is one of the principal white pigments developed in the 18th century and was used by the Impressionist painters. ZnO as artists' pigment has occasionally been characterized by X-ray and ion beam techniques, but these studies are limited by the potential for visible radiation effect. Ion beam modifications of zinc oxide have extensively been investigated, but mainly for electronic and industrial applications. In this paper, we focus our investigation on ion beam modification of ZnO used as pigment. Two irradiation conditions have been used: an external 3 MeV proton micro-beam representative of PIXE analysis and 2 MeV H+ and 1.2 MeV Au + beams in vacuum to investigate irradiation modifications in electronic and nuclear energy loss regimes. Ion beam modification was characterized by ex situ and in situ micro-Raman spectrometry and XPS. The results shows that IBA of zinc white can be carried out safely in historical paintings with low current and dose.

Superior characteristics of microscale light emitting diodes through tightly lateral oxide-confined scheme

NASA Astrophysics Data System (ADS)

Huang, Shen-Che; Li, Heng; Zhang, Zhe-Han; Chen, Hsiang; Wang, Shing-Chung; Lu, Tien-Chang

2017-01-01

We report on the design of the geometry and chip size-controlled structures of microscale light-emitting diodes (micro-LEDs) with a shallow-etched oxide-refilled current aperture and their performance. The proposed structure, which combines an indium-tin-oxide layer and an oxide-confined aperture, exhibited not only uniform current distribution but also remarkably tight current confinement. An extremely high injection level of more than 90 kA/cm2 was achieved in the micro-LED with a 5-μm aperture. Current spreading and the droop mechanism in the investigated devices were characterized through electroluminescence measurements, optical microscopy, and beam-view imaging. Furthermore, we utilized the β-model and S-model to elucidate current crowding and the efficiency droop phenomenon in the investigated micro-LEDs. The luminescence results evidenced the highly favorable performance of the fabricated micro-LEDs, which is a result of their more uniform current spreading and lower junction temperature relative to conventional LEDs. Moreover, the maximum endured current density could be further increased by reducing the aperture size of the micro-LEDs. The proposed design, which is expected to be beneficial for the development of high-performance array-based micro-LEDs, is practicable through current state-of-the-art processing techniques.

Bolt beam propagation analysis

NASA Astrophysics Data System (ADS)

Shokair, I. R.

BOLT (Beam on Laser Technology) is a rocket experiment to demonstrate electron beam propagation on a laser ionized plasma channel across the geomagnetic field in the ion focused regime (IFR). The beam parameters for BOLT are: beam current I(sub b) = 100 Amps, beam energy of 1--1.5 MeV (gamma =3-4), and a Gaussian beam and channel of radii r(sub b) = r(sub c) = 1.5 cm. The N+1 ionization scheme is used to ionize atomic oxygen in the upper atmosphere. This scheme utilizes 130 nm light plus three IR lasers to excite and then ionize atomic oxygen. The limiting factor for the channel strength is the energy of the 130 nm laser, which is assumed to be 1.6 mJ for BOLT. At a fixed laser energy and altitude (fixing the density of atomic oxygen), the range can be varied by adjusting the laser tuning, resulting in a neutralization fraction axial profile of the form: f(z) = f(sub 0) e(exp minus z)/R, where R is the range. In this paper we consider the propagation of the BOLT beam and calculate the range of the electron beam taking into account the fact that the erosion rates (magnetic and inductive) vary with beam length as the beam and channel dynamically respond to sausage and hose instabilities.

cAMP modulates multiple K+ currents, increasing spike duration and excitability in Aplysia sensory neurons.

PubMed

Goldsmith, B A; Abrams, T W

1992-12-01

Enhancement of the defensive withdrawal reflex of Aplysia involves a prolongation of the action potentials of mechanosensory neurons, which contributes to facilitation of transmitter release from these cells. Recent reports have suggested that whereas cAMP-dependent modulation of K+ current increases sensory neuron excitability, a cAMP-independent decrease in K+ current may increase the action potential duration and, thus, facilitate transmitter release. We have tested this proposal using Walsh cAMP-dependent protein kinase inhibitor or activators of the cAMP cascade and found that cAMP plays a major role in the spike-broadening effects of facilitatory transmitter; however, broadening requires higher levels of activation of the cAMP-dependent kinase than does increasing excitability. A steeply voltage-dependent transient K+ current, termed IKV,early, and the slowly activating S-type K+ (S-K+) current are both reduced by activation of the cAMP cascade, although with different sensitivities to the second messenger, enabling excitability and spike duration to be regulated independently. Differences in cAMP sensitivity also suggested that the originally described S-K+ current actually consists of two independent components, a slowly activating component and a time-independent, "steady-state" current that is activated at rest.

A simple thick target for production of 89Zr using an 11MeV cyclotron

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

Link, Jeanne M.; Krohn, Kenneth A.; O'Hara, Matthew J.

2017-04-01

The growing interest but limited availability of 89Zr for PET led us to test targets for the 89(p,n) reaction. The goal was an easily constructed target for an 11 MeV Siements cyclotron. Yttrium foils were tested at different thicknesses, angles and currents. A 90 degree foil tolerated 41 microAmp without damage and produced ~800 MBq/hr, >20 mCi, an amount adequate for radiochemistry research and human doses in a widely available accelerator. This method should translate to higher energy cyclotrons.

A high brightness proton injector for the Tandetron accelerator at Jožef Stefan Institute

NASA Astrophysics Data System (ADS)

Pelicon, Primož; Podaru, Nicolae C.; Vavpetič, Primož; Jeromel, Luka; Ogrinc Potocnik, Nina; Ondračka, Simon; Gottdang, Andreas; Mous, Dirk J. M.

2014-08-01

Jožef Stefan Institute recently commissioned a high brightness H- ion beam injection system for its existing tandem accelerator facility. Custom developed by High Voltage Engineering Europa, the multicusp ion source has been tuned to deliver at the entrance of the Tandetron™ accelerator H- ion beams with a measured brightness of 17.1 A m-2 rad-2 eV-1 at 170 μA, equivalent to an energy normalized beam emittance of 0.767 π mm mrad MeV1/2. Upgrading the accelerator facility with the new injection system provides two main advantages. First, the high brightness of the new ion source enables the reduction of object slit aperture and the reduction of acceptance angle at the nuclear microprobe, resulting in a reduced beam size at selected beam intensity, which significantly improves the probe resolution for micro-PIXE applications. Secondly, the upgrade strongly enhances the accelerator up-time since H and He beams are produced by independent ion sources, introducing a constant availability of 3He beam for fusion-related research with NRA. The ion beam particle losses and ion beam emittance growth imply that the aforementioned beam brightness is reduced by transport through the ion optical system. To obtain quantitative information on the available brightness at the high-energy side of the accelerator, the proton beam brightness is determined in the nuclear microprobe beamline. Based on the experience obtained during the first months of operation for micro-PIXE applications, further necessary steps are indicated to obtain optimal coupling of the new ion source with the accelerator to increase the normalized high-energy proton beam brightness at the JSI microprobe, currently at 14 A m-2 rad-2 eV-1, with the output current at 18% of its available maximum.

Optical wireless communications for micromachines

NASA Astrophysics Data System (ADS)

O'Brien, Dominic C.; Yuan, Wei Wen; Liu, Jing Jing; Faulkner, Grahame E.; Elston, Steve J.; Collins, Steve; Parry-Jones, Lesley A.

2006-08-01

A key challenge for wireless sensor networks is minimizing the energy required for network nodes to communicate with each other, and this becomes acute for self-powered devices such as 'smart dust'. Optical communications is a potentially attractive solution for such devices. The University of Oxford is currently involved in a project to build optical wireless links to smart dust. Retro-reflectors combined with liquid crystal modulators can be integrated with the micro-machine to create a low power transceiver. When illuminated from a base station a modulated beam is returned, transmitting data. Data from the base station can be transmitted using modulation of the illuminating beam and a receiver at the micro-machine. In this paper we outline the energy consumption and link budget considerations in the design of such micro-machines, and report preliminary experimental results.

Receptors for VIP and PACAP in guinea pig cerebral cortex: effects on cyclic AMP synthesis and characterization by 125I-VIP binding.

PubMed

Zawilska, Jolanta B; Dejda, Agnieszka; Niewiadomski, Pawel; Gozes, Illana; Nowak, Jerzy Z

2005-01-01

Receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in guinea pig cerebral cortex were characterized by (1) radioreceptor binding of 125I-labeled VIP (human/rat/porcine), and (2) cyclic AMP (cAMP) formation. Saturation analysis of 125I-VIP binding to membranes of guinea pig cerebral cortex resulted in a linear Scatchard plot, suggesting the presence of a single class of high-affinity receptor-binding sites, with a Kd of 0.63 nM and a B(max) of 77 fmol/mg protein. Various peptides from the PACAP/VIP/secretin family displaced the specific binding of 125I-VIP to guinea pig cerebrum with the relative rank order of potency: chicken VIP (cVIP) > or = PACAP38 approximately PACAP27 approximately guinea pig VIP (gpVIP) > or = mammalian (human/rat/porcine) VIP (mVIP) > peptide histidine-methionine (PHM) > peptide histidine-isoleucine (PHI) > secretin. Analysis of the competition curves revealed displacement of 125I-VIP from high- and lower-affinity binding sites, with IC50 values in the picomolar and the nanomolar range, respectively. About 70% of the specific 125I-VIP-binding sites in guinea pig cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), PACAP27, cVIP, gpVIP, mVIP, PHM, and PHI stimulated cAMP production in [3H]adenine-prelabeled slices of guinea pig cerebral cortex in a concentration-dependent manner. Of the tested peptides, the most effective were PACAP38 and PACAP27, which at a 1 microM concentration produced a 17- to 19-fold rise in cAMP synthesis, increasing the nucleotide production to approx 11% conversion above the control value. The three forms of VIP (cVIP, mVIP, and gpVIP) at the highest concentration used, i.e., 3 microM, produced net increases in cAMP production in the range of 8-9% conversion, whereas 5 microM PHM and PHI, by, respectively, 6.7% and 4.9% conversion. It is concluded that cerebral cortex of guinea pig contains VPAC- type receptors positively linked to cAMP formation. In addition, the observed stronger action of PACAP (both PACAP38 and PACAP27), when compared to any form of VIP, on cAMP production in this tissue, suggests its interaction with both PAC1 and VPAC receptors.

Multistable wireless micro-actuator based on antagonistic pre-shaped double beams

NASA Astrophysics Data System (ADS)

Liu, X.; Lamarque, F.; Doré, E.; Pouille, P.

2015-07-01

This paper presents a monolithic multistable micro-actuator based on antagonistic pre-shaped double beams. The designed micro-actuator is formed by two rows of bistable micro-actuators providing four stable positions. The bistable mechanism for each row is a pair of antagonistic pre-shaped beams. This bistable mechanism has an easier pre-load operation compared to the pre-compressed bistable beams method. Furthermore, it solves the asymmetrical force output problem of parallel pre-shaped bistable double beams. At the same time, the geometrical limit is lower than parallel pre-shaped bistable double beams, which ensures a smaller stroke of the micro-actuator with the same dimensions. The designed micro-actuator is fabricated using laser cutting machine on medium density fiberboard (MDF). The bistability and merits of antagonistic pre-shaped double beams are experimentally validated. Finally, a contactless actuation test is performed using 660 nm wavelength laser heating shape memory alloy (SMA) active elements.

Structural insights into Cn-AMP1, a short disulfide-free multifunctional peptide from green coconut water.

PubMed

Santana, Mábio J; de Oliveira, Aline L; Queiroz Júnior, Luiz H K; Mandal, Santi M; Matos, Carolina O; Dias, Renata de O; Franco, Octavio L; Lião, Luciano M

2015-02-27

Multifunctional and promiscuous antimicrobial peptides (AMPs) can be used as an efficient strategy to control pathogens. However, little is known about the structural properties of plant promiscuous AMPs without disulfide bonds. CD and NMR were used to elucidate the structure of the promiscuous peptide Cn-AMP1, a disulfide-free peptide isolated from green coconut water. Data here reported shows that peptide structure is transitory and could be different according to the micro-environment. In this regard, Cn-AMP1 showed a random coil in a water environment and an α-helical structure in the presence of SDS-d25 micelles. Moreover, deuterium exchange experiments showed that Gly4, Arg5 and Met9 residues are less accessible to solvent, suggesting that flexibility and cationic charges seem to be essential for Cn-AMP1 multiple activities. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Distinct pools of cAMP centre on different isoforms of adenylyl cyclase in pituitary-derived GH3B6 cells.

PubMed

Wachten, Sebastian; Masada, Nanako; Ayling, Laura-Jo; Ciruela, Antonio; Nikolaev, Viacheslav O; Lohse, Martin J; Cooper, Dermot M F

2010-01-01

Microdomains have been proposed to explain specificity in the myriad of possible cellular targets of cAMP. Local differences in cAMP levels can be generated by phosphodiesterases, which control the diffusion of cAMP. Here, we address the possibility that adenylyl cyclases, the source of cAMP, can be primary architects of such microdomains. Distinctly regulated adenylyl cyclases often contribute to total cAMP levels in endogenous cellular settings, making it virtually impossible to determine the contribution of a specific isoform. To investigate cAMP dynamics with high precision at the single-isoform level, we developed a targeted version of Epac2-camps, a cAMP sensor, in which the sensor was tagged to a catalytically inactive version of the Ca(2+)-stimulable adenylyl cyclase 8 (AC8). This sensor, and less stringently targeted versions of Epac2-camps, revealed opposite regulation of cAMP synthesis in response to Ca(2+) in GH(3)B(6) pituitary cells. Ca(2+) release triggered by thyrotropin-releasing hormone stimulated the minor endogenous AC8 species. cAMP levels were decreased by inhibition of AC5 and AC6, and simultaneous activation of phosphodiesterases, in different compartments of the same cell. These findings demonstrate the existence of distinct adenylyl-cyclase-centered cAMP microdomains in live cells and open the door to their molecular micro-dissection.

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.

Laser microprocessing and nanoengineering of large-area functional micro/nanostructures

NASA Astrophysics Data System (ADS)

Tang, M.; Xie, X. Z.; Yang, J.; Chen, Z. C.; Xu, L.; Choo, Y. S.; Hong, M. H.

2011-12-01

Laser microprocessing and nanoengineering are of great interest to both scientists and engineers, since the inspired properties of functional micro/nanostructures over large areas can lead to numerous unique applications. Currently laser processing systems combined with high speed automation ensure the focused laser beam to process various materials at a high throughput and a high accuracy over large working areas. UV lasers are widely used in both laser microprocessing and nanoengineering. However by improving the processing methods, green pulsed laser is capable of replacing UV lasers to make high aspect ratio micro-grooves on fragile and transparent sapphire substrates. Laser micro-texturing can also tune the wetting property of metal surfaces from hydrophilic to super-hydrophobic at a contact angle of 161° without chemical coating. Laser microlens array (MLA) can split a laser beam into multiple laser beams and reduce the laser spot size down to sub-microns. It can be applied to fabricate split ring resonator (SRR) meta-materials for THz sensing, surface plasmonic resonance (SPR) structures for NIR and molding tools for soft lithography. Furthermore, laser interference lithography combined with thermal annealing can obtain a large area of sub-50nm nano-dot clusters used for SPR applications.

The aniracetam metabolite 2-pyrrolidinone induces a long-term enhancement in AMPA receptor responses via a CaMKII pathway.

PubMed

Nishizaki, Tomoyuki; Matsumura, Takuro

2002-01-31

The present study was conducted to assess the effect of aniracetam and its metabolites, such as 2-pyrrolidinone, p-anisic acid, and anisamide butyrate, on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, heteromerically formed of GluR1,2 (GluR1 and GluR2), GluR1,3 (GluR1 and GluR3), and GluR1,2,3 (GluR1, GluR2, and GluR3), expressed in Xenopus oocytes. 2-Pyrrolidinone potentiated kainate-evoked currents through GluR1,2,3 channels in a bell-shaped dose-dependent manner at concentrations ranged from 1 nM to 300 microM, with a maximal effect at 100 microM. The potentiation was long-lasting, reaching approximately 180% of basal levels 60 min after 5-min treatment with 2-pyrrolidinone at 100 microM. 2-Pyrrolidinone (100 microM) potentiated GluR1,3 channel currents as observed in GluR1,2,3, but instead it depressed GluR1,2 currents. Aniracetam and p-anisic acid potentiated GluR1,2,3 channel currents, but to a lesser extent, each about 130 and 103% of basal levels 60 min after treatment at 100 microM. In contrast, anisamide butyrate had no potentiating effect on the currents. Potentiation of GluR1,2,3 channel currents obtained with 2-pyrrolidinone was inhibited by KN-93, a selective inhibitor of calcium/calmodulin-dependent protein kinase (CaMKII), while it was not affected by GF109203X, a selective inhibitor of protein kinase C or H-89, a selective inhibitor of cAMP-dependent protein kinase. The results of the present study suggest that 2-pyrrolidinone persistently enhances activity of the Ca2+-permeable AMPA receptors, GluR1,3 and GluR1,2,3, by interacting with CaMKII.

A xanthine-based epithelium-dependent airway relaxant KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) increases respiratory performance and protects against tumor necrosis factor-alpha-induced tracheal contraction, involving nitric oxide release and expression of cGMP and protein kinase G.

PubMed

Lin, Rong-Jyh; Wu, Bin-Nan; Lo, Yi-Ching; An, Li-Mei; Dai, Zen-Kong; Lin, Young-Tso; Tang, Chao-Shun; Chen, Ing-Jun

2006-02-01

KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) was investigated in guinea pig tracheal smooth muscle. Intratracheal instillation of tumor necrosis factor (TNF)-alpha (0.01 mg/kg/300 microl) induced bronchoconstriction, increases of lung resistance, and decreases of dynamic lung compliance. Instillation of KMUP-3 (0.5-2.0 mg/kg) reversed this situation. In isolated trachea precontracted with carbachol, KMUP-3 (10-100 microM)-caused relaxations were attenuated by epithelium removal and by pretreatments with an inhibitor of K(+) channel, tetraethylammonium (10 mm); K(ATP) channel, glibenclamide (1 microM); voltage-dependent K(+) channel, 4-aminopyridine (100 microM); Ca(2+)-dependent K(+) channel, charybdotoxin (0.1 microM) or apamin (1 microM); soluble guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1one (ODQ, 1 microM); nitric-oxide (NO) synthase, N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM); and adenylate cyclase, SQ 22536 [9-(terahydro-2-furanyl)-9H-purin-6-amine] (100 microM). KMUP-3 (0.01-100 microM) induced increases of cGMP and cAMP in primary culture of tracheal smooth muscle cells (TSMCs). The increase in cGMP by KMUP-3 was reduced by ODQ and L-NAME; the increase in cAMP was reduced by SQ 22536. Western blot analysis indicated that KMUP-3 (1 microM) induced expression of protein kinase A (PKA)(ri) and protein kinase G (PKG)(1alpha 1beta) in TSMCs.SQ 22536 inhibited KMUP-3-induced expression of (PKA)(ri). On the contrary, ODQ inhibited KMUP-3-induced expression of PKG(1alpha 1beta) In epithelium-intact trachea, KMUP-3 increased the NO release. Activation of sGC, NO release, and inhibition of phosphodiesterases in TSMCs by KMUP-3 may result in increases of intracellular cGMP and cAMP, which subsequently activate PKG and PKA, efflux of K(+) ion, and associated reduction in Ca(2+) influx in vitro, indicating the action mechanism to protect against TNF-alpha-induced airway dysfunction in vivo.

Heavy Ion Current Transients in SiGe HBTs

NASA Technical Reports Server (NTRS)

Pellish, Jonathan A.; Reed, Robert A.; Vizkelethy, Gyorgy; McMorrow, Dale; Ferlet-Cavrois, Veronique; Baggio, Jacques; Paillet, Philipe; Duhanel, Olivier; Phillips, Stanley D.; Sutton, Akil K.;

The effect of plasma density and emitter geometry on space charge limits for field emitter array electron charge emission into a space plasma

NASA Astrophysics Data System (ADS)

Morris, Dave; Gilchrist, Brian; Gallimore, Alec

2001-02-01

Field Emitter Array Cathodes (FEACs) are a new technology being developed for several potential spacecraft electron emission and charge control applications. Instead of a single hot (i.e., high powered) emitter, or a gas dependant plasma contactor, FEAC systems consist of many (hundreds or thousands) of small (micron level) cathode/gate pairs printed on a semiconductor wafer that effect cold field emission at relatively low voltages. Each individual cathode emits only micro-amp level currents, but a functional array is capable of amp/cm2 current densities. It is hoped that thus FEAC offers the possibility of a relatively low-power, simple to integrate, and inexpensive technique for the high level of current emissions that are required for an electrodynamic tether (EDT) propulsion mission. Space charge limits are a significant concern for the EDT application. Vacuum chamber tests and PIC simulations are being performed at the University of Michigan Plasmadynamics and Electric Propulsion Laboratory and Space Physics Research Laboratory to determine the effect of plasma density and emitter geometry on space charge limitations. The results of this work and conclusions to date of how to best mitigate space charge limits will be presented. .

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

Micro-beam friction liner and method of transferring energy

DOEpatents

Mentesana, Charles [Leawood, KS

2007-07-17

A micro-beam friction liner adapted to increase performance and efficiency and reduce wear in a piezoelectric motor or actuator or other device using a traveling or standing wave to transfer energy in the form of torque and momentum. The micro-beam friction liner comprises a dense array of micro-beam projections having first ends fixed relative to a rotor and second ends projecting substantially toward a plurality of teeth of a stator, wherein the micro-beam projections are compressed and bent during piezoelectric movement of the stator teeth, thereby storing the energy, and then react against the stator teeth to convert the stored energy stored to rotational energy in the rotor.

Can Coulomb repulsion for charged particle beams be overcome?

NASA Astrophysics Data System (ADS)

Retsky, Michael W.

2004-01-01

Mutual repulsion of discrete charged particles or Coulomb repulsion is widely considered to be an ultimate hard limit in charged particle optics. It prevents the ability to finely focus high current beams into a small spots at large distances from the defining apertures. A classic example is the 1970s era "Star Wars" study of an electron beam directed energy weapon as an orbiting antiballistic missile device. After much analysis, it was considered physically impossible to focus a 1000-amp 1-GeV beam into a 1-cm diameter spot 1000-km from the beam generator. The main reason was that a 1-cm diameter beam would spread to 5-m diameter at 1000-km due to Coulomb repulsion. Since this could not be overcome, the idea was abandoned. But is this true? What if the rays were reversed? That is, start with a 5-m beam converging slightly with the same nonuniform angular and energy distribution as the electrons from the original problem were spreading at 1000-km distance. Could Coulomb repulsion be overcome? Looking at the terms in computational studies, some are reversible while others are not. Since the nonreversible terms should be small, it might be possible to construct an electron beam directed energy weapon.

Current status of Kumgang laser system

NASA Astrophysics Data System (ADS)

Kong, Hong Jin; Park, Sangwoo; Ahn, HeeKyung; Lee, Hwihyeong; Oh, Jungsuk; Kim, Jom Sool

2015-02-01

In KAIST, Kumgang laser is being developed for demonstration of the kW level coherent beam combination using stimulated Brillouin scattering phase conjugation mirrors. It will combine 4 modules of DPSSL rod amplifier which produces 1 kW output power. It is composed of the single frequency front-end, pre-amplifier module, and main amplifier. The output powers of the pre-amp and main amplifier module are 200 W (20 mJ @ 10 kHz / 10 ns) and 1.07kW (107 mJ @ 10 kHz / 10 ns), respectively.

BRIEF COMMUNICATION: Electrothermal bistability tuning in a large displacement micro actuator

NASA Astrophysics Data System (ADS)

Gerson, Y.; Krylov, S.; Ilic, B.

2010-11-01

We report on an approach allowing simple yet efficient tuning of the bistability properties in large displacement micro actuators. The devices fabricated from silicon on insulator (SOI) wafers using a deep reactive ion etching (DRIE)-based process incorporate elastic suspension realized as a pair of beams initially curved in-plane and are operated electrostatically by a comb-drive transducer. The curvature of beam and therefore the stability characteristics of the suspension are controlled by passing a current through the suspension and resistive heating the beam material. Experimental results, which are in good agreement with the finite elements model predictions, demonstrate the feasibility of the suggested approach and show that the application of a small tuning current increases the device deflection from 42 to 56 µm, allows adjustment of the critical snap-through and snap-back voltages and makes it possible the control of latching without an additional electrode. The approach can be efficiently implemented in electrical and optical switches and threshold inertial and mass sensors where the use of long displacement actuators with an adjustable bistability range is beneficial.

Micro-Bunched Beam Production at FAST for Narrow Band THz Generation Using a Slit-Mask

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

Hyun, J.; Crawford, D.; Edstrom Jr, D.

We discuss simulations and experiments on creating micro-bunch beams for generating narrow band THz radiation at the Fermilab Accelerator Science and Technology (FAST) facility. The low-energy electron beamline at FAST consists of a photoinjector-based RF gun, two Lband superconducting accelerating cavities, a chicane, and a beam dump. The electron bunches are lengthened with cavity phases set off-crest for better longitudinal separation and then micro-bunched with a slit-mask installed in the chicane. We carried out the experiments with 30 MeV electron beams and detected signals of the micro-bunching using a skew quadrupole magnet in the chicane. In this paper, the detailsmore » of micro-bunch beam production, the detection of micro-bunching and comparison with simulations are described.« less

Enhanced corrosion resistance of strontium hydroxyapatite coating on electron beam treated surgical grade stainless steel

NASA Astrophysics Data System (ADS)

Gopi, D.; Rajeswari, D.; Ramya, S.; Sekar, M.; R, Pramod; Dwivedi, Jishnu; Kavitha, L.; Ramaseshan, R.

2013-12-01

The surface of 316L stainless steel (316L SS) is irradiated by high energy low current DC electron beam (HELCDEB) with energy of 500 keV and beam current of 1.5 mA followed by the electrodeposition of strontium hydroxyapatite (Sr-HAp) to enhance its corrosion resistance in physiological fluid. The coatings were characterised by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and High resolution scanning electron microscopy (HRSEM). The Sr-HAp coating on HELCDEB treated 316L SS exhibits micro-flower structure. Electrochemical results show that the Sr-HAp coating on HELCDEB treated 316L SS possesses maximum corrosion resistance in Ringer's solution.

The Abort Kicker System for the PEP-II Storage Rings at SLAC.

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

Delamare, Jeffrey E

2003-06-20

The PEP-II project has two storage rings. The HER (High Energy Ring) has up to 1.48 A of election beam at 9 GeV, and the LER (Low Energy Ring) has up to 2.14 A of positron beam at 3.1 GeV. To protect the HER and LER beam lines in the event of a ring component failure, each ring has an abort kicker system which directs the beam into a dump when a failure is detected. Due to the high current of the beams, the beam kick is tapered from 100% to 80% in 7.33 {micro}S (the beam transit time aroundmore » the ring). This taper distributes the energy evenly across the window which separates the ring from the beam dump such that the window is not damaged. The abort kicker trigger is synchronized with the ion clearing gap of the beam allowing for the kicker field to rise from 0-80% while there is no beam in the kicker magnet. Originally the kicker system was designed for a rise time of 370nS [1], but because the ion clearing gap was reduced in half, so was the rise time requirement for the kicker. This report discusses the design of the system interlocks, diagnostics, and modulator with the modifications necessary to accommodate an ion clearing gap of 185nS.« less

Overview on the recent study of antimicrobial peptides: origins, functions, relative mechanisms and application.

PubMed

Li, Yanmei; Xiang, Qi; Zhang, Qihao; Huang, Yadong; Su, Zhijian

2012-10-01

Antimicrobial peptides (AMPs), which are produced by several species including insects, other animals, micro-organisms and synthesis, are a critical component of the natural defense system. With the growing problem of pathogenic organisms resistant to conventional antibiotics, especially with the emergence of NDM-1, there is increased interest in the pharmacological application of AMPs. They can protect against a broad array of infectious agents, such as bacteria, fungi, parasite, virus and cancer cells. AMPs have a very good future in the application in pharmaceuticals industry and food additive. This review focuses on the AMPs from different origins in these recent years, and discusses their various functions and relative mechanisms of action. It will provide some detailed files for clinical research of pharmaceuticals industry and food additive in application. Copyright © 2012 Elsevier Inc. All rights reserved.

Build-up and surface dose measurements on phantoms using micro-MOSFET in 6 and 10 MV x-ray beams and comparisons with Monte Carlo calculations.

PubMed

Xiang, Hong F; Song, Jun S; Chin, David W H; Cormack, Robert A; Tishler, Roy B; Makrigiorgos, G Mike; Court, Laurence E; Chin, Lee M

2007-04-01

This work is intended to investigate the application and accuracy of micro-MOSFET for superficial dose measurement under clinically used MV x-ray beams. Dose response of micro-MOSFET in the build-up region and on surface under MV x-ray beams were measured and compared to Monte Carlo calculations. First, percentage-depth-doses were measured with micro-MOSFET under 6 and 10 MV beams of normal incidence onto a flat solid water phantom. Micro-MOSFET data were compared with the measurements from a parallel plate ionization chamber and Monte Carlo dose calculation in the build-up region. Then, percentage-depth-doses were measured for oblique beams at 0 degrees-80 degrees onto the flat solid water phantom with micro-MOSFET placed at depths of 2 cm, 1 cm, and 2 mm below the surface. Measurements were compared to Monte Carlo calculations under these settings. Finally, measurements were performed with micro-MOSFET embedded in the first 1 mm layer of bolus placed on a flat phantom and a curved phantom of semi-cylindrical shape. Results were compared to superficial dose calculated from Monte Carlo for a 2 mm thin layer that extends from the surface to a depth of 2 mm. Results were (1) Comparison of measurements with MC calculation in the build-up region showed that micro-MOSFET has a water-equivalence thickness (WET) of 0.87 mm for 6 MV beam and 0.99 mm for 10 MV beam from the flat side, and a WET of 0.72 mm for 6 MV beam and 0.76 mm for 10 MV beam from the epoxy side. (2) For normal beam incidences, percentage depth dose agree within 3%-5% among micro-MOSFET measurements, parallel-plate ionization chamber measurements, and MC calculations. (3) For oblique incidence on the flat phantom with micro-MOSFET placed at depths of 2 cm, 1 cm, and 2 mm, measurements were consistent with MC calculations within a typical uncertainty of 3%-5%. (4) For oblique incidence on the flat phantom and a curved-surface phantom, measurements with micro-MOSFET placed at 1.0 mm agrees with the MC calculation within 6%, including uncertainties of micro-MOSFET measurements of 2%-3% (1 standard deviation), MOSFET angular dependence of 3.0%-3.5%, and 1%-2% systematical error due to phantom setup geometry asymmetry. Micro-MOSFET can be used for skin dose measurements in 6 and 10 MV beams with an estimated accuracy of +/- 6%.

Nonlinear primary resonance of micro/nano-beams made of nanoporous biomaterials incorporating nonlocality and strain gradient size dependency

NASA Astrophysics Data System (ADS)

Sahmani, S.; Aghdam, M. M.

2018-03-01

A wide range of biological applications such as drug delivery, biosensors and hemodialysis can be provided by nanoporous biomaterials due to their uniform pore size as well as considerable pore density. In the current study, the size dependency in the nonlinear primary resonance of micro/nano-beams made of nanoporous biomaterials is anticipated. To accomplish this end, a refined truncated cube is introduced to model the lattice structure of nanoporous biomaterial. Accordingly, analytical expressions for the mechanical properties of material are derived as functions of pore size. After that, based upon a nonlocal strain gradient beam model, the size-dependent nonlinear Duffing type equation of motion is constructed. The Galerkin technique together with the multiple time-scales method is employed to obtain the nonlocal strain gradient frequency-response and amplitude-response related to the nonlinear primary resonance of a micro/nano-beam made of the nanoporous biomaterial with different pore sizes. It is indicated that the nonlocality causes to decrease the response amplitudes associated with the both bifurcation points of the jump phenomenon, while the strain gradient size dependency causes to increase them. Also, it is found that increasing the pore size leads to enhance the nonlinearity, so the maximum deflection of response occurs at higher excitation frequency.

A new evaluation method of electron optical performance of high beam current probe forming systems.

PubMed

Fujita, Shin; Shimoyama, Hiroshi

2005-10-01

A new numerical simulation method is presented for the electron optical property analysis of probe forming systems with point cathode guns such as cold field emitters and the Schottky emitters. It has long been recognized that the gun aberrations are important parameters to be considered since the intrinsically high brightness of the point cathode gun is reduced due to its spherical aberration. The simulation method can evaluate the 'threshold beam current I(th)' above which the apparent brightness starts to decrease from the intrinsic value. It is found that the threshold depends on the 'electron gun focal length' as well as on the spherical aberration of the gun. Formulas are presented to estimate the brightness reduction as a function of the beam current. The gun brightness reduction must be included when the probe property (the relation between the beam current l(b) and the probe size on the sample, d) of the entire electron optical column is evaluated. Formulas that explicitly consider the gun aberrations into account are presented. It is shown that the probe property curve consists of three segments in the order of increasing beam current: (i) the constant probe size region, (ii) the brightness limited region where the probe size increases as d approximately I(b)(3/8), and (iii) the angular current intensity limited region in which the beam size increases rapidly as d approximately I(b)(3/2). Some strategies are suggested to increase the threshold beam current and to extend the effective beam current range of the point cathode gun into micro ampere regime.

An added-mass partition algorithm for fluid–structure interactions of compressible fluids and nonlinear solids

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

Banks, J.W., E-mail: banksj3@rpi.edu; Henshaw, W.D., E-mail: henshw@rpi.edu; Kapila, A.K., E-mail: kapila@rpi.edu

We describe an added-mass partitioned (AMP) algorithm for solving fluid–structure interaction (FSI) problems involving inviscid compressible fluids interacting with nonlinear solids that undergo large rotations and displacements. The computational approach is a mixed Eulerian–Lagrangian scheme that makes use of deforming composite grids (DCG) to treat large changes in the geometry in an accurate, flexible, and robust manner. The current work extends the AMP algorithm developed in Banks et al. [1] for linearly elasticity to the case of nonlinear solids. To ensure stability for the case of light solids, the new AMP algorithm embeds an approximate solution of a nonlinear fluid–solidmore » Riemann (FSR) problem into the interface treatment. The solution to the FSR problem is derived and shown to be of a similar form to that derived for linear solids: the state on the interface being fundamentally an impedance-weighted average of the fluid and solid states. Numerical simulations demonstrate that the AMP algorithm is stable even for light solids when added-mass effects are large. The accuracy and stability of the AMP scheme is verified by comparison to an exact solution using the method of analytical solutions and to a semi-analytical solution that is obtained for a rotating solid disk immersed in a fluid. The scheme is applied to the simulation of a planar shock impacting a light elliptical-shaped solid, and comparisons are made between solutions of the FSI problem for a neo-Hookean solid, a linearly elastic solid, and a rigid solid. The ability of the approach to handle large deformations is demonstrated for a problem of a high-speed flow past a light, thin, and flexible solid beam.« less

Amps particle accelerator definition study

NASA Technical Reports Server (NTRS)

Sellen, J. M., Jr.

1975-01-01

The Particle Accelerator System of the AMPS (Atmospheric, Magnetospheric, and Plasmas in Space) payload is a series of charged particle accelerators to be flown with the Space Transportation System Shuttle on Spacelab missions. In the configuration presented, the total particle accelerator system consists of an energetic electron beam, an energetic ion accelerator, and both low voltage and high voltage plasma acceleration devices. The Orbiter is illustrated with such a particle accelerator system.

GTP-Binding Proteins Inhibit cAMP Activation of Chloride Channels in Cystic Fibrosis Airway Epithelial Cells

NASA Astrophysics Data System (ADS)

Schwiebert, Erik M.; Kizer, Neil; Gruenert, Dieter C.; Stanton, Bruce A.

1992-11-01

Cystic fibrosis (CF) is a genetic disease characterized, in part, by defective regulation of Cl^- secretion by airway epithelial cells. In CF, cAMP does not activate Cl^- channels in the apical membrane of airway epithelial cells. We report here whole-cell patch-clamp studies demonstrating that pertussis toxin, which uncouples heterotrimeric GTP-binding proteins (G proteins) from their receptors, and guanosine 5'-[β-thio]diphosphate, which prevents G proteins from interacting with their effectors, increase Cl^- currents and restore cAMP-activated Cl^- currents in airway epithelial cells isolated from CF patients. In contrast, the G protein activators guanosine 5'-[γ-thio]triphosphate and AlF^-_4 reduce Cl^- currents and inhibit cAMP from activating Cl^- currents in normal airway epithelial cells. In CF cells treated with pertussis toxin or guanosine 5'-[β-thio]diphosphate and in normal cells, cAMP activates a Cl^- conductance that has properties similar to CF transmembrane-conductance regulator Cl^- channels. We conclude that heterotrimeric G proteins inhibit cAMP-activated Cl^- currents in airway epithelial cells and that modulation of the inhibitory G protein signaling pathway may have the therapeutic potential for improving cAMP-activated Cl^- secretion in CF.

Polymerization of room-temperature ionic liquid monomers by electron beam irradiation with the aim of fabricating three-dimensional micropolymer/nanopolymer structures.

PubMed

Minamimoto, H; Irie, H; Uematsu, T; Tsuda, T; Imanishi, A; Seki, S; Kuwabata, S

2015-04-14

A novel method for fabricating microsized and nanosized polymer structures from a room-temperature ionic liquid (RTIL) on a Si substrate was developed by the patterned irradiation of an electron beam (EB). An extremely low vapor pressure of the RTIL, 1-allyl-3-ethylimidazolium bis((trifluoromethane)sulfonyl)amide, allows it to be introduced into the high-vacuum chamber of an electron beam apparatus to conduct a radiation-induced polymerization in the nanoregion. We prepared various three-dimensional (3D) micro/nanopolymer structures having high aspect ratios of up to 5 with a resolution of sub-100 nm. In addition, the effects of the irradiation dose and beam current on the physicochemical properties of the deposited polymers were investigated by recording the FT-IR spectra and Young's modulus. Interestingly, the overall shapes of the obtained structures were different from those prepared in our recent study using a focused ion beam (FIB) even if the samples were irradiated in a similar manner. This may be due to the different transmission between the two types of beams as discussed on the basis of the theoretical calculations of the quantum beam trajectories. Perceptions obtained in this study provide facile preparation procedures for the micro/nanostructures.

Dose and Chemical Modification Considerations for Continuous Cyclic AMP Analog Delivery to the Injured CNS

PubMed Central

Fouad, Karim; Ghosh, Mousumi; Vavrek, Romana; Tse, Arthur D.

2009-01-01

Abstract In this investigation, two cell-permeable synthetic analogs of cAMP, dibutyryl-cAMP (db-cAMP) and 8-bromo-cAMP, which are widely used to elevate intracellular cAMP levels under experimental conditions, were investigated for their ability to dose-dependently improve histological and functional outcomes following continuous delivery in two models of incomplete spinal cord injury (SCI). The cAMP analogs were delivered via osmotic minipumps at 1–250 mM through an indwelling cortical cannula or by intrathecal infusion for up to 4 weeks after either a T8 unilateral over-hemisection or a C2-3 dorsolateral quadrant lesion, respectively. In both SCI models, continuous db-cAMP delivery was associated with histopathological changes that included sporadic micro-hemorrhage formation and cavitation, enhanced macrophage infiltration and tissue damage at regions beyond the immediate application site; no deleterious or beneficial effect of agent delivery was observed at the spinal injury site. Furthermore, these changes were accompanied by pronounced behavioral deficits that included an absence of progressive locomotor recovery, increased extensor tone, paralysis, and sensory abnormalities. These deleterious effects were not observed in saline-treated animals, in animals in which the db-cAMP dose did not exceed 1 mM, or in those animals that received a high dose (250 mM) of the alternative cAMP analog, 8-bromo-cAMP. These results demonstrate that, for continuous intraparenchymal or intrathecal administration of cAMP analogs for the study of biological or therapeutic effects within the central nervous system (CNS), consideration of the effective concentration applied as well as the potential toxicity of chemical moieties on the parent molecule and/or their activity needs to be taken into account. PMID:19397425

A Robust High Current Density Electron Gun

NASA Astrophysics Data System (ADS)

Mako, F.; Peter, W.; Shiloh, J.; Len, L. K.

1996-11-01

Proof-of-principle experiments are proposed to validate a new concept for a robust, high-current density Pierce electron gun (RPG) for use in klystrons and high brightness electron sources for accelerators. This rugged, long-life electron gun avoids the difficulties associated with plasma cathodes, thermionic emitters, and field emission cathodes. The RPG concept employs the emission of secondary electrons in a transmission mode as opposed to the conventional mode of reflection, i.e., electrons exit from the back face of a thin negative electron affinity (NEA) material, and in the same direction as the incident beam. Current amplification through one stage of a NEA material could be over 50 times. The amplification is accomplished in one or more stages consisting of one primary emitter and one or more secondary emitters. The primary emitter is a low current density robust emitter (e.g., thoriated tungsten). The secondary emitters are thin NEA electrodes which emit secondary electrons in the same direction as the incident beam. Specific application is targeted for a klystron gun to be used by SLAC with a cold cathode at 30-40 amps/cm^2 output from the secondary emission stage, a ~2 μs pulse length, and ~200 pulses/second.

Harmonics generation of a terahertz wakefield free-electron laser from a dielectric loaded waveguide excited by a direct current electron beam.

PubMed

Li, Weiwei; Lu, Yalin; He, Zhigang; Jia, Qika; Wang, Lin

2016-06-01

We propose to generate high-power terahertz (THz) radiation from a cylindrical dielectric loaded waveguide (DLW) excited by a direct-current electron beam with the harmonics generation method. The DLW supports a discrete set of modes that can be excited by an electron beam passing through the structure. The interaction of these modes with the co-propagating electron beam results in micro-bunching and the coherent enhancement of the wakefield radiation, which is dominated by the fundamental mode. By properly choosing the parameters of DLW and beam energy, the high order modes can be the harmonics of the fundamental one; thus, high frequency radiation corresponding to the high order modes will benefit from the dominating bunching process at the fundamental eigenfrequency and can also be coherently excited. With the proposed method, high power THz radiation can be obtained with an easily achievable electron beam and a large DLW structure.

Incoherent pair generation in a beam-beam interaction simulation

NASA Astrophysics Data System (ADS)

Rimbault, C.; Bambade, P.; Mönig, K.; Schulte, D.

2006-03-01

This paper deals with two topics: the generation of incoherent pairs in two beam-beam simulation programs, GUINEA-PIG and CAIN, and the influence of the International Linear Collider (ILC) beam parameter choices on the background in the micro vertex detector (VD) induced by direct hits. One of the processes involved in incoherent pair creation (IPC) is equivalent to a four fermions interaction and its cross section can be calculated exactly with a dedicated generator, BDK. A comparison of GUINEA-PIG and CAIN results with BDK allows to identify and quantify the uncertainties on IPC background predictions and to benchmark the GUINEA-PIG calculation. Based on this simulation and different VD designs, the five currently suggested ILC beam parameter sets have been compared regarding IPC background induced in the VD by direct IPC hits. We emphasize that the high luminosity set, as it is currently defined, would constrain both the choices of magnetic field and VD inner layer radius.

Electromagnetic interference assessment of an ion drive electric propulsion system

NASA Technical Reports Server (NTRS)

Whittlesey, A. C.

1979-01-01

The electromagnetic interference (EMI) form elements of an ion drive electric propulsion system was analyzed, and the effects of EMI interaction with a typical interplanetary spacecraft engineering and scientific subsystems were predicted. SEMCAP, a computerized electromagnetic compatibility assessment code, was used to analyze the impact of EMI noise sources on 65 engineering/telemetry circuits and 48 plasma wave and planetary radio astronomy channels measuring over the range of 100 Hz to 40 MHz in a spacecraft of the Voyager type; manual methods were used to evaluate electrostatics, magnetics, and communications effects. Results indicate that some conducted and radiated spectra are in excess of electromagnetic compatibility specification limits; direct design changes may be required for filtering and shielding of thrust system elements. The worst source of broadband radiated noise appears to be the power processor. The magnetic field necessary to thruster operation is equivalent to about 18 amp-sq m per amp of beam current at right angles to the axis caused by the neutralizer/plume loop.

Progress On Neutrino-Proton Neutral-Current Scattering In MicroBooNE

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

Pate, Stephen

2017-01-16

The MicroBooNE Experiment at the Fermi National Accelerator Laboratory, an 89-ton active mass liquid argon time projection chamber, affords a unique opportunity to observe low-more » $Q^2$ neutral-current neutrino-proton scattering events. Neutral-current neutrino-proton scattering at $Q^2 < 1$ GeV$^2$ is dominated by the proton's axial form factor, which can be written as a combination of contributions from the up, down, and strange quarks: $$G_A(Q^2) = \\frac{1}{2}[-G_A^u(Q^2)+G_A^d(Q^2)+G_A^s(Q^2)]$$. The contribution from up and down quarks has been established in past charged-current measurements. The contribution from strange quarks at low $Q^2$ remains unmeasured; this is of great interest since the strange quark contribution to the proton spin can be determined from the low-$Q^2$ behavior: $$\\Delta S = G_A^s(Q^2=0)$$. MicroBooNE began operating in the Booster Neutrino Beam in October 2015. I will present the status in observing isolated proton tracks in the MicroBooNE detector as a signature for neutral-current neutrino-proton events. The sensitivity of the MicroBooNE experiment for measuring the strange quark contribution to the proton spin will be discussed.« less

Separate Cl^- Conductances Activated by cAMP and Ca2+ in Cl^--Secreting Epithelial Cells

NASA Astrophysics Data System (ADS)

Cliff, William H.; Frizzell, Raymond A.

1990-07-01

We studied the cAMP- and Ca2+-activated secretory Cl^- conductances in the Cl^--secreting colonic epithelial cell line T84 using the whole-cell patch-clamp technique. Cl^- and K^+ currents were measured under voltage clamp. Forskolin or cAMP increased Cl^- current 2-15 times with no change in K^+ current. The current-voltage relation for cAMP-activated Cl^- current was linear from -100 to +100 mV and showed no time-dependent changes in current during voltage pulses. Ca2+ ionophores or increased pipette Ca2+ increased both Cl^- and K^+ currents 2-30 times. The Ca2+-activated Cl^- current was outwardly rectified, activated during depolarizing voltage pulses, and inactivated during hyperpolarizing voltage pulses. Addition of ionophore after forskolin further increased Cl^- conductance 1.5-5 times, and the current took on the time-dependent characteristics of that stimulated by Ca2+. Thus, cAMP and Ca2+ activate Cl^- conductances with different properties, implying that these second messengers activate different Cl^- channels or that they induce different conductive and kinetic states in the same Cl^- channel.

Short wavelength limits of current shot noise suppression

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

Nause, Ariel, E-mail: arielnau@post.tau.ac.il; Dyunin, Egor; Gover, Avraham

Shot noise in electron beam was assumed to be one of the features beyond control of accelerator physics. Current results attained in experiments at Accelerator Test Facility in Brookhaven and Linac Coherent Light Source in Stanford suggest that the control of the shot noise in electron beam (and therefore of spontaneous radiation and Self Amplified Spontaneous Emission of Free Electron Lasers) is feasible at least in the visible range of the spectrum. Here, we present a general linear formulation for collective micro-dynamics of e-beam noise and its control. Specifically, we compare two schemes for current noise suppression: a quarter plasmamore » wavelength drift section and a combined drift/dispersive (transverse magnetic field) section. We examine and compare their limits of applicability at short wavelengths via considerations of electron phase-spread and the related Landau damping effect.« less

Coulomb repulsion and the electron beam directed energy weapon

NASA Astrophysics Data System (ADS)

Retsky, Michael W.

2004-09-01

Mutual repulsion of discrete charged particles or Coulomb repulsion is widely considered to be an ultimate hard limit in charged particle optics. It prevents the ability to finely focus high current beams into small spots at large distances from defining apertures. A classic example is the 1970s era "Star Wars" study of an electron beam directed energy weapon as an orbiting antiballistic missile device. After much analysis, it was considered physically impossible to focus a 1000-amp 1-GeV beam into a 1-cm diameter spot 1000-km from the beam generator. The main reason was that a 1-cm diameter beam would spread to 5-m diameter at 1000-km due to Coulomb repulsion. Since this could not be overcome, the idea was abandoned. But is this true? What if the rays were reversed? That is, start with a 5-m beam converging slightly with the same nonuniform angular and energy distribution as the electrons from the original problem were spreading at 1000-km distance. Could Coulomb repulsion be overcome? Looking at the terms in computational studies, some are reversible while others are not. Based on estimates, the nonreversible terms should be small - of the order of 0.1 mm. If this is true, it is possible to design a practical electron beam directed weapon not limited by Coulomb repulsion.

Electron-beam-induced topographical, chemical, and structural patterning of amorphous titanium oxide films.

PubMed

Kern, P; Müller, Y; Patscheider, J; Michler, J

2006-11-30

Electrolytically deposited amorphous TiO2 films on steel are remarkably sensitive to electron beam (e-beam) irradiation at moderate energies at 20 keV, resulting in controlled local oxide reduction and crystallization, opening the possibility for local topographical, chemical, and structural modifications within a biocompatible, amorphous, and semiconducting matrix. The sensitivity is shown to vary significantly with the annealing temperature of as-deposited films. Well-defined irradiation conditions in terms of probe current IP (5 microA) and beam size were achieved with an electron probe microanalyzer. As shown by atomic force and optical microscopy, micro-Raman spectroscopy, wavelength-dispersive X-ray (WDX), and Auger analyses, e-beam exposure below 1 Acm-2 immediately leads to electron-stimulated oxygen desorption, resulting in a well-defined volume loss primarily limited to the irradiated zone under the electron probe and in a blue color shift in this zone because of the presence of Ti2O3. Irradiation at 5 Acm(-2) (IP = 5 microA) results in local crystallization into anatase phase within 1 s of exposure and in reduction to TiO after an extended exposure of 60 s. Further reduction to the metallic state could be observed after 60 s of exposure at approximately 160 Acm(-2). The local reduction could be qualitatively sensed with WDX analysis and Auger line scans. An estimation of the film temperature in the beam center indicates that crystallization occurs at less than 150 degrees C, well below the atmospheric crystallization temperature of the present films. The high e-beam sensitivity in combination with the well-defined volume loss from oxygen desorption allows for precise electron lithographic topographical patterning of the present oxides. Irradiation effects leading to the observed reduction and crystallization phenomena under moderate electron energies are discussed.

Rapid, efficient charging of lead-acid and nickel-zinc traction cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1978-01-01

Lead-acid and nickel-zinc traction cells were rapidly and efficiently charged using a high rate tapered direct current (HRTDC) charge method which could possibly be used for on-the-road service recharge of electric vehicles. The HRTDC method takes advantage of initial high cell charge acceptance and uses cell gassing rate and temperature as an indicator of charging efficiency. On the average, in these preliminary tests, 300 amp-hour nickel-zinc traction cells were given a HRTDC (initial current 500 amps, final current 100 amps) to 78 percent of rated amp-hour capacity within 53 minutes at an amp-hour efficiency of 92 percent and an energy efficiency of 52 percent. Three hundred amp-hour lead-acid traction cells were charged to 69 percent of rated amp-hour capacity within 46 minutes at an amp-hour efficiency of 91 percent with an energy efficiency of 64 percent. In order to find ways to further decrease the recharge times, the effect of periodically (0 to 400 Hz) pulse discharging cells during a constant current charging process (94% duty cycle) was investigated. Preliminary data indicate no significant effect of this type of pulse discharging during charge on charge acceptance of lead-acid or nickel-zinc cells.

Closed-form solution for static pull-in voltage of electrostatically actuated clamped-clamped micro/nano beams under the effect of fringing field and van der Waals force

NASA Astrophysics Data System (ADS)

Bhojawala, V. M.; Vakharia, D. P.

2017-12-01

This investigation provides an accurate prediction of static pull-in voltage for clamped-clamped micro/nano beams based on distributed model. The Euler-Bernoulli beam theory is used adapting geometric non-linearity of beam, internal (residual) stress, van der Waals force, distributed electrostatic force and fringing field effects for deriving governing differential equation. The Galerkin discretisation method is used to make reduced-order model of the governing differential equation. A regime plot is presented in the current work for determining the number of modes required in reduced-order model to obtain completely converged pull-in voltage for micro/nano beams. A closed-form relation is developed based on the relationship obtained from curve fitting of pull-in instability plots and subsequent non-linear regression for the proposed relation. The output of regression analysis provides Chi-square (χ 2) tolerance value equals to 1  ×  10-9, adjusted R-square value equals to 0.999 29 and P-value equals to zero, these statistical parameters indicate the convergence of non-linear fit, accuracy of fitted data and significance of the proposed model respectively. The closed-form equation is validated using available data of experimental and numerical results. The relative maximum error of 4.08% in comparison to several available experimental and numerical data proves the reliability of the proposed closed-form equation.

The Effect of Experimental Variables on Industrial X-Ray Micro-Computed Sensitivity

NASA Technical Reports Server (NTRS)

Roth, Don J.; Rauser, Richard W.

2014-01-01

A study was performed on the effect of experimental variables on radiographic sensitivity (image quality) in x-ray micro-computed tomography images for a high density thin wall metallic cylinder containing micro-EDM holes. Image quality was evaluated in terms of signal-to-noise ratio, flaw detectability, and feature sharpness. The variables included: day-to-day reproducibility, current, integration time, voltage, filtering, number of frame averages, number of projection views, beam width, effective object radius, binning, orientation of sample, acquisition angle range (180deg to 360deg), and directional versus transmission tube.

Hydrogen peroxide inhibits iodide uptake and iodine organification in cultured porcine thyroid follicles.

PubMed

Fukayama, H; Murakami, S; Nasu, M; Sugawara, M

1991-01-01

We investigated the effect of hydrogen peroxide on the process of thyroid hormone formation in a physiologic culture system of porcine thyroid follicles that we recently established. Porcine thyroid follicles cultured in medium containing 1 mU/mL TSH were exposed to 0 to 500 microM hydrogen peroxide in the presence of 0.1 microCi carrier-free Na125 and sodium iodide for 2 h. Iodide uptake and iodine organification were measured in this incubation system. The kinetics of iodide uptake were used to explain the action of hydrogen peroxide. In addition, cAMP content and Na+,K(+)-ATPase activity (an enzyme necessary for iodide uptake) were measured to investigate the mechanism of hydrogen peroxide action. Hydrogen peroxide at concentrations of 100, 200, and 500 microM inhibited iodide uptake in a dose-dependent manner. Iodide organification was inhibited only when the concentration of hydrogen peroxide was greater than 200 microM. The kinetics of iodide uptake indicated that hydrogen peroxide was a noncompetitive inhibitor with iodide. Inhibition of iodide uptake and iodine organification by hydrogen peroxide were not mediated by alteration of cAMP content of Na+,K(+)-ATPase activity, since exposure to even 500 microM hydrogen peroxide did not change these parameters in the follicle when compared with those of control samples. Our results suggest that the iodide transport system in the thyroid follicle is inhibited at 200 microM hydrogen peroxide or greater.

Micro-optics technology and sensor systems applications

NASA Technical Reports Server (NTRS)

Gal, George; Herman, B.; Anderson, W.; Whitney, R.; Morrow, H.

1993-01-01

The current generation of electro-optical sensors utilizing refractive and reflective optical elements require sophisticated, complex, and expensive designs. Advanced-technology-based electro-optical sensors of minimum size and weight require miniaturization of optical, electrical, and mechanical devices with an increasing trend toward integration of various components. Micro-optics technology has the potential in a number of areas to simplify optical design with improved performance. This includes internally cooled apertures, hybrid optical design, microlenses, dispersive multicolor microlenses, active dither, electronically controlled optical beam steer, and microscopic integration of micro-optics, detectors, and signal processing layers. This paper describes our approach to the development of micro-optics technology with our main emphasis for sensors applications.

Characteristics and performance of a micro-MOSFET: an "imageable" dosimeter for image-guided radiotherapy.

PubMed

Rowbottoma, Carl G; Jaffray, David A

2004-03-01

The performance and characteristics of a miniature metal oxide semiconductor field effect transistor (micro-MOSFET) detector was investigated for its potential application to integral system tests for image-guided radiotherapy. In particular, the position of peak response to a slit of radiation was determined for the three principal axes to define the co-ordinates for the center of the active volume of the detector. This was compared to the radiographically determined center of the micro-MOSFET visible using cone-beam CT. Additionally, the angular sensitivity of the micro-MOSFET was measured. The micro-MOSFETs are clearly visible on the cone-beam CT images, and produce no artifacts. The center of the active volume of the micro-MOSFET aligned with the center of the visible micro-MOSFET on the cone-beam CT images for the x and y axes to within 0.20 mm and 0.15 mm, respectively. In z, the long axis of the detector, the peak response was found to be 0.79 mm from the tip of the visible micro-MOSFET. Repeat experiments verified that the position of the peak response of the micro-MOSFET was reproducible. The micro-MOSFET response for 360 degrees of rotation in the axial plane to the micro-MOSFET was +/-2%, consistent with values quoted by the manufacturer. The location of the active volume of the micro-MOSFETs under investigation can be determined from the centroid of the visible micro-MOSFET on cone-beam CT images. The CT centroid position corresponds closely to the center of the detector response to radiation. The ability to use the cone-beam CT to locate the active volume to within 0.20 mm allows their use in an integral system test for the imaging of and dose delivery to a phantom containing an array of micro-MOSFETs. The small angular sensitivity allows the investigation of noncoplanar beams.

Simulation and characterization of a laterally-driven inertial micro-switch

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

Chen, Wenguo; Wang, Yang; Wang, Huiying

2015-04-15

A laterally-driven inertial micro-switch was designed and fabricated using surface micromachining technology. The dynamic response process was simulated by ANSYS software, which revealed the vibration process of movable electrode when the proof mass is shocked by acceleration in sensitive direction. The test results of fabricated inertial micro-switches with and without anti-shock beams indicated that the contact process of micro-switch with anti-shock beams is more reliable than the one without anti-shock beams. The test results indicated that three contact signals had been observed in the contact process of the inertial switch without anti-shock beams, and only one contact signal in themore » inertial switch with anti-shock beams, which demonstrated that the anti-shock beams can effectively constrain the vibration in non-sensitive direction.« less

Protein kinase C is involved in cyclic adenosine monophosphate formation due to PGF2 alpha desensitization in bovine iris sphincter.

PubMed

Tachado, S D; Zhang, Y; Abdel-Latif, A A

1993-05-01

To examine the mechanisms underlying the effects of PGF2 alpha receptor desensitization on agonist-induced second messenger formation and contraction in bovine iris sphincter. Short-term PGF2 alpha receptor desensitization of the bovine iris sphincter was carried out by incubating the tissue in Krebs-Ringer bicarbonate buffer containing 25 microM PGF2 alpha for 45 min at 37 degrees C. The effects of PGF2 alpha and other pharmacologic agents on inositol 1,4,5-triphosphate (IP3) production and cyclic adenosine monophosphate (cAMP) formation in desensitized and nondesensitized tissues were monitored by anion-exchange chromatography and radioimmunoassay. In the isolated bovine iris sphincter, protein kinase C (PKC) is involved in the activation of adenylate cyclase and the desensitization of prostaglandin F2 alpha receptor-mediated responses supported by these findings. (A) Exposure of the tissue to phorbol 12,13-dibutyrate, used to activate PKC, enhanced basal cAMP formation in a dose (EC50 = 8.8 x 10(-8) M) and time (t1/2 = 7.5 min) dependent manner. Phorbol 12,13-dibutyrate increased cAMP levels by twofold and it potentiated the isoproterenol-induced cAMP formation. The biologically inactive phorbol ester, 4 alpha-phorbol had no effect. Staurosporine, a potent PKC inhibitor, inhibited phorbol 12,13-dibutyrate-induced cAMP formation in a dose-dependent manner (IC50 of 0.25 microM). The increase in cAMP levels by phorbol 12,13-dibutyrate results from stimulation of adenylate cyclase, rather than from inhibition of cAMP phosphodiesterase, and it is not mediated through Ca2+ mobilization. Pretreatment of the tissue with phorbol 12,13-dibutyrate inhibited IP3 production in response to PGF2 alpha. (B) Desensitization of the sphincter with PGF2 alpha for 45 min increased cAMP formation and attenuated IP3 production and contraction. The effects of PGF2 alpha desensitization were reversed by pretreatment of the tissue with staurosporine. Down-regulation of PKC prevented the PGF2 alpha-stimulated increase in cAMP formation. In the desensitized tissue, diacylglycerol, the endogenous activator of PKC, may arise from phosphatidylcholine, via phospholipase D. (A) Activation of PKC in the bovine iris sphincter leads to stimulation of adenylate cyclase and to an increase in cAMP formation. The cAMP formed inhibits IP3 production and muscle contraction. (B) PGF2 alpha desensitization results in adenylate cyclase activation, mediated through PKC. (C) PGF2 alpha desensitization could uncouple the receptor from the Gq and Gi proteins and enhance PG stimulation of adenylate cyclase activity through the Gs protein. (D) Uncoupling of the G proteins from the PG receptor and activation of PKC, both of which result in enhanced cAMP formation, may underlie the mechanism of PGF2 alpha desensitization. (E) These observations demonstrate "cross talk" between the two second messenger systems and their physiologic consequences.

Micro-unmanned aerodynamic vehicle

DOEpatents

Reuel, Nigel [Rio Rancho, NM; Lionberger, Troy A [Ann Arbor, MI; Galambos, Paul C [Albuquerque, NM; Okandan, Murat [Albuquerque, NM; Baker, Michael S [Albuquerque, NM

2008-03-11

A MEMS-based micro-unmanned vehicle includes at least a pair of wings having leading wing beams and trailing wing beams, at least two actuators, a leading actuator beam coupled to the leading wing beams, a trailing actuator beam coupled to the trailing wing beams, a vehicle body having a plurality of fulcrums pivotally securing the leading wing beams, the trailing wing beams, the leading actuator beam and the trailing actuator beam and having at least one anisotropically etched recess to accommodate a lever-fulcrum motion of the coupled beams, and a power source.

TEBPP: Theoretical and Experimental study of Beam-Plasma-Physics

NASA Technical Reports Server (NTRS)

Anderson, H. R.; Bernstein, W.; Linson, L. M.; Papadopoulos, K.; Kellogg, P. J.; Szuszczewicz, E. P.; Hallinan, T. J.; Leinbach, H.

1980-01-01

The interaction of an electron beam (0 to 10 keV, 0 to 1.5 Amp) with the plasma and neutral atmospheres at 200 to 400 km altitude is studied with emphasis on applications to near Earth and cosmical plasmas. The interaction occurs in four space time regions: (1) near electron gun, beam coming into equilibrium with medium; (2) equilibrium propagation in ionosphere; (3) ahead of beam pulse, temporal and spatial precursors; (4) behind a beam pulse. While region 2 is of the greatest interest, it is essential to study Region 1 because it determines the characteristics of the beam as it enters 2 through 4.

Focused ion beam-assisted technology in sub-picolitre micro-dispenser fabrication

NASA Astrophysics Data System (ADS)

Lopez, M. J.; Caballero, D.; Campo, E. M.; Perez-Castillejos, R.; Errachid, A.; Esteve, J.; Plaza, J. A.

2008-07-01

Novel medical and biological applications are driving increased interest in the fabrication of micropipette or micro-dispensers. Reduced volume samples and drug dosages are prime motivators in this effort. We have combined microfabrication technology with ion beam milling techniques to successfully produce cantilever-type polysilicon micro-dispensers with 3D enclosed microchannels. The microfabrication technology described here allows for the designing of nozzles with multiple shapes. The contribution of ion beam milling has had a large impact on the fabrication process and on further customizing shapes of nozzles and inlet ports. Functionalization tests were conducted to prove the viability of ion beam-fabricated micro-dispensers. Self-assembled monolayers were successfully formed when a gold surface was patterned with a thiol solution dispensed by the fabricated micro-dispensers.

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

Wolf, Z.; Ruland, R.; Dix, B.

The Stanford Linear Accelerator Center is evaluating the feasibility of placing a free electron laser (FEL) at the end of the linear accelerator. The proposal is to inject electrons two thirds of the way down the linac, accelerate the electrons for the last one third of the linac, and then send the electrons into the FEL. This project is known as the LCLS (Linac Coherent Light Source). To test the feasibility of the LCLS, a smaller experiment VISA (Visual to Infrared SASE (Self Amplified Stimulated Emission) Amplifier) is being performed at Brookhaven National Laboratory. VISA consists of four wiggler segments,more » each 0.99 m long. The four segments are required to be aligned to the beam axis with an rms error less than 50 {micro}m [1]. This very demanding alignment is carried out in two steps [2]. First the segments are fiducialized using a pulsed wire system. Then the wiggler segments are placed along a reference laser beam which coincides with the electron beam axis. In the wiggler segment fiducialization, a wire is stretched through a wiggler segment and a current pulse is sent down the wire. The deflection of the wire is monitored. The deflection gives information about the electron beam trajectory. The wire is moved until its x position, the coordinate without wire sag, is on the ideal beam trajectory. (The y position is obtained by rotating the wiggler 90{sup o}.) Once the wire is on the ideal beam trajectory, the wire's location is measured relative to tooling balls on the wiggler segment. To locate the wire, a device was constructed which measures the wire position relative to tooling balls on the device. The device is called the wire finder. It will be discussed in this paper. To place the magnets along the reference laser beam, the position of the laser beam must be determined. A device which can locate the laser beam relative to tooling balls was constructed and is also discussed in this paper. This device is called the laser finder. With a total alignment error budget less than 50 {micro}m, both the fiducialization and magnet placement must be performed with errors much smaller than 50 {micro}m. It is desired to keep the errors from the wire finder and laser finder at the few {micro}m level.« less

Brightness measurement of an electron impact gas ion source for proton beam writing applications

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

Liu, N.; Santhana Raman, P.; Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583

We are developing a high brightness nano-aperture electron impact gas ion source, which can create ion beams from a miniature ionization chamber with relatively small virtual source sizes, typically around 100 nm. A prototype source of this kind was designed and successively micro-fabricated using integrated circuit technology. Experiments to measure source brightness were performed inside a field emission scanning electron microscope. The total output current was measured to be between 200 and 300 pA. The highest estimated reduced brightness was found to be comparable to the injecting focused electron beam reduced brightness. This translates into an ion reduced brightness thatmore » is significantly better than that of conventional radio frequency ion sources, currently used in single-ended MeV accelerators.« less

Brightness measurement of an electron impact gas ion source for proton beam writing applications.

PubMed

Liu, N; Xu, X; Pang, R; Raman, P Santhana; Khursheed, A; van Kan, J A

2016-02-01

We are developing a high brightness nano-aperture electron impact gas ion source, which can create ion beams from a miniature ionization chamber with relatively small virtual source sizes, typically around 100 nm. A prototype source of this kind was designed and successively micro-fabricated using integrated circuit technology. Experiments to measure source brightness were performed inside a field emission scanning electron microscope. The total output current was measured to be between 200 and 300 pA. The highest estimated reduced brightness was found to be comparable to the injecting focused electron beam reduced brightness. This translates into an ion reduced brightness that is significantly better than that of conventional radio frequency ion sources, currently used in single-ended MeV accelerators.

Identification of New Lithic Clasts in Lunar Breccia 14305 by Micro-CT and Micro-XRF Analysis

NASA Technical Reports Server (NTRS)

Zeigler, Ryan A.; Carpenter, Paul K.; Jolliff, Bradley L.

2014-01-01

From 1969 to 1972, Apollo astronauts collected 382 kg of rocks, soils, and core samples from six locations on the surface of the Moon. The samples were initially characterized, largely by binocular examination, in a custom-built facility at Johnson Space Center (JSC), and the samples have been curated at JSC ever since. Despite over 40 years of study, demand for samples remains high (500 subsamples per year are allocated to scientists around the world), particularly for plutonic (e.g., anorthosites, norites, etc.) and evolved (e.g., granites, KREEP basalts) lithologies. The reason for the prolonged interest is that as new scientists and new techniques examine the samples, our understanding of how the Moon, Earth, and other inner Solar System bodies formed and evolved continues to grow. Scientists continually clamor for new samples to test their emerging hypotheses. Although all of the large Apollo samples that are igneous rocks have been classified, many Apollo samples are complex polymict breccias that have previously yielded large (cm-sized) igneous clasts. In this work we present the initial efforts to use the non-destructive techniques of micro-computed tomography (micro-CT) and micro x-ray fluorescence (micro-XRF) to identify large lithic clasts in Apollo 14 polymict breccia sample 14305. The sample in this study is 14305,483, a 150 g slab of regolith breccia 14305 measuring 10x6x2 cm (Figure 1a). The sample was scanned at the University of Texas High-Resolution X-ray CT Facility on an Xradia MicroXCT scanner. Two adjacent overlapping volumes were acquired at 49.2 micrometer resolution and stitched together, resulting in 1766 slices. Each volume was acquired at 100 kV accelerating voltage and 98 mA beam current with a 1 mm CaF2 filter, with 2161 views gathered over 360deg at 3 seconds acquisition time per view. Micro-XRF analyses were done at Washington University in St. Louis, Missouri on an EDAX Orbis PC micro-XRF instrument. Multiple scans were made at 40 kV accelerating voltage, 800 mA beam current, 30 µm beam diameter, and a beam spacing of 30-120 micrometer. The micro-CT scan of 14305,483 (Figure 2) was able to identify several large lithic clasts (approx. 1 cm) within the interior of the slab. These clasts will be exposed by band-sawing or chipping of the slab, and their composition more fully characterized by subsequent micro-XRF analysis. In addition to lithic clasts, the micro-CT scans identified numerous mineral clasts, including many FeNi metal grains, as well as the prominent fractures within the slab. The micro-XRF analyses (Figure 1b,c) of the slab surfaces revealed the bulk chemical compositions (qualitative) of the different clast types observed. In particular, by looking at the ratios of major elements (e.g. Ca:Mg:Fe), differences among the many observed clast types are readily observed. Moreover, several clasts not apparent to the naked eye were revealed in the K:Al:Si ratio map. The scans are also able to identify small grains of Zr- and P-rich minerals (not shown), which could in turn yield important age dates for the samples.

A quality assurance phantom for the performance evaluation of volumetric micro-CT systems

NASA Astrophysics Data System (ADS)

Du, Louise Y.; Umoh, Joseph; Nikolov, Hristo N.; Pollmann, Steven I.; Lee, Ting-Yim; Holdsworth, David W.

2007-12-01

Small-animal imaging has recently become an area of increased interest because more human diseases can be modeled in transgenic and knockout rodents. As a result, micro-computed tomography (micro-CT) systems are becoming more common in research laboratories, due to their ability to achieve spatial resolution as high as 10 µm, giving highly detailed anatomical information. Most recently, a volumetric cone-beam micro-CT system using a flat-panel detector (eXplore Ultra, GE Healthcare, London, ON) has been developed that combines the high resolution of micro-CT and the fast scanning speed of clinical CT, so that dynamic perfusion imaging can be performed in mice and rats, providing functional physiological information in addition to anatomical information. This and other commercially available micro-CT systems all promise to deliver precise and accurate high-resolution measurements in small animals. However, no comprehensive quality assurance phantom has been developed to evaluate the performance of these micro-CT systems on a routine basis. We have designed and fabricated a single comprehensive device for the purpose of performance evaluation of micro-CT systems. This quality assurance phantom was applied to assess multiple image-quality parameters of a current flat-panel cone-beam micro-CT system accurately and quantitatively, in terms of spatial resolution, geometric accuracy, CT number accuracy, linearity, noise and image uniformity. Our investigations show that 3D images can be obtained with a limiting spatial resolution of 2.5 mm-1 and noise of ±35 HU, using an acquisition interval of 8 s at an entrance dose of 6.4 cGy.

Operational test of micro-oven for 48Ca beam

NASA Astrophysics Data System (ADS)

Ozeki, K.; Kageyama, T.; Kidera, M.; Higurashi, Y.; Nakagawa, T.

2014-02-01

In order to supply a high-intensity and stable 48Ca beam from the RIKEN 18-GHz electron cyclotron resonance ion source, we are conducting operational tests of a micro-oven. A mixture of CaO and Al powders is placed into the crucible of the micro-oven and heated to produce metallic calcium by a reductive reaction. The successful production of a calcium beam was confirmed. In addition, we reduced the material consumption rate by using a so-called "hot liner," and we enhanced the beam intensity by applying a negative voltage bias to the micro-oven, the effect of which is similar to the effect of a "biased disk."

Changes in Ca(2+) channel expression upon differentiation of SN56 cholinergic cells.

PubMed

Kushmerick, C; Romano-Silva, M A; Gomez, M V; Prado, M A

2001-10-19

The SN56 cell line, a fusion of septal neurons and neuroblastoma cells, has been used as a model for central cholinergic neurons. These cells show increased expression of cholinergic neurochemical features upon differentiation, but little is known about how differentiation affects their electrophysiological properties. We examined the changes in Ca(2+) channel expression that occur as these cells undergo morphological differentiation in response to serum withdrawal and exposure to dibutyryl-cAMP. Undifferentiated cells expressed a T-type current with biophysical and pharmacological properties similar, although not identical, to those reported for the current generated by the alpha(1H) (CaV3.2) Ca(2+) channel subunit. Differentiated cells expressed, in addition to this T-type current, high voltage activated currents which were inhibited 38% by the L-type channel antagonist nifedipine (5 microM), 37% by the N-type channel antagonist omega-conotoxin-GVIA (1 microM), and 15% by the P/Q-type channel antagonist omega-agatoxin-IVA (200 nM). Current resistant to these inhibitors accounted for 15% of the high voltage activated current in differentiated SN56 cells. Our data demonstrate that differentiation increases the expression of neuronal type voltage gated Ca(2+) channels in this cell line, and that the channels expressed are comparable to those reported for native basal forebrain cholinergic neurons. This cell line should thus provide a useful model system to study the relationship between calcium currents and cholinergic function and dysfunction.

Mega-Amp Opening Switch with Nested Electrodes/Pulsed Generator of Ion and Ion Cluster Beams

DTIC Science & Technology

1987-07-30

The use of a plasma focus as a mega-amp opening switch has been demonstrated by two modes of operation: (a) Single shot mode; (b) Repetitive Mode...energy level and under the same voltage and filling-pressure conditions but without field distortion elements. Misfirings of the plasma focus machine...are also virtually eliminated by using FDE at the coaxial electrode breech. The tests (based on about 10000 shots and five plasma focus machines

Inhibition by salmeterol and cilomilast of fluticasone-enhanced IP-10 release in airway epithelial cells.

PubMed

Reddy, P J; Aksoy, Mark O; Yang, Yi; Li, Xiu Xia; Ji, Rong; Kelsen, Steven G

2008-02-01

The CXC chemokines, IP-10/CXCL10 and IL-8/CXCL8, play a role in obstructive lung disease by attracting Th1/Tc1 lymphocytes and neutrophils, respectively. Inhaled corticosteroids (ICS) and long acting beta 2-agonists (LABA) are widely used. However, their effect(s) on the release of IP-10 and IL-8 by airway epithelial cells are poorly understood. This study examined the effects of fluticasone, salmeterol, and agents which raise intracellular cAMP (cilomilast and db-cAMP) on the expression of IP-10 and IL-8 protein and mRNA. Studies were performed in cultured human airway epithelial cells during cytokine-stimulated IP-10 and IL-8 release. Cytokine treatment (TNF-alpha, IL-1beta and IFN-gamma) increased IP-10 and IL-8 protein and mRNA levels. Fluticasone (0.1 nM to 1 microM) increased IP-10 but reduced IL-8 protein release without changing IP-10 mRNA levels assessed by real time RT-PCR. The combination of salmeterol (1 micro M) and cilomilast (1-10 mu M) reduced IP-10 but had no effect on IL-8 protein. Salmeterol alone (1 micro M) and db-cAMP alone (1 mM) antagonised the effects of fluticasone on IP-10 but not IL-8 protein. In human airway epithelial cells, inhibition by salmeterol of fluticasone-enhanced IP-10 release may be an important therapeutic effect of the LABA/ICS combination not present when the two drugs are used separately.

Role of calcium in the regulation of theca cell androstenedione production in the domestic hen.

PubMed

Levorse, J M; Tilly, J L; Johnson, A L

1991-05-01

Theca cells were collected from the second largest preovulatory follicle. Chelation of extracellular calcium with EGTA attenuated LH (10 ng)-induced androstenedione production by theca cells, and this effect was more pronounced in calcium-deficient than in calcium-replete incubation medium. Incubation of theca cells with steroidogenic agonists in the presence of the calcium channel blocker verapamil (100 microM) suppressed androstenedione production stimulated by LH (a 57% decrease), the adenylate cyclase activator forskolin (a 59% decrease) and the cyclic adenosine monophosphate (cAMP) analog 8-bromo-cAMP (a 61% decrease). Furthermore, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), a putative inhibitor of intracellular calcium mobilization, suppressed LH-induced androstenedione production in a dose-dependent fashion. The calmodulin inhibitors trifluoperazine (100 microM) and R24571 (50 microM) inhibited androstenedione production stimulated by hormonal (LH) and non-hormonal (forskolin, 8-bromo-cAMP) agonists (decreases ranging from 76 to 98%). While increasing the intracellular calcium ion concentrations with the calcium ionophore A23187 did not affect basal concentrations of androstenedione, treatment of LH-stimulated cells with the ionophore caused dose-dependent inhibition of androstenedione production; these effects were enhanced by coincubation with phorbol 12-myristate 13-acetate (a known activator of protein kinase C). We conclude that the mobilization of calcium is critical for agonist-stimulated steroidogenesis in hen theca cells, apparently requiring the interaction of calcium with its binding protein, calmodulin. Furthermore, increased cytosolic calcium concentrations may be involved in the suppression of androstenedione production, possibly as a result of an interaction with protein kinase C.

Novel Programmable Shape Memory Polystyrene Film: A Thermally Induced Beam-power Splitter.

PubMed

Li, Peng; Han, Yu; Wang, Wenxin; Liu, Yanju; Jin, Peng; Leng, Jinsong

2017-03-09

Micro/nanophotonic structures that are capable of optical wave-front shaping are implemented in optical waveguides and passive optical devices to alter the phase of the light propagating through them. The beam division directions and beam power distribution depend on the design of the micro/nanostructures. The ultimate potential of advanced micro/nanophotonic structures is limited by their structurally rigid, functional singleness and not tunable against external impact. Here, we propose a thermally induced optical beam-power splitter concept based on a shape memory polystyrene film with programmable micropatterns. The smooth film exhibits excellent transparency with a transmittance of 95% in the visible spectrum and optical stability during a continuous heating process up to 90 °C. By patterning double sided shape memory polystyrene film into erasable and switchable micro-groove gratings, the transmission light switches from one designed light divided directions and beam-power distribution to another because of the optical diffraction effect of the shape changing micro gratings during the whole thermal activated recovery process. The experimental and theoretical results demonstrate a proof-of-principle of the beam-power splitter. Our results can be adapted to further extend the applications of micro/nanophotonic devices and implement new features in the nanophotonics.

Novel Programmable Shape Memory Polystyrene Film: A Thermally Induced Beam-power Splitter

PubMed Central

Li, Peng; Han, Yu; Wang, Wenxin; Liu, Yanju; Jin, Peng; Leng, Jinsong

2017-01-01

Micro/nanophotonic structures that are capable of optical wave-front shaping are implemented in optical waveguides and passive optical devices to alter the phase of the light propagating through them. The beam division directions and beam power distribution depend on the design of the micro/nanostructures. The ultimate potential of advanced micro/nanophotonic structures is limited by their structurally rigid, functional singleness and not tunable against external impact. Here, we propose a thermally induced optical beam-power splitter concept based on a shape memory polystyrene film with programmable micropatterns. The smooth film exhibits excellent transparency with a transmittance of 95% in the visible spectrum and optical stability during a continuous heating process up to 90 °C. By patterning double sided shape memory polystyrene film into erasable and switchable micro-groove gratings, the transmission light switches from one designed light divided directions and beam-power distribution to another because of the optical diffraction effect of the shape changing micro gratings during the whole thermal activated recovery process. The experimental and theoretical results demonstrate a proof-of-principle of the beam-power splitter. Our results can be adapted to further extend the applications of micro/nanophotonic devices and implement new features in the nanophotonics. PMID:28276500

Novel Programmable Shape Memory Polystyrene Film: A Thermally Induced Beam-power Splitter

NASA Astrophysics Data System (ADS)

Li, Peng; Han, Yu; Wang, Wenxin; Liu, Yanju; Jin, Peng; Leng, Jinsong

2017-03-01

Micro/nanophotonic structures that are capable of optical wave-front shaping are implemented in optical waveguides and passive optical devices to alter the phase of the light propagating through them. The beam division directions and beam power distribution depend on the design of the micro/nanostructures. The ultimate potential of advanced micro/nanophotonic structures is limited by their structurally rigid, functional singleness and not tunable against external impact. Here, we propose a thermally induced optical beam-power splitter concept based on a shape memory polystyrene film with programmable micropatterns. The smooth film exhibits excellent transparency with a transmittance of 95% in the visible spectrum and optical stability during a continuous heating process up to 90 °C. By patterning double sided shape memory polystyrene film into erasable and switchable micro-groove gratings, the transmission light switches from one designed light divided directions and beam-power distribution to another because of the optical diffraction effect of the shape changing micro gratings during the whole thermal activated recovery process. The experimental and theoretical results demonstrate a proof-of-principle of the beam-power splitter. Our results can be adapted to further extend the applications of micro/nanophotonic devices and implement new features in the nanophotonics.

The organochlorine o,p'-DDD disrupts the adrenal steroidogenic signaling pathway in rainbow trout (Oncorhynchus mykiss).

PubMed

Lacroix, Martin; Hontela, Alice

2003-08-01

The mechanisms of action of o,p'-DDD on adrenal steroidogenesis were investigated in vitro in rainbow trout (Oncorhynchus mykiss). Acute exposures to o,p'-DDD inhibited ACTH-stimulated cortisol secretion while cell viability decreased significantly only at the highest concentration tested (200 microM o,p'-DDD). Stimulation of cortisol secretion with a cAMP analogue (dibutyryl-cAMP) was inhibited at a higher concentration than that needed to inhibit ACTH-stimulated cortisol synthesis in cells exposed to o,p'-DDD. Forskolin-stimulated cortisol secretion and cAMP production, and NaF-stimulated cAMP production were inhibited in a concentration-dependent manner by o,p'-DDD. In contrast, basal cortisol secretion was stimulated while basal cAMP production was unaffected by o,p'-DDD. Pregnenolone-stimulated cortisol secretion was enhanced by o,p'-DDD at a physiologically relevant pregnenolone concentration, while o,p'-DDD inhibited cortisol secretion when a pharmacological concentration of pregnenolone was used. Our results suggest that the cAMP generation step is a target in o,p'-DDD-mediated disruption of ACTH-stimulated adrenal steroidogenesis in rainbow trout but that other downstream targets such as steroidogenic enzymes responsible for cortisol synthesis might also be affected.

Analysis of optical route in a micro high-speed magneto-optic switch

NASA Astrophysics Data System (ADS)

Weng, Zihua; Yang, Guoguang; Huang, Yuanqing; Chen, Zhimin; Zhu, Yun; Wu, Jinming; Lin, Shufen; Mo, Weiping

2005-02-01

A novel micro high-speed 2x2 magneto-optic switch and its optical route, which is used in high-speed all-optical communication network, is designed and analyzed in this paper. The study of micro high-speed magneto-optic switch mainly involves the optical route and high-speed control technique design. The optical route design covers optical route design of polarization in optical switch, the performance analysis and material selection of magneto-optic crystal and magnetic path design in Faraday rotator. The research of high-speed control technique involves the study of nanosecond pulse generator, high-speed magnetic field and its control technique etc. High-speed current transients from nanosecond pulse generator are used to switch the magnetization of the magneto-optic crystal, which propagates a 1550nm optical beam. The optical route design schemes and electronic circuits of high-speed control technique are both simulated on computer and test by the experiments respectively. The experiment results state that the nanosecond pulse generator can output the pulse with rising edge time 3~35ns, voltage amplitude 10~90V and pulse width 10~100ns. Under the control of CPU singlechip, the optical beam can be stably switched and the switching time is less than 1μs currently.

Kinetics of activation of the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein.

PubMed Central

Hoggett, J G; Brierley, I

1992-01-01

The activation of transcription initiation from the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein (CRP) has been investigated using a fluorescence abortive initiation assay. The effect of the cyclic-AMP/CRP complex on the linear P4 promoter was to increase the initial binding (KB) of RNA polymerase to the promoter by about a factor of 10, but the rate of isomerization of closed to open complex (kf) was unaffected. One molecule of CRP per promoter was required for activation, and the concentration of cyclic AMP producing half-maximal stimulation was about 7-8 microM. Supercoiling caused a 2-3-fold increase in the rate of isomerization of the CRP-activated promoter, but weakened the initial binding of polymerase by about one order of magnitude. The unactivated supercoiled promoter was too weak to allow reliable assessment of kinetic parameters against the high background rate originating from the rest of the plasmid. PMID:1445251

Kinetics of activation of the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein.

PubMed

Hoggett, J G; Brierley, I

1992-11-01

The activation of transcription initiation from the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein (CRP) has been investigated using a fluorescence abortive initiation assay. The effect of the cyclic-AMP/CRP complex on the linear P4 promoter was to increase the initial binding (KB) of RNA polymerase to the promoter by about a factor of 10, but the rate of isomerization of closed to open complex (kf) was unaffected. One molecule of CRP per promoter was required for activation, and the concentration of cyclic AMP producing half-maximal stimulation was about 7-8 microM. Supercoiling caused a 2-3-fold increase in the rate of isomerization of the CRP-activated promoter, but weakened the initial binding of polymerase by about one order of magnitude. The unactivated supercoiled promoter was too weak to allow reliable assessment of kinetic parameters against the high background rate originating from the rest of the plasmid.

Description of a 2.3 kW power transformer for space applications

NASA Technical Reports Server (NTRS)

Hansen, I.

1979-01-01

The principle features and special testing of a high voltage high power transformer designed and developed for space application are described. The transformer is operated in a series resonant inverter supplying beam power to a 30 cm mercury ion thruster. Electrical requirements include operation of 2.3 kW continuous power output, primary currents to 35 amps rms, and frequencies up to 20 kHz. High efficiency was obtained through detailed considerations of the tradeoffs available in core materials, wire selection, coil configurations and thermal control. A number of novel heat removal techniques are discussed which control the winding temperature using only the available conductive cooling.

100 GeV SLAC Linac

NASA Astrophysics Data System (ADS)

Farkas, Z. D.

2002-03-01

The SLAC beam energy can be increased from the current 50 GeV to 100 GeV, if we change the operating frequency from the present 2856 MHz to 11424 MHz, using technology developed for the NLC. We replace the power distribution system with a proposed NLC distribution system as shown in Fig. 1. The four 3 meter s-band 820 nS .ll time accelerator sections are replaced by six 2 meter x-band 120 nS .ll time sections. Thus the accelerator length per klystron retains the same length, 12 meters. The 4050 65MW- 3.5microS klystrons are replaced by 75MW-1.5microS permanent magnet klystrons developed here and in Japan. The present input to the klystrons would be multiplied by a factor of 4 and possibly ampli.ed. The SLED cavities have to be replaced. The increase in beam voltage is due to the higher elastance to group velocity ratio, higher compression ratio and higher unloaded to external Q ratio of the new SLED cavities. The average power input is reduced because of the narrower klystron pulse width and because the klystron electro-magnets are replaced by permanent magnets.

Electrostatically Driven Large Aperture Micro-Mirror Actuator Assemblies for High Fill-Factor, Agile Optical Phase Arrays

DTIC Science & Technology

2015-06-18

platform assembly 2, with micro-mirror platform deflection, measured on actuation side ( PFa ) and side opposite actuation (PFo...beam micro-mirror platform assembly 1; micro-mirror platform deflection, measured on actuation side ( PFa ) and side opposite actuation (PFo...side ( PFa ) and side opposite actuation (PFo) ........................................................ 106 xiv Figure 73: Graph of measured 10-beam

Effect of cAMP on short-circuit current in isolated human ciliary body.

PubMed

Wu, Ren-yi; Ma, Ning; Hu, Qian-qian

2013-07-01

Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current, Isc) across the ciliary processes in pigs. The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change. In an Ussing-type chamber system, the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed. The involvement of Cl(-) component in the bath solution was investigated. The effect of Cl(-) channel (10 µmol/L niflumic acid and 1 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)), K(+) channel (10 mmol/L tetraethylammonium chloride (TEA)), or Na(+) channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied. Dose-dependently, 8-bromo-cAMP (10 nmol/L-30 µmol/L) or forskolin (10 nmol/L-3 µmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue. Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side. When the tissue was bathed in low Cl(-) solutions, the Isc increase was significantly inhibited. Finally, niflumic acid and DIDS, but not TEA or amiloride, significantly prevented the Isc increase induced by 8-bromo-cAMP. cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes. Chloride is likely to be among the ions, the transportation of which across the tissue is triggered by cAMP, suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.

75 FR 22503 - Airworthiness Directives; Bombardier, Inc. Model DHC-8-400 Series Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... an inrush current less than or equal to 1.6 amps, before further flight, replace the vane with a new... AOA vane is found to have an inrush current greater than 1.6 amps, repeat the measurement of the vane... the serviceable AOA transducer is-- Then repeat the measurement-- More than 1.60 amps, but less than...

An overview of antimicrobial peptides and the latest advances in their development.

PubMed

Sierra, Josep M; Fusté, Ester; Rabanal, Francesc; Vinuesa, Teresa; Viñas, Miguel

2017-06-01

The recent dramatic increase in the incidence of antimicrobial resistance has been recognized by organizations such as the United Nations and World Health Organization as well as the governments of the USA and several European countries. A relatively new weapon in the fight against severe infections caused by multi-drug resistant bacteria is antimicrobial peptides (AMPs). These include colistin, currently regarded as the last line of antimicrobial therapy against multi-drug resistant microorganisms. Areas covered: Here, the authors provide an overview of the current research on AMPs. The focus is AMPs currently being developed for the treatment of recalcitrant bacterial infections, the synergies of AMPs and antibiotics, and the activity of AMPs against biofilm. This review also includes a brief introduction into the use of AMPs in infections caused by Mycobacterium, fungi, and parasites. Expert opinion: In research into new antimicrobials, AMPs are gaining increasing attention. While many are natural and are produced by a wide variety of organisms, others are being newly designed and chemically synthesized in the laboratory to achieve novel antimicrobial agents. The same strategy to fight infections in nature is thus being effectively exploited to safeguard human and animal health.

Effect of Micro-Bubbles in Water on Beam Patterns of Parametric Array

NASA Astrophysics Data System (ADS)

Hashiba, Kunio; Masuzawa, Hiroshi

2003-05-01

The improvement in efficiency of a parametric array by nonlinear oscillation of micro-bubbles in water is studied in this paper. The micro-bubble oscillation can increase the nonlinear coefficient of the acoustic medium. The amplitude of the difference-frequency wave along the longitudinal axis and its beam patterns in the field including the layer with micro-bubbles were analyzed using a Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation. As a result, the largest improvement in efficiency was obtained and a narrow parametric beam was formed by forming a layer with micro-bubbles in front of a parametric sound radiator as thick as about the shock formation distance. If the layer becomes significantly thicker than the distance, the beam of the difference-frequency wave in the far-field will become broader. If the layer is significantly thinner than the distance, the intensity level of the wave in the far-field will be too low.

Vacuum injection of hydrogen micro-sphere beams

NASA Astrophysics Data System (ADS)

Trostell, Bertil

1995-02-01

The design, construction and operation of a facility producing hydrogen micro-sphere beams in vacuum are summarized. A scheme is utilized, where a liquid hydrogen jet is broken up into droplets, which are injected into vacuum through a capillary at continuum gas flow conditions. In a typical beam, 40 μm diameter micro-spheres, generated at a frequency of 70 kHz, travel at free flight speeds of 60 m/s. The angular divergence of the beam amounts to ±0.04°. The intention is to use the micro-sphere beams as high luminosity internal targets in the WASA experimental station at the CELSIUS cooler storage ring in Uppsala. A time averaged target density profile, having a FWHM and peak density of 3.5 mm and 5 × 10 16 atoms/cm 2, respectively, is obtained 2.5 m downstream of the capillary exit.

Solid core dipoles and switching power supplies: lower cost light sources?

NASA Astrophysics Data System (ADS)

Benesch, J.; Philip, S.

2015-05-01

As a result of improvements in power semiconductors, moderate frequency switching supplies can now provide the hundreds of amps typically required by accelerators with zero-to-peak noise in the kHz region ~ 0.06% in current or voltage mode. Modeling was undertaken using a finite electromagnetic program to determine if eddy currents induced in the solid steel of CEBAF magnets and small supplemental additions would bring the error fields down to the 5ppm level needed for beam quality. The expected maximum field of the magnet under consideration is 0.85 T and the DC current required to produce that field is used in the calculations. An additional 0.1% current ripple is added to the DC current at discrete frequencies 360 Hz, 720 Hz or 7200 Hz. Over the region of the pole within 0.5% of the central integrated BdL the resulting AC field changes can be reduced to less than 1% of the 0.1% input ripple for all frequencies, and a sixth of that at 7200 Hz. Doubling the current, providing 1.5 T central field, yielded the same fractional reduction in ripple at the beam for the cases checked. A small dipole was measured at 60, 120, 360 and 720 Hz in two conditions and the results compared to the larger model for the latter two frequencies with surprisingly good agreement. For light sources with aluminum vacuum vessels and full energy linac injection, the combination of solid core dipoles and switching power supplies may result in significant cost savings. The work may also be used to guide retrofit of existing machines to reduce the level of ripple in the particle beam path.

The role of a microDiamond detector in the dosimetry of proton pencil beams.

PubMed

Gomà, Carles; Marinelli, Marco; Safai, Sairos; Verona-Rinati, Gianluca; Würfel, Jan

2016-03-01

In this work, the performance of a microDiamond detector in a scanned proton beam is studied and its potential role in the dosimetric characterization of proton pencil beams is assessed. The linearity of the detector response with the absorbed dose and the dependence on the dose-rate were tested. The depth-dose curve and the lateral dose profiles of a proton pencil beam were measured and compared to reference data. The feasibility of calibrating the beam monitor chamber with a microDiamond detector was also studied. It was found the detector reading is linear with the absorbed dose to water (down to few cGy) and the detector response is independent of both the dose-rate (up to few Gy/s) and the proton beam energy (within the whole clinically-relevant energy range). The detector showed a good performance in depth-dose curve and lateral dose profile measurements; and it might even be used to calibrate the beam monitor chambers-provided it is cross-calibrated against a reference ionization chamber. In conclusion, the microDiamond detector was proved capable of performing an accurate dosimetric characterization of proton pencil beams. Copyright © 2015. Published by Elsevier GmbH.

AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation

PubMed Central

Weng, Yingfeng; Lin, Jixian; Liu, Hui; Wu, Hui; Yan, Zhimin; Zhao, Jing

2018-01-01

The current study tested the potential neuroprotective function of Tanshinone IIA (ThIIA) in neuronal cells with oxygen-glucose deprivation (ODG) and re-oxygenation (OGDR). In SH-SY5Y neuronal cells and primary murine cortical neurons, ThIIA pre-treatment attenuated OGDR-induced viability reduction and apoptosis. Further, OGDR-induced mitochondrial depolarization, reactive oxygen species production, lipid peroxidation and DNA damages in neuronal cells were significantly attenuated by ThIIA. ThIIA activated AMP-activated protein kinase (AMPK) signaling, which was essential for neuroprotection against OGDR. AMPKα1 knockdown or complete knockout in SH-SY5Y cells abolished ThIIA-induced AMPK activation and neuroprotection against OGDR. Further studies found that ThIIA up-regulated microRNA-135b to downregulate the AMPK phosphatase Ppm1e. Notably, knockdown of Ppm1e by targeted shRNA or forced microRNA-135b expression also activated AMPK and protected SH-SY5Y cells from OGDR. Together, AMPK activation by ThIIA protects neuronal cells from OGDR. microRNA-135b-mediated silence of Ppm1e could be the key mechanism of AMPK activation by ThIIA. PMID:29435120

SU-F-T-68: Characterizes of Microdetectors in Electron Beam Dosimetry

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

Das, I; Andersen, A; Akino, Y

Purpose: Electron beam dosimetry requires high resolution data due to finite range that can be accomplished with small volume detectors. The small-field used in advance technologies in photon beam has created a market for microdetectors, however characteristics are significantly variable in photon beams and relatively unknown in electron beam that is investigated in this study. Methods: Among nearly 2 dozen microdetectors that have been investigated in small fields of photon beam, two popular detectors (microDiamond 60019 (PTW)) and W1 plastic scintillator detector (Standard Imaging)) that are tissue equivalent and have very small sensitive volume are selected. Electron beams from Varianmore » linear accelerators were used to investigate dose linearity dose rate dependence, energy dependence, depth dose and profiles in a reference condition in a water phantom. For W1 that has its own Supermax electrometer point by point measurements were performed. For microDiamond, a PTW-scanning tank was used for both scanning and point dose measurements. Results: W1 detector showed excellent dose linearity (r{sup 2} =1.0) from 5–500 MU either with variation of dose rate or beam energy. Similar findings were also observed for microdiamond with r{sup 2}=1.0. Percent variations in dose/MU for W1 and microDiamond were 0.2–1.1% and 0.4–1.2%, respectively among dose rate and beam energy. This variation was random for microDiamond, whereas it decreased with beam energy and dose rate for W1. The depth dose and profiles were within ±1 mm for both detectors. Both detectors did not show any energy dependence in electron beams. Conclusion: Both microDiamond and W1 detectors provided superior characteristics of beam parameters in electron beam including dose, dose rate linearity and energy independence. Both can be used in electron beam except W1 require point by point measurements and microdiamond requires 1500 MU for initial quenching.« less

Modulation of secretagogue-induced chloride secretion by intracellular bicarbonate.

PubMed

Dagher, P C; Morton, T Z; Joo, C S; Taglietta-Kohlbrecher, A; Egnor, R W; Charney, A N

1994-05-01

We have previously demonstrated inhibition of basal Cl- secretion by intracellular bicarbonate concentration ([HCO3-]i) in rat distal colon. We now examined whether secretagogue-induced Cl- secretion is inhibited by [HCO3-]i as well. Stripped segments of distal colon from male Sprague-Dawley rats and the colon tumor cell line T84 were studied. Flux measurements were performed in the Ussing chamber under short-circuit conditions. [HCO3-]i was calculated from intracellular pH (pHi) values that were estimated with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) and carbachol were used as secretagogues. In both distal colon and T84 cells, [HCO3-]i did not affect cAMP-induced Cl- secretion. However, carbachol-induced secretion was inhibited by [HCO3-]i; in rat colon, Cl- secretion decreased from 2.3 to 1.5 mueq.cm-2.h-1 when [HCO3-]i was increased from 15.0 to 28.4 mM (P < 0.05). In T84 cells, the change in short-circuit current decreased from 8.1 to 1.1 microA/cm2 over a range of [HCO3-]i from 0 to 15.6 mM (P < 0.001). We conclude that [HCO3-]i is an important modulator of carbachol-stimulated Cl- secretion in both rat distal colon and the T84 cell line. cAMP-mediated secretion is not affected by [HCO3-]i.

Micro-Bubble Experiments at the Van de Graaff Accelerator

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

Sun, Z. J.; Wardle, Kent E.; Quigley, K. J.

In order to test and verify the experimental designs at the linear accelerator (LINAC), several micro-scale bubble ("micro-bubble") experiments were conducted with the 3-MeV Van de Graaff (VDG) electron accelerator. The experimental setups included a square quartz tube, sodium bisulfate solution with different concentrations, cooling coils, gas chromatography (GC) system, raster magnets, and two high-resolution cameras that were controlled by a LabVIEW program. Different beam currents were applied in the VDG irradiation. Bubble generation (radiolysis), thermal expansion, thermal convection, and radiation damage were observed in the experiments. Photographs, videos, and gas formation (O 2 + H 2) data were collected.more » The micro-bubble experiments at VDG indicate that the design of the full-scale bubble experiments at the LINAC is reasonable.« less

Study of Electromagnetic Interactions with the MicroBooNE Detector

NASA Astrophysics Data System (ADS)

Caratelli, David; MicroBooNE Collaboration

2017-01-01

MicroBooNE is an experiment which employs the Liquid Argon Time Projection Chamber (LArTPC) detector technology to study neutrinos produced with the Fermilab Booster Neutrino Beam. As for any accelerator-based detector interested in studying neutrino oscillations, it is essential to be able to identify and reconstruct the kinematic properties of electrons and photons produced in μν and νe interactions. We report current progress in reconstructing electron and photon electromagnetic (EM) showers using data from the MicroBooNE LArTPC. These studies cover EM showers in the tens to hundreds of MeV energy range; they lay the foundation for MicroBooNE's investigation of the excess of low-energy EM events reported by MiniBooNE, and are of interest to the wider LArTPC neutrino community.

cAMP Stimulates Transepithelial Short-Circuit Current and Fluid Transport Across Porcine Ciliary Epithelium.

PubMed

Cheng, Angela King-Wah; Civan, Mortimer M; To, Chi-Ho; Do, Chi-Wai

2016-12-01

To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc). Addition of niflumic acid (NFA) to the aqueous surface effectively blocked the cAMP-induced Isc stimulation. The administration of cAMP to the stromal side (pigmented ciliary epithelium, PE) triggered a significant stimulation of Isc only at 100 μM. No additive effect was observed with bilateral application of cAMP. Likewise, forskolin caused a significant stimulation of Isc when applied to the aqueous side. Concomitantly, cAMP and forskolin increased fluid transport across porcine ciliary epithelium, and this stimulation was effectively inhibited by aqueous NFA. Depleting Cl- in the bathing solution abolished the baseline Isc and inhibited the subsequent stimulation by cAMP. Pretreatment with protein kinase A (PKA) blockers (H89/KT5720) significantly inhibited the cAMP- and forskolin-induced Isc responses. Our results suggest that cAMP triggers a sustained stimulation of Cl- and fluid transport across porcine ciliary epithelium; Cl- channels in the NPE cells are potentially a cellular site for this PKA-sensitive cAMP-mediated response.

Development of a miniature microwave electron cyclotron resonance plasma ion thruster for exospheric micro-propulsion

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

Dey, Indranuj, E-mail: indranuj@aees.kyushu-u.ac.jp; Toyoda, Yuji; Yamamoto, Naoji

A miniature microwave electron cyclotron resonance plasma source [(discharge diameter)/(microwave cutoff diameter) < 0.3] has been developed at Kyushu University to be used as an ion thruster in micro-propulsion applications in the exosphere. The discharge source uses both radial and axial magnetostatic field confinement to facilitate electron cyclotron resonance and increase the electron dwell time in the volume, thereby enhancing plasma production efficiency. Performance of the ion thruster is studied at 3 microwave frequencies (1.2 GHz, 1.6 GHz, and 2.45 GHz), for low input powers (<15 W) and small xenon mass flow rates (<40 μg/s), by experimentally measuring the extractedmore » ion beam current through a potential difference of ≅1200 V. The discharge geometry is found to operate most efficiently at an input microwave frequency of 1.6 GHz. At this frequency, for an input power of 8 W, and propellant (xenon) mass flow rate of 21 μg/s, 13.7 mA of ion beam current is obtained, equivalent to an calculated thrust of 0.74 mN.« less

Fully utilizing high power diode lasers by synergizing diode laser light sources and beam shaping micro-optics

NASA Astrophysics Data System (ADS)

Fan, Yingmin; Wang, Jingwei; Cai, Lei; Mitra, Thomas; Hauschild, Dirk; Zah, Chung-En; Liu, Xingsheng

2018-02-01

High power diode lasers (HPDLs) offer the highest wall-plug efficiency, highest specific power (power-to-weight ratio), arguably the lowest cost and highest reliability among all laser types. However, the poor beam quality of commercially HPDLs is the main bottleneck limiting their direct applications requiring high brightness at least in one dimension. In order to expand the applications of HPDLs, beam shaping and optical design are essential. In this work, we report the recent progresses on maximizing applications of HPDLs by synergizing diode laser light source and beam shaping micro-optics. Successful examples of matching of diode laser light sources and beam shaping micro-optics driving new applications are presented.

Miniature modified Faraday cup for micro electron beams

DOEpatents

Teruya, Alan T.; Elmer, John W.; Palmer, Todd A.; Walton, Chris C.

2008-05-27

A micro beam Faraday cup assembly includes a refractory metal layer with an odd number of thin, radially positioned traces in this refractory metal layer. Some of the radially positioned traces are located at the edge of the micro modified Faraday cup body and some of the radially positioned traces are located in the central portion of the micro modified Faraday cup body. Each set of traces is connected to a separate data acquisition channel to form multiple independent diagnostic networks. The data obtained from the two diagnostic networks are combined and inputted into a computed tomography algorithm to reconstruct the beam shape, size, and power density distribution.

Review on structured optical field generated from array beams

NASA Astrophysics Data System (ADS)

Hou, Tianyue; Zhou, Pu; Ma, Yanxing; Zhi, Dong

2018-03-01

Structured optical field (SOF), which includes vortex beams, non-diffraction beams, cylindrical vector beams and so on, has been under intensive investigation theoretically and experimentally in recent years. Generally, current research focus on the extraordinary properties (non-diffraction propagation, helical wavefront, rotation of electrical field, et al), which can be widely applied in micro-particle manipulation, super-resolution imaging, free-space communication and so on. There are mainly two technical routes, that is, inner-cavity and outer-cavity (spatial light modulators, diffractive phase holograms, q-plates). To date, most of the SOFs generated from both technical routes involves with single monolithic beam. As a novel technical route, SOF based on array beams has the advantage in more flexible freedom degree and power scaling potential. In this paper, research achievements in SOF generation based on array beams are arranged and discussed in detail. Moreover, experiment of generating exotic beam by array beams is introduced, which illustrates that SOF generated from array beams is theoretically valid and experimentally feasible. SOF generated from array beams is also beneficial for capacity increasing and data receiving for free-space optical communication systems at long distance.

Concepts, characterization, and modeling of MEMS microswitches with gold contacts in MUMPs

NASA Astrophysics Data System (ADS)

Lafontan, Xavier; Dufaza, Christian; Robert, Michel; Pressecq, Francis; Perez, Guy

2001-04-01

This paper demonstrates that RF MEMS micro-switches can be realized with a low cost MEMS technology such as MUMPs. Two different switches are proposed, namely the hinged beam switch and the gold overflowing switch. Their concepts, design and characterization are described in details. On-resistance as low as 5 - 6 (Omega) for the gold overflowing switch and 2 - 3 (Omega) for the hinged beam switch have been measured. Finally, experimental measurements showed that force and electrical current had strong influences on the overall electrical contact.

Palmatine, a protoberberine alkaloid, inhibits both Ca2+- and cAMP-activated Cl− secretion in isolated rat distal colon

PubMed Central

Wu, D Z; Yuan, J Y; Shi, H L; Hu, Z B

2008-01-01

Background and purpose: The protoberberine alkaloid berberine has been reported to inhibit colonic Cl− secretion. However, it is not known if other protoberberine alkaloids share these effects. We have therefore selected another protoberberine alkaloid, palmatine, to assess its effects on active ion transport across rat colonic epithelium. Experimental approach: Rat colonic mucosa was mounted in Ussing chambers and short circuit current (I SC), apical Cl− current and basolateral K+ current were recorded. Intracellular cAMP content was determined by an enzyme immunoassay. Intracellular Ca2+ concentration was measured with Fura-2 AM. Key results: Palmatine inhibited carbachol-induced Ca2+-activated Cl− secretion and the carbachol-induced increase of intracellular Ca2+ concentration. Palmatine also inhibited cAMP-activated Cl− secretion induced by prostaglandin E2 (PGE2) or forskolin. Palmatine prevented the elevation of intracellular cAMP by forskolin. Determination of apical Cl− currents showed that palmatine suppressed the forskolin-stimulated, apical cAMP-activated Cl− current but not the carbachol-stimulated apical Ca2+-activated Cl− current. Following permeabilization of apical membranes with nystatin, we found that palmatine inhibited a carbachol-stimulated basolateral K+ current that was sensitive to charybdotoxin and resistant to chromanol 293B. However, the forskolin-stimulated basolateral K+ current inhibited by palmatine was specifically blocked by chromanol 293B and not by charybdotoxin. Conclusions and implications: Palmatine attenuated Ca2+-activated Cl− secretion through inhibiting basolateral charybdotoxin-sensitive, SK4 K+ channels, whereas it inhibited cAMP-activated Cl− secretion by inhibiting apical CFTR Cl− channels and basolateral chromanol 293B-sensitive, KvLQT1 K+ channels. PMID:18204477

Characterization of the homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase.

PubMed

Dix, C J; Habberfield, A D; Cooke, B A

1984-06-15

The homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase induced by lutropin (LH) was characterized with the aid of forskolin and cholera toxin. Forskolin stimulated cyclic AMP production in a dose-dependent manner, with linear kinetics up to 2h. Forskolin also potentiated the action of LH on cyclic AMP production, but was only additive with cholera toxin. Preincubation of rat Leydig tumour cells with LH (1.0 micrograms/ml) for 1 h produced a desensitization of the subsequent LH (1.0 micrograms/ml)-stimulated cyclic AMP production, whereas the responses to cholera toxin (5.0 micrograms/ml), forskolin (100 microM), LH plus forskolin or cholera toxin plus forskolin were unaltered. In contrast, preincubation with LH for 20h produced a desensitization to all the stimuli tested. When rat Leydig tumour cells were preincubated for 1h with forskolin or dibutyryl cyclic AMP, the only subsequent response that was significantly altered was that to LH plus forskolin after preincubation with forskolin. However, preincubation for 20h with forskolin or dibutyryl cyclic AMP induced a desensitization to all stimuli subsequently tested. LH produced a rapid (0-1h) homologous desensitization, which was followed by a slower (2-8h)-onset heterologous desensitization. Forskolin and dibutyryl cyclic AMP were only able to induce heterologous desensitization. The rate of desensitization induced by either forskolin or dibutyryl cyclic AMP was similar to the rate of heterologous desensitization induced by LH. These results demonstrate that in purified rat Leydig tumour cells LH produces an initial homologous desensitization of adenylate cyclase that involves a cyclic AMP-independent lesion at or proximal to the guanine nucleotide regulatory protein (G-protein). This is followed by heterologous desensitization, which can also be induced by forskolin or dibutyryl cyclic AMP, thus indicating that LH-induced heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase involves a cyclic AMP-dependent lesion that is after the G-protein.

Using NCAP to predict RFI effects in linear bipolar integrated circuits

NASA Astrophysics Data System (ADS)

Fang, T.-F.; Whalen, J. J.; Chen, G. K. C.

1980-11-01

Applications of the Nonlinear Circuit Analysis Program (NCAP) to calculate RFI effects in electronic circuits containing discrete semiconductor devices have been reported upon previously. The objective of this paper is to demonstrate that the computer program NCAP also can be used to calcuate RFI effects in linear bipolar integrated circuits (IC's). The IC's reported upon are the microA741 operational amplifier (op amp) which is one of the most widely used IC's, and a differential pair which is a basic building block in many linear IC's. The microA741 op amp was used as the active component in a unity-gain buffer amplifier. The differential pair was used in a broad-band cascode amplifier circuit. The computer program NCAP was used to predict how amplitude-modulated RF signals are demodulated in the IC's to cause undesired low-frequency responses. The predicted and measured results for radio frequencies in the 0.050-60-MHz range are in good agreement.

Characterization of a microDiamond detector in high-dose-per-pulse electron beams for intra operative radiation therapy.

PubMed

Di Venanzio, C; Marinelli, Marco; Tonnetti, A; Verona-Rinati, G; Falco, M D; Pimpinella, M; Ciccotelli, A; De Stefano, S; Felici, G; Marangoni, F

2015-12-01

To characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator. The dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.). The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors. A good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under (60)Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R50 values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes. The microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

The Race To X-ray Microbeam and Nanobeam Science

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

Ice, Gene E; Budai, John D; Pang, Judy

2011-01-01

X-ray microbeams are an emerging characterization tool with transformational implications for broad areas of science ranging from materials structure and dynamics, geophysics and environmental science to biophysics and protein crystallography. In this review, we discuss the race toward sub-10 nm- x-ray beams with the ability to penetrate tens to hundreds of microns into most materials and with the ability to determine local (crystal) structure. Examples of science enabled by current micro/nanobeam technologies are presented and we provide a perspective on future directions. Applications highlighted are chosen to illustrate the important features of various submicron beam strategies and to highlight themore » directions of current and future research. While it is clear that x-ray microprobes will impact science broadly, the practical limit for hard x-ray beam size, the limit to trace element sensitivity, and the ultimate limitations associated with near-atomic structure determinations are the subject of ongoing research.« less

Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

PubMed

Kokel, Anne; Torok, Marianna

2018-01-17

Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Although further research is needed taking into account both environmental and human health consequences of novel AMPs several of these compounds are promising drug candidates for use in sustainable medicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of signal compounds and incubation conditions on the culturability of freshwater bacterioplankton.

PubMed

Bruns, Alke; Nübel, Ulrich; Cypionka, Heribert; Overmann, Jörg

2003-04-01

The effect of signal compounds and of different incubation conditions on the culturability (i.e., the fraction of all cells capable of growth) of natural bacterioplankton from the eutrophic lake Zwischenahner Meer was investigated over a period of 20 months. Numbers of growing cells were determined by the most-probable-number technique in liquid media containing low concentrations (10 micro M) of the signal compounds N-(oxohexanoyl)-DL-homoserine lactone, N-(butyryl)-DL-homoserine lactone, cyclic AMP (cAMP), or ATP. cAMP was the most effective signal compound, leading to significantly increased cultivation efficiencies of up to 10% of the total bacterial counts. Microautoradiography with [2,8-(3)H]cAMP, combined with fluorescence in situ hybridization, demonstrated that cAMP was taken up by 18% of all cells. The bacterial cAMP uptake systems had a very low K(m) value of

Micro-controller based air pressure monitoring instrumentation system using optical fibers as sensor

NASA Astrophysics Data System (ADS)

Hazarika, D.; Pegu, D. S.

2013-03-01

This paper describes a micro-controller based instrumentation system to monitor air pressure using optical fiber sensors. The principle of macrobending is used to develop the sensor system. The instrumentation system consists of a laser source, a beam splitter, two multi mode optical fibers, two Light Dependent Resistance (LDR) based timer circuits and a AT89S8252 micro-controller. The beam splitter is used to divide the laser beam into two parts and then these two beams are launched into two multi mode fibers. One of the multi mode fibers is used as the sensor fiber and the other one is used as the reference fiber. The use of the reference fiber is to eliminate the environmental effects while measuring the air pressure magnitude. The laser beams from the sensor and reference fibers are applied to two identical LDR based timer circuits. The LDR based timer circuits are interfaced to a micro-controller through its counter pins. The micro-controller samples the frequencies of the timer circuits using its counter-0 and counter-1 and the counter values are then processed to provide the measure of air pressure magnitude.

Retrospective study of urinalysis for dl-amphetamine and dl-methamphetamine analysis under current Department of Defense guidelines.

PubMed

Shippee, R L; Kippenberger, D J

2000-09-01

Under current Department of Defense (DOD) directive, the laboratories certified to conduct urinalyis testing in support of the DOD Drug Deterrence Program are required to conduct dl-isomer analysis on all specimens that confirm at a concentration greater than 500 ng/mL methamphetamine (METH). Although the same cutoff concentration is required for amphetamine (AMP) reporting, there is no requirement for dl-isomer analysis of AMP-positive specimens. Of the 894,823 specimens screened by the Army Drug Testing Laboratory at Ft. Meade, MD during a 19-month period, 339 confirmed positive for METH. From this positive population, seven specimens failed to confirm at or above the DOD cutoff of > 20% d-isomer. One of the seven specimens contained 534 ng/mL l-AMP and was reported positive for AMP. Although 100% of the AMP was the l-isomer, under current DOD directive, this information was not passed along to the Medical Review Officers (MRO) to assist them during the interview process. Although this situation appears to be a rare event, consideration should be given to requiring dl-isomer analysis of AMP-positive specimens and forwarding this information to the MRO.

Deducing the magma chamber processes of middle Eocene volcanics, Sivas and Tokat regions; NE Turkey: Insights from clinopyroxene chemistry

NASA Astrophysics Data System (ADS)

Göçmengil, Gönenç; Karacık, Zekiye; Genç, Ş. Can; Prelevic, Dejan

2016-04-01

Middle Eocene Tokat and Sivas volcanic successions occur within the İzmir-Ankara-Erzincan suture zone. Different models are suggested for the development of the middle Eocene volcanism such as post-collisional, delamination and slab-breakoff models as well as the arc magmatism. In both areas, volcanic units cover all the basement units with a regional disconformity and comprise lavas spanning a compositional range from mainly basalt-basaltic andesite to a lesser amount trachyte. Here, we report mineral chemistry of different basaltic lavas through transect from northern continent (Tokat region, Pontides) to southern continent (Sivas region, Kırşehir block) to deduce the characteristics of the magma chamber processes which are active during the middle Eocene. Basaltic lavas include olivine bearing basalts (Ol-basalt: ± olivine + clinopyroxene + plagioclase); amphibole bearing basaltic andesite (Amp-basaltic andesite: amphibole + clinopyroxene + plagioclase ± biotite) and pyroxene bearing basaltic andesite (Px-basaltic andesite: clinopyroxene + plagioclase). Microlitic, glomeroporphyric and pilotaxitic texture are common. Clinopyroxene phenocrystals (macro ≥ 750 μm and micro ≤300 μm) are common in all three lava series which are investigated by transecting core to rim compositional profiles. They are generally augite and diopside; euhedral to subhedral in shape with oscillatory, normal and reverse zoning patterns. Also, all clinopyroxene phenocrystals are marked by moderately high Mg# (for Ol-basalt: 67-91; avg. 80; Amp-basaltic andesite: 76-83, avg: 80; Px -basaltic andesite 68-95, avg: 81). In Ol-basalt, clinopyroxene phenocrystals show normal zonation (high Mg# cores and low Mg# rims). In Amp-basaltic andesite, clinopyroxenes are generally homogenous in composition with minor variation of Mg# towards the rims. On the contrary, in Px-basaltic andesite, clinopyroxene macro phenocrystals show reverse zonation with the core with low Mg# and the rims with higher. Also, within the same unit, there are clinopyroxene micro phenocrystals compositionally resembling the rims of the macro phenocrystals. Barometric calculations from clinopyroxene phenocrystals display large range of crystallization pressure for the Ol-basalt (2-9 kbar; average ~4 kbar) and Amp-basaltic andesite (2-5 kbar; average ~4 kbar). Besides, in Px-basaltic andesite macro phenocrystals have high crystallization pressure in the cores (6.5-8 kbar) and low pressures at the rims (3-6.5 kbar). Similarly, micro phenocrystals also show the similar pressure ranges as macro phenocrystal rims. Regarding the data presented above, clinopyroxene phenocrystals from Ol- and Amp-basalts generally show normal zonation which can be explained by time depended fractionation of magma. Besides, in Px-basaltic andesites, macro phenocrystal cores might be inherited from antecrysts crystallized at the deeper level of the same system. Reverse zonation and high Mg# and lower pressure crystallization of macro phenocrystal rims and micro phenocrystals indicate that injection and/or mixing of primitive magma within the host magma chamber. Differences in crystallization pressures and chemical compositions from the same volcanic sequence show the existence of different conduit levels or magma reservoirs.

Progress towards an intense beam of positrons created by a Van de Graaff accelerator

NASA Astrophysics Data System (ADS)

Lund, K. R.; Weber, M. H.; Lynn, K. G.; Jennings, J.; Minnal, C.; Narimannezhad, A.; Rao, R.; Monster, K. A. W.

2017-12-01

A 4MV Van de Graaff accelerator was used to induce the nuclear reaction 12C(d,n)13N in order to produce an intense beam of positrons. The graphite target was heated so the radioactive 13N would desorb from the bulk into the vacuum. This radioactive gas is frozen onto a cryogenic freezer where it decays to produce an antiparticle beam of positrons. This high current beam is then guided into a superconducting magnet with field strength up to 7 Tesla where the positrons will be stored in a newly designed Micro-Penning-Malmberg trap. Several source geometries have been experimented on and found a maximum antimatter beam with a positron flux of greater than 0.55 ± 0.03 × 106 e+s-1 was achieved. This beam was produced using a solid rare gas moderator composed of krypton (Kr) at a temperature of 25 ± 5 K. Due to geometric restrictions on this set up and other loss mechanisms, 107-108 e+s-1 of the total number of positrons are lost. Simulations and preliminary experiments suggest a new geometry, currently under testing, will produce a beam of 107 e+s-1 or more. The setup and preliminary results for the new geometry will be discussed as well.

Micro-crystallography comes of age.

PubMed

Smith, Janet L; Fischetti, Robert F; Yamamoto, Masaki

2012-10-01

The latest revolution in macromolecular crystallography was incited by the development of dedicated, user friendly, micro-crystallography beam lines. Brilliant X-ray beams of diameter 20 μm or less, now available at most synchrotron sources, enable structure determination from samples that previously were inaccessible. Relative to traditional crystallography, crystals with one or more small dimensions have diffraction patterns with vastly improved signal-to-noise when recorded with an appropriately matched beam size. Structures can be solved from isolated, well diffracting regions within inhomogeneous samples. This review summarizes the technological requirements and approaches to producing micro-beams and how they continue to change the practice of crystallography. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical radiation therapy measurements with a new commercial synthetic single crystal diamond detector

PubMed Central

Crilly, Richard

2014-01-01

A commercial version of a synthetic single crystal diamond detector (SCDD) in a Schottky diode configuration was recently released as the new type 60019 microDiamond detector (PTW‐Freiburg, Germany). In this study we investigate the dosimetric properties of this detector to independently confirm that findings from the developing group of the SCDDs still hold true for the commercial version of the SCDDs. We further explore if the use of the microDiamond detector can be expanded to high‐energy photon beams of up to 15 MV and to large field measurements. Measurements were performed with an Elekta Synergy linear accelerator delivering 6, 10, and 15 MV X‐rays, as well as 6, 9, 12, 15, and 20 MeV electron beams. The dependence of the microdiamond detector response on absorbed dose after connecting the detector was investigated. Furthermore, the dark current of the diamond detector was observed after irradiation. Results are compared to similar results from measurements with a diamond detector type 60003. Energy dependency was investigated, as well. Photon depth‐dose curves were measured for field sizes 3×3,10×10, and 30×30cm2. PDDs were measured with the Semiflex type 31010 detector, microLion type 31018 detector, P Diode type 60016, SRS Diode type 60018, and the microDiamond type 60019 detector (all PTW‐Freiburg). Photon profiles were measured at a depth of 10 cm. Electron depth‐dose curves normalized to the dose maximum were measured with the 14×14cm2 electron cone. PDDs were measured with a Markus chamber type 23343, an E Diode type 60017 and the microDiamond type 60019 detector (all PTW‐Freiburg). Profiles were measured with the E Diode and microDiamond at half of D90,D90,D70, and D50 depths and for electron cone sizes of 6×6cm2, 14×14cm2, and 20×20cm2. Within a tolerance of 0.5% detector response of the investigated detector was stable without any preirradiation. After preirradition with approximately 250 cGy the detector response was stable within 0.1%. A dark current after irradiation was not observed. The microDiamond detector shows no energy dependence in high energy photon or electron dosimetry. Electron PDD measurements with the E Diode and microDiamond are in good agreement. However, compared to E Diode measurements, dose values in the bremsstrahlungs region are about 0.5% lower when measured with the microDiamond detector. Markus detector measurements agree with E Diode measurements in the bremsstrahlungs region. For depths larger than dmax, depth‐dose curves of photon beams measured with the microDiamond detector are in close agreement to those measured with the microLion detector for small fields and with those measured with a Semiflex 0.125 cc ionization chamber for large fields. Differences are in the range of 0.25% and less. For profile measurements, microDiamond detector measurements agree well with microLion and P Diode measurements in the high‐dose region of the profile and the penumbra region. For areas outside the open field, P Diode measurements are about 0.5%–1.0% higher than microDiamond and microLion measurements. Thus it becomes evident that the investigated diamond detector (type 60019) is suitable for a wide range of applications in high‐energy photon and electron dosimetry and is interesting for relative, as well as absolute, dosimetry. PACS numbers: 00.06, 80.87 PMID:25493512

Roles of cyclic AMP and Ca in epithelial ion transport across corneal epithelium: a review.

PubMed

Reinach, P S

1985-04-01

The messenger roles of cyclic AMP and the calcium ion in stimulus-secretion coupling are considered in the frog and bovine corneal epithelium, respectively. In the frog cornea, epinephrine stimulates net C1 transport by increasing cyclic AMP content. This stimulation is associated with a larger apical membrane C1 conductance and basolateral membrane ionic conductance. The response of the apical membrane conductance is thought to result from an increase in cyclic AMP content whereas the basolateral membrane ionic conductance increase is unrelated based on measurements of the effects of the calcium channel antagonist, diltiazem, and the beta agonist, isoproterenol, on the electrical parameters and cyclic AMP content. The basolateral membrane is essentially K permselective since the K channel blocker, Ba, depolarized the intracellular potential difference and increased the basolateral membrane resistance. Diltiazem had even larger effects on these parameters suggesting that this compound is a more effective inhibitor of K channel activity than barium. In broken cell preparations of bovine corneal epithelium, a high affinity form of Ca + Mg activated ATPase is present (Km = .06 microM for Ca) and is essentially of plasma membrane origin. This ATPase activation is at a Ca activity similar to the expected intracellular value and suggests that this activity is the enzymatic basis for net Ca transport.

Expression of PKA inhibitor (PKI) gene abolishes cAMP-mediated protection to endothelial barrier dysfunction.

PubMed

Lum, H; Jaffe, H A; Schulz, I T; Masood, A; RayChaudhury, A; Green, R D

1999-09-01

We investigated the hypothesis that cAMP-dependent protein kinase (PKA) protects against endothelial barrier dysfunction in response to proinflammatory mediators. An E1-, E3-, replication-deficient adenovirus (Ad) vector was constructed containing the complete sequence of PKA inhibitor (PKI) gene (AdPKI). Infection of human microvascular endothelial cells (HMEC) with AdPKI resulted in overexpression of PKI. Treatment with 0.5 microM thrombin increased transendothelial albumin clearance rate (0.012 +/- 0.003 and 0.035 +/- 0.005 microl/min for control and thrombin, respectively); the increase was prevented with forskolin + 3-isobutyl-1-methylxanthine (F + I) treatment. Overexpression of PKI resulted in abrogation of the F + I-induced inhibition of the permeability increase. However, with HMEC infected with ultraviolet-inactivated AdPKI, the F + I-induced inhibition was present. Also, F + I treatment of HMEC transfected with reporter plasmid containing the cAMP response element-directed transcription of the luciferase gene resulted in an almost threefold increase in luciferase activity. Overexpression of PKI inhibited this induction of luciferase activity. The results show that Ad-mediated overexpression of PKI in endothelial cells abrogated the cAMP-mediated protection against increased endothelial permeability, providing direct evidence that cAMP-dependent protein kinase promotes endothelial barrier function.

P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport

PubMed Central

Köttgen, Michael; Löffler, Thomas; Jacobi, Christoph; Nitschke, Roland; Pavenstädt, Hermann; Schreiber, Rainer; Frische, Sebastian; Nielsen, Søren; Leipziger, Jens

2003-01-01

Extracellular nucleotides are important regulators of epithelial ion transport. Here we investigated nucleotide-mediated effects on colonic NaCl secretion and the signal transduction mechanisms involved. Basolateral UDP induced a sustained activation of Cl– secretion, which was completely inhibited by 293B, a specific inhibitor of cAMP-stimulated basolateral KCNQ1/KCNE3 K+ channels. We therefore speculated that a basolateral P2Y6 receptor could increase cAMP. Indeed UDP elevated cAMP in isolated crypts. We identified an epithelial P2Y6 receptor using crypt [Ca2+]i measurements, RT-PCR, and immunohistochemistry. To investigate whether the rat P2Y6elevates cAMP, we coexpressed the P2Y1 or P2Y6 receptor together with the cAMP-regulated cystic fibrosis transmembrane conductance regulator (CFTR) Cl– channel in Xenopus oocytes. A two-electrode voltage clamp was used to monitor nucleotide-induced Cl– currents. In oocytes expressing the P2Y1 receptor, ATP transiently activated the endogenous Ca2+-activated Cl– current, but not CFTR. In contrast, in oocytes expressing the P2Y6receptor, UDP transiently activated the Ca2+-activated Cl– current and subsequently CFTR. CFTR Cl– currents were identified by their halide conductance sequence. In summary we find a basolateral P2Y6 receptor in colonic epithelial cells stimulating sustained NaCl secretion by way of a synergistic increase of [Ca2+]i and cAMP. In support of these data P2Y6 receptor stimulation differentially activates CFTR in Xenopus oocytes. PMID:12569163

Blocking adenylyl cyclase inhibits olfactory generator currents induced by "IP(3)-odors".

PubMed

Chen, S; Lane, A P; Bock, R; Leinders-Zufall, T; Zufall, F

2000-07-01

Vertebrate olfactory receptor neurons (ORNs) transduce odor stimuli into electrical signals by means of an adenylyl cyclase/cAMP second messenger cascade, but it remains widely debated whether this cAMP cascade mediates transduction for all odorants or only certain odor classes. To address this problem, we have analyzed the generator currents induced by odors that failed to produce cAMP in previous biochemical assays but instead produced IP(3) ("IP(3)-odors"). We show that in single salamander ORNs, sensory responses to "cAMP-odors" and IP(3)-odors are not mutually exclusive but coexist in the same cells. The currents induced by IP(3)-odors exhibit identical biophysical properties as those induced by cAMP odors or direct activation of the cAMP cascade. By disrupting adenylyl cyclase to block cAMP formation using two potent antagonists of adenylyl cyclase, SQ22536 and MDL12330A, we show that this molecular step is necessary for the transduction of both odor classes. To assess whether these results are also applicable to mammals, we examine the electrophysiological responses to IP(3)-odors in intact mouse main olfactory epithelium (MOE) by recording field potentials. The results show that inhibition of adenylyl cyclase prevents EOG responses to both odor classes in mouse MOE, even when "hot spots" with heightened sensitivity to IP(3)-odors are examined.

Electrostatically frequency tunable micro-beam-based piezoelectric fluid flow energy harvester

NASA Astrophysics Data System (ADS)

Rezaee, Mousa; Sharafkhani, Naser

2017-07-01

This research investigates the dynamic behavior of a sandwich micro-beam based piezoelectric energy harvester with electrostatically adjustable resonance frequency. The system consists of a cantilever micro-beam immersed in a fluid domain and is subjected to the simultaneous action of cross fluid flow and nonlinear electrostatic force. Two parallel piezoelectric laminates are extended along the length of the micro-beam and connected to an external electric circuit which generates an output power as a result of the micro-beam oscillations. The fluid-coupled structure is modeled using Euler-Bernoulli beam theory and the equivalent force terms for the fluid flow. Fluid induced forces comprise the added inertia force which is evaluated using equivalent added mass and the drag and lift forces which are evaluated using relative velocity and Van der Pol equation. In addition to flow velocity and fluid density, the influence of several design parameters such as external electrical resistance, piezo layer position, and dc voltage on the generated power are investigated by using Galerkin and step by step linearization method. It is shown that for given flowing fluid parameters, i.e., density and velocity, one can adjust the applied dc voltage to tune resonance frequency so that the lock-in phenomenon with steady large amplitude oscillations happens, also by adjusting the harvester parameters including the mechanical and electrical ones, the maximal output power of the harvester becomes possible.

Field emission and explosive electron emission process in focused ion beam fabricated platinum and tungsten three-dimensional overhanging nanostructure

NASA Astrophysics Data System (ADS)

Singh, Abhishek Kumar

2018-06-01

Three-dimensional platinum and tungsten overhanging nanogap (∼70 nm) electrodes are fabricated on a glass substrate using focused ion beam milling and chemical vapour deposition processes. Current-voltage (I-V) characteristics of the devices measured at a pressure of ∼10-6 mbar shows space-charge emission followed by the Fowler-Nordheim (F-N) field emission. After the F-N emission, the system enters into an explosive emission process, at a higher voltage generating a huge current. We observe a sharp and abrupt rise in the emission current which marks the transition from the F-N emission to the explosive emission state. The explosive emission process is destructive in nature and yields micro-/nano-size spherical metal particles. The chemical compositions and the size-distribution of such particles are performed.

Comparison of time-gated surface-enhanced Raman spectroscopy (TG-SERS) and classical SERS based monitoring of Escherichia coli cultivation samples.

PubMed

Kögler, Martin; Paul, Andrea; Anane, Emmanuel; Birkholz, Mario; Bunker, Alex; Viitala, Tapani; Maiwald, Michael; Junne, Stefan; Neubauer, Peter

2018-06-08

The application of Raman spectroscopy as a monitoring technique for bioprocesses is severely limited by a large background signal originating from fluorescing compounds in the culture media. Here we compare time-gated Raman (TG-Raman)-, continuous wave NIR-process Raman (NIR-Raman) and continuous wave micro-Raman (micro-Raman) approaches in combination with surface enhanced Raman spectroscopy (SERS) for their potential to overcome this limit. For that purpose, we monitored metabolite concentrations of Escherichia coli bioreactor cultivations in cell-free supernatant samples. We investigated concentration transients of glucose, acetate, AMP and cAMP at alternating substrate availability, from deficiency to excess. Raman and SERS signals were compared to off-line metabolite analysis of carbohydrates, carboxylic acids and nucleotides. Results demonstrate that SERS, in almost all cases, led to a higher number of identifiable signals and better resolved spectra. Spectra derived from the TG-Raman were comparable to those of micro-Raman resulting in well-discernable Raman peaks, which allowed for the identification of a higher number of compounds. In contrast, NIR-Raman provided a superior performance for the quantitative evaluation of analytes, both with and without SERS nanoparticles when using multivariate data analysis. This article is protected by copyright. All rights reserved. © 2018 American Institute of Chemical Engineers.

Activation of G proteins mediates flow-induced prostaglandin E2 production in osteoblasts

NASA Technical Reports Server (NTRS)

Reich, K. M.; McAllister, T. N.; Gudi, S.; Frangos, J. A.

1997-01-01

Interstitial fluid flow may play a role in load-induced bone remodeling. Previously, we have shown that fluid flow stimulates osteoblast production of cAMP inositol trisphosphate (IP3), and PGE2. Flow-induced increases in cAMP and IP3 were shown to be a result of PG production. Thus, PGE2 production appears to be an important component in fluid flow induced signal transduction. In the present study, we investigated the mechanism of flow-induced PGE2 synthesis. Flow-induced a 20-fold increase in PGE2 production in osteoblasts. Increases were also observed with ALF4-(10mM) (98-fold), an activator of guanidine nucleotide-binding proteins (G proteins), and calcium ionophore A23187 (2 microM) (100-fold) in stationary cells. We then investigated whether flow stimulation is mediated by G proteins and increases in intracellular calcium. Flow-induced PGE2 production was inhibited by the G protein inhibitors GDP beta S (100 microM) and pertussis toxin (1 microgram/ml) by 83% and 72%, respectively. Chelation of extracellular calcium by EGTA (2 mM) and intracellular calcium by quin-2/AM (30 microM) blocked flow stimulation by 87% and 67%, respectively. These results suggest that G proteins and calcium play an important role in mediating mechanochemical signal transduction in osteoblasts.

An online proton beam monitor for cancer therapy based on ionization chambers with micro pattern readout

NASA Astrophysics Data System (ADS)

Basile, E.; Carloni, A.; Castelluccio, D. M.; Cisbani, E.; Colilli, S.; De Angelis, G.; Fratoni, R.; Frullani, S.; Giuliani, F.; Gricia, M.; Lucentini, M.; Santavenere, F.; Vacca, G.

2012-03-01

A unique compact LINAC accelerator for proton therapy is under development in Italy within the TOP-IMPLART project. The proton beam will reach the kinetic energy of 230 MeV, it will have a widely variable current intensity (0.1-10 μA, with average up to 3.5 nA) associated with a high pulse repetition frequency (1-3.5 μs long pulses at 10-100 Hz). The TOP-IMPLART system will provide a fully active 3+1D dose delivery, that is longitudinal (energy modulation), transverse active spot scanning, and current intensity modulation. These accelerator features will permit a highly conformational dose distribution, which therefore requires an effective, online, beam monitor system with wide dynamic range, good sensitivity, adequate spatial resolution and rapid response. In order to fulfill these requisites a new device is under development for the monitoring of the beam intensity profile, its centroid and direction; it is based on transmission, segmented, ionization chambers with typical active area of 100 × 100 mm2. Micro pattern x/y pad like design has been used for the readout plane in order to maximize the field uniformity, reduce the chamber thickness and obtain both beam coordinates on a single chamber. The chamber prototype operates in ionization region to minimize saturation and discharge effects. Simulations (based on FLUKA) have been carried on to study the perturbation of the chamber on the beam parameters and the effects on the delivered dose (on a water phantom). The charge collected in each channel is integrated by dedicated auto-ranging readout electronics: an original scheme has been developed in order to have an input dynamic range greater than 104 with sensitivity better than 3%. This is achieved by a dynamical adjustment of the integrating capacitance to the signal intensity.

Determination of electron beam polarization using electron detector in Compton polarimeter with less than 1% statistical and systematic uncertainty

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

Narayan, Amrendra

2015-05-01

The Q-weak experiment aims to measure the weak charge of proton with a precision of 4.2%. The proposed precision on weak charge required a 2.5% measurement of the parity violating asymmetry in elastic electron - proton scattering. Polarimetry was the largest experimental contribution to this uncertainty and a new Compton polarimeter was installed in Hall C at Jefferson Lab to make the goal achievable. In this polarimeter the electron beam collides with green laser light in a low gain Fabry-Perot Cavity; the scattered electrons are detected in 4 planes of a novel diamond micro strip detector while the back scatteredmore » photons are detected in lead tungstate crystals. This diamond micro-strip detector is the first such device to be used as a tracking detector in a nuclear and particle physics experiment. The diamond detectors are read out using custom built electronic modules that include a preamplifier, a pulse shaping amplifier and a discriminator for each detector micro-strip. We use field programmable gate array based general purpose logic modules for event selection and histogramming. Extensive Monte Carlo simulations and data acquisition simulations were performed to estimate the systematic uncertainties. Additionally, the Moller and Compton polarimeters were cross calibrated at low electron beam currents using a series of interleaved measurements. In this dissertation, we describe all the subsystems of the Compton polarimeter with emphasis on the electron detector. We focus on the FPGA based data acquisition system built by the author and the data analysis methods implemented by the author. The simulations of the data acquisition and the polarimeter that helped rigorously establish the systematic uncertainties of the polarimeter are also elaborated, resulting in the first sub 1% measurement of low energy (?1 GeV) electron beam polarization with a Compton electron detector. We have demonstrated that diamond based micro-strip detectors can be used for tracking in a high radiation environment and it has enabled us to achieve the desired precision in the measurement of the electron beam polarization which in turn has allowed the most precise determination of the weak charge of the proton.« less

Determination of electron beam polarization using electron detector in Compton polarimeter with less than 1% statistical and systematic uncertainty

NASA Astrophysics Data System (ADS)

Narayan, Amrendra

The Q-weak experiment aims to measure the weak charge of proton with a precision of 4.2%. The proposed precision on weak charge required a 2.5% measurement of the parity violating asymmetry in elastic electron - proton scattering. Polarimetry was the largest experimental contribution to this uncertainty and a new Compton polarimeter was installed in Hall C at Jefferson Lab to make the goal achievable. In this polarimeter the electron beam collides with green laser light in a low gain Fabry-Perot Cavity; the scattered electrons are detected in 4 planes of a novel diamond micro strip detector while the back scattered photons are detected in lead tungstate crystals. This diamond micro-strip detector is the first such device to be used as a tracking detector in a nuclear and particle physics experiment. The diamond detectors are read out using custom built electronic modules that include a preamplifier, a pulse shaping amplifier and a discriminator for each detector micro-strip. We use field programmable gate array based general purpose logic modules for event selection and histogramming. Extensive Monte Carlo simulations and data acquisition simulations were performed to estimate the systematic uncertainties. Additionally, the Moller and Compton polarimeters were cross calibrated at low electron beam currents using a series of interleaved measurements. In this dissertation, we describe all the subsystems of the Compton polarimeter with emphasis on the electron detector. We focus on the FPGA based data acquisition system built by the author and the data analysis methods implemented by the author. The simulations of the data acquisition and the polarimeter that helped rigorously establish the systematic uncertainties of the polarimeter are also elaborated, resulting in the first sub 1% measurement of low energy (~1GeV) electron beam polarization with a Compton electron detector. We have demonstrated that diamond based micro-strip detectors can be used for tracking in a high radiation environment and it has enabled us to achieve the desired precision in the measurement of the electron beam polarization which in turn has allowed the most precise determination of the weak charge of the proton.

Down-regulation of parathyroid hormone (PTH) receptors in cultured bone cells is associated with agonist-specific intracellular processing of PTH-receptor complexes.

PubMed

Teitelbaum, A P; Silve, C M; Nyiredy, K O; Arnaud, C D

1986-02-01

Exposure of cultured embryonic chicken bone cells to the PTH agonists bovine (b) PTH-(1-34) and [8Nle, 18Nle, 34Tyr]bPTH-(1-34)amide [bPTH-(1-34)A] reduces the subsequent cAMP response to the hormone and decreases the specific binding of 125I-labeled PTH to these cultures. To determine whether PTH receptor down-regulation in cultured bone cells is mediated by cellular internalization of PTH-receptor complexes, we measured the uptake of [125I]bPTH-(1-34) into an acid-resistant compartment. Uptake of radioactivity into this compartment was inhibited by incubating cells at 4 C with phenylarsineoxide and unlabeled bPTH-(1-34). Tracer uptake into the acid-resistant compartment at any time was directly proportional to total cell binding at 22 C. Thus, it is likely that PTH-receptor complexes are internalized by bone cells. This mechanism may explain the loss of cell surface receptors after PTH pretreatment. To determine whether internalized PTH-receptor complexes are reinserted into the plasma membrane, we measured PTH binding and PTH stimulation of cAMP production after cells were exposed to monensin, a known inhibitor of receptor recycling. Monensin (25 microM) had no effect on PTH receptor number or affinity and did not alter PTH-stimulated cAMP accumulation. However, monensin (25 microM) incubated with cells pretreated with various concentrations of bPTH-(1-34) for 1 h potentiated the effect of the hormone to reduce subsequent [125I]bPTH-(1-34) binding and PTH-stimulated cAMP accumulation by more than 2 orders of magnitude. Chloroquine also potentiated PTH-induced down-regulation of PTH receptors. By contrast, neither agent influenced PTH binding or PTH-stimulated cAMP production in cells pretreated with the antagonist bPTH-(3-34)A. Thus, monensin potentiated PTH receptor loss only in cells pretreated with PTH agonists, indicating that antagonist-occupied receptors may be processed differently from agonist-occupied receptors in bone cells. The data further suggest that the attenuation of PTH stimulation of cAMP production in treated bone cells may be, at least in part, due to receptor-mediated endocytosis of the hormone.

Divergent mechanisms of insulin-like growth factor I and II on rat hepatocyte proliferation.

PubMed

Raper, S; Kothary, P; Ishoo, E; Dikin, M; Kokudo, N; Hashimoto, M; DeMatteo, R P

1995-07-21

Insulin-like growth factors I and II are peptides with a structural homology for proinsulin, and are involved in hepatocyte proliferation. IGF-I and IGF-II, however, have different metabolic roles, and their mechanisms of action are incompletely known. We hypothesized that IGF-I and IGF-II act by different signal transduction pathways. To test this hypothesis, hepatocytes from 200 g male Sprague-Dawley rats were isolated by a two-step collagenase perfusion technique and plated at a density of 10(5) cells/16 mm Primaria plate. Proliferation was measured by [3H]thymidine ([3H]thy) incorporation into DNA, and an autoradiographic nuclear labeling index (LI). To analyze signal transduction, cyclic AMP (cAMP) levels were measured 5 min after addition of reagents by a radioimmunoassay. Reagents (doses) used were: IGF-I (2 nM), IGF-II (2 nM), the inhibitory peptide somatostatin-14 (SS14) (10 nM), and the adenylyl cyclase antagonist dideoxyadenosine (DDA) (10 microM). A summary of the findings is as follows: (1) IGF-I stimulates [3H]thy, LI and cAMP accumulation. (2) IGF-II stimulates [3H]thy and LI but not cAMP; (3) IGF-I but not IGF-II effects are inhibited by SS14 and DDA. We conclude that the hepatotrophic effects of IGF-I and IGF-II occur by different mechanisms: IGF-I is cAMP-dependent, IGF-II is cAMP-independent.

A method of measuring micro-impulse with torsion pendulum based on multi-beam laser heterodyne

NASA Astrophysics Data System (ADS)

Li, Yan-Chao; Wang, Chun-Hui

2012-02-01

In this paper, we propose a novel method of multi-beam laser heterodyne measurement for micro-impulse. The measurement of the micro-impulse, which is converted into the measurement of the small tuning angle of the torsion pendulum, is realized by considering the interaction between pulse laser and working medium. Based on Doppler effect and heterodyne technology, the information regarding the small tuning angle is loaded to the frequency difference of the multi-beam laser heterodyne signal by the frequency modulation of the oscillating mirror, thereby obtaining many values of the small tuning angle after the multi-beam laser heterodyne signal demodulation simultaneously. Processing these values by weighted-average, the small tuning angle can be obtained accurately and the value of the micro-impulse can eventually be calculated. Using Polyvinylchlorid+2%C as a working medium, this novel method is used to simulate the value of the micro-impulse by MATLAB which is generated by considering the interaction between the pulse laser and the working medium, the obtained result shows that the relative error of this method is just 0.5%.

New micro-beam beamline at SPring-8, targeting at protein micro-crystallography

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

Hirata, Kunio; Ueno, Go; Nisawa, Atsushi

2010-06-23

A new protein micro-crystallography beamline BL32XU at SPring-8 is under construction and scheduled to start operation in 2010. The beamline is designed to provide the stabilized and brilliant micro-beam to collect high-quality data from micro-crystals. The beamline consists of a hybrid in-vacuum undulator, a liquid-nitrogen cooled double crystal monochromator, and K-B focusing mirrors with large magnification factor. Development of data acquisition system and end station consists of high-precision diffractometer, high-efficiency area detector, sample auto-changer etc. are also in progress.

Exchange protein activated by cAMP (Epac) mediates cAMP-dependent but protein kinase A-insensitive modulation of vascular ATP-sensitive potassium channels

PubMed Central

Purves, Gregor I; Kamishima, Tomoko; Davies, Lowri M; Quayle, John M; Dart, Caroline

2009-01-01

Exchange proteins directly activated by cyclic AMP (Epacs or cAMP-GEF) represent a family of novel cAMP-binding effector proteins. The identification of Epacs and the recent development of pharmacological tools that discriminate between cAMP-mediated pathways have revealed previously unrecognized roles for cAMP that are independent of its traditional target cAMP-dependent protein kinase (PKA). Here we show that Epac exists in a complex with vascular ATP-sensitive potassium (KATP) channel subunits and that cAMP-mediated activation of Epac modulates KATP channel activity via a Ca2+-dependent mechanism involving the activation of Ca2+-sensitive protein phosphatase 2B (PP-2B, calcineurin). Application of the Epac-specific cAMP analogue 8-pCPT-2′-O-Me-cAMP, at concentrations that activate Epac but not PKA, caused a 41.6 ± 4.7% inhibition (mean ±s.e.m.; n= 7) of pinacidil-evoked whole-cell KATP currents recorded in isolated rat aortic smooth muscle cells. Importantly, similar results were obtained when cAMP was elevated by addition of the adenylyl cyclase activator forskolin in the presence of the structurally distinct PKA inhibitors, Rp-cAMPS or KT5720. Activation of Epac by 8-pCPT-2′-O-Me-cAMP caused a transient 171.0 ± 18.0 nm (n= 5) increase in intracellular Ca2+ in Fura-2-loaded aortic myocytes, which persisted in the absence of extracellular Ca2+. Inclusion of the Ca2+-specific chelator BAPTA in the pipette-filling solution or preincubation with the calcineurin inhibitors, cyclosporin A or ascomycin, significantly reduced the ability of 8-pCPT-2′-O-Me-cAMP to inhibit whole-cell KATP currents. These results highlight a previously undescribed cAMP-dependent regulatory mechanism that may be essential for understanding the physiological and pathophysiological roles ascribed to arterial KATP channels in the control of vascular tone and blood flow. PMID:19491242

3D model of filler melting with micro-beam plasma arc based on additive manufacturing technology

NASA Astrophysics Data System (ADS)

Chen, Weilin; Yang, Tao; Yang, Ruixin

2017-07-01

Additive manufacturing technology is a systematic process based on discrete-accumulation principle, which is derived by the dimension of parts. Aiming at the dimension mathematical model and slicing problems in additive manufacturing process, the constitutive relations between micro-beam plasma welding parameters and the dimension of part were investigated. The slicing algorithm and slicing were also studied based on the dimension characteristics. By using the direct slicing algorithm according to the geometric characteristics of model, a hollow thin-wall spherical part was fabricated by 3D additive manufacturing technology using micro-beam plasma.

Staging of RF-accelerating Units in a MEMS-based Ion Accelerator

NASA Astrophysics Data System (ADS)

Persaud, A.; Seidl, P. A.; Ji, Q.; Feinberg, E.; Waldron, W. L.; Schenkel, T.; Ardanuc, S.; Vinayakumar, K. B.; Lal, A.

Multiple Electrostatic Quadrupole Array Linear Accelerators (MEQALACs) provide an opportunity to realize compact radio- frequency (RF) accelerator structures that can deliver very high beam currents. MEQALACs have been previously realized with acceleration gap distances and beam aperture sizes of the order of centimeters. Through advances in Micro-Electro-Mechanical Systems (MEMS) fabrication, MEQALACs can now be scaled down to the sub-millimeter regime and batch processed on wafer substrates. In this paper we show first results from using three RF stages in a compact MEMS-based ion accelerator. The results presented show proof-of-concept with accelerator structures formed from printed circuit boards using a 3 × 3 beamlet arrangement and noble gas ions at 10 keV. We present a simple model to describe the measured results. We also discuss some of the scaling behaviour of a compact MEQALAC. The MEMS-based approach enables a low-cost, highly versatile accelerator covering a wide range of currents (10 μA to 100 mA) and beam energies (100 keV to several MeV). Applications include ion-beam analysis, mass spectrometry, materials processing, and at very high beam powers, plasma heating.

Staging of RF-accelerating Units in a MEMS-based Ion Accelerator

DOE PAGES

Persaud, A.; Seidl, P. A.; Ji, Q.; ...

2017-10-26

Multiple Electrostatic Quadrupole Array Linear Accelerators (MEQALACs) provide an opportunity to realize compact radio- frequency (RF) accelerator structures that can deliver very high beam currents. MEQALACs have been previously realized with acceleration gap distances and beam aperture sizes of the order of centimeters. Through advances in Micro-Electro-Mechanical Systems (MEMS) fabrication, MEQALACs can now be scaled down to the sub-millimeter regime and batch processed on wafer substrates. In this paper we show first results from using three RF stages in a compact MEMS-based ion accelerator. The results presented show proof-of-concept with accelerator structures formed from printed circuit boards using a 3more » × 3 beamlet arrangement and noble gas ions at 10 keV. We present a simple model to describe the measured results. We also discuss some of the scaling behaviour of a compact MEQALAC. The MEMS-based approach enables a low-cost, highly versatile accelerator covering a wide range of currents (10 μA to 100 mA) and beam energies (100 keV to several MeV). Applications include ion-beam analysis, mass spectrometry, materials processing, and at very high beam powers, plasma heating.« less

Staging of RF-accelerating Units in a MEMS-based Ion Accelerator

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

Persaud, A.; Seidl, P. A.; Ji, Q.

Multiple Electrostatic Quadrupole Array Linear Accelerators (MEQALACs) provide an opportunity to realize compact radio- frequency (RF) accelerator structures that can deliver very high beam currents. MEQALACs have been previously realized with acceleration gap distances and beam aperture sizes of the order of centimeters. Through advances in Micro-Electro-Mechanical Systems (MEMS) fabrication, MEQALACs can now be scaled down to the sub-millimeter regime and batch processed on wafer substrates. In this paper we show first results from using three RF stages in a compact MEMS-based ion accelerator. The results presented show proof-of-concept with accelerator structures formed from printed circuit boards using a 3more » × 3 beamlet arrangement and noble gas ions at 10 keV. We present a simple model to describe the measured results. We also discuss some of the scaling behaviour of a compact MEQALAC. The MEMS-based approach enables a low-cost, highly versatile accelerator covering a wide range of currents (10 μA to 100 mA) and beam energies (100 keV to several MeV). Applications include ion-beam analysis, mass spectrometry, materials processing, and at very high beam powers, plasma heating.« less

Multiple regulation by external ATP of nifedipine-insensitive, high voltage-activated Ca(2+) current in guinea-pig mesenteric terminal arteriole.

PubMed

Morita, Hiromitsu; Sharada, Thapaliya; Takewaki, Tadashi; Ito, Yushi; Inoue, Ryuji

2002-03-15

We investigated the receptor-mediated regulation of nifedipine-insensitive, high voltage-activated Ca(2+) currents in guinea-pig terminal mesenteric arterioles (I(mVDCC)) using the whole-cell clamp technique. Screening of various vasoactive substances revealed that ATP, histamine and substance P exert modulatory effects on I(mVDCC). The effects of ATP on I(mVDCC) after complete P2X receptor desensitization exhibited a complex concentration dependence. With 5 mM Ba(2+), ATP potentiated I(mVDCC) at low concentrations (approximately 1-100 microM), but inhibited it at higher concentrations (>100 microM). The potentiating effects of ATP were abolished by suramin (100 microM) and PPADS (10 microM) and by intracellular application of GDPbetaS (500 microM), whereas a substantial part of I(mVDCC) inhibition by milimolar concentrations of ATP remained unaffected; due probably to its divalent cation chelating actions. In divalent cation-free solution, I(mVDCC) was enlarged and underwent biphasic effects by ATPgammaS and ADP, while 2-methylthio ATP (2MeSATP) exerted only inhibition, and pyrimidines such as UTP and UDP were ineffective. ATP-induced I(mVDCC) potentiation was selectively inhibited by anti-Galpha(s) antibodies or protein kinase A (PKA) inhibitory peptides and mimicked by dibutyryl cAMP. In contrast, ATP-induced inhibition was selectively inhibited by Galpha(q/11) antibodies or protein kinase C (PKC) inhibitory peptides and mimicked by PDBu. Pretreatment with pertussis toxin was ineffective. The apparent efficacy for I(mVDCC) potentiation with PKC inhibitors was: ATPgammaS > ATP>/=ADP and for inhibition with PKA inhibitors was: 2MeSATP > ATPgammaS > ATP > ADP. Neither I(mVDCC) potentiation nor inhibition showed voltage dependence. These results suggest that I(mVDCC) is multi-phasically regulated by external ATP via P2Y(11)-resembling receptor/G(s)/PKA pathway, P2Y(1)-like receptor/G(q/11)/PKC pathway, and metal chelation.

Development of a pepper pot emittance probe and its application for ECR ion beam studies.

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

Kondrashev, S.; Barcikowski, A.; Mustapha, B.

2009-07-21

A pepper pot-scintillator screen system has been developed and used to measure the emittance of DC ion beams extracted from a high-intensity permanent magnet ECR ion source. The system includes a fast beam shutter with a minimum dwell time of 18 ms to reduce the degradation of the CsI(Tl) scintillator by DC ion beam irradiation and a CCD camera with a variable shutter speed in the range of 1 {micro}s-65 s. On-line emittance measurements are performed by an application code developed on a LabVIEW platform. The sensitivity of the device is sufficient to measure the emittance of DC ion beamsmore » with current densities down to about 100 nA/cm{sup 2}. The emittance of all ion species extracted from the ECR ion source and post-accelerated to an energy of 75-90 keV/charge have been measured downstream of the LEBT. As the mass-to-charge ratio of ion species increases, the normalized RMS emittances in both transverse phase planes decrease from 0.5-1.0 {pi} mm mrad for light ions to 0.05-0.09 {pi} mm mrad for highly charged {sup 209}Bi ions. The dependence of the emittance on ion's mass-to-charge ratio follows very well the dependence expected from beam rotation induced by decreasing ECR axial magnetic field. The measured emittance values cannot be explained by only ion beam rotation for all ion species and the contribution to emittance of ion temperature in plasma, non-linear electric fields and non-linear space charge is comparable or even higher than the contribution of ion beam rotation.« less

A Micro-Force Sensor with Slotted-Quad-Beam Structure for Measuring the Friction in MEMS Bearings

PubMed Central

Liu, Huan; Yang, Shuming; Zhao, Yulong; Jiang, Zhuangde; Liu, Yan; Tian, Bian

2013-01-01

Presented here is a slotted-quad-beam structure sensor for the measurement of friction in micro bearings. Stress concentration slots are incorporated into a conventional quad-beam structure to improve the sensitivity of force measurements. The performance comparison between the quad-beam structure sensor and the slotted-quad-beam structure sensor are performed by theoretical modeling and finite element (FE) analysis. A hollow stainless steel probe is attached to the mesa of the sensor chip by a tailor-made organic glass fixture. Concerning the overload protection of the fragile beams, a glass wafer is bonded onto the bottom of sensor chip to limit the displacement of the mesa. The calibration of the packaged device is experimentally performed by a tri-dimensional positioning stage, a precision piezoelectric ceramic and an electronic analytical balance, which indicates its favorable sensitivity and overload protection. To verify the potential of the proposed sensor being applied in micro friction measurement, a measurement platform is established. The output of the sensor reflects the friction of bearing resulting from dry friction and solid lubrication. The results accord with the theoretical modeling and demonstrate that the sensor has the potential application in measuring the micro friction force under stable stage in MEMS machines. PMID:24084112

Inhibitory mechanism of monensin on high K+-induced contraction in guniea-pig urinary bladder.

PubMed

Kaneda, Takeharu; Takeuchi, Mayumi; Shimizu, Kazumasa; Urakawa, Norimoto; Nakajyo, Shinjiro; Mochizuki-Kobayashi, Mariko; Ueda, Fukiko; Hondo, Ryo

2006-02-01

In this study, we examined the inhibitory mechanism of monensin on high K+-induced contraction in guinea-pig urinary bladder. The relaxant effect of monensin (0.001 - 10 microM) was more potent than those of NaCN (100 microM - 1 mM) and forskolin (3 - 10 microM). Monensin (0.1 microM), NaCN (300 microM), or forskolin (10 microM) inhibited high K+-induced contraction without decreasing [Ca2+]i level. Monensin and NaCN remarkably decreased creatine phosphate and ATP contents. Monensin and NaCN inhibited high K+-induced increases in flavoprotein fluorescence, which is involved in mitochondrial respiration. Forskolin increased cAMP content but monensin did not. Monensin increased Na+ content at 10 microM but not at 0.1 microM that induced maximum relaxation. In the alpha-toxin-permeabilized muscle, forskolin significantly inhibited the Ca2+-induced contraction, but monensin did not affect it. These results suggest that the relaxation mechanism of monensin in smooth muscle of urinary bladder may be an inhibition of oxidative metabolism.

DARHT Axis-I Diode Simulations II: Geometrical Scaling

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

Ekdahl, Carl A. Jr.

2012-06-14

Flash radiography of large hydrodynamic experiments driven by high explosives is a venerable diagnostic technique in use at many laboratories. Many of the largest hydrodynamic experiments study mockups of nuclear weapons, and are often called hydrotests for short. The dual-axis radiography for hydrodynamic testing (DARHT) facility uses two electron linear-induction accelerators (LIA) to produce the radiographic source spots for perpendicular views of a hydrotest. The first of these LIAs produces a single pulse, with a fixed {approx}60-ns pulsewidth. The second axis LIA produces as many as four pulses within 1.6-{micro}s, with variable pulsewidths and separation. There are a wide varietymore » of hydrotest geometries, each with a unique radiographic requirement, so there is a need to adjust the radiographic dose for the best images. This can be accomplished on the second axis by simply adjusting the pulsewidths, but is more problematic on the first axis. Changing the beam energy or introducing radiation attenuation also changes the spectrum, which is undesirable. Moreover, using radiation attenuation introduces significant blur, increasing the effective spot size. The dose can also be adjusted by changing the beam kinetic energy. This is a very sensitive method, because the dose scales as the {approx}2.8 power of the energy, but it would require retuning the accelerator. This leaves manipulating the beam current as the best means for adjusting the dose, and one way to do this is to change the size of the cathode. This method has been proposed, and is being tested. This article describes simulations undertaken to develop scaling laws for use as design tools in changing the Axis-1 beam current by changing the cathode size.« less

Micro-crystallography comes of age

PubMed Central

Smith, Janet L.; Fischetti, Robert F.; Yamamoto, Masaki

2012-01-01

The latest revolution in macromolecular crystallography was incited by the development of dedicated, user friendly, micro-crystallography beamlines. Brilliant X-ray beams of diameter 20 microns or less, now available at most synchrotron sources, enable structure determination from samples that previously were inaccessible. Relative to traditional crystallography, crystals with one or more small dimensions have diffraction patterns with vastly improved signal-to-noise when recorded with an appropriately matched beam size. Structures can be solved from isolated, well diffracting regions within inhomogeneous samples. This review summarizes the technological requirements and approaches to producing micro-beams and how they continue to change the practice of crystallography. PMID:23021872

Negative feedback exerted by cAMP-dependent protein kinase and cAMP phosphodiesterase on subsarcolemmal cAMP signals in intact cardiac myocytes: an in vivo study using adenovirus-mediated expression of CNG channels.

PubMed

Rochais, Francesca; Vandecasteele, Grégoire; Lefebvre, Florence; Lugnier, Claire; Lum, Hazel; Mazet, Jean-Luc; Cooper, Dermot M F; Fischmeister, Rodolphe

2004-12-10

Intracardiac cAMP levels are modulated by hormones and neuromediators with specific effects on contractility and metabolism. To understand how the same second messenger conveys different information, mutants of the rat olfactory cyclic nucleotide-gated (CNG) channel alpha-subunit CNGA2, encoded into adenoviruses, were used to monitor cAMP in adult rat ventricular myocytes. CNGA2 was not found in native myocytes but was strongly expressed in infected cells. In whole cell patch-clamp experiments, the forskolin analogue L-858051 (L-85) elicited a non-selective, Mg2+ -sensitive current observed only in infected cells, which was thus identified as the CNG current (ICNG). The beta-adrenergic agonist isoprenaline (ISO) also activated ICNG, although the maximal efficiency was approximately 5 times lower than with L-85. However, ISO and L-85 exerted a similar maximal increase of the L-type Ca2+ current. The use of a CNGA2 mutant with a higher sensitivity for cAMP indicated that this difference is caused by the activation of a localized fraction of CNG channels by ISO. cAMP-dependent protein kinase (PKA) blockade with H89 or PKI, or phosphodiesterase (PDE) inhibition with IBMX, dramatically potentiated ISO- and L-85-stimulated ICNG. A similar potentiation of beta-adrenergic stimulation occurred when PDE4 was blocked, whereas PDE3 inhibition had a smaller effect (by 2-fold). ISO and L-85 increased total PDE3 and PDE4 activities in cardiomyocytes, although this effect was insensitive to H89. However, in the presence of IBMX, H89 had no effect on ISO stimulation of ICNG. This study demonstrates that subsarcolemmal cAMP levels are dynamically regulated by a negative feedback involving PKA stimulation of subsarcolemmal cAMP-PDE.

Solid core dipoles and switching power supplies: Lower cost light sources?

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

Benesch, Jay; Philip, Sarin

As a result of improvements in power semiconductors, moderate frequency switching supplies can now provide the hundreds of amps typically required by accelerators with zero-to-peak noise in the kHz region ~ 0.06% in current or voltage mode. Modeling was undertaken using a finite electromagnetic program to determine if eddy currents induced in the solid steel of CEBAF magnets and small supplemental additions would bring the error fields down to the 5ppm level needed for beam quality. The expected maximum field of the magnet under consideration is 0.85 T and the DC current required to produce that field is used inmore » the calculations. An additional 0.1% current ripple is added to the DC current at discrete frequencies 360 Hz, 720 Hz or 7200 Hz. Over the region of the pole within 0.5% of the central integrated BdL the resulting AC field changes can be reduced to less than 1% of the 0.1% input ripple for all frequencies, and a sixth of that at 7200 Hz. Doubling the current, providing 1.5 T central field, yielded the same fractional reduction in ripple at the beam for the cases checked. A small dipole was measured at 60, 120, 360 and 720 Hz in two conditions and the results compared to the larger model for the latter two frequencies with surprisingly good agreement. Thus, for light sources with aluminum vacuum vessels and full energy linac injection, the combination of solid core dipoles and switching power supplies may result in significant cost savings.« less

MEMS fabrication and frequency sweep for suspending beam and plate electrode in electrostatic capacitor

NASA Astrophysics Data System (ADS)

Zhu, Jianxiong; Song, Weixing

2018-01-01

We report a MEMS fabrication and frequency sweep for a high-order mode suspending beam and plate layer in electrostatic micro-gap semiconductor capacitor. This suspended beam and plate was designed with silicon oxide (SiO2) film which was fabricated using bulk silicon micromachining technology on both side of a silicon substrate. The designed semiconductor capacitors were driven by a bias direct current (DC) and a sweep frequency alternative current (AC) in a room temperature for an electrical response test. Finite element calculating software was used to evaluate the deformation mode around its high-order response frequency. Compared a single capacitor with a high-order response frequency (0.42 MHz) and a 1 × 2 array parallel capacitor, we found that the 1 × 2 array parallel capacitor had a broader high-order response range. And it concluded that a DC bias voltage can be used to modulate a high-order response frequency for both a single and 1 × 2 array parallel capacitors.

Reduced ischemia-reperfusion injury with isoproterenol in non-heart-beating donor lungs.

PubMed

Jones, D R; Hoffmann, S C; Sellars, M; Egan, T M

1997-05-01

Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia-reperfusion injury (IRI) to the lung can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, as measured by Kfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). Using an in situ isolated perfused lung model, lungs were retrieved from non-heart-beating donor rats ventilated with O2 or not at varying intervals after death. The lungs were reperfused with or without iso (10 microM). Kfc, lung viability, and pulmonary hemodynamics were measured, and tissue levels of adenine nucleotides and cAMP were measured by HPLC. Iso-reperfusion decreased Kfc significantly (P < 0.05) compared to non-iso-reperfused groups at all postmortem ischemic times, irrespective of preharvest ventilation status. Pulmonary arterial pressures and resistances increased and venous resistances decreased with iso-reperfusion. Total adenine nucleotide (TAN) levels correlated with Kfc in non-iso-reperfused (r = 0.65) and iso-perfused (r = 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated with Kfc (r = 0.87) in iso-reperfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beating donor rats results in decreased capillary permeability and increased lung tissue cAMP levels. Pharmacologic augmentation of tissue TAN and cAMP levels may further ameliorate the increased capillary permeability seen in lungs retrieved from non-heart-beating donors.

Calculation of the force acting on a micro-sized particle with optical vortex array laser beam tweezers

NASA Astrophysics Data System (ADS)

Kuo, Chun-Fu; Chu, Shu-Chun

2013-03-01

Optical vortices possess several special properties, including carrying optical angular momentum (OAM) and exhibiting zero intensity. Vortex array laser beams have attracts many interests due to its special mesh field distributions, which show great potential in the application of multiple optical traps and dark optical traps. Previously study developed an Ince-Gaussian Mode (IGM)-based vortex array laser beam1. This study develops a simulation model based on the discrete dipole approximation (DDA) method for calculating the resultant force acting on a micro-sized spherical dielectric particle that situated at the beam waist of the IGM-based vortex array laser beams1.

Micro-beam Laue alignment of multi-reflection Bragg coherent diffraction imaging measurements

DOE PAGES

Hofmann, Felix; Phillips, Nicholas W.; Harder, Ross J.; ...

2017-08-08

Multi-reflection Bragg coherent diffraction imaging has the potential to allow three-dimensional (3D) resolved measurements of the full lattice strain tensor in specific micro-crystals. Until now such measurements were hampered by the need for laborious, time-intensive alignment procedures. Here, in this paper, a different approach is demonstrated, using micro-beam Laue X-ray diffraction to first determine the lattice orientation of the micro-crystal. This information is then used to rapidly align coherent diffraction measurements of three or more reflections from the crystal. Based on these, 3D strain and stress fields in the crystal are successfully determined. This approach is demonstrated on a focusedmore » ion beam milled micro-crystal from which six reflections could be measured. Since information from more than three independent reflections is available, the reliability of the phases retrieved from the coherent diffraction data can be assessed. Lastly, our results show that rapid, reliable 3D coherent diffraction measurements of the full lattice strain tensor in specific micro-crystals are now feasible and can be successfully carried out even in heavily distorted samples.« less

Micro-beam Laue alignment of multi-reflection Bragg coherent diffraction imaging measurements

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

Hofmann, Felix; Phillips, Nicholas W.; Harder, Ross J.

Multi-reflection Bragg coherent diffraction imaging has the potential to allow three-dimensional (3D) resolved measurements of the full lattice strain tensor in specific micro-crystals. Until now such measurements were hampered by the need for laborious, time-intensive alignment procedures. Here, in this paper, a different approach is demonstrated, using micro-beam Laue X-ray diffraction to first determine the lattice orientation of the micro-crystal. This information is then used to rapidly align coherent diffraction measurements of three or more reflections from the crystal. Based on these, 3D strain and stress fields in the crystal are successfully determined. This approach is demonstrated on a focusedmore » ion beam milled micro-crystal from which six reflections could be measured. Since information from more than three independent reflections is available, the reliability of the phases retrieved from the coherent diffraction data can be assessed. Lastly, our results show that rapid, reliable 3D coherent diffraction measurements of the full lattice strain tensor in specific micro-crystals are now feasible and can be successfully carried out even in heavily distorted samples.« less

Micro-beam Laue alignment of multi-reflection Bragg coherent diffraction imaging measurements.

PubMed

Hofmann, Felix; Phillips, Nicholas W; Harder, Ross J; Liu, Wenjun; Clark, Jesse N; Robinson, Ian K; Abbey, Brian

2017-09-01

Multi-reflection Bragg coherent diffraction imaging has the potential to allow three-dimensional (3D) resolved measurements of the full lattice strain tensor in specific micro-crystals. Until now such measurements were hampered by the need for laborious, time-intensive alignment procedures. Here a different approach is demonstrated, using micro-beam Laue X-ray diffraction to first determine the lattice orientation of the micro-crystal. This information is then used to rapidly align coherent diffraction measurements of three or more reflections from the crystal. Based on these, 3D strain and stress fields in the crystal are successfully determined. This approach is demonstrated on a focused ion beam milled micro-crystal from which six reflections could be measured. Since information from more than three independent reflections is available, the reliability of the phases retrieved from the coherent diffraction data can be assessed. Our results show that rapid, reliable 3D coherent diffraction measurements of the full lattice strain tensor in specific micro-crystals are now feasible and can be successfully carried out even in heavily distorted samples.

Micro-beam Laue Alignment of Multi-Reflection Bragg Coherent Diffraction Imaging Measurements

PubMed Central

Hofmann, Felix; Phillips, Nicholas W.; Harder, Ross J.; Liu, Wenjun; Clark, Jesse N.; Robinson, Ian K.; Abbey, Brian

2017-01-01

Multi-reflection Bragg coherent diffraction imaging has the potential to allow 3D resolved measurements of the full lattice strain tensor in specific micro-crystals. Until now such measurements were hampered by the need for laborious, time-intensive alignment procedures. Here we demonstrate a different approach, using micro-beam Laue X-ray diffraction to first determine the lattice orientation of the micro-crystal. This information is then used to rapidly align coherent diffraction measurements of three or more reflections from the crystal. Based on these, 3D strain and stress fields in the crystal are successfully determined. This approach is demonstrated on a focussed ion beam milled micro-crystal from which six reflections could be measured. Since information from more than three independent reflections is available, the reliability of the phases retrieved from the coherent diffraction data can be assessed. Our results show that rapid, reliable 3D coherent diffraction measurements of the full lattice strain tensor in specific micro-crystals are now feasible and can be successfully carried out even in heavily distorted samples. PMID:28862628

Dosimetric characterization of a microDiamond detector in clinical scanned carbon ion beams.

PubMed

Marinelli, Marco; Prestopino, G; Verona, C; Verona-Rinati, G; Ciocca, M; Mirandola, A; Mairani, A; Raffaele, L; Magro, G

2015-04-01

To investigate for the first time the dosimetric properties of a new commercial synthetic diamond detector (PTW microDiamond) in high-energy scanned clinical carbon ion beams generated by a synchrotron at the CNAO facility. The detector response was evaluated in a water phantom with actively scanned carbon ion beams ranging from 115 to 380 MeV/u (30-250 mm Bragg peak depth in water). Homogeneous square fields of 3 × 3 and 6 × 6 cm(2) were used. Short- and medium-term (2 months) detector response stability, dependence on beam energy as well as ion type (carbon ions and protons), linearity with dose, and directional and dose-rate dependence were investigated. The depth dose curve of a 280 MeV/u carbon ion beam, scanned over a 3 × 3 cm(2) area, was measured with the microDiamond detector and compared to that measured using a PTW Advanced Markus ionization chamber, and also simulated using fluka Monte Carlo code. The detector response in two spread-out-Bragg-peaks (SOBPs), respectively, centered at 9 and 21 cm depths in water and calculated using the treatment planning system (TPS) used at CNAO, was measured. A negligible drift of detector sensitivity within the experimental session was seen, indicating that no detector preirradiation was needed. Short-term response reproducibility around 1% (1 standard deviation) was found. Only 2% maximum variation of microDiamond sensitivity was observed among all the evaluated proton and carbon ion beam energies. The detector response showed a good linear behavior. Detector sensitivity was found to be dose-rate independent, with a variation below 1.3% in the evaluated dose-rate range. A very good agreement between measured and simulated Bragg curves with both microDiamond and Advanced Markus chamber was found, showing a negligible LET dependence of the tested detector. A depth dose curve was also measured by positioning the microDiamond with its main axis oriented orthogonally to the beam direction. A strong distortion in Bragg peak measurement was observed, confirming manufacturer recommendation on avoiding such configuration. Very good results were obtained for SOBP measurements, with a difference below 1% between measured and TPS-calculated doses. The stability of detector sensitivity in the observation period was within the experimental uncertainty. Dosimetric characterization of a PTW microDiamond detector in high-energy scanned carbon ion beams was performed. The results of the present study showed that this detector is suitable for dosimetry of clinical carbon ion beams, with a negligible LET and dose-rate dependence.

Generation of Controllable Time-Mean Microvortices to Mimic Insect Flights

DTIC Science & Technology

2010-01-01

force to drive the suspended MEMs-based microplate to in-plane resonance. 15. SUBJECT TERMS Fluid Mechanics, Micro Air Vehicles (MAVs), Microvortices...suspended MEMS-based microplate to in-plane resonance. Briefly, AC current flows through suspended beam-like microelectrode structure – a microplate ... microplate . As a result, the observed flow features are time-mean microvortices. Computational effort centers around optimization of a range of

Identification and functional characterization of an uncharacterized antimicrobial peptide from a ciliate Paramecium caudatum.

PubMed

Cui, Pengfei; Dong, Yuan; Li, Zhijian; Zhang, Yubo; Zhang, Shicui

2016-07-01

The global ever-growing concerns about multi-drug resistant (MDR) microbes leads to urgent demands for exploration of new antibiotics including antimicrobial peptides (AMPs). Here we demonstrated that a cDNA from Ciliata Paramecium caudatum, designated Pcamp1, coded for a protein with features characteristic of AMPs, which is not homologous to any AMPs currently known. Both the C-terminal 91 amino acid residues of PcAMP1, cPcAMP1, expressed in Escherichia coli and the C-terminal 26 amino acid residues (predicted mature AMP), cPcAMP1/26, synthesized, underwent a coil-to-helix transition in the presence of TFE, SDS or DPC. Functional assays revealed that cPcAMP1 and cPcAMP1/26 were both able to kill Aeromonas hydrophila and Staphylococcus aureus. ELISA showed that cPcAMP1 and cPcAMP1/26 were able to bind to microbe-associated molecular pattern molecules LPS and LTA, which was further corroborated by the observations that cPcAMP1 could deposit onto the bacterial membranes. Importantly, both cPcAMP1 and cPcAMP1/26 were able to induce bacterial membrane permeabilization and depolarization, and to increase intracellular ROS levels. Additionally, cPcAMP1 and cPcAMP1/26 were not cytotoxic to mammalian cells. Taken together, our results show that PcAMP1 is a potential AMP with a membrane selectivity towards bacterial cells, which renders it a promising template for the design of novel peptide antibiotics against MDR microbes. It also shows that use of signal conserved sequence of AMPs can be an effective tool to identify potential AMPs across different animal classes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of laser beam conditioning on fabrication of clean micro-channel on stainless steel 316L using second harmonic of Q-switched Nd:YAG laser

NASA Astrophysics Data System (ADS)

Singh, Sanasam Sunderlal; Baruah, Prahlad Kr; Khare, Alika; Joshi, Shrikrishna N.

2018-02-01

Laser micromachining of metals for fabrication of micro-channels generate ridge formation along the edges accompanied by ripples along the channel bed. The ridge formation is due to the formation of interference pattern formed by back reflections from the beam splitter and other optical components involved before focusing on the work piece. This problem can be curtailed by using a suitable aperture or Iris diaphragm so as to cut the unwanted portion of the laser beam before illuminating the sample. This paper reports an experimental investigation on minimizing this problem by conditioning the laser beam using an Iris diaphragm and using optimum process parameters. In this work, systematic experiments have been carried out using the second harmonic of a Q-switched Nd:YAG laser to fabricate micro-channels. Initial experiments revealed that formation of ridges along the sides of micro-channel can easily be minimized with the help of Iris diaphragm. Further it is noted that a clean micro-channel of depth 43.39 μm, width up to 64.49 μm and of good surface quality with average surface roughness (Ra) value of 370 nm can be machined on stainless steel (SS) 316L by employing optimum process condition: laser beam energy of 30 mJ/pulse, 11 number of laser scans and scan speed of 169.54 μm/s with an opening of 4 mm diameter of Iris diaphragm in the path of the laser beam.

Modulation by cyclic GMP of the odour sensitivity of vertebrate olfactory receptor cells

NASA Technical Reports Server (NTRS)

Leinders-Zufall, T.; Shepherd, G. M.; Zufall, F.

1996-01-01

Recent evidence has indicated a significant role for the cGMP second messenger system in vertebrate olfactory transduction but no clear functions have been identified for cGMP so far. Here, we have examined the effects of 8-Br-cGMP and carbon monoxide (CO) on odour responses of salamander olfactory receptor neurons using perforated patch recordings. We report that 8-Br-cGMP strongly down-regulates the odour sensitivity of the cells, with a K1/2 of 460 nM. This adaptation-like effect can be mimicked by CO, an activator of soluble guanylyl cyclase, with a K1/2 of 1 microM. Sensitivity modulation is achieved through a regulatory chain of events in which cGMP stimulates a persistent background current due to the activation of cyclic nucleotide-gated channels. This in turn leads to sustained Ca2+ entry providing a negative feedback signal. One consequence of the Ca2+ entry is a shift to the right of the stimulus-response curve and a reduction in saturating odour currents. Together, these two effects can reduce the sensory generator current by up to twenty-fold. Thus, cGMP functions to control the gain of the G-protein coupled cAMP pathway. Another consequence of the action of cGMP is a marked prolongation of the odour response kinetics. The effects of CO/cGMP are long-lasting and can continue for minutes. Hence, we propose that cGMP helps to prevent saturation of the cell's response by adjusting the operational range of the cAMP cascade and contributes to olfactory adaptation by decreasing the sensitivity of olfactory receptor cells to repeated odour stimuli.

Overview of Advanced Space Propulsion Activities in the Space Environmental Effects Team at MSFC

NASA Technical Reports Server (NTRS)

Edwards, David; Carruth, Ralph; Vaughn, Jason; Schneider, Todd; Kamenetzky, Rachel; Gray, Perry

2000-01-01

Exploration of our solar system, and beyond, requires spacecraft velocities beyond our current technological level. Technologies addressing this limitation are numerous. The Space Environmental Effects (SEE) Team at the Marshall Space Flight Center (MSFC) is focused on three discipline areas of advanced propulsion; Tethers, Beamed Energy, and Plasma. This presentation will give an overview of advanced propulsion related activities in the Space Environmental Effects Team at MSFC. Advancements in the application of tethers for spacecraft propulsion were made while developing the Propulsive Small Expendable Deployer System (ProSEDS). New tether materials were developed to meet the specifications of the ProSEDS mission and new techniques had to be developed to test and characterize these tethers. Plasma contactors were developed, tested and modified to meet new requirements. Follow-on activities in tether propulsion include the Air-SEDS activity. Beamed energy activities initiated with an experimental investigation to quantify the momentum transfer subsequent to high power, 5J, ablative laser interaction with materials. The next step with this experimental investigation is to quantify non-ablative photon momentum transfer. This step was started last year and will be used to characterize the efficiency of solar sail materials before and after exposure to Space Environmental Effects (SEE). Our focus with plasma, for propulsion, concentrates on optimizing energy deposition into a magnetically confined plasma and integration of measurement techniques for determining plasma parameters. Plasma confinement is accomplished with the Marshall Magnetic Mirror (M3) device. Initial energy coupling experiments will consist of injecting a 50 amp electron beam into a target plasma. Measurements of plasma temperature and density will be used to determine the effect of changes in magnetic field structure, beam current, and gas species. Experimental observations will be compared to predictions from computer modeling.

Trapping of a micro-bubble by non-paraxial Gaussian beam: computation using the FDTD method.

PubMed

Sung, Seung-Yong; Lee, Yong-Gu

2008-03-03

Optical forces on a micro-bubble were computed using the Finite Difference Time Domain method. Non-paraxial Gaussian beam equation was used to represent the incident laser with high numerical aperture, common in optical tweezers. The electromagnetic field distribution around a micro-bubble was computed using FDTD method and the electromagnetic stress tensor on the surface of a micro-bubble was used to compute the optical forces. By the analysis of the computational results, interesting relations between the radius of the circular trapping ring and the corresponding stability of the trap were found.

A newly synthetic chromium complex-chromium (D-phenylalanine)3 activates AMP-activated protein kinase and stimulates glucose transport.

PubMed

Zhao, Peng; Wang, Jingying; Ma, Heng; Xiao, Yao; He, Leilei; Tong, Chao; Wang, Zhenhua; Zheng, Qiusheng; Dolence, E Kurt; Nair, Sreejayan; Ren, Jun; Li, Ji

2009-03-15

We synthesized the chromium (phenylalanine)(3) [Cr(D-phe)(3)] by chelating chromium(III) with D-phenylalanine ligand in aqueous solution to improve the bioavailability of chromium, and reported that Cr(D-phe)(3) improved insulin sensitivity. AMP-activated protein kinase (AMPK) is a key mediator for glucose uptake and insulin sensitivity. To address the molecular mechanisms by which Cr(d-phe)(3) increases insulin sensitivity, we investigated whether Cr(D-phe)(3) stimulates glucose uptake via activation of AMPK signaling pathway. H9c2 myoblasts and isolated cardiomyocytes were treated with Cr(D-phe)(3) (25microM). Western blotting was used for signaling determination. The glucose uptake was determined by 2-deoxy-D-glucose-(3)H accumulation. HPLC measured concentrations of AMP. The mitochondrial membrane potential (Deltapsi) was detected by JC-1 fluorescence assay. Cr(D-phe)(3) stimulated the phosphorylation of alpha catalytic subunit of AMPK at Thr(172), as well the downstream targets of AMPK, acetyl-CoA carboxylase (ACC, Ser(212)) and eNOS (Ser(1177)). Moreover, Cr(D-phe)(3) significantly stimulated glucose uptake in both H9c2 cells and cardiomyocytes. AMPK inhibitor compound C (10microM) dramatically inhibited the glucose uptake stimulated by Cr(D-phe)(3), while it did not affect insulin stimulation of glucose uptake. Furthermore, in vivo studies showed that Cr(D-phe)(3) also activated cardiac AMPK signaling pathway. The increase of cardiac AMP concentration and the decrease of mitochondrial membrane potential (Deltapsi) may contribute to the activation of AMPK induced by Cr(D-phe)(3). Cr(D-phe)(3) is a novel compound that activates AMPK signaling pathway, which contributes to the regulation of glucose transport during stress conditions that may be associated the role of AMPK in increasing insulin sensitivity.

Atom chips in the real world: the effects of wire corrugation

NASA Astrophysics Data System (ADS)

Schumm, T.; Estève, J.; Figl, C.; Trebbia, J.-B.; Aussibal, C.; Nguyen, H.; Mailly, D.; Bouchoule, I.; Westbrook, C. I.; Aspect, A.

2005-02-01

We present a detailed model describing the effects of wire corrugation on the trapping potential experienced by a cloud of atoms above a current carrying micro wire. We calculate the distortion of the current distribution due to corrugation and then derive the corresponding roughness in the magnetic field above the wire. Scaling laws are derived for the roughness as a function of height above a ribbon shaped wire. We also present experimental data on micro wire traps using cold atoms which complement some previously published measurements [CITE] and which demonstrate that wire corrugation can satisfactorily explain our observations of atom cloud fragmentation above electroplated gold wires. Finally, we present measurements of the corrugation of new wires fabricated by electron beam lithography and evaporation of gold. These wires appear to be substantially smoother than electroplated wires.

The Design of Operational Amplifier for Low Voltage and Low Current Sound Energy Harvesting System

NASA Astrophysics Data System (ADS)

Fang, Liew Hui; Rahim, Rosemizi Bin Abd; Isa, Muzamir; Idris Syed Hassan, Syed; Ismail, Baharuddin Bin

2018-03-01

The objective of this paper is to design a combination of an operational amplifier (op-amp) with a rectifier used in an alternate current (ac) to direct current (dc) power conversion. The op-amp was designed to specifically work at low voltage and low current for a sound energy harvesting system. The goal of the op-amp design with adjustable gain was to control output voltage based on the objectives of the experiment conducted. The op-amp was designed for minimum power dissipation performance, with the means of increasing the output current when receiving a large amount of load. The harvesting circuits which designed further improved the power output efficiency by shortening the fully charged time needed by a supercapacitor bank. It can fulfil the long-time power demands for low power device. Typically, a small amount of energy sources were converted to electricity and stored in the supercapacitor bank, which was built by 10 pieces of capacitors with 0.22 F each, arranged in parallel connection. The highest capacitance was chosen based on the characteristic that have the longest discharging time to support the applications of a supercapacitor bank. Testing results show that the op-amp can boost the low input ac voltage (∼3.89 V) to high output dc voltage (5.0 V) with output current of 30 mA and stored the electrical energy in a big supercapacitor bank having a total of 2.2 F, effectively. The measured results agree well with the calculated results.

Extragalactic circuits, transmission lines, and CR particle acceleration

NASA Astrophysics Data System (ADS)

Kronberg, Philipp P.; Lovelace, Richard V. E.

2015-08-01

A non-negligible fraction of a Supermassive Black Hole's (SMBH) rest mass energy gets transported into extragalactic space by a remarkable process in jets which are incompletely understood. What are the physical processes which transport this energy? It is likely that the energy flows electromagnetically, rather than via a particle beam flux. The deduced electromagnetic fields may produce particles of energy as high as ˜ 1020 eV. The energetics of SMBH accretion disk models and the electromagnetic energy transfer imply that a SMBH should generate a 1018 - 1019 Ampères current close to the black hole and its accretion disk. We describe the so far best observation-based estimate of the magnitude of the current flow along the axis of the jet extending from the nucleus of the active galaxy in 3C303. The current is measured to be I ˜ 1018 Ampères at ˜ 40 kpc away from the AGN. This indicates that organised current flow remains intact over multi-kpc distances. The electric current I transports electromagnetic power into free space, P = I2Z, where Z ˜ 30 Ohms is related to the impedance of free space, and this points to the existence of cosmic electric circuit. The associated electric potential drop, V = IZ, is of the order of that required to generate Ultra High Energy Cosmic Rays (UHECR). We also explore further implications, including disruption/deflection of the power flow and also why such measurements, exemplified by those on 3C303, are currently very difficult to make and to unambiguously interpret. This naturally leads to the topic of how such measurements can be extended and improved in the future. We describe the analogy of electromagnetically dominated jets with transmission lines. High powered jets in vacuo can be understood by approximate analogy with a waveguide. The importance of inductance, impedance, and other laboratory electrical concepts are discussed in this context.

Cyclic AMP efflux inhibitors as potential therapeutic agents for leukemia.

PubMed

Perez, Dominique R; Smagley, Yelena; Garcia, Matthew; Carter, Mark B; Evangelisti, Annette; Matlawska-Wasowska, Ksenia; Winter, Stuart S; Sklar, Larry A; Chigaev, Alexandre

2016-06-07

Apoptotic evasion is a hallmark of cancer. We propose that some cancers may evade cell death by regulating 3'-5'-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling. We hypothesize that leukemic cells possess mechanisms that efflux cAMP from the cytoplasm, thus protecting them from apoptosis. Accordingly, cAMP efflux inhibition should result in: cAMP accumulation, activation of cAMP-dependent downstream signaling, viability loss, and apoptosis. We developed a novel assay to assess cAMP efflux and performed screens to identify inhibitors. In an acute myeloid leukemia (AML) model, several identified compounds reduced cAMP efflux, appropriately modulated pathways that are responsive to cAMP elevation (cAMP-responsive element-binding protein phosphorylation, and deactivation of Very Late Antigen-4 integrin), and induced mitochondrial depolarization and caspase activation. Blocking adenylyl cyclase activity was sufficient to reduce effects of the most potent compounds. These compounds also decreased cAMP efflux and viability of B-lineage acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples, but not of normal primary peripheral blood mononuclear cells. Our data suggest that cAMP efflux is a functional feature that could be therapeutically targeted in leukemia. Furthermore, because some of the identified drugs are currently used for treating other illnesses, this work creates an opportunity for repurposing.

Maskless micro-ion-beam reduction lithography system

DOEpatents

Leung, Ka-Ngo; Barletta, William A.; Patterson, David O.; Gough, Richard A.

2005-05-03

A maskless micro-ion-beam reduction lithography system is a system for projecting patterns onto a resist layer on a wafer with feature size down to below 100 nm. The MMRL system operates without a stencil mask. The patterns are generated by switching beamlets on and off from a two electrode blanking system or pattern generator. The pattern generator controllably extracts the beamlet pattern from an ion source and is followed by a beam reduction and acceleration column.

The cAMP-dependent protein kinase inhibitor H-89 attenuates the bioluminescence signal produced by Renilla Luciferase.

PubMed

Herbst, Katie J; Allen, Michael D; Zhang, Jin

2009-05-21

Investigations into the regulation and functional roles of kinases such as cAMP-dependent protein kinase (PKA) increasingly rely on cellular assays. Currently, there are a number of bioluminescence-based assays, for example reporter gene assays, that allow the study of the regulation, activity, and functional effects of PKA in the cellular context. Additionally there are continuing efforts to engineer improved biosensors that are capable of detecting real-time PKA signaling dynamics in cells. These cell-based assays are often utilized to test the involvement of PKA-dependent processes by using H-89, a reversible competitive inhibitor of PKA. We present here data to show that H-89, in addition to being a competitive PKA inhibitor, attenuates the bioluminescence signal produced by Renilla luciferase (RLuc) variants in a population of cells and also in single cells. Using 10 microM of luciferase substrate and 10 microM H-89, we observed that the signal from RLuc and RLuc8, an eight-point mutation variant of RLuc, in cells was reduced to 50% (+/-15%) and 54% (+/-14%) of controls exposed to the vehicle alone, respectively. In vitro, we showed that H-89 decreased the RLuc8 bioluminescence signal but did not compete with coelenterazine-h for the RLuc8 active site, and also did not affect the activity of Firefly luciferase. By contrast, another competitive inhibitor of PKA, KT5720, did not affect the activity of RLuc8. The identification and characterization of the adverse effect of H-89 on RLuc signal will help deconvolute data previously generated from RLuc-based assays looking at the functional effects of PKA signaling. In addition, for the current application and future development of bioluminscence assays, KT5720 is identified as a more suitable PKA inhibitor to be used in conjunction with RLuc-based assays. These principal findings also provide an important lesson to fully consider all of the potential effects of experimental conditions on a cell-based assay readout before drawing conclusions from the data.

Coexpression of alpha and beta subunits of the rod cyclic GMP-gated channel restores native sensitivity to cyclic AMP: role of D604/N1201.

PubMed Central

Pagès, F; Ildefonse, M; Ragno, M; Crouzy, S; Bennett, N

2000-01-01

Coexpression of the betawt and alphawt subunits of the bovine rod channel restores two characteristics of the native channels: higher sensitivity to cAMP and potentiation of cGMP-induced currents by low cAMP concentrations. To test whether the increased sensitivity to cAMP is due to the uncharged nature of the asparagine residue (N1201) situated in place of aspartate D604 in the beta subunit as previously suggested (, Neuron. 15:619-625), we compared currents from wild-type (alphawt and alphawt/betawt) and from mutated channels (alphaD604N, alphaD604N/betawt, and alphawt/betaN1201D). The results show that the sensitivity to cAMP and cAMP potentiation is partly but not entirely determined by the charge of residue 1201 in the beta subunit. The D604N mutation in the alpha subunit and, to a lesser extent, coexpression of the betawt subunit with the alphawt subunit reduce the open probability for cGMP compared to that of the alphawt channel. Interpretation of the data with the MWC allosteric model (model of Monod, Wyman, Changeux;, J. Mol. Biol. 12:88-118) suggests that the D604N mutation in the alpha subunits and coassembly of alpha and beta subunits alter the free energy of gating by cAMP more than that of cAMP binding. PMID:10692312

Design, synthesis and biological evaluation of a bivalent micro opiate and adenosine A1 receptor antagonist.

PubMed

Mathew, Smitha C; Ghosh, Nandita; By, Youlet; Berthault, Aurélie; Virolleaud, Marie-Alice; Carrega, Louis; Chouraqui, Gaëlle; Commeiras, Laurent; Condo, Jocelyne; Attolini, Mireille; Gaudel-Siri, Anouk; Ruf, Jean; Parrain, Jean-Luc; Rodriguez, Jean; Guieu, Régis

2009-12-01

The cross talk between different membrane receptors is the source of increasing research. We designed and synthesized a new hetero-bivalent ligand that has antagonist properties on both A(1) adenosine and mu opiate receptors with a K(i) of 0.8+/-0.05 and 0.7+/-0.03 microM, respectively. This hybrid molecule increases cAMP production in cells that over express the mu receptor as well as those over expressing the A(1) adenosine receptor and reverses the antalgic effects of mu and A(1) adenosine receptor agonists in animals.

Inhibition of muscarinic-stimulated polyphosphoinositide hydrolysis and Ca2+ mobilization in cat iris sphincter smooth muscle cells by cAMP-elevating agents.

PubMed

Ding, K H; Husain, S; Akhtar, R A; Isales, C M; Abdel-Latif, A A

1997-09-01

The effects of carbachol (CCh) on inositol 1,4,5-trisphosphate (IP3) production and intracellular calcium ([Ca2+]i) mobilization, and their regulation by cAMP-elevating agents were investigated in SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. CCh produced time- and dose-dependent increases in IP3 production; the t1/2 and EC50 values were 68 s and 0.5 microM, respectively. The muscarinic agonist provoked a transient increase in [Ca2+]i which reached maximum within 77 s, and increased [Ca2+]i mobilization in a concentration-dependent manner with an EC50 of 1.4 microM. Thapsigargin, a Ca(2+)-pump inhibitor, caused a rapid rise in [Ca2+]i and subsequent addition of CCh was without effect. Both CCh-induced IP3 production and CCh-induced [Ca2+]i mobilization were more potently antagonized by 4-DAMP, an M3 muscarinic receptor antagonist, than by pirenzepine, an M1 receptor antagonist, suggesting that both responses are mediated through the M3 receptor subtype. Treatment of the cells with U73122, a phospholipase C (PLC) inhibitor, resulted in a concentration-dependent decrease in both CCh-stimulated IP3 production and [Ca2+]i mobilization. These data indicate close correlation between enhanced IP3 production and [Ca2+]i mobilization in these smooth muscle cells and suggest that the CCh-stimulated increase in [Ca2+]i could be mediated through increased IP3 production. Isoproterenol (ISO) inhibited CCh-induced IP3 production (IC50 = 80 nM) and [Ca2+]i mobilization (IC50 = 0.17 microM) in a concentration-dependent manner. Microsomal fractions isolated from SV-CISM-2 cells contained phospholipase C (PLC) which was stimulated by CCh (10 microM) and GTP gamma S (0.1 microM). Pretreatment of the cells with ISO or forskolin, 5 microM each, produced membrane fractions in which CCh-stimulated PLC activity was significantly attenuated. Furthermore, when microsomal fractions isolated from SV-CISM-2 cells were phosphorylated with Protein kinase A (PKA), the CCh- and GTP gamma S-stimulated IP3 production were significantly inhibited. It can be concluded from these studies that in SV-CISM-2 cells, activation of M3 muscarinic receptors results in stimulation of PLC-mediated PIP2 hydrolysis, generating IP3 which mobilizes [Ca2+]i. Furthermore, elevation of cAMP may inhibit IP3 production and [Ca2+]i mobilization through mechanisms involving PKA-dependent phosphorylation of PLC, G-proteins, IP3 receptor and/or IP3 metabolizing enzymes.

Linear Collider Test Facility: Twiss Parameter Analysis at the IP/Post-IP Location of the ATF2 Beam Line

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

Bolzon, Benoit; /Annecy, LAPP; Jeremie, Andrea

2012-07-02

At the first stage of the ATF2 beam tuning, vertical beam size is usually bigger than 3 {micro}m at the IP. Beam waist measurements using wire scanners and a laser wire are usually performed to check the initial matching of the beam through to the IP. These measurements are described in this paper for the optics currently used ({beta}{sub x} = 4cm and {beta}{sub y} = 1mm). Software implemented in the control room to automate these measurements with integrated analysis is also described. Measurements showed that {beta} functions and emittances were within errors of measurements when no rematching and couplingmore » corrections were done. However, it was observed that the waist in the horizontal (X) and vertical (Y) plane was abnormally shifted and simulations were performed to try to understand these shifts. They also showed that multiknobs are needed in the current optics to correct simultaneously {alpha}{sub x}, {alpha}{sub y} and the horizontal dispersion (D{sub x}). Such multiknobs were found and their linearity and orthogonality were successfully checked using MAD optics code. The software for these multiknobs was implemented in the control room and waist scan measurements using the {alpha}{sub y} knob were successfully performed.« less

Continuous angle steering of an optically- controlled phased array antenna based on differential true time delay constituted by micro-optical components.

PubMed

Wang, Jian; Hou, Peipei; Cai, Haiwen; Sun, Jianfeng; Wang, Shunan; Wang, Lijuan; Yang, Fei

2015-04-06

We propose an optically controlled phased array antenna (PAA) based on differential true time delay constructed optical beamforming network (OBFN). Differential true time delay is realized by stack integrated micro-optical components. Optically-controlled angle steering of radio frequency (RF) beams are realized and demonstrated by this configuration. Experimental results demonstrate that OBFN based PAA can accomplish RF-independent broadband beam steering without beam squint effect and can achieve continuous angle steering. In addition, multi-beams for different steering angles are acquired synchronously.

Upgrade of beamline BL25SU for soft x-ray imaging and spectroscopy of solid using nano- and micro-focused beams at SPring-8

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

Senba, Yasunori, E-mail: ysenba@spring8.or.jp; Ohashi, Haruhiko; Kotani, Yoshinori

2016-07-27

Substantial upgrades have been made to the beamline BL25SU at SPring-8 for soft X-ray imaging and spectroscopy of solid-state materials. The upgraded beamline consists of two branches: a micro-beam branch with high energy resolution, and a nano-beam branch with small angular divergence. The beamline has been available for use since October 2014, following a half year commissioning period. We present here the beamline performance parameters, including resolving power, photon flux, and focused beam size, which are consistent with designed specifications.

Towards manipulating relativistic laser pulses with micro-tube plasma lenses

PubMed Central

Ji, L. L.; Snyder, J.; Pukhov, A.; Freeman, R. R.; Akli, K. U.

2016-01-01

Efficient coupling of intense laser pulses to solid-density matter is critical to many applications including ion acceleration for cancer therapy. At relativistic intensities, the focus has been mainly on investigating various laser beams irradiating initially overdense flat interfaces with little or no control over the interaction. Here, we propose a novel approach that leverages recent advancements in 3D direct laser writing (DLW) of materials and high contrast lasers to manipulate the laser-matter interactions on the micro-scales. We demonstrate, via simulations, that usable intensities ≥1023 Wcm−2 could be achieved with current tabletop lasers coupled to micro-engineered plasma lenses. We show that these plasma optical elements act as a lens to focus laser light. These results open new paths to engineering light-matter interactions at ultra-relativistic intensities. PMID:26979657

2000W high beam quality diode laser for direct materials processing

NASA Astrophysics Data System (ADS)

Qin, Wen-bin; Liu, You-qiang; Cao, Yin-hua; Gao, Jing; Pan, Fei; Wang, Zhi-yong

2011-11-01

This article describes high beam quality and kilowatt-class diode laser system for direct materials processing, using optical design software ZEMAX® to simulate the diode laser optical path, including the beam shaping, collimation, coupling, focus, etc.. In the experiment, the diode laser stack of 808nm and the diode laser stack of 915nm were used for the wavelength coupling, which were built vertical stacks up to 16 bars. The threshold current of the stack is 6.4A, the operating current is 85A and the output power is 1280W. Through experiments, after collimating the diode laser beam with micro-lenses, the fast axis BPP of the stack is less than 60mm.mrad, and the slow-axis BPP of the stack is less than 75mm.mrad. After shaping the laser beam and improving the beam quality, the fast axis BPP of the stack is still 60mm.mrad, and the slow-axis BPP of the stack is less than 19mm.mrad. After wavelength coupling and focusing, ultimately the power of 2150W was obtained, focal spot size of 1.5mm * 1.2mm with focal length 300mm. The laser power density is 1.2×105W/cm2, and that can be used for metal remelting, alloying, cladding and welding. The total optical coupling conversion efficiency is 84%, and the total electrical - optical conversion efficiency is 50%.

Micro-polarimeter for high performance liquid chromatography

DOEpatents

Yeung, Edward E.; Steenhoek, Larry E.; Woodruff, Steven D.; Kuo, Jeng-Chung

1985-01-01

A micro-polarimeter interfaced with a system for high performance liquid chromatography, for quantitatively analyzing micro and trace amounts of optically active organic molecules, particularly carbohydrates. A flow cell with a narrow bore is connected to a high performance liquid chromatography system. Thin, low birefringence cell windows cover opposite ends of the bore. A focused and polarized laser beam is directed along the longitudinal axis of the bore as an eluent containing the organic molecules is pumped through the cell. The beam is modulated by air gap Faraday rotators for phase sensitive detection to enhance the signal to noise ratio. An analyzer records the beams's direction of polarization after it passes through the cell. Calibration of the liquid chromatography system allows determination of the quantity of organic molecules present from a determination of the degree to which the polarized beam is rotated when it passes through the eluent.

Design and fabrication of vibration based energy harvester using microelectromechanical system piezoelectric cantilever for low power applications.

PubMed

Kim, Moonkeun; Lee, Sang-Kyun; Yang, Yil Suk; Jeong, Jaehwa; Min, Nam Ki; Kwon, Kwang-Ho

2013-12-01

We fabricated dual-beam cantilevers on the microelectromechanical system (MEMS) scale with an integrated Si proof mass. A Pb(Zr,Ti)O3 (PZT) cantilever was designed as a mechanical vibration energy-harvesting system for low power applications. The resonant frequency of the multilayer composition cantilevers were simulated using the finite element method (FEM) with parametric analysis carried out in the design process. According to simulations, the resonant frequency, voltage, and average power of a dual-beam cantilever was 69.1 Hz, 113.9 mV, and 0.303 microW, respectively, at optimal resistance and 0.5 g (gravitational acceleration, m/s2). Based on these data, we subsequently fabricated cantilever devices using dual-beam cantilevers. The harvested power density of the dual-beam cantilever compared favorably with the simulation. Experiments revealed the resonant frequency, voltage, and average power density to be 78.7 Hz, 118.5 mV, and 0.34 microW, respectively. The error between the measured and simulated results was about 10%. The maximum average power and power density of the fabricated dual-beam cantilever at 1 g were 0.803 microW and 1322.80 microW cm(-3), respectively. Furthermore, the possibility of a MEMS-scale power source for energy conversion experiments was also tested.

Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

PubMed

Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

2017-01-01

Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enrichment of cardiac pacemaker-like cells: neuregulin-1 and cyclic AMP increase I(f)-current density and connexin 40 mRNA levels in fetal cardiomyocytes.

PubMed

Ruhparwar, Arjang; Er, Fikret; Martin, Ulrich; Radke, Kristin; Gruh, Ina; Niehaus, Michael; Karck, Matthias; Haverich, Axel; Hoppe, Uta C

2007-02-01

Generation of a large number of cells belonging to the cardiac pacemaker system would constitute an important step towards their utilization as a biological cardiac pacemaker system. The aim of the present study was to identify factors, which might induce transformation of a heterogenous population of fetal cardiomyocytes into cells with a pacemaker-like phenotype. Neuregulin-1 (alpha- and beta-isoform) or the cAMP was added to fresh cell cultures of murine embryonic cardiomyocytes. Quantitative northern blot analysis and flowcytometry were performed to detect the expression of connexins 40, 43 and 45. Patch clamp recordings in the whole cell configuration were performed to determine current density of I (f), a characteristic ion current of pacemaker cells. Fetal cardiomyocytes without supplement of neuregulin or cAMP served as control group. Neuregulin and cAMP significantly increased mRNA levels of connexin 40 (Cx-40), a marker of the early differentiating conduction system in mice. On the protein level, flowcytometry revealed no significant differences between treated and untreated groups with regard to the expression of connexins 40, 43 and 45. Treatment with cAMP (11.2 +/- 2.24 pA/pF; P < 0.001) and neuregulin-1-beta (6.23 +/- 1.07 pA/pF; P < 0.001) significantly increased the pacemaker current density compared to control cardiomyocytes (1.76 +/- 0.49 pA/pF). Our results indicate that neuregulin-1 and cAMP possess the capacity to cause significant transformation of a mixed population of fetal cardiomyocytes into cardiac pacemaker-like cells as shown by electrophysiology and increase of Cx-40 mRNA. This method may allow the development of a biological cardiac pacemaker system when applied to adult or embryonic stem cells.

Butyltin exposure causes a rapid decrease in cyclic AMP levels in human lymphocytes.

PubMed

Whalen, M M; Loganathan, B G

2001-03-15

Natural killer (NK) cells are a subset of lymphocytes that are capable of killing tumor cells, virally infected cells, and antibody-coated cells. Butyltins (BTs) are used in a variety of consumer products and industrial applications. Tributyltin (TBT) is found in dairy products, meat, and fish. Dibutyltin (DBT) is found in plastic products, beverages stored in PVC pipes during manufacturing, and poultry products. BTs appear to increase the risk of cancer and viral infections in exposed individuals. This increased risk may be due in part to the inhibitory effect of these compounds on the cytotoxic function of NK cells. A 24-h exposure of NK cells to 200 nM TBT or 1.5 microM DBT decreased the cytotoxic function of NK cells by greater than 90%. Higher concentrations of TBT and DBT decreased the cytotoxic function of NK cells (by greater than 90%) after only a 1-h exposure. A 24-h exposure to either TBT or DBT decreased intracellular ATP levels by about 30%. However, as much as a 1-h exposure to either 300 nM TBT or 10 microM DBT caused no significant decrease in ATP levels. Thus, a decrease in ATP levels is a longer-term consequence of BT exposure. Intracellular levels of cAMP are decreased by as much as 80% within 5 min of exposure to either TBT or DBT. This rapid decline in cAMP levels in NK cells may be a consequence of BT exposure that is related to the rapid decrease in the cytotoxic function of NK cells. Copyright 2001 Academic Press.

Micro-fabrication method of graphite mesa microdevices based on optical lithography technology

NASA Astrophysics Data System (ADS)

Zhang, Cheng; Wen, Donghui; Zhu, Huamin; Zhang, Xiaorui; Yang, Xing; Shi, Yunsheng; Zheng, Tianxiang

2017-12-01

Graphite mesa microdevices have incommensurate contact nanometer interfaces, superlubricity, high-speed self-retraction, and other characteristics, which have potential applications in high-performance oscillators and micro-scale switches, memory devices, and gyroscopes. However, the current method of fabricating graphite mesa microdevices is mainly based on high-cost, low efficiency electron beam lithography technology. In this paper, the processing technologies of graphite mesa microdevices with various shapes and sizes were investigated by a low-cost micro-fabrication method, which was mainly based on optical lithography technology. The characterization results showed that the optical lithography technology could realize a large-area of patterning on the graphite surface, and the graphite mesa microdevices, which have a regular shape, neat arrangement, and high verticality could be fabricated in large batches through optical lithography technology. The experiments and analyses showed that the graphite mesa microdevices fabricated through optical lithography technology basically have the same self-retracting characteristics as those fabricated through electron beam lithography technology, and the maximum size of the graphite mesa microdevices with self-retracting phenomenon can reach 10 µm  ×  10 µm. Therefore, the proposed method of this paper can realize the high-efficiency and low-cost processing of graphite mesa microdevices, which is significant for batch fabrication and application of graphite mesa microdevices.

Characterization of the allosteric binding pocket of human liver fructose-1,6-bisphosphatase by protein crystallography and inhibitor activity studies.

PubMed

Iversen, L F; Brzozowski, M; Hastrup, S; Hubbard, R; Kastrup, J S; Larsen, I K; Naerum, L; Nørskov-Lauridsen, L; Rasmussen, P B; Thim, L; Wiberg, F C; Lundgren, K

1997-05-01

The structures of three complexes of human fructose-1,6-bisphosphatase (FB) with the allosteric inhibitor AMP and two AMP analogues have been determined and all fully refined. The data used for structure determination were collected at cryogenic temperature (110 K), and with the use of synchrotron radiation. The structures reveal a common mode of binding for AMP and formycine monophosphate (FMP). 5-Amino-4-carboxamido-1 beta-D-5-phosphate-ribofuranosyl-1H-imidazole (AICAR-P) shows an unexpected mode of binding to FB, different from that of the other two ligands. The imidazole ring of AICAR-P is rotated 180 degrees compared to the AMP and FMP bases. This rotation results in a slightly different hydrogen bonding pattern and minor changes in the water structure in the binding pocket. Common features of binding are seen for the ribose and phosphate moieties of all three compounds. Although binding in a different mode, AICAR-P is still capable of making all the important interactions with the residues building the allosteric binding pocket. The IC50 values of AMP, FMP, and AICAR-P were determined to be 1.7, 1.4, and 20.9 microM, respectively. Thus, the approximately 10 times lower potency of AICAR-P is difficult to explain solely from the variations observed in the binding pocket. Only one water molecule in the allosteric binding pocket was found to be conserved in all four subunits in all three structures. This water molecule coordinates to a phosphate oxygen atom and the N7 atom of the AMP molecule, and to similarly situated atoms in the FMP and AICAR-P complexes. This implies an important role of the conserved water molecule in binding of the ligand.

Characterization of the allosteric binding pocket of human liver fructose-1,6-bisphosphatase by protein crystallography and inhibitor activity studies.

PubMed Central

Iversen, L. F.; Brzozowski, M.; Hastrup, S.; Hubbard, R.; Kastrup, J. S.; Larsen, I. K.; Naerum, L.; Nørskov-Lauridsen, L.; Rasmussen, P. B.; Thim, L.; Wiberg, F. C.; Lundgren, K.

1997-01-01

The structures of three complexes of human fructose-1,6-bisphosphatase (FB) with the allosteric inhibitor AMP and two AMP analogues have been determined and all fully refined. The data used for structure determination were collected at cryogenic temperature (110 K), and with the use of synchrotron radiation. The structures reveal a common mode of binding for AMP and formycine monophosphate (FMP). 5-Amino-4-carboxamido-1 beta-D-5-phosphate-ribofuranosyl-1H-imidazole (AICAR-P) shows an unexpected mode of binding to FB, different from that of the other two ligands. The imidazole ring of AICAR-P is rotated 180 degrees compared to the AMP and FMP bases. This rotation results in a slightly different hydrogen bonding pattern and minor changes in the water structure in the binding pocket. Common features of binding are seen for the ribose and phosphate moieties of all three compounds. Although binding in a different mode, AICAR-P is still capable of making all the important interactions with the residues building the allosteric binding pocket. The IC50 values of AMP, FMP, and AICAR-P were determined to be 1.7, 1.4, and 20.9 microM, respectively. Thus, the approximately 10 times lower potency of AICAR-P is difficult to explain solely from the variations observed in the binding pocket. Only one water molecule in the allosteric binding pocket was found to be conserved in all four subunits in all three structures. This water molecule coordinates to a phosphate oxygen atom and the N7 atom of the AMP molecule, and to similarly situated atoms in the FMP and AICAR-P complexes. This implies an important role of the conserved water molecule in binding of the ligand. PMID:9144768

Relationship between inhibition of cyclic AMP production in Chinese hamster ovary cells expressing the rat D2(444) receptor and antagonist/agonist binding ratios.

PubMed Central

Harley, E. A.; Middlemiss, D. N.; Ragan, C. I.

1995-01-01

1. Radioligand binding assays using [3H]-(-)-sulpiride, in the presence of 1 mM ethylenediaminetetraacetic acid (EDTA) and 100 microM guanylylimidodiphosphate (GppNHp) and [3H]-N0437 were developed to label the low and high agonist affinity states of the rD2(444) receptor (long form of the rat D2 receptor) respectively. The ratios of the affinities of compounds in these two assays (Kapp [3H]-(-)-supiride/Kapp [3H]-N-0437) were then calculated. 2. The prediction that the binding ratio reflected the functional efficacy of a compound was supported by measurement of the ability of a number of compounds acting at dopamine receptors to inhibit rD2(444)-mediated inhibition of cyclic AMP production. When the rank order of the ratios of a number of these compounds was compared to their ability to inhibit the production of cyclic AMP, a significant correlation was seen (Spearman rank correlation coefficient = 0.943, P = 0.01). 3. In conclusion, the sulpiride/N-0437 binding ratio reliably predicted the efficacy of compounds acting at dopamine receptors to inhibit cyclic AMP production mediated by the rD2(444) receptor. PMID:7582561

Hard x-ray micro-tomography of a human head post-mortem as a gold standard to compare x-ray modalities

NASA Astrophysics Data System (ADS)

Dalstra, M.; Schulz, G.; Dagassan-Berndt, D.; Verna, C.; Müller-Gerbl, M.; Müller, B.

2016-10-01

An entire human head obtained at autopsy was micro-CT scanned in a nano/micro-CT scanner in a 6-hour long session. Despite the size of the head, it could still be scanned with a pixel size of 70 μm. The aim of this study was to obtain an optimal quality 3D data-set to be used as baseline control in a larger study comparing the image quality of various cone beam CT systems currently used in dentistry. The image quality of the micro-CT scans was indeed better than the ones of the clinical imaging modalities, both with regard to noise and streak artifacts due to metal dental implants. Bony features in the jaws, like the trabecular architecture and the thin wall of the alveolar bone were clearly visible. Therefore, the 3D micro-CT data-set can be used as the gold standard for linear, angular, and volumetric measurements of anatomical features in and around the oral cavity when comparing clinical imaging modalities.

Expression profiles of antimicrobial peptides (AMPs) and their regulation by Relish

NASA Astrophysics Data System (ADS)

Wang, Dongdong; Li, Fuhua; Li, Shihao; Wen, Rong; Xiang, Jianhai

2012-07-01

Antimicrobial peptides (AMPs), as key immune effectors, play important roles in the innate immune system of invertebrates. Different types of AMPs, including Penaeidin, Crustin, ALF (antilipopolysaccharide factor) have been identified in different penaeid shrimp; however, systematic analyses on the function of different AMPs in shrimp responsive to different types of bacteria are very limited. In this study, we analyzed the expression profiles of AMPs in the Chinese shrimps, Fenneropenaeus chinensis, simultaneously by real-time RT-PCR (reverse transcription-polymerase chain reaction) when shrimp were challenged with Micrococcus lysodeikticus (Gram-positive, G+) or Vibrio anguillarium (Gram-negative, G-). Different AMPs showed different expression profiles when shrimp were injected with one type of bacterium, and one AMP also showed different expression profiles when shrimp were challenged with different bacteria. Furthermore, the expression of these AMPs showed temporal expression profiles, suggesting that different AMPs function coordinately in bacteria-infected shrimp. An RNA interference approach was used to study the function of the Relish transcription factor in regulating the transcription of different AMPs. The current study showed that Relish could regulate the transcription of different AMPs in shrimp. Differential expression profiles of AMPs in shrimp injected with different types of bacteria indicated that a complicated antimicrobial response network existed in shrimp. These data contribute to our understanding of immunity in shrimp and may provide a strategy for the control of disease in shrimp.

Beam dynamics studies of a 30 MeV RF linac for neutron production

NASA Astrophysics Data System (ADS)

Nayak, B.; Krishnagopal, S.; Acharya, S.

2018-02-01

Design of a 30 MeV, 10 Amp RF linac as neutron source has been carried out by means of ASTRA simulation code. Here we discuss details of design simulations for three different cases i.e Thermionic , DC and RF photocathode guns and compare them as injectors to a 30 MeV RF linac for n-ToF production. A detailed study on choice of input parameters of the beam from point of view of transmission efficiency and beam quality at the output have been described. We found that thermionic gun isn't suitable for this application. Both DC and RF photocathode gun can be used. RF photocathode gun would be of better performance.

Micro and Nano Systems for Space Exploration

NASA Technical Reports Server (NTRS)

Manohara, Harish

2007-01-01

This slide presentation reviews the use of micro and nano systems in Space exploration. Included are: an explanation of the rationales behind nano and micro technologies for space exploration, a review of how the devices are fabricated, including details on lithography with more information on Electron Beam (E-Beam) lithography, and X-ray lithography, a review of micro gyroscopes and inchworm Microactuator as examples of the use of MicroElectoMechanical (MEMS) technology. Also included is information on Carbon Nanotubes, including a review of the CVD growth process. These micro-nano systems have given rise to the next generation of miniature X-ray Diffraction, X-ray Fluorescence instruments, mass spectrometers, and terahertz frequency vacuum tube oscillators and amplifiers, scanning electron microscopes and energy dispersive x-ray spectroscope. The nanotechnology has also given rise to coating technology, such as silicon nanotip anti-reflection coating.

Micro Penning Trap for Continuous Magnetic Field Monitoring in High Radiation Environments

NASA Astrophysics Data System (ADS)

Latorre, Javiera; Bollen, Georg; Gulyuz, Kerim; Ringle, Ryan; Bado, Philippe; Dugan, Mark; Lebit Team; Translume Collaboration

2016-09-01

As new facilities for rare isotope beams, like FRIB at MSU, are constructed, there is a need for new instrumentation to monitor magnetic fields in beam magnets that can withstand the higher radiation level. Currently NMR probes, the instruments used extensively to monitor magnetic fields, do not have a long lifespans in radiation-high environments. Therefore, a radiation-hard replacement is needed. We propose to use Penning trap mass spectrometry techniques to make high precision magnetic field measurements. Our Penning microtrap will be radiation resistant as all of the vital electronics will be at a safe distance from the radiation. The trap itself is made from materials not subject to radiation damage. Penning trap mass spectrometers can determine the magnetic field by measuring the cyclotron frequency of an ion with a known mass and charge. This principle is used on the Low Energy Beam Ion Trap (LEBIT) minitrap at NSCL which is the foundation for the microtrap. We have partnered with Translume, who specialize in glass micro-fabrication, to develop a microtrap in fused-silica glass. A microtrap is finished and ready for testing at NSCL with all of the electronic and hardware components setup. DOE Phase II SBIR Award No. DE-SC0011313, NSF Award Number 1062410 REU in Physics, NSF under Grant No. PHY-1102511.

Large scale ab initio modeling of structurally uncharacterized antimicrobial peptides reveals known and novel folds.

PubMed

Kozic, Mara; Fox, Stephen J; Thomas, Jens M; Verma, Chandra S; Rigden, Daniel J

2018-05-01

Antimicrobial resistance within a wide range of infectious agents is a severe and growing public health threat. Antimicrobial peptides (AMPs) are among the leading alternatives to current antibiotics, exhibiting broad spectrum activity. Their activity is determined by numerous properties such as cationic charge, amphipathicity, size, and amino acid composition. Currently, only around 10% of known AMP sequences have experimentally solved structures. To improve our understanding of the AMP structural universe we have carried out large scale ab initio 3D modeling of structurally uncharacterized AMPs that revealed similarities between predicted folds of the modeled sequences and structures of characterized AMPs. Two of the peptides whose models matched known folds are Lebocin Peptide 1A (LP1A) and Odorranain M, predicted to form β-hairpins but, interestingly, to lack the intramolecular disulfide bonds, cation-π or aromatic interactions that generally stabilize such AMP structures. Other examples include Ponericin Q42, Latarcin 4a, Kassinatuerin 1, Ceratotoxin D, and CPF-B1 peptide, which have α-helical folds, as well as mixed αβ folds of human Histatin 2 peptide and Garvicin A which are, to the best of our knowledge, the first linear αββ fold AMPs lacking intramolecular disulfide bonds. In addition to fold matches to experimentally derived structures, unique folds were also obtained, namely for Microcin M and Ipomicin. These results help in understanding the range of protein scaffolds that naturally bear antimicrobial activity and may facilitate protein design efforts towards better AMPs. © 2018 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Species differences in the effects of prostaglandins on inositol trisphosphate accumulation, phosphatidic acid formation, myosin light chain phosphorylation and contraction in iris sphincter of the mammalian eye: interaction with the cyclic AMP system.

PubMed

Yousufzai, S Y; Chen, A L; Abdel-Latif, A A

1988-12-01

Comparative studies on the effects of prostaglandins (PGs) on 1,2-diacylglycerol, measured as phosphatidic acid (PA), and inositol trisphosphate (IP3) production, cyclic AMP (cAMP) formation, myosin light chain (MLC) phosphorylation and contraction in the iris sphincter smooth muscle of rabbit, bovine and other mammalian species were undertaken and functional and biochemical relationships between the IP3-Ca++ and cAMP second messenger systems were demonstrated. The findings obtained from these studies can be summarized as follows: 1) all PGs investigated, including PGE2, PGF2 alpha, PGF2 alpha-ester, PGE1 and PGA2 increased IP3 accumulation and PA formation, and the extent of stimulation was dependent on the animal species. Thus, PGF2 alpha-ester (1 microM), the most potent of the PGs, increased IP3 accumulation in rabbit and bovine sphincters by 33 and 58%, respectively, and increased PA formation by 67 and 56%, respectively. The PG increased IP3 accumulation in both rabbit and bovine sphincters very rapidly (T1/2 values about 26 sec) and in a dose-dependent manner. 2) The PG had no effect on MLC phosphorylation in the rabbit sphincter, but it increased that of the bovine by 36%. 3) The PG increased cAMP formation by 75% in the rabbit sphincter but it had no effect on that of the bovine. 4) The PG induced a maximal contractile response in the bovine sphincter but it had no effect on that of the rabbit. 5) In the bovine, PGA2 induced IP3 accumulation and contraction, without an effect on cAMP formation; however, in the rabbit, cat and dog it increased cAMP formation and had no effect on IP3 accumulation and contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

AMP Is an Adenosine A1 Receptor Agonist*

PubMed Central

Rittiner, Joseph E.; Korboukh, Ilia; Hull-Ryde, Emily A.; Jin, Jian; Janzen, William P.; Frye, Stephen V.; Zylka, Mark J.

2012-01-01

Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5′-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5′-monophosphonate, ACP) directly activated the adenosine A1 receptor (A1R). In contrast, AMP only activated the adenosine A2B receptor (A2BR) after hydrolysis to adenosine by ecto-5′-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A1R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A1R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A1R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A1R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine. PMID:22215671

AMP is an adenosine A1 receptor agonist.

PubMed

Rittiner, Joseph E; Korboukh, Ilia; Hull-Ryde, Emily A; Jin, Jian; Janzen, William P; Frye, Stephen V; Zylka, Mark J

2012-02-17

Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5'-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5'-monophosphonate, ACP) directly activated the adenosine A(1) receptor (A(1)R). In contrast, AMP only activated the adenosine A(2B) receptor (A(2B)R) after hydrolysis to adenosine by ecto-5'-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A(1)R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A(1)R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A(1)R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A(1)R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine.

Net field-aligned currents observed by Triad

NASA Technical Reports Server (NTRS)

Sugiura, M.; Potemra, T. A.

1975-01-01

From the Triad magnetometer observation of a step-like level shift in the east-west component of the magnetic field at 800 km altitude, the existence of a net current flowing into or away from the ionosphere in a current layer was inferred. The current direction is toward the ionosphere on the morning side and away from it on the afternoon side. The field aligned currents observed by Triad are considered as being an important element in the electro-dynamical coupling between the distant magnetosphere and the ionosphere. The current density integrated over the thickness of the layer increases with increasing magnetic activity, but the relation between the current density and Kp in individual cases is not a simple linear relation. An extrapolation of the statistical relation to Kp = 0 indicates existence of a sheet current of order 0.1 amp/m even at extremely quiet times. During periods of higher magnetic activity an integrated current of approximately 1 amp/m and average current density of order 0.000001 amp/sq m are observed. The location and the latitudinal width of the field aligned current layer carrying the net current very roughly agree with those of the region of high electron intensities in the trapping boundary.

R&D in micro-nano-bio systems and contribution to pHealth.

PubMed

Lymberis, Andreas

2012-01-01

The capacity to research, develop and manufacture systems that employ components based on nano- and microstructures with biological functionality, and are capable to share, ubiquitously, information is at the forefront of worldwide competition. A new generation of advanced materials, processes and emerging technologies is building up enabling highly integrated, miniaturized and smart micro-nano-bio-systems to be engineered. These fast technology developments are also stimulating the explosive growth in life sciences, which is leading to an ever increasing understanding of life at the sub-cellular and molecular level. By bringing these parallel developments to biomedicine and health, ultrafast and sensitive systems can be developed to prevent illness, to support lifestyle, to make early diagnosis or treat diseases with high accuracy and less invasiveness, and to support body functions or to replace lost functionality. Such systems will enable the delivery of individualized health services with better access and outcomes at lower costs than previously deemed possible, making a substantial contribution to bringing healthcare expenditures under control and increase its productivity. The MNBS (Micro-Nano-Bio Systems) group of EU funded projects aims at speeding up the convergence of micro- and nanotechnology with the life sciences and accelerating the development of highly integrated diagnostic, monitoring and therapeutics devices. This paper presents R&D activities supported through the MNBS group that are relevant to pHealth and discusses directions to be taken in order to overcome the current problems. Finally, it addresses future challenges to build highly integrated and reliable systems including innovation and usability issues.

Regulation of aromatase activity in bone-derived cells: possible role of mitogen-activated protein kinase.

PubMed

Shozu, M; Sumitani, H; Murakami, K; Segawa, T; Yang, H J; Inoue, M

2001-12-01

Fetal human osteoblast-like cells and the THP-1 cell line that differentiates into macrophage/osteoblast-like cells in the presence of Vitamin D3 and which possesses high aromatase activity, constitute a useful model with which to study the regulation of aromatase in bone. We showed that dexamethasone (DEX)-induced aromatase activity in the THP-1 cell line is completely suppressed by forskolin and by dibutyryl cAMP. We therefore investigated the contribution of mitogen-activated protein kinase (MAPK) to the regulation of aromatase, because cAMP inhibits MAPK in many cells. We examined the role of MAPK on aromatase activity using PD98059, a selective inhibitor of MEK-1. PD98059 (100 microM) reduced DEX+interleukin (IL)-1beta-induced aromatase activity in human osteoblast-like cells by more than 90%, whereas 50% of the aromatase mRNA concentration was retained compared with the control incubated with DEX+IL-1beta. PD98059 (50 microM) reduced the activity of aromatase in THP-1 cells by 80% without significantly affecting the mRNA level. These results indicated that MAPK plays an important role in aromatase activation at the post-transcriptional level.

Observation of coherent Smith-Purcell and transition radiation driven by single bunch and micro-bunched electron beams

NASA Astrophysics Data System (ADS)

Liang, Yifan; Du, Yingchao; Su, Xiaolu; Wang, Dan; Yan, Lixin; Tian, Qili; Zhou, Zheng; Wang, Dong; Huang, Wenhui; Gai, Wei; Tang, Chuanxiang; Konoplev, I. V.; Zhang, H.; Doucas, G.

2018-01-01

Generation of coherent Smith-Purcell (cSPr) and transition/diffraction radiation using a single bunch or a pre-modulated relativistic electron beam is one of the growing research areas aiming at the development of radiation sources and beam diagnostics for accelerators. We report the results of comparative experimental studies of terahertz radiation generation by an electron bunch and micro-bunched electron beams and the spectral properties of the coherent transition and SP radiation. The properties of cSPr spectra are investigated and discussed, and excitations of the fundamental and second harmonics of cSPr and their dependence on the beam-grating separation are shown. The experimental and theoretical results are compared, and good agreement is demonstrated.

Antimicrobial peptides: Possible anti-infective agents.

PubMed

Lakshmaiah Narayana, Jayaram; Chen, Jyh-Yih

2015-10-01

Multidrug-resistant bacterial, fungal, viral, and parasitic infections are major health threats. The Infectious Diseases Society of America has expressed concern on the decrease of pharmaceutical companies working on antibiotic research and development. However, small companies, along with academic research institutes, are stepping forward to develop novel therapeutic methods to overcome the present healthcare situation. Among the leading alternatives to current drugs are antimicrobial peptides (AMPs), which are abundantly distributed in nature. AMPs exhibit broad-spectrum activity against a wide variety of bacteria, fungi, viruses, and parasites, and even cancerous cells. They also show potential immunomodulatory properties, and are highly responsive to infectious agents and innate immuno-stimulatory molecules. In recent years, many AMPs have undergone or are undergoing clinical development, and a few are commercially available for topical and other applications. In this review, we outline selected anion and cationic AMPs which are at various stages of development, from preliminary analysis to clinical drug development. Moreover, we also consider current production methods and delivery tools for AMPs, which must be improved for the effective use of these agents. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells.

PubMed

Fischer, Horst; Machen, Terry E; Widdicombe, Jonathan H; Carlson, Thomas J S; King, Steven R; Chow, John W S; Illek, Beate

2004-08-01

An oligomeric proanthocyanidin (SP-303) extracted from the bark latex of the tree Croton lechleri (family Euphorbiaceae) is a potent inhibitor of cholera toxin-induced fluid accumulation and chloride secretion. The manufacturing process for SP-303 was optimized and simplified to produce an increased yield of the herbal extract. The novel extract (named SB-300) contained on average 70.6+/-7.2% SP-303 by weight (mean +/- S.D.; n=56 lots). Here, we describe the effectiveness of SB-300 on cAMP-regulated chloride secretion, which is mediated by the cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) in human colonic T84 cells. Exposure of the apical surface to SB-300 blocked forskolin-stimulated Cl- secretion by 92.2+/-3.0% with a half-maximal inhibition constant (KB) of 4.8+/-0.8 microM. For SP-303, stimulated Cl- currents were decreased by 98.0+/-7.2 % and KB averaged 4.1+/-1.3 microM. There was no significant difference between the blocking kinetics of SP-303 and SB-300. Forskolin-stimulated whole cell Cl- currents were effectively blocked by extracellular addition of SB-300 (63+/-8.5%; n=3) and to a similar extent by SP-303 (83 +/- 0.6%; n=2; at 50 microM each). Both extracts inhibited a time- and voltage-independent Cl- conductance, which indicated the involvement of CFTR Cl- channels. We conclude that both SP-303 (used in Provir) and SB-300 (used in NSF Normal Stool Formula) are novel natural products that target the CFTR Cl- channel. SB-300 is a low cost herbal extract and may present a complementary and alternative medicine approach for the treatment of fluid loss in watery diarrhea.

Particle damage sources for fused silica optics and their mitigation on high energy laser systems.

PubMed

Bude, J; Carr, C W; Miller, P E; Parham, T; Whitman, P; Monticelli, M; Raman, R; Cross, D; Welday, B; Ravizza, F; Suratwala, T; Davis, J; Fischer, M; Hawley, R; Lee, H; Matthews, M; Norton, M; Nostrand, M; VanBlarcom, D; Sommer, S

2017-05-15

High energy laser systems are ultimately limited by laser-induced damage to their critical components. This is especially true of damage to critical fused silica optics, which grows rapidly upon exposure to additional laser pulses. Much progress has been made in eliminating damage precursors in as-processed fused silica optics (the advanced mitigation process, AMP3), and very high damage resistance has been demonstrated in laboratory studies. However, the full potential of these improvements has not yet been realized in actual laser systems. In this work, we explore the importance of additional damage sources-in particular, particle contamination-for fused silica optics fielded in a high-performance laser environment, the National Ignition Facility (NIF) laser system. We demonstrate that the most dangerous sources of particle contamination in a system-level environment are laser-driven particle sources. In the specific case of the NIF laser, we have identified the two important particle sources which account for nearly all the damage observed on AMP3 optics during full laser operation and present mitigations for these particle sources. Finally, with the elimination of these laser-driven particle sources, we demonstrate essentially damage free operation of AMP3 fused silica for ten large optics (a total of 12,000 cm 2 of beam area) for shots from 8.6 J/cm 2 to 9.5 J/cm 2 of 351 nm light (3 ns Gaussian pulse shapes). Potentially many other pulsed high energy laser systems have similar particle sources, and given the insight provided by this study, their identification and elimination should be possible. The mitigations demonstrated here are currently being employed for all large UV silica optics on the National Ignition Facility.

Laser beam micro-milling of nickel alloy: dimensional variations and RSM optimization of laser parameters

NASA Astrophysics Data System (ADS)

Ahmed, Naveed; Alahmari, Abdulrahman M.; Darwish, Saied; Naveed, Madiha

2016-12-01

Micro-channels are considered as the integral part of several engineering devices such as micro-channel heat exchangers, micro-coolers, micro-pulsating heat pipes and micro-channels used in gas turbine blades for aerospace applications. In such applications, a fluid flow is required to pass through certain micro-passages such as micro-grooves and micro-channels. The fluid flow characteristics (flow rate, turbulence, pressure drop and fluid dynamics) are mainly established based on the size and accuracy of micro-passages. Variations (oversizing and undersizing) in micro-passage's geometry directly affect the fluid flow characteristics. In this study, the micro-channels of several sizes are fabricated in well-known aerospace nickel alloy (Inconel 718) through laser beam micro-milling. The variations in geometrical characteristics of different-sized micro-channels are studied under the influences of different parameters of Nd:YAG laser. In order to have a minimum variation in the machined geometries of each size of micro-channel, the multi-objective optimization of laser parameters has been carried out utilizing the response surface methodology approach. The objective was set to achieve the targeted top widths and depths of micro-channels with minimum degree of taperness associated with the micro-channel's sidewalls. The optimized sets of laser parameters proposed for each size of micro-channel can be used to fabricate the micro-channels in Inconel 718 with minimum amount of geometrical variations.

Cystic Fibrosis Gene Encodes a cAMP-Dependent Chloride Channel in Heart

NASA Astrophysics Data System (ADS)

Hart, Padraig; Warth, John D.; Levesque, Paul C.; Collier, Mei Lin; Geary, Yvonne; Horowitz, Burton; Hume, Joseph R.

1996-06-01

cAMP-dependent chloride channels in heart contribute to autonomic regulation of action potential duration and membrane potential and have been inferred to be due to cardiac expression of the epithelial cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. In this report, a cDNA from rabbit ventricle was isolated and sequenced, which encodes an exon 5 splice variant (exon 5-) of CFTR, with >90% identity to human CFTR cDNA present in epithelial cells. Expression of this cDNA in Xenopus oocytes gave rise to robust cAMP-activated chloride currents that were absent in control water-injected oocytes. Antisense oligodeoxynucleotides directed against CFTR significnatly reduced the density of cAMP-dependent chloride currents in acutely cultured myocytes, thereby establishing a direct functional link between cardiac expression of CFTR protein and an endogenous chloride channel in native cardiac myocytes.

Application of wire beam electrode technique to investigate initiation and propagation of rebar corrosion

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

Shi, Wei; Dong, Ze Hua, E-mail: zehua.dong@gmail.com; Kong, De Jie

Multi-electrode technique named as wire beam electrode (WBE) was used to study pitting corrosion of rebar under concrete cover. When WBE embedded mortar sample was immersed in NaCl solution, uneven distributions of galvanic current and open circuit potential (OCP) on the WBE were observed due to the initiation of pitting corrosion. The following oxygen depletion in mortar facilitated the negative shift of the OCP and the smoothing of the current and potential distributions. Wetting–drying cycle experiments showed that corrosion products instead of oxygen in wet mortar specimen sustained the propagation of pitting corrosion due to Fe (III) taking part inmore » cathodic depolarization during oxygen-deficient wet period, which was confirmed by micro-Raman spectroscopy. In addition, new pitting corrosion occurred mainly near the corrosion products, leading to preferentially horizontal propagation of rust layer on the WBE. A localized corrosion factor was further presented to quantify the localised corrosion based on galvanic current maps.« less

Electron beam machining using rotating and shaped beam power distribution

DOEpatents

Elmer, J.W.; O`Brien, D.W.

1996-07-09

An apparatus and method are disclosed for electron beam (EB) machining (drilling, cutting and welding) that uses conventional EB guns, power supplies, and welding machine technology without the need for fast bias pulsing technology. The invention involves a magnetic lensing (EB optics) system and electronic controls to: (1) concurrently bend, focus, shape, scan, and rotate the beam to protect the EB gun and to create a desired effective power-density distribution, and (2) rotate or scan this shaped beam in a controlled way. The shaped beam power-density distribution can be measured using a tomographic imaging system. For example, the EB apparatus of this invention has the ability to drill holes in metal having a diameter up to 1,000 {micro}m (1 mm or larger), compared to the 250 {micro}m diameter of laser drilling. 5 figs.

cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP).

PubMed

Roberts, Owain Llŷr; Dart, Caroline

2014-02-01

The second messenger cAMP plays a central role in mediating vascular smooth muscle relaxation in response to vasoactive transmitters and in strengthening endothelial cell-cell junctions that regulate the movement of solutes, cells and macromolecules between the blood and the surrounding tissue. The vasculature expresses three cAMP effector proteins: PKA (protein kinase A), CNG (cyclic-nucleotide-gated) ion channels, and the most recently discovered Epacs (exchange proteins directly activated by cAMP). Epacs are a family of GEFs (guanine-nucleotide-exchange factors) for the small Ras-related GTPases Rap1 and Rap2, and are being increasingly implicated as important mediators of cAMP signalling, both in their own right and in parallel with the prototypical cAMP target PKA. In the present paper, we review what is currently known about the role of Epac within blood vessels, particularly with regard to the regulation of vascular tone, endothelial barrier function and inflammation.

Dosimetry of cone-defined stereotactic radiosurgery fields with a commercial synthetic diamond detector.

PubMed

Morales, Johnny E; Crowe, Scott B; Hill, Robin; Freeman, Nigel; Trapp, J V

2014-11-01

Small field x-ray beam dosimetry is difficult due to lack of lateral electronic equilibrium, source occlusion, high dose gradients, and detector volume averaging. Currently, there is no single definitive detector recommended for small field dosimetry. The objective of this work was to evaluate the performance of a new commercial synthetic diamond detector, namely, the PTW 60019 microDiamond, for the dosimetry of small x-ray fields as used in stereotactic radiosurgery (SRS). Small field sizes were defined by BrainLAB circular cones (4-30 mm diameter) on a Novalis Trilogy linear accelerator and using the 6 MV SRS x-ray beam mode for all measurements. Percentage depth doses (PDDs) were measured and compared to an IBA SFD and a PTW 60012 E diode. Cross profiles were measured and compared to an IBA SFD diode. Field factors, ΩQclin,Qmsr (fclin,fmsr) , were calculated by Monte Carlo methods using BEAMnrc and correction factors, kQclin,Qmsr (fclin,fmsr) , were derived for the PTW 60019 microDiamond detector. For the small fields of 4-30 mm diameter, there were dose differences in the PDDs of up to 1.5% when compared to an IBA SFD and PTW 60012 E diode detector. For the cross profile measurements the penumbra values varied, depending upon the orientation of the detector. The field factors, ΩQclin,Qmsr (fclin,fmsr) , were calculated for these field diameters at a depth of 1.4 cm in water and they were within 2.7% of published values for a similar linear accelerator. The corrections factors, kQclin,Qmsr (fclin,fmsr) , were derived for the PTW 60019 microDiamond detector. The authors conclude that the new PTW 60019 microDiamond detector is generally suitable for relative dosimetry in small 6 MV SRS beams for a Novalis Trilogy linear equipped with circular cones.

Chalcogenide molded freeform optics for mid-infrared lasers

NASA Astrophysics Data System (ADS)

Chenard, Francois; Alvarez, Oseas; Yi, Allen

2017-05-01

High-precision chalcogenide molded micro-lenses were produced to collimate mid-infrared Quantum Cascade Lasers (QCLs). Molded cylindrical micro-lens prototypes with aspheric contour (acylindrical), high numerical aperture (NA 0.8) and small focal length (f<2 mm) were fabricated to collimate the QCL fast-axis beam. Another innovative freeform micro-lens has an input acylindrical surface to collimate the fast axis and an orthogonal output acylindrical surface to collimate the slow axis. The thickness of the freeform lens is such that the output fast- and slow-axis beams are circular. This paper presents results on the chalcogenide molded freeform micro-lens designed to collimate and circularize QCL at 4.6 microns.

Micro-scanning mirrors for high-power laser applications in laser surgery

NASA Astrophysics Data System (ADS)

Sandner, Thilo; Kimme, Simon; Grasshoff, Thomas; Todt, Ulrich; Graf, Alexander; Tulea, Cristian; Lenenbach, Achim; Schenk, Harald

2014-03-01

We present two novel micro scanning mirrors with large aperture and HR dielectric coatings suitable for high power laser applications in a miniaturized laser-surgical instrument for neurosurgery to cut skull tissue. An electrostatic driven 2D-raster scanning mirror with 5x7.1mm aperture is used for dynamic steering of a ps-laser beam of the laser cutting process. A second magnetic 2D-beam steering mirror enables a static beam correction of a hand guided laser instrument. Optimizations of a magnetic gimbal micro mirror with 6 mm x 8 mm mirror plate are presented; here static deflections of 3° were reached. Both MEMS devices were successfully tested with a high power ps-laser at 532nm up to 20W average laser power.

Distinct profiling of antimicrobial peptide families

PubMed Central

Khamis, Abdullah M.; Essack, Magbubah; Gao, Xin; Bajic, Vladimir B.

2015-01-01

Motivation: The increased prevalence of multi-drug resistant (MDR) pathogens heightens the need to design new antimicrobial agents. Antimicrobial peptides (AMPs) exhibit broad-spectrum potent activity against MDR pathogens and kills rapidly, thus giving rise to AMPs being recognized as a potential substitute for conventional antibiotics. Designing new AMPs using current in-silico approaches is, however, challenging due to the absence of suitable models, large number of design parameters, testing cycles, production time and cost. To date, AMPs have merely been categorized into families according to their primary sequences, structures and functions. The ability to computationally determine the properties that discriminate AMP families from each other could help in exploring the key characteristics of these families and facilitate the in-silico design of synthetic AMPs. Results: Here we studied 14 AMP families and sub-families. We selected a specific description of AMP amino acid sequence and identified compositional and physicochemical properties of amino acids that accurately distinguish each AMP family from all other AMPs with an average sensitivity, specificity and precision of 92.88%, 99.86% and 95.96%, respectively. Many of our identified discriminative properties have been shown to be compositional or functional characteristics of the corresponding AMP family in literature. We suggest that these properties could serve as guides for in-silico methods in design of novel synthetic AMPs. The methodology we developed is generic and has a potential to be applied for characterization of any protein family. Contact: vladimir.bajic@kaust.edu.sa Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25388148

Design of a 100 MW X-band klystron

NASA Astrophysics Data System (ADS)

Eppley, Kenneth

1989-02-01

Future linear colliders will require klystrons with higher peak power at higher frequency than are currently in use. SLAC is currently designing a 100 MW klystron at 11.4 GHz as a prototype for such a tube. The gun has been designed for 440 kV and 510 amps. Transporting this beam through a 5 mm radius X-band drift tube presents the major design problem. The area convergence ratio of 190 to one is over ten times higher than is found in conventional klystrons. Even with high magnetic fields of 6 to 7 kilogauss careful matching is required to prevent excessive scalloping. Extensive EGUN and CONDOR simulations have been made to optimize the transmission and RF efficiency. The EGUN simulations indicate that better matching is possible by using resonant magnetic focusing. CONDOR calculations indicate efficiencies of 45 percent are possible with a double output cavity. We will discuss the results of the simulations and the status of the experimental program.

Antimicrobial Peptides: An Emerging Category of Therapeutic Agents.

PubMed

Mahlapuu, Margit; Håkansson, Joakim; Ringstad, Lovisa; Björn, Camilla

2016-01-01

Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

Vacuum testing of high efficiency AMTEC cells

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

Schuller, M.; Phillips, P.H.; Sievers, R.

1996-12-31

The Phillips Laboratory Power and Thermal Management Division (PL/VTP), in cooperation with JPL, AMPS, Creare, and ORION, is performing vacuum testing of high performance Alkali Metal Thermal to Electric Conversion (AMTEC) cells, including the Micro-Machined Evaporator (MME) and PL-9A cells. The MME cell was designed to test an improved evaporator, which should allow long term operation at evaporator temperatures as high as 1,100 K. The PL-9A cell was designed and built by AMPS under contract to ORION to test an improved heat shield assembly. The testing at Phillips Lab is done in a vacuum test stand which simulates the environmentmore » of an AMTEC cell operating as part of a spacecraft power system. The test configuration consists of the MME cell (later replaced by by the PL-9A cell) in the center of an array of six other AMTEC cells. The seven cells are encased in multifoil insulation. Testing shows that there is little difference between cell current/voltage performance when measured in vacuum tests compared to guard heater tests. The author are also examining the differences between fast I-V curve sweeps, recorded manually, with the cell operating at constant heat input, over a period of five minutes or less, and equilibrium I-V curve sweeps, in which the cell reaches thermal equilibrium at each data point.« less

Laboratory-based micro-X-ray fluorescence setup using a von Hamos crystal spectrometer and a focused beam X-ray tube

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

Kayser, Y., E-mail: yves.kayser@psi.ch; Paul Scherrer Institut, 5232 Villigen-PSI; Błachucki, W.

2014-04-15

The high-resolution von Hamos bent crystal spectrometer of the University of Fribourg was upgraded with a focused X-ray beam source with the aim of performing micro-sized X-ray fluorescence (XRF) measurements in the laboratory. The focused X-ray beam source integrates a collimating optics mounted on a low-power micro-spot X-ray tube and a focusing polycapillary half-lens placed in front of the sample. The performances of the setup were probed in terms of spatial and energy resolution. In particular, the fluorescence intensity and energy resolution of the von Hamos spectrometer equipped with the novel micro-focused X-ray source and a standard high-power water-cooled X-raymore » tube were compared. The XRF analysis capability of the new setup was assessed by measuring the dopant distribution within the core of Er-doped SiO{sub 2} optical fibers.« less

Ion beam radiation effects on natural halite crystals

NASA Astrophysics Data System (ADS)

Arun, T.; Ram, S. S.; Karthikeyan, B.; Ranjith, P.; Ray, D. K.; Rout, B.; Krishna, J. B. M.; Sengupta, Pranesh; Parlapalli, Venkata Satyam

2017-10-01

Halites are one of the interesting material due to its color variations. Natural halites whose color ranges from transparent to dark blue were studied by UV-VIS and Raman spectroscopy. The halite crystals were irradiated with 3 MeV proton micro-beam (∼20 μm beam width with ∼80 PA beam current) for 10 and 90 min to study the radiation damage. After 10 mins of irradiation, small spot developed on the surface of transparent halite crystal whereas after 90 mins of irradiation the spot spread inside the bulk leading to a brown coloration (20 μm initial size to ∼2.0 mm final size). The irradiated portion and the un-irradiated portion of the halites was characterized by Raman spectroscopic technique. The variation in the population density was observed from the UV-Vis spectra. The change in the Raman band intensities was observed for transparent, blue colored and proton beam irradiation halites. Such variation of spectroscopic characteristics due to proton irradiation suggests that the halite can be used for the radiation monitoring.

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

Lill, R.; Sereno, N.; Yang, B.

The Advanced Photon Source (APS) is currently in the preliminary design phase for the multi-bend achromat (MBA) lattice upgrade. Beam stability is critical for the MBA and will require long term drift defined as beam mo-tion over a seven-day timescale to be no more than 1 mi-cron at the insertion device locations and beam angle change no more than 0.25 micro-radian. Mechanical stabil-ity of beam position monitor (BPM) pickup electrodes mounted on insertion device vacuum chambers place a fun-damental limitation on long-term beam stability for inser-tion device beamlines. We present the design and imple-mentation of prototype mechanical motion system (MMS)more » instrumentation for quantifying this type of motion specif-ically in the APS accelerator tunnel and experiment hall floor under normal operating conditions. The MMS pres-ently provides critical position information on the vacuum chamber and BPM support systems. Initial results of the R&D prototype systems have demonstrated that the cham-ber movements far exceed the long-term drift tolerance specified for the APS Upgrade MBA storage ring.« less

Modafinil inhibits K(Ca)3.1 currents and muscle contraction via a cAMP-dependent mechanism.

PubMed

Choi, Shinkyu; Kim, Moon Young; Joo, Ka Young; Park, Seonghee; Kim, Ji Aee; Jung, Jae-Chul; Oh, Seikwan; Suh, Suk Hyo

2012-07-01

Modafinil has been used as a psychostimulant for the treatment of narcolepsy. However, its primary mechanism of action remains elusive. Therefore, we examined the effects of modafinil on K(Ca)3.1 channels and vascular smooth muscle contraction. K(Ca)3.1 currents and channel activity were measured using a voltage-clamp technique and inside-out patches in mouse embryonic fibroblast cell line, NIH-3T3 fibroblasts. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration was measured, and the phosphorylation of K(Ca)3.1 channel protein was examined using western blotting in NIH-3T3 fibroblasts and/or primary cultured mouse aortic smooth muscle cells (SMCs). Muscle contractions were recorded from mouse aorta and rat pulmonary artery by using a myograph developed in-house. Modafinil was found to inhibit K(Ca)3.1 currents in a concentration-dependent manner, and the half-maximal inhibition (IC(50)) of modafinil for the current inhibition was 6.8 ± 0.7 nM. The protein kinase A (PKA) activator forskolin also inhibited K(Ca)3.1 currents. The inhibitory effects of modafinil and forskolin on K(Ca)3.1 currents were blocked by the PKA inhibitors PKI(14-22) or H-89. In addition, modafinil relaxed blood vessels (mouse aorta and rat pulmonary artery) in a concentration-dependent manner. Modafinil increased cAMP concentrations in NIH-3T3 fibroblasts or primary cultured mouse aortic SMCs and phosphorylated K(Ca)3.1 channel protein in NIH-3T3 fibroblasts. However, open probability and single-channel current amplitudes of K(Ca)3.1 channels were not changed by modafinil. From these results, we conclude that modafinil inhibits K(Ca)3.1 channels and vascular smooth muscle contraction by cAMP-dependent phosphorylation, suggesting that modafinil can be used as a cAMP-dependent K(Ca)3.1 channel blocker and vasodilator. Copyright © 2012 Elsevier Ltd. All rights reserved.

Defensins: antifungal lessons from eukaryotes

PubMed Central

Silva, Patrícia M.; Gonçalves, Sónia; Santos, Nuno C.

2014-01-01

Over the last years, antimicrobial peptides (AMPs) have been the focus of intense research toward the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components) are presented. Additionally, recent works on antifungal defensins structure, activity, and cytotoxicity are also reviewed. PMID:24688483

Bypass Diode Temperature Tests of a Solar Array Coupon Under Space Thermal Environment Conditions

NASA Technical Reports Server (NTRS)

Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie; Wu, Gordon

2016-01-01

Tests were performed on a 56-cell Advanced Triple Junction solar array coupon whose purpose was to determine margin available for bypass diodes integrated with new, large multi-junction solar cells that are manufactured from a 4-inch wafer. The tests were performed under high vacuum with coupon back side thermal conditions of both cold and ambient. The bypass diodes were subjected to a sequence of increasing discrete current steps from 0 Amp to 2.0 Amp in steps of 0.25 Amp. At each current step, a temperature measurement was obtained via remote viewing by an infrared camera. This paper discusses the experimental methodology, experiment results, and the thermal model.

By-Pass Diode Temperature Tests of a Solar Array Coupon Under Space Thermal Environment Conditions

NASA Technical Reports Server (NTRS)

Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie

2016-01-01

Tests were performed on a 56-cell Advanced Triple Junction solar array coupon whose purpose was to determine margin available for bypass diodes integrated with new, large multi-junction solar cells that are manufactured from a 4-inch wafer. The tests were performed under high vacuum with cold and ambient coupon back-side. The bypass diodes were subjected to a sequence of increasing discrete current steps from 0 Amp to 2.0 Amp in steps of 0.25 Amp. At each current step, a temperature measurement was obtained via remote viewing by an infrared camera. This paper discusses the experimental methodology, including the calibration of the thermal imaging system, and the results.

Nano-stepper-driven optical shutter for applications in free-space micro-optics

NASA Astrophysics Data System (ADS)

Zawadzka, Justyna; Li, Lijie; Unamuno, Anartz; Uttamchandani, Deepak G.

2002-09-01

In this paper we report a simple design of a micro-optical shutter/attenuator. The standard MUMPS process was used to fabricate the device. A vertically erected, gold-coated, 200x300 mm side length micro-mirror was precisely placed between the end faces of two closely spaced optical fibers. The position of the micro-mirror with respect to the optical fiber end face was controlled by a nano-stepping motor array. Optical and mechanical tests were performed on the device. A 1.55 mm laser beam was sent along the optical fiber. When the micro-mirror was removed from the front of the fiber, the coupling efficiency between two fibers was -10 dBm. Once the micro-mirror was placed in the optical path the coupling efficiency dropped to -51.5 dBm. The best attenuation was obtained when the micro-mirror blocked the whole cross-section of the laser beam diameter. It is evident that the device can operate as a high precision fiber optic attenuator or shutter.

Long-Wavelength Beam Steerer Based on a Micro-Electromechanical Mirror

PubMed Central

Kos, Anthony B; Gerecht, Eyal

2013-01-01

Commercially available mirrors for scanning long-wavelength beams are too large for high-speed imaging. There is a need for a smaller, more agile pointing apparatus to provide images in seconds, not minutes or hours. A fast long-wavelength beam steerer uses a commercial micro-electro-mechanical system (MEMS) mirror controlled by a high-performance digital signal processor (DSP). The DSP allows high-speed raster scanning of the incident radiation, which is focused to a small waist onto the 9mm2, gold-coated, MEMS mirror surface, while simultaneously acquiring an undistorted, high spatial-resolution image of an object. The beam steerer hardware, software and performance are described. The system can also serve as a miniaturized, high-performance long-wavelength beam chopper for lock-in detection. PMID:26401426

Electron-beam lithography for micro and nano-optical applications

NASA Technical Reports Server (NTRS)

Wilson, Daniel W.; Muller, Richard E.; Echternach, Pierre M.

2005-01-01

Direct-write electron-beam lithography has proven to be a powerful technique for fabricating a variety of micro- and nano-optical devices. Binary E-beam lithography is the workhorse technique for fabricating optical devices that require complicated precision nano-scale features. We describe a bi-layer resist system and virtual-mark height measurement for improving the reliability of fabricating binary patterns. Analog E-beam lithography is a newer technique that has found significant application in the fabrication of diffractive optical elements. We describe our techniques for fabricating analog surface-relief profiles in E-beam resist, including some discussion regarding overcoming the problems of resist heating and charging. We also describe a multiple-field-size exposure scheme for suppression of field-stitch induced ghost diffraction orders produced by blazed diffraction gratings on non-flat substrates.

Micro-strip sensors based on CVD diamond

NASA Astrophysics Data System (ADS)

Adam, W.; Berdermann, E.; Bergonzo, P.; Bertuccio, G.; Bogani, F.; Borchi, E.; Brambilla, A.; Bruzzi, M.; Colledani, C.; Conway, J.; D'Angelo, P.; Dabrowski, W.; Delpierre, P.; Deneuville, A.; Dulinski, W.; van Eijk, B.; Fallou, A.; Fizzotti, F.; Foulon, F.; Friedl, M.; Gan, K. K.; Gheeraert, E.; Hallewell, G.; Han, S.; Hartjes, F.; Hrubec, J.; Husson, D.; Kagan, H.; Kania, D.; Kaplon, J.; Kass, R.; Koeth, T.; Krammer, M.; Logiudice, A.; Lu, R.; mac Lynne, L.; Manfredotti, C.; Meier, D.; Mishina, M.; Moroni, L.; Oh, A.; Pan, L. S.; Pernicka, M.; Peitz, A.; Perera, L.; Pirollo, S.; Procario, M.; Riester, J. L.; Roe, S.; Rousseau, L.; Rudge, A.; Russ, J.; Sala, S.; Sampietro, M.; Schnetzer, S.; Sciortino, S.; Stelzer, H.; Stone, R.; Suter, B.; Tapper, R. J.; Tesarek, R.; Trischuk, W.; Tromson, D.; Vittone, E.; Walsh, A. M.; Wedenig, R.; Weilhammer, P.; Wetstein, M.; White, C.; Zeuner, W.; Zoeller, M.; RD42 Collaboration

2000-10-01

In this article we present the performance of recent chemical vapour deposition (CVD) diamond micro-strip sensors in beam tests. In addition, we present the first comparison of a CVD diamond micro-strip sensor before and after proton irradiation.

Opportunities to improve the in vivo measurement of manganese in human hands.

PubMed

Aslam; Chettle, D R; Pejović-Milić, A; Waker, A J

2009-01-07

Manganese (Mn) is an element which is both essential for regulating neurological and skeletal functions in the human body and also toxic when humans are exposed to excessive levels. Its excessive inhalation as a result of exposure through industrial and environmental emissions can cause neurological damage, which may manifest as memory deficit, loss of motor control and reduction in the refinement of certain body motions. A number of clinical studies demonstrate that biological monitoring of Mn exposure using body fluids, particularly blood, plasma/serum and urine is of very limited use and reflect only the most recent exposure and rapidly return to within normal ranges. In this context, a non-invasive neutron activation technique has been developed at the McMaster University accelerator laboratory that could provide an alternative to measure manganese stored in the bones of exposed subjects. In a first pilot study we conducted recently on non-exposed human subjects to measure the ratio of Mn to Ca in hand bones, it was determined that the technique needed further development to improve the precision of the measurements. It could be achieved by improving the minimum detection limit (MDL) of the system from 2.1 microg Mn/g Ca to the reference value of 0.6 microg g(-1) Ca (range: 0.16-0.78 microg Mn/g Ca) for the non-exposed population. However, the developed procedure might still be a suitable means of screening patients and people exposed to excessive amounts of Mn, who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. To improve the MDL of the technique to the expected levels of Mn in a reference population, the present study investigates further optimization of irradiation conditions, which includes the optimal selection of proton beam energy, beam current and irradiation time and the effect of upgrading the 4pi detection system. The maximum local dose equivalent that could be given to the hand as a result of irradiation was constrained to be less than 150 mSv as opposed to the previously imposed dose equivalent limit of 20 mSv. A maximum beam current, which could be delivered on the lithium target to produce neutrons, was restricted to 500 microA. The length of irradiation intervals larger than 10 min, was considered inconvenient and impractical to implement with Mn measurements in humans. To fulfil the requirements for developing a protocol for in vivo bone Mn measurements, a revised estimate of the dose equivalent has been presented here. Beam energy of 1.98 MeV was determined to be optimal to complete the irradiation procedure within 10 min using 500 microA beam current. The local dose equivalent given to hand was estimated as 118 mSv, which is lower by a factor of 1.5 compared to that of 2.00 MeV. The optimized beam parameters are expected to improve the currently obtained detection limit of 2.1 microg Mn/g Ca to 0.6 microg Mn/g Ca. Using this dose equivalent delivered to the central location of the hand, the average dose equivalent to the hand of 74 mSv and an effective dose of approximately 70 microSv will be accompanying the non-invasive, in vivo measurements of bone Mn, which is little over the chest radiograph examination dose.

Determination of the active volumes of solid-state photon-beam dosimetry detectors using the PTB proton microbeam.

PubMed

Poppinga, Daniela; Delfs, Bjoern; Meyners, Jutta; Langner, Frank; Giesen, Ulrich; Harder, Dietrich; Poppe, Bjoern; Looe, Hui K

2018-05-04

This study aims at the experimental determination of the diameters and thicknesses of the active volumes of solid-state photon-beam detectors for clinical dosimetry. The 10 MeV proton microbeam of the PTB (Physikalisch-Technische Bundesanstalt, Braunschweig) was used to examine two synthetic diamond detectors, type microDiamond (PTW Freiburg, Germany), and the silicon detectors Diode E (PTW Freiburg, Germany) and Razor Diode (Iba Dosimetry, Germany). The knowledge of the dimensions of their active volumes is essential for their Monte Carlo simulation and their applications in small-field photon-beam dosimetry. The diameter of the active detector volume was determined from the detector current profile recorded by radially scanning the proton microbeam across the detector. The thickness of the active detector volume was determined from the detector's electrical current, the number of protons incident per time interval and their mean stopping power in the active volume. The mean energy of the protons entering this volume was assessed by comparing the measured and the simulated influence of the thickness of a stack of aluminum preabsorber foils on the detector signal. For all detector types investigated, the diameters measured for the active volume closely agreed with the manufacturers' data. For the silicon Diode E detector, the thickness determined for the active volume agreed with the manufacturer's data, while for the microDiamond detectors and the Razor Diode, the thicknesses measured slightly exceeded those stated by the manufacturers. The PTB microbeam facility was used to analyze the diameters and thicknesses of the active volumes of photon dosimetry detectors for the first time. A new method of determining the thickness values with an uncertainty of ±10% was applied. The results appear useful for further consolidating detailed geometrical knowledge of the solid-state detectors investigated, which are used in clinical small-field photon-beam dosimetry. © 2018 American Association of Physicists in Medicine.

Structural and emission characteristics of ion-irradiated Reticulated Vitreous Carbon

NASA Astrophysics Data System (ADS)

Chacon, Judith Rebecca

Cathodes formed from Reticulated Vitreous Carbon (RVC) were treated under varying conditions of Argon-ion beam current, beam voltage and irradiation duration. Surface structures, such as balls, cones, nanowires, and nanowhiskers were formed in the RVC network through a series of ion-impact sputtering and self-diffusion reactions. Raman shifts to the D and E2g' peak suggest C=C bonding within the original RVC structure was converted to the lesser-bound C-C bonding structure. Cathodes demonstrating the most stable electronic configuration exhibited significant vertical growth to graphitic domains as determined by calculations based on XRD measurements. Carbon nanotubes at the surface were observed at the surface through micro-Raman techniques. The surface structures formed by argon-bombardment, are responsible for cathodes exhibiting lower field-emission extraction fields. The electric field required for the onset of electron emission was measured to change from 6.03 V/micron in non-irradiated RVC to 1.62V/micron for RVC irradiated for 15 minutes at a beam voltage of 1200V and beam current of 200mA (ion-beam current density 2.24mA/cm2). Treated surfaces were also responsible for increased stability in emission over time. For untreated RVC, the field required for emission dropped 25% over a 48 hour training period, whilst modestly treated RVC (15min, 1200V, 100mA, or 1.52mA/cm2) rose as little as 3%. Field-emissive RVC, is an inexpensively produced, mechanically robust cathode with potential applications in lighting, displays and microwave sources.

Ca(2+)-Calmodulin regulation of testicular androgen production in Mozambique tilapia (Oreochromis mossambicus).

PubMed

Martins, Rute S T; Fuentes, Juan; Almeida, Olinda; Power, Deborah M; Canario, Adelino V M

2009-06-01

The Ca(2+)-Calmodulin (CaM) signaling pathway has previously been shown to be involved in the regulation of teleost fish ovarian steroidogenesis. However, a putative role of CaM in testicular steroidogenesis and potential targets has not been examined. To examine whether basal steroidogenesis is modulated by Ca(2+) and CaM levels in the testis of Mozambique tilapia (Oreochromis mossambicus) we have incubated testicular fragments in vitro under different conditions and analyzed steroid output. Calcium-free medium with or without EGTA did not affect testicular basal 11-ketotestosterone (11-KT) and testosterone (T) secretion. However, addition of 80microM the CaM inhibitor W7 significantly reduced basal 11-KT, T and androstenedione secretion. Interestingly, the decreased androgen production by 80microM of W7 was accompanied by increased 11-desoxicortisol output and by the activation of cortisol synthesis in the testis, the latter undetected in untreated tissues. However, production of 17,20alpha-dihydroxy-4-pregnen-3-one was unaltered by W7. This suggests that C17,20 desmolase, 21-hydroxylase and possibly 11beta-hydroxysteroid dehydrogenase are targets for CaM. In addition, androgen production was also found to be regulated by the level of cAMP since incubations with forskolin (FK) significantly increased 11-KT and T output. A cross-talk between the cAMP and Ca(2+)-CaM signaling pathways was detected since W7 administration also decreased FK stimulated androgen production. Altogether, these data show that both basal and cAMP stimulated androgen levels were modulated by intracellular Ca(2+)-dependent CaM and that possibly Ca(2+)-CaM determines the shift in steroidogenesis from C21 steroids to androgens.

A study on the suitability of the PTW microDiamond detector for kilovoltage x-ray beam dosimetry.

PubMed

Damodar, Joshita; Odgers, David; Pope, Dane; Hill, Robin

2018-05-01

Kilovoltage x-ray beams are widely used in treating skin cancers and in biological irradiators. In this work, we have evaluated four dosimeters (ionization chambers and solid state detectors) in their suitability for relative dosimetry of kilovoltage x-ray beams in the energy range of 50 - 280kVp. The solid state detectors, which have not been investigated with low energy x-rays, were the PTW 60019 microDiamond synthetic diamond detector and the PTW 60012 diode. The two ionization chambers used were the PTW Advanced Markus parallel plate chamber and the PTW PinPoint small volume chamber. For each of the dosimeters, percentage depth doses were measured in water over the full range of x-ray beams and for field sizes ranging from 2cm diameter to 12 × 12cm. In addition, depth doses were measured for a narrow aperture (7mm diameter) using the PTW microDiamond detector. For comparison, the measured data was compared with Monte Carlo calculated doses using the EGSnrc Monte Carlo package. The depth dose results indicate that the Advanced Markus parallel plate and PinPoint ionization chambers were suitable for depth dose measurements in the beam quality range with an uncertainty of less than 3%, including in the regions closer to the surface of the water as compared with Monte Carlo depth dose data for all six energy beams. The response of the PTW Diode E detector was accurate to within 4% for all field sizes in the energy range of 50-125kVp but showed larger variations for higher energies of up to 12% with the 12 × 12cm field size. In comparison, the microDiamond detector had good agreement over all energies for both smaller and larger field sizes generally within 1% as compared to the Advanced Markus chamber field and Monte Carlo calculations. The only exceptions were in measuring the dose at the surface of the water phantom where larger differences were found. For the 7mm diameter field, the agreement between the microDiamond detector and Monte Carlo calculations was good being better than 1% except at the surface. Based on these results, the PTW microDiamond detector has shown to be a suitable detector for relative dosimetry of low energy x-ray beams over a wide range of x-ray beam energies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multi Response Optimization of Laser Micro Marking Process:A Grey- Fuzzy Approach

NASA Astrophysics Data System (ADS)

Shivakoti, I.; Das, P. P.; Kibria, G.; Pradhan, B. B.; Mustafa, Z.; Ghadai, R. K.

2017-07-01

The selection of optimal parametric combination for efficient machining has always become a challenging issue for the manufacturing researcher. The optimal parametric combination always provides a better machining which improves the productivity, product quality and subsequently reduces the production cost and time. The paper presents the hybrid approach of Grey relational analysis and Fuzzy logic to obtain the optimal parametric combination for better laser beam micro marking on the Gallium Nitride (GaN) work material. The response surface methodology has been implemented for design of experiment considering three parameters with their five levels. The parameter such as current, frequency and scanning speed has been considered and the mark width, mark depth and mark intensity has been considered as the process response.

It may be possible to use Microscopic Black Holes as a Propulsion Beam

NASA Astrophysics Data System (ADS)

Kriske, Richard

2017-04-01

Several years ago during the commissioning of the LHC, the question as to whether a miniature Black Hole would be formed, and what to do with it if it was, came up as a legitimate topic of discussion. It was calculated at that time that although it was possible, the possibility was extremely small, and it would evaporate quickly, and would be safely ejected into space, as its mass would be so great as to simply continue along its inertial path, out the end of the circular LHC accelerator. New improvements to the LHC are the increase in energy to about 15 TEV. Linear accelerators, such as the ILC, claim to be able to produce much higher TEV, as they collide electrons and positrons, as opposed to Protons, as does the LHC. This author has heard incredible numbers, such as 250 TEV, with a beam current of 1 Amp. With this incredible increase in Energy and Current, one could turn the Black Hole investigation around, and try to determine how one could produce a steady stream of Microscopic Black Holes. A Black Hole machine. When the Black Holes evaporate do they expand, space in space time. Would the old theory of expanding space behind a craft warp space, and enable the craft to exceed the speed of light. The warp theory was proposed before Star Trek, is it now feasible to prove?

A Rapid Phenotypic Whole Cell Screening Approach for the Identification of Small Molecule Inhibitors that Counter Beta-lactamase Resistance in Pseudomonas aeruginosa

PubMed Central

Collia, Deanna; Bannister, Thomas D.; Tan, Hao; Jin, Shouguang; Langaee, Taimour; Shumate, Justin; Scampavia, Louis; Spicer, Timothy P.

2017-01-01

Pseudomonas aeruginosa is an opportunistic human pathogen which is prevalent in hospitals and continues to develop resistance to multiple classes of antibiotics. Historically, β-lactam antibiotics have been the first line of therapeutic defense. However, the emergence of multidrug-resistant (MDR) strains of P. aeruginosa, such as AmpC β-lactamase overproducing mutants, limits the effectiveness of current antibiotics. Among AmpC hyper producing clinical isolates, inactivation of AmpG, which is essential for the expression of AmpC, increases bacterial sensitivity to β-lactam antibiotics. We hypothesize that inhibition of AmpG activity will enhance the efficacy of β-lactams against P. aeruginosa. Here, using a highly drug resistant AmpC inducible laboratory strain PAO1, we describe an ultra-high throughput whole cell turbidity assay designed to identify small molecule inhibitors of the AmpG. We screened 645K compounds to identify compounds with the ability to inhibit bacterial growth in the presence of Cefoxitin; an AmpC inducer, and identified 2,663 inhibitors which were also tested in the absence of Cefoxitin to determine AmpG specificity. The Z′ and S:B were robust at 0.87 ± 0.05 and 2.2 ± 0.2, respectively. Through a series of secondary and tertiary studies, including a novel luciferase based counterscreen, we ultimately identified 8 potential AmpG specific inhibitors. PMID:28850797

A Rapid Phenotypic Whole-Cell Screening Approach for the Identification of Small-Molecule Inhibitors That Counter β-Lactamase Resistance in Pseudomonas aeruginosa.

PubMed

Collia, Deanna; Bannister, Thomas D; Tan, Hao; Jin, Shouguang; Langaee, Taimour; Shumate, Justin; Scampavia, Louis; Spicer, Timothy P

2018-01-01

Pseudomonas aeruginosa is an opportunistic human pathogen that is prevalent in hospitals and continues to develop resistance to multiple classes of antibiotics. Historically, β-lactam antibiotics have been the first line of therapeutic defense. However, the emergence of multidrug-resistant (MDR) strains of P. aeruginosa, such as AmpC β-lactamase overproducing mutants, limits the effectiveness of current antibiotics. Among AmpC hyperproducing clinical isolates, inactivation of AmpG, which is essential for the expression of AmpC, increases bacterial sensitivity to β-lactam antibiotics. We hypothesize that inhibition of AmpG activity will enhance the efficacy of β-lactams against P. aeruginosa. Here, using a highly drug-resistant AmpC-inducible laboratory strain PAO1, we describe an ultra-high-throughput whole-cell turbidity assay designed to identify small-molecule inhibitors of the AmpG. We screened 645,000 compounds to identify compounds with the ability to inhibit bacterial growth in the presence of cefoxitin, an AmpC inducer, and identified 2663 inhibitors that were also tested in the absence of cefoxitin to determine AmpG specificity. The Z' and signal-to-background ratio were robust at 0.87 ± 0.05 and 2.2 ± 0.2, respectively. Through a series of secondary and tertiary studies, including a novel luciferase-based counterscreen, we ultimately identified eight potential AmpG-specific inhibitors.

TU-F-BRE-08: Significant Variations in Measured Small Cone Output Factor for FFF Beams

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

Sudhyadhom, A; Ma, L; Kirby, N

2014-06-15

Purpose: To evaluate the measurement accuracy of several dosimeters for small cone output factors in two SRS/SBRT dedicated systems with Flattening Filter Free (FFF) beams: a Varian TrueBeam STx (TB) and an Accuray CyberKnife VSI (CK). Output factors (OFs) were measured for both machines and for CK, compared against a Monte Carlo model. Methods: Dose measurements were taken using three different FFF beams (TB 6XFFF, TB 10XFFF, and CK 6XFFF). Three commonly used types of dosimeters were examined in this work: a micro-ion chamber (Exradin A16), two shielded diodes (PTW TN60008 and PTW TN60017), and radiochromic film (Gafchromic EBT2). Measuredmore » OFs from these dosimeters were compared with each other and OFs measured with an Exradin W1 scintillator. Monte Carlo determined correction factors for the CK beam for the micro-ion chamber and diodes were applied to the respective OF measurements and compared against scintillator measured OFs corrected for volume averaging. Results: OFs measured for the smallest fields using the micro-ion chamber, diodes, scintillator, and film varied substantially (with up to a 16% difference between dosimeters). Micro-ion chamber and film OF measurements were up to 9% and 10%, respectively, lower than scintillator measurements for the smallest fields. OF measurements by diode were up to 6% greater than scintillator measurements for the smallest fields. With correction factors, the micro-ion chamber and diode measured OFs showed good agreement with scintillator measured OFs for the CK 6XFFF beam (within 3% and 1.5%, respectively). Conclusion: Uncorrected small field OFs vary significantly with dosimeter. The accuracy of scintillator measurements for small field OFs may be greater than the other dosimeters studied in this work (when uncorrected). Measurements involving EBT2 film may Result in lower accuracy for smaller fields (less than 10mm). Care should be taken in the choice of the dosimeter used for small field OF measurements.« less

A hollow cathode neutralizer for a 30-cm diameter bombardment thruster

NASA Technical Reports Server (NTRS)

Bechtel, R. T.

1973-01-01

Recent improvements in overall thrustor performance have imposed new constraints on neutralizer performance. The use of compensated grid extraction system requires a re-evaluation of neutralizer position. In addition a suitable control logic for the neutralizer has proven difficult. A series of tests were conducted to determine what effect neutralizer cathode geometry has on performance. The parameters investigated included orifice diameter and length, and cathode diameter. Similar tests investigated open and enclosed keeper geometries. Neutralizer position tests with compensated grids suggest positions approximately 10 cm from the accelerator and radially out of the beam envelope should result in satisfactory performance and long life. Finally operation at keeper currents of 1.5 amp has resulted in lower total neutralizer power, the elimination of tip heater power, and suitable closed loop control of the neutralizer vaporizer.

Ion Beam Etching: Replication of Micro Nano-structured 3D Stencil Masks

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

Weber, Patrick; Guibert, Edouard; Mikhailov, Serguei

2009-03-10

Ion beam LIGA allows the etching of 3D nano-structures by direct writing with a nano-sized beam. However, this is a relatively time consuming process. We propose here another approach for etching structures on large surfaces and faster, compared to the direct writing process. This approach consists of replicating 3D structured masks, by scanning an unfocused ion beam. A polymer substrate is placed behind the mask, as in UV photolithography. But the main advantage is that the 3D structure of the mask can be replicated into the polymer. For that purpose, the masks (developped at LMIS1, EPFL) are made of amore » silicon nitride membrane 100 nm thick, on which 3D gold structures up to 200 nm thick, are deposited. The 3D Au structures are made with the nanostencil method, based on successive gold deposition. The IMA institute, from HE-Arc, owns a High Voltage Engineering 1.7 MV Tandetron with both solid and gaseous negative ion sources, able to generate ions from almost every chemical element in a broad range of energies comprised between 400 keV and 6.8 MeV. The beam composition and energy are chosen in such a way, that ions lose a significant fraction of their energy when passing through the thickest regions of the mask. Ions passing through thinner regions of the mask loose a smaller fraction of their energy and etch the polymer with larger thicknesses, allowing a replication of the mask into the polymer. For our trials, we have used a carbon beam with an energy of 500 keV. The beam was focussed to a diameter of 5 mm with solid slits, in order to avoid border effects and thus ensure a homogeneous dose distribution on the beam diameter. The feasibility of this technique has been demonstrated, allowing industrial applications for micro-mould fabrication, micro-fluidics and micro-optics.« less

microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients.

PubMed

van Agthoven, Ton; Eijkenboom, Wil M H; Looijenga, Leendert H J

2017-08-01

α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up. We investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers. At primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma. The ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.

Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design

PubMed Central

Li, Jianguo; Koh, Jun-Jie; Liu, Shouping; Lakshminarayanan, Rajamani; Verma, Chandra S.; Beuerman, Roger W.

2017-01-01

Antimicrobial peptides (AMPs) are promising next generation antibiotics that hold great potential for combating bacterial resistance. AMPs can be both bacteriostatic and bactericidal, induce rapid killing and display a lower propensity to develop resistance than do conventional antibiotics. Despite significant progress in the past 30 years, no peptide antibiotic has reached the clinic yet. Poor understanding of the action mechanisms and lack of rational design principles have been the two major obstacles that have slowed progress. Technological developments are now enabling multidisciplinary approaches including molecular dynamics simulations combined with biophysics and microbiology toward providing valuable insights into the interactions of AMPs with membranes at atomic level. This has led to increasingly robust models of the mechanisms of action of AMPs and has begun to contribute meaningfully toward the discovery of new AMPs. This review discusses the detailed action mechanisms that have been put forward, with detailed atomistic insights into how the AMPs interact with bacterial membranes. The review further discusses how this knowledge is exploited toward developing design principles for novel AMPs. Finally, the current status, associated challenges, and future directions for the development of AMP therapeutics are discussed. PMID:28261050

Diversity, evolution and medical applications of insect antimicrobial peptides

PubMed Central

Mylonakis, Eleftherios; Podsiadlowski, Lars; Muhammed, Maged

2016-01-01

Antimicrobial peptides (AMPs) are short proteins with antimicrobial activity. A large portion of known AMPs originate from insects, and the number and diversity of these molecules in different species varies considerably. Insect AMPs represent a potential source of alternative antibiotics to address the limitation of current antibiotics, which has been caused by the emergence and spread of multidrug-resistant pathogens. To get more insight into AMPs, we investigated the diversity and evolution of insect AMPs by mapping their phylogenetic distribution, allowing us to predict the evolutionary origins of selected AMP families and to identify evolutionarily conserved and taxon-specific families. Furthermore, we highlight the use of the nematode Caenorhabditis elegans as a whole-animal model in high-throughput screening methods to identify AMPs with efficacy against human pathogens, including Acinetobacter baumanii and methicillin-resistant Staphylococcus aureus. We also discuss the potential medical applications of AMPs, including their use as alternatives for conventional antibiotics in ectopic therapies, their combined use with antibiotics to restore the susceptibility of multidrug-resistant pathogens, and their use as templates for the rational design of peptidomimetic drugs that overcome the disadvantages of therapeutic peptides. The article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’. PMID:27160593

Antimicrobial Activity of Cationic Antimicrobial Peptides against Gram-Positives: Current Progress Made in Understanding the Mode of Action and the Response of Bacteria.

PubMed

Omardien, Soraya; Brul, Stanley; Zaat, Sebastian A J

2016-01-01

Antimicrobial peptides (AMPs) have been proposed as a novel class of antimicrobials that could aid the fight against antibiotic resistant bacteria. The mode of action of AMPs as acting on the bacterial cytoplasmic membrane has often been presented as an enigma and there are doubts whether the membrane is the sole target of AMPs. Progress has been made in clarifying the possible targets of these peptides, which is reported in this review with as focus gram-positive vegetative cells and spores. Numerical estimates are discussed to evaluate the possibility that targets, other than the membrane, could play a role in susceptibility to AMPs. Concerns about possible resistance that bacteria might develop to AMPs are addressed. Proteomics, transcriptomics, and other molecular techniques are reviewed in the context of explaining the response of bacteria to the presence of AMPs and to predict what resistance strategies might be. Emergent mechanisms are cell envelope stress responses as well as enzymes able to degrade and/or specifically bind (and thus inactivate) AMPs. Further studies are needed to address the broadness of the AMP resistance and stress responses observed.

Antimicrobial Activity of Cationic Antimicrobial Peptides against Gram-Positives: Current Progress Made in Understanding the Mode of Action and the Response of Bacteria

PubMed Central

Omardien, Soraya; Brul, Stanley; Zaat, Sebastian A. J.

2016-01-01

Antimicrobial peptides (AMPs) have been proposed as a novel class of antimicrobials that could aid the fight against antibiotic resistant bacteria. The mode of action of AMPs as acting on the bacterial cytoplasmic membrane has often been presented as an enigma and there are doubts whether the membrane is the sole target of AMPs. Progress has been made in clarifying the possible targets of these peptides, which is reported in this review with as focus gram-positive vegetative cells and spores. Numerical estimates are discussed to evaluate the possibility that targets, other than the membrane, could play a role in susceptibility to AMPs. Concerns about possible resistance that bacteria might develop to AMPs are addressed. Proteomics, transcriptomics, and other molecular techniques are reviewed in the context of explaining the response of bacteria to the presence of AMPs and to predict what resistance strategies might be. Emergent mechanisms are cell envelope stress responses as well as enzymes able to degrade and/or specifically bind (and thus inactivate) AMPs. Further studies are needed to address the broadness of the AMP resistance and stress responses observed. PMID:27790614

Integrated Micro-Optics for Microfluidic Detection.

PubMed

Kazama, Yuto; Hibara, Akihide

2016-01-01

A method of embedding micro-optics into a microfluidic device was proposed and demonstrated. First, the usefulness of embedded right-angle prisms was demonstrated in microscope observation. Lateral-view microscopic observation of an aqueous dye flow in a 100-μm-sized microchannel was demonstrated. Then, the embedded right-angle prisms were utilized for multi-beam laser spectroscopy. Here, crossed-beam thermal lens detection of a liquid sample was applied to glucose detection.

Spatiotemporal regulation of cAMP signaling controls the human trophoblast fusion

PubMed Central

Gerbaud, Pascale; Taskén, Kjetil; Pidoux, Guillaume

2015-01-01

During human placentation, mononuclear cytotrophoblasts fuse to form multinucleated syncytia ensuring hormonal production and nutrient exchanges between the maternal and fetal circulation. Syncytial formation is essential for the maintenance of pregnancy and for fetal growth. The cAMP signaling pathway is the major route to trigger trophoblast fusion and its activation results in phosphorylation of specific intracellular target proteins, in transcription of fusogenic genes and assembly of macromolecular protein complexes constituting the fusogenic machinery at the plasma membrane. Specificity in cAMP signaling is ensured by generation of localized pools of cAMP controlled by cAMP phosphodiesterases (PDEs) and by discrete spatial and temporal activation of protein kinase A (PKA) in supramolecular signaling clusters inside the cell organized by A-kinase-anchoring proteins (AKAPs) and by organization of signal termination by protein phosphatases (PPs). Here we present original observations on the available components of the cAMP signaling pathway in the human placenta including PKA, PDE, and PP isoforms as well as AKAPs. We continue to discuss the current knowledge of the spatiotemporal regulation of cAMP signaling triggering trophoblast fusion. PMID:26441659

Dark matter beams at LBNF

DOE PAGES

Coloma, Pilar; Dobrescu, Bogdan A.; Frugiuele, Claudia; ...

2016-04-08

High-intensity neutrino beam facilities may produce a beam of light dark matter when protons strike the target. Searches for such a dark matter beam using its scattering in a nearby detector must overcome the large neutrino background. We characterize the spatial and energy distributions of the dark matter and neutrino beams, focusing on their differences to enhance the sensitivity to dark matter. We find that a dark matter beam produced by a Zmore » $$^{'}$$ boson in the GeV mass range is both broader and more energetic than the neutrino beam. The reach for dark matter is maximized for a detector sensitive to hard neutral-current scatterings, placed at a sizable angle off the neutrino beam axis. In the case of the Long-Baseline Neutrino Facility (LBNF), a detector placed at roughly 6 degrees off axis and at a distance of about 200 m from the target would be sensitive to Z$$^{'}$$ couplings as low as 0.05. This search can proceed symbiotically with neutrino measurements. We also show that the MiniBooNE and MicroBooNE detectors, which are on Fermilab’s Booster beamline, happen to be at an optimal angle from the NuMI beam and could perform searches with existing data. As a result, this illustrates potential synergies between LBNF and the short-baseline neutrino program if the detectors are positioned appropriately.« less

Micro-Photoluminescence (micro-PL) Study of Core-Shell GaAs/GaAsSb Nanowires Grown by Self-Assisted Molecular Beam Epitaxy

DTIC Science & Technology

2015-06-18

public release; distribution is unlimited. Micro-Photoluminescence (micro-PL) Study of Core-Shell GaAs/GaAsSb Nanowires grown by Self-Assisted Molecular...U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 GaAsSb, Core Shell Nanowires , Micro Photoluminescence...University 1601 East Market Street Greensboro, NC 27411 -0001 ABSTRACT Micro-Photoluminescence (micro-PL) Study of Core-Shell GaAs/GaAsSb Nanowires grown by

Three-dimensional evaluation of human jaw bone microarchitecture: correlation between the microarchitectural parameters of cone beam computed tomography and micro-computer tomography.

PubMed

Kim, Jo-Eun; Yi, Won-Jin; Heo, Min-Suk; Lee, Sam-Sun; Choi, Soon-Chul; Huh, Kyung-Hoe

2015-12-01

To evaluate the potential feasibility of cone beam computed tomography (CBCT) in the assessment of trabecular bone microarchitecture. Sixty-eight specimens from four pairs of human jaw were scanned using both micro-computed tomography (micro-CT) of 19.37-μm voxel size and CBCT of 100-μm voxel size. The correlation of 3-dimensional parameters between CBCT and micro-CT was evaluated. All parameters, except bone-specific surface and trabecular thickness, showed linear correlations between the 2 imaging modalities (P < .05). Among the parameters, bone volume, percent bone volume, trabecular separation, and degree of anisotropy (DA) of CBCT images showed strong correlations with those of micro-CT images. DA showed the strongest correlation (r = 0.693). Most microarchitectural parameters from CBCT were correlated with those from micro-CT. Some microarchitectural parameters, especially DA, could be used as strong predictors of bone quality in the human jaw. Copyright © 2015 Elsevier Inc. All rights reserved.

Atmosphere, Magnetosphere and Plasmas in Space (AMPS). Spacelab payload definition study. Volume 7, book 3: Supporting Research and Technology (SR and T) report

NASA Technical Reports Server (NTRS)

1976-01-01

The items identified as required to support the AMPS mission and requiring SR and T support and further work are: (1) a general purpose Experiment Pointing Mount; (2) a technique for measuring the attitude of the pallet-mounted or deployed experiments; (3) the development of a common optics cryogenically cooled interferometer spectrometer; (4) the development of a differential absorption lidar system for the measurement of ozone densitites in the earth's atmosphere; (5) the development of dc to dc power processors which are capable of converting energy stored in a capacitor system at 500 V to energy supplied to equipment operating at 40 kV and at 20 kW (eventually up to 100 kW); and (6) the development of a magnetic or possibly electrostatic deflection system capable of bending the beam of an electron accelerator. A data sheet is included for each item, briefly describing the background and need for each item, and the general objectives of the required development, and identifying the schedule requirements in support of the AMPS program.

Region-of-interest image reconstruction in circular cone-beam microCT

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

Cho, Seungryong; Bian, Junguo; Pelizzari, Charles A.

2007-12-15

Cone-beam microcomputed tomography (microCT) is one of the most popular choices for small animal imaging which is becoming an important tool for studying animal models with transplanted diseases. Region-of-interest (ROI) imaging techniques in CT, which can reconstruct an ROI image from the projection data set of the ROI, can be used not only for reducing imaging-radiation exposure to the subject and scatters to the detector but also for potentially increasing spatial resolution of the reconstructed images. Increasing spatial resolution in microCT images can facilitate improved accuracy in many assessment tasks. A method proposed previously for increasing CT image spatial resolutionmore » entails the exploitation of the geometric magnification in cone-beam CT. Due to finite detector size, however, this method can lead to data truncation for a large geometric magnification. The Feldkamp-Davis-Kress (FDK) algorithm yields images with artifacts when truncated data are used, whereas the recently developed backprojection filtration (BPF) algorithm is capable of reconstructing ROI images without truncation artifacts from truncated cone-beam data. We apply the BPF algorithm to reconstructing ROI images from truncated data of three different objects acquired by our circular cone-beam microCT system. Reconstructed images by use of the FDK and BPF algorithms from both truncated and nontruncated cone-beam data are compared. The results of the experimental studies demonstrate that, from certain truncated data, the BPF algorithm can reconstruct ROI images with quality comparable to that reconstructed from nontruncated data. In contrast, the FDK algorithm yields ROI images with truncation artifacts. Therefore, an implication of the studies is that, when truncated data are acquired with a configuration of a large geometric magnification, the BPF algorithm can be used for effective enhancement of the spatial resolution of a ROI image.« less

Progress on Background-Limited Membrane-Isolated TES Bolometers for Far-IR/Submillimeter Spectroscopy

NASA Technical Reports Server (NTRS)

Kenyon, M.; Day, P. K.; Bradford, C. M.; Bock, J. J.; Leduc, H. G.

2006-01-01

To determine the lowest attainable phonon noise equivalent power (NEP) for membrane-isolation bolometers, we fabricated and measured the thermal conductance of suspended Si3N4 beams with different geometries via a noise thermometry technique. We measured beam cross-sectional areas ranging from 0.35 x 0.5 (micro)m(sup 2) to 135 x 1.0 (micro)m(sup 2) and beam lengths ranging from (micro)m to 8300 (micro)m. The measurements directly imply that membrane-isolation bolometers are capable of reaching a phonon noise equivalent power (NEP) of 4 x 10(sup -20)W/Hz(sup 1)/O . This NEP adequate for the Background-Limited Infrared-Submillimeter Spectrograph (BLISS) proposed for the Japanese SPICA observatory, and adequate for NASA's SAFIR observatory, a 10-meter, 4 K telescope to be deployed at L2. Further, we measured the heat capacity of a suspended Si3N4 membrane and show how this result implies that one can make membrane-isolation bolometers with a response time which is fast enough for BLISS.

Multiple Facets of cAMP Signalling and Physiological Impact: cAMP Compartmentalization in the Lung

PubMed Central

Oldenburger, Anouk; Maarsingh, Harm; Schmidt, Martina

2012-01-01

Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP) are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD). Characteristics of COPD are airway obstruction, airway inflammation and airway remodelling, processes encompassed by increased airway smooth muscle mass, epithelial changes, goblet cell and submucosal gland hyperplasia. In addition to inflammatory cells, airway smooth muscle cells and (myo)fibroblasts, epithelial cells underpin a variety of key responses in the airways such as inflammatory cytokine release, airway remodelling, mucus hypersecretion and airway barrier function. Cigarette smoke, being next to environmental pollution the main cause of COPD, is believed to cause epithelial hyperpermeability by disrupting the barrier function. Here we will focus on the most recent progress on compartmentalized signalling by cAMP. In addition to G protein-coupled receptors, adenylyl cyclases, cAMP-specific phospho-diesterases (PDEs) maintain compartmentalized cAMP signalling. Intriguingly, spatially discrete cAMP-sensing signalling complexes seem also to involve distinct members of the A-kinase anchoring (AKAP) superfamily and IQ motif containing GTPase activating protein (IQGAPs). In this review, we will highlight the interaction between cAMP and the epithelial barrier to retain proper lung function and to alleviate COPD symptoms and focus on the possible molecular mechanisms involved in this process. Future studies should include the development of cAMP-sensing multiprotein complex specific disruptors and/or stabilizers to orchestrate cellular functions. Compartmentalized cAMP signalling regulates important cellular processes in the lung and may serve as a therapeutic target. PMID:24281338

Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions.

PubMed

Schmidt, Martina; Dekker, Frank J; Maarsingh, Harm

2013-04-01

Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and gene transcription, is reflected by the award of five Nobel prizes. The discovery of Epac (exchange protein directly activated by cAMP) has ignited a new surge of cAMP-related research and has depicted novel cAMP properties independent of protein kinase A and cyclic nucleotide-gated channels. The multidomain architecture of Epac determines its activity state and allows cell-type specific protein-protein and protein-lipid interactions that control fine-tuning of pivotal biologic responses through the "old" second messenger cAMP. Compartmentalization of cAMP in space and time, maintained by A-kinase anchoring proteins, phosphodiesterases, and β-arrestins, contributes to the Epac signalosome of small GTPases, phospholipases, mitogen- and lipid-activated kinases, and transcription factors. These novel cAMP sensors seem to implement certain unexpected signaling properties of cAMP and thereby to permit delicate adaptations of biologic responses. Agonists and antagonists selective for Epac are developed and will support further studies on the biologic net outcome of the activation of Epac. This will increase our current knowledge on the pathophysiology of devastating diseases, such as diabetes, cognitive impairment, renal and heart failure, (pulmonary) hypertension, asthma, and chronic obstructive pulmonary disease. Further insights into the cAMP dynamics executed by the Epac signalosome will help to optimize the pharmacological treatment of these diseases.

The cyclic AMP cascade is altered in the fragile X nervous system.

PubMed

Kelley, Daniel J; Davidson, Richard J; Elliott, Jamie L; Lahvis, Garet P; Yin, Jerry C P; Bhattacharyya, Anita

2007-09-26

Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3', 5'-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling.

Radio constraints on the mass-loss rate of the Type Ia SN 2018gv

NASA Astrophysics Data System (ADS)

Ryder, S. D.; Lundqvist, P.; Perez-Torres, M. A.; Kundu, E.; Kool, E. C.; Bjornsson, C.-I.; Fransson, C.

2018-01-01

The young Type Ia SN 2018gv (ATel #11175, #11177) in the galaxy NGC 2525 has been observed with the Australia Telescope Compact Array (ATCA) at 5.5 and 9.0 GHz on 2018 Jan 18.6 UT. No radio emission was detected at the reported location, to a 3-sigma upper limit of 120 microJy/beam (5.5 GHz) and 30 microJy/beam (9.0 GHz).

Voltage-dependent Ca2+ release from the SR of feline ventricular myocytes is explained by Ca2+-induced Ca2+ release.

PubMed

Piacentino, V; Dipla, K; Gaughan, J P; Houser, S R

2000-03-15

1. Direct voltage-gated (voltage-dependent Ca2+ release, VDCR) and Ca2+ influx-gated (Ca2+-induced Ca2+ release, CICR) sarcoplasmic reticulum (SR) Ca2+ release were studied in feline ventricular myocytes. The voltage-contraction relationship predicted by the VDCR hypothesis is sigmoidal with large contractions at potentials near the Ca2+ equilibrium potential (ECa). The relationship predicted by the CICR hypothesis is bell-shaped with no contraction at ECa. 2. The voltage dependence of contraction was measured in ventricular myocytes at physiological temperature (37 C), resting membrane potential and physiological [K+]. Experiments were performed with cyclic adenosine 3',5'-monophosphate (cAMP) in the pipette or in the presence of the beta-adrenergic agonist isoproterenol (isoprenaline; ISO). 3. The voltage-contraction relationship was bell-shaped in Na+-free solutions (to eliminate the Na+ current and Na+-Ca2+ exchange, NCX) but the relationship was broader than the L-type Ca2+ current (ICa,L)-voltage relationship. 4. Contractions induced with voltage steps from normal resting potentials to -40 mV are thought to represent VDCR rather than CICR. We found that cAMP and ISO shifted the voltage dependence of ICa,L activation to more negative potentials so that ICa,L was always present with steps to -40 mV. ICa,L at -40 mV inactivated when the holding potential was decreased (VŁ = -57.8 +/- 0.49 mV). 5. ISO increased inward current, SR Ca2+ load and contraction in physiological [Na+] and a broad bell-shaped voltage-contraction relationship was observed. Inhibition of reverse-mode NCX, decreasing ICa,L and decreasing SR Ca2+ loading all decreased contractions at strongly positive potentials near ECa. 6. The voltage-contraction relationship in 200 microM cadmium (Cd2+) was bell-shaped, supporting a role of ICa,L rather than VDCR. 7. All results could be accounted for by the CICR hypothesis, and many results exclude the VDCR hypothesis.

The pro-apoptotic protein Bim is a convergence point for cAMP/protein kinase A- and glucocorticoid-promoted apoptosis of lymphoid cells.

PubMed

Zhang, Lingzhi; Insel, Paul A

2004-05-14

The mechanisms by which cAMP mediates apoptosis are not well understood. In the current studies, we used wild-type (WT) S49 T-lymphoma cells and the kin(-) variant (which lacks protein kinase A (PKA)) to examine cAMP/PKA-mediated apoptosis. The cAMP analog, 8-CPT-cAMP, increased phosphorylation of the cAMP response element-binding protein (CREB), activated caspase-3, and induced apoptosis in WT but not in kin(-) S49 cells. Using an array of 96 apoptosis-related genes, we found that treatment of WT cells with 8-CPT-cAMP for 24 h induced expression of mRNA for the pro-apoptotic gene, Bim. Real-time PCR analysis indicated that 8-CPT-cAMP increased Bim RNA in WT cells in <2 h and maintained this increase for >24 h. Bim protein expression increased in WT but not kin(-) cells treated with 8-CPT-cAMP or with the beta-adrenergic receptor agonist isoproterenol. Both apoptosis and Bim expression were reversible with removal of 8-CPT-cAMP after <6 h. The glucocorticoid dexamethasone also promoted apoptosis and Bim expression in S49 cells. In contrast, both UV light and anti-mouse Fas monoclonal antibody promoted apoptosis in S49 cells but did not induce Bim expression. 8-CPT-cAMP also induced Bim expression and enhanced dexamethasone-promoted apoptosis in human T-cell leukemia CEM-C7-14 (glucocorticoid-sensitive) and CEM-C1-15 (glucocorticoid-resistant) cells; increased Bim expression in 8-CPT-cAMP-treated CEM-C1-15 cells correlated with conversion of the cells from resistance to sensitivity to glucocorticoid-promoted apoptosis. Induction of Bim appears to be a key event in cAMP-promoted apoptosis in both murine and human T-cell lymphoma and leukemia cells and thus appears to be a convergence point for the killing of such cells by glucocorticoids and agents that elevate cAMP.

Fiber optic engine for micro projection display.

PubMed

Arabi, Hesam Edin; An, Sohee; Oh, Kyunghwan

2010-03-01

A novel compact optical engine for a micro projector display is experimentally demonstrated, which is composed of RGB light sources, a tapered 3 x 1 Fiber Optic Color Synthesizer (FOCS) along with a fiberized ball-lens, and a two dimensional micro electromechanical scanning mirror. In the proposed optical engine, we successfully employed an all-fiber beam shaping technique combining optical fiber taper and fiberized ball lens that can render a narrow beam and enhance the resolution of the screened image in the far field. Optical performances of the proposed device assembly are investigated in terms of power loss, collimating strength of the collimator assembly, and color gamut of the output.

A Computational approach in optimizing process parameters of GTAW for SA 106 Grade B steel pipes using Response surface methodology

NASA Astrophysics Data System (ADS)

Sumesh, A.; Sai Ramnadh, L. V.; Manish, P.; Harnath, V.; Lakshman, V.

2016-09-01

Welding is one of the most common metal joining techniques used in industry for decades. As in the global manufacturing scenario the products should be more cost effective. Therefore the selection of right process with optimal parameters will help the industry in minimizing their cost of production. SA 106 Grade B steel has a wide application in Automobile chassis structure, Boiler tubes and pressure vessels industries. Employing central composite design the process parameters for Gas Tungsten Arc Welding was optimized. The input parameters chosen were weld current, peak current and frequency. The joint tensile strength was the response considered in this study. Analysis of variance was performed to determine the statistical significance of the parameters and a Regression analysis was performed to determine the effect of input parameters over the response. From the experiment the maximum tensile strength obtained was 95 KN reported for a weld current of 95 Amp, frequency of 50 Hz and peak current of 100 Amp. With an aim of maximizing the joint strength using Response optimizer a target value of 100 KN is selected and regression models were optimized. The output results are achievable with a Weld current of 62.6148 Amp, Frequency of 23.1821 Hz, and Peak current of 65.9104 Amp. Using Die penetration test the weld joints were also classified in to 2 categories as good weld and weld with defect. This will also help in getting a defect free joint when welding is performed using GTAW process.

Electron Beam Diagnostics Of The JLAB UV FEL

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

Evtushenko, Pavel; Benson, Stephen; Biallas, George

2011-03-01

In this contribution we describe various systems and aspects of the electron beam diagnostics of the JLab UV FEL. The FEL is installed on a new bypass beam line at the existing 10 kW IR Upgrade FEL. Here, we describe a set of the following systems. A combination of OTR and phosphor viewers is used for measurements of the transverse beam profile, transverse emittance, and Twiss parameters. This system is also used for alignment of the optical cavity of the UV oscillator and to ensure the overlap between the electron beam and optical mode in the FEL wiggler. A systemmore » of beam position monitors equipped with log-amp based BPM electronics. Bunch length on the order of 120 fs RMS is measured with the help of a modified Martin-Puplett interferometer. The longitudinal transfer function measurement system is used to set up bunch compression in an optimal way, such that the LINAC RF curvature is compensated using only higher order magnetic elements of the beam transport. This set of diagnostic systems made a significant contribution in achieving first lasing of the FEL after only about 60 hours of beam operation.« less

Sodium and calcium currents in neuroblastoma x glioma hybrid cells before and after morphological differentiation by dibutyryl cyclic AMP.

PubMed

Bodewei, R; Hering, S; Schubert, B; Wollenberger, A

1985-04-01

Sodium and calcium inward currents (INa and ICa) were measured in neuroblastoma X glioma hybrid cells of clones 108CC5 and 108CC15 by a single suction pipette method for internal perfusion and voltage clamp. Morphologically undifferentiated, exponentially growing cells were compared with cells differentiated by cultivation with 1 mmol/l dibutyryl cyclic AMP. Outward currents were eliminated by perfusing the cells with a K+-free solution. Voltage dependence and ion selectivity as well as steady state inactivation characteristics of INa and ICa resembled those of differentiated mouse neuroblastoma cells, clone N1E-115 (Moolenaar and Spector 1978, 1979). These parameters were identical in undifferentiated and differentiated cells of both clones. After differentiation the average density of the peak sodium and calcium currents was increased two and four-fold, respectively, in both cell lines. Our data indicate that exponentially growing, morphologically undifferentiated 108CC5 and 108CC15 neuroblastoma X glioma hybrid cells possess functional Na+ and Ca2+ channels undistinguishable from those of non-proliferating cells of these clones differentiated morphologically by treatment with dibutyryl cyclic AMP. That Na+ and Ca2+ spikes were not detected by other authors in these cells prior to morphological differentiation by dibutyryl cyclic AMP may be attributed to the fact that at the low resting membrane potential measured the Na+ and Ca2+ channels are inactivated.

Surface hardening of 30CrMnSiA steel using continuous electron beam

NASA Astrophysics Data System (ADS)

Fu, Yulei; Hu, Jing; Shen, Xianfeng; Wang, Yingying; Zhao, Wansheng

2017-11-01

30CrMnSiA high strength low alloy (HSLA) carbon structural steel is typically applied in equipment manufacturing and aerospace industries. In this work, the effects of continuous electron beam treatment on the surface hardening and microstructure modifications of 30CrMnSiA are investigated experimentally via a multi-purpose electron beam machine Pro-beam system. Micro hardness value in the electron beam treated area shows a double to triple increase, from 208 HV0.2 on the base metal to 520 HV0.2 on the irradiated area, while the surface roughness is relatively unchanged. Surface hardening parameters and mechanisms are clarified by investigation of the microstructural modification and the phase transformation both pre and post irradiation. The base metal is composed of ferrite and troostite. After continuous electron beam irradiation, the micro structure of the electron beam hardened area is composed of acicular lower bainite, feathered upper bainite and part of lath martensite. The optimal input energy density for 30CrMnSiA steel in this study is of 2.5 kJ/cm2 to attain the proper hardened depth and peak hardness without the surface quality deterioration. When the input irradiation energy exceeds 2.5 kJ/cm2 the convective mixing of the melted zone will become dominant. In the area with convective mixing, the cooling rate is relatively lower, thus the micro hardness is lower. The surface quality will deteriorate. Chemical composition and surface roughness pre and post electron beam treatment are also compared. The technology discussed give a picture of the potential of electron beam surface treatment for improving service life and reliability of the 30CrMnSiA steel.

17beta-estradiol potently suppresses cAMP-induced insulin-like growth factor-I gene activation in primary rat osteoblast cultures

NASA Technical Reports Server (NTRS)

McCarthy, T. L.; Ji, C.; Shu, H.; Casinghino, S.; Crothers, K.; Rotwein, P.; Centrella, M.

1997-01-01

Insulin-like growth factor-I (IGF-I) is a key factor in bone remodeling. In osteoblasts, IGF-I synthesis is enhanced by parathyroid hormone and prostaglandin E2 (PGE2) through cAMP-activated protein kinase. In rats, estrogen loss after ovariectomy leads to a rise in serum IGF-I and an increase in bone remodeling, both of which are reversed by estrogen treatment. To examine estrogen-dependent regulation of IGF-I expression at the molecular level, primary fetal rat osteoblasts were co-transfected with the estrogen receptor (hER, to ensure active ER expression), and luciferase reporter plasmids controlled by promoter 1 of the rat IGF-I gene (IGF-I P1), used exclusively in these cells. As reported, 1 microM PGE2 increased IGF-I P1 activity by 5-fold. 17beta-Estradiol alone had no effect, but dose-dependently suppressed the stimulatory effect of PGE2 by up to 90% (ED50 approximately 0.1 nM). This occurred within 3 h, persisted for at least 16 h, required ER, and appeared specific, since 17alpha-estradiol was 100-300-fold less effective. By contrast, 17beta-estradiol stimulated estrogen response element (ERE)-dependent reporter expression by up to 10-fold. 17beta-Estradiol also suppressed an IGF-I P1 construct retaining only minimal promoter sequence required for cAMP-dependent gene activation, but did not affect the 60-fold increase in cAMP induced by PGE2. There is no consensus ERE in rat IGF-I P1, suggesting novel downstream interactions in the cAMP pathway that normally enhances IGF-I expression in skeletal cells. To explore this, nuclear extract from osteoblasts expressing hER were examined by electrophoretic mobility shift assay using the atypical cAMP response element in IGF-I P1. Estrogen alone did not cause DNA-protein binding, while PGE2 induced a characteristic gel shift complex. Co-treatment with both hormones caused a gel shift greatly diminished in intensity, consistent with their combined effects on IGF-I promoter activity. Nonetheless, hER did not bind IGF-I cAMP response element or any adjacent sequences. These results provide new molecular evidence that estrogen may temper the biological effects of hormones acting through cAMP to regulate skeletal IGF-I expression and activity.

Micro And Nanostructured Materials For Fluid And Ion Transport For Miniaturized Applications

DTIC Science & Technology

2016-06-08

micromachined tip. The setup is shown in Figure 7(a). The RPA instrument consists of a Faraday cup collector and a set of grids placed in between the...collector. Therefore, by varying the retarding potential and measuring the current arriving to the Faraday cup, it is possible to obtain the beam energy...distribution. The instrument consists of seven grids followed by a Faraday cup. The first grid is a 90% transparent tungsten mesh, which is grounded

Functional desensitization to isoproterenol without reducing cAMP production in canine failing cardiocytes.

PubMed

Laurent, C E; Cardinal, R; Rousseau, G; Vermeulen, M; Bouchard, C; Wilkinson, M; Armour, J A; Bouvier, M

2001-02-01

To corroborate alterations in the functional responses to beta-adrenergic receptor (beta-AR) stimulation with changes in beta-AR signaling in failing cardiomyocytes, contractile and L-type Ca(2+) current responses to isoproterenol along with stimulated cAMP generation were compared among cardiomyocytes isolated from canines with tachycardia-induced heart failure or healthy hearts. The magnitude of shortening of failing cardiomyocytes was significantly depressed (by 22 +/- 4.4%) under basal conditions, and the maximal response to isoproterenol was significantly reduced (by 45 +/- 18%). Similar results were obtained when the responses in the rate of contraction and rate of relaxation to isoproterenol were considered. The L-type Ca(2+) current amplitude measured in failing cardiomyocytes under basal conditions was unchanged, but the responses to isoproterenol were significantly reduced compared with healthy cells. Isoproterenol-stimulated cAMP generation was similar in sarcolemmal membranes derived from the homogenates of failing (45 +/- 6.8) and healthy cardiomyocytes (52 +/- 8.5 pmol cAMP. mg protein(-1). min(-1)). However, stimulated cAMP generation was found to be significantly reduced when the membranes were derived from the homogenates of whole tissue (failing: 67 +/- 8.1 vs. healthy: 140 +/- 27.8 pmol cAMP. mg protein(-1). min(-1)). Total beta-AR density was not reduced in membranes derived from either whole tissue or isolated cardiomyocyte homogenates, but the beta(1)/beta(2) ratio was significantly reduced in the former (failing: 45/55 vs. healthy: 72/28) without being altered in the latter (failing: 72/28, healthy: 77/23). We thus conclude that, in tachycardia-induced heart failure, reduction in the functional responses of isolated cardiomyocytes to beta-AR stimulation may be attributed to alterations in the excitation-contraction machinery rather than to limitation of cAMP generation.

Trace element mapping in Parkinsonian brain by quantitative ion beam microscopy

NASA Astrophysics Data System (ADS)

Barapatre, Nirav; Morawski, Markus; Butz, Tilman; Reinert, Tilo

2010-06-01

The role of iron in the pathogenesis of the Parkinson's disease (PD) is a current subject of research in Neurochemistry, since an abnormal increase in iron is reported in the substantia nigra (SN) of Parkinsonian patients. A severe loss of the cells containing dopamine in the SN in the PD has also drawn attention towards the function of a browny-black pigment called neuromelanin, which accumulates predominantly in these dopaminergic neurons. The neuromelanin has an ability to chelate metal ions, which, in free state, may cause considerable damage to cells by reacting with their lipid-rich membranes. However, it could also potentiate free radical production if it releases the bound metal ions. The highly sensitive and non-destructive micro-PIXE method suits best to quantify and map the trace elements in the SN. The accuracy in charge measurement for such microanalysis studies is of utmost importance for quantitative analysis. Since a Faraday cup is usually placed behind the thin biological sample to measure the charge, the primary and the secondary electrons, knocked out from the sample by traversing ion beam, hamper an exact charge determination. Hence, a new non-interceptive technique was developed for precise charge measurement and for continuous monitoring of beam current.

Automated Proton Track Identification in MicroBooNE Using Gradient Boosted Decision Trees

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

Woodruff, Katherine

MicroBooNE is a liquid argon time projection chamber (LArTPC) neutrino experiment that is currently running in the Booster Neutrino Beam at Fermilab. LArTPC technology allows for high-resolution, three-dimensional representations of neutrino interactions. A wide variety of software tools for automated reconstruction and selection of particle tracks in LArTPCs are actively being developed. Short, isolated proton tracks, the signal for low- momentum-transfer neutral current (NC) elastic events, are easily hidden in a large cosmic background. Detecting these low-energy tracks will allow us to probe interesting regions of the proton's spin structure. An effective method for selecting NC elastic events is tomore » combine a highly efficient track reconstruction algorithm to find all candidate tracks with highly accurate particle identification using a machine learning algorithm. We present our work on particle track classification using gradient tree boosting software (XGBoost) and the performance on simulated neutrino data.« less

Holographic memory using beam steering

NASA Technical Reports Server (NTRS)

Chao, Tien-Hsin (Inventor); Hanan, Jay C. (Inventor); Reyes, George F. (Inventor); Zhou, Hanying (Inventor)

2006-01-01

A method, apparatus, and system provide the ability for storing holograms at high speed. A single laser diode emits a collimated laser beam to both write to and read from a photorefractice crystal. One or more liquid crystal beam steering spatial light modulators (BSSLMs) or Micro-Electro-Mechanical Systems (MEMS) mirrors steer a reference beam, split from the collimated laser beam, at high speed to the photorefractive crystal.

High current multicharged metal ion source using high power gyrotron heating of vacuum arc plasma.

PubMed

Vodopyanov, A V; Golubev, S V; Khizhnyak, V I; Mansfeld, D A; Nikolaev, A G; Oks, E M; Savkin, K P; Vizir, A V; Yushkov, G Yu

2008-02-01

A high current, multi charged, metal ion source using electron heating of vacuum arc plasma by high power gyrotron radiation has been developed. The plasma is confined in a simple mirror trap with peak magnetic field in the plug up to 2.5 T, mirror ratio of 3-5, and length variable from 15 to 20 cm. Plasma formed by a cathodic vacuum arc is injected into the trap either (i) axially using a compact vacuum arc plasma gun located on axis outside the mirror trap region or (ii) radially using four plasma guns surrounding the trap at midplane. Microwave heating of the mirror-confined, vacuum arc plasma is accomplished by gyrotron microwave radiation of frequency 75 GHz, power up to 200 kW, and pulse duration up to 150 micros, leading to additional stripping of metal ions by electron impact. Pulsed beams of platinum ions with charge state up to 10+, a mean charge state over 6+, and total (all charge states) beam current of a few hundred milliamperes have been formed.

Under-response of a PTW-60019 microDiamond detector in the Bragg peak of a 62 MeV/n carbon ion beam

NASA Astrophysics Data System (ADS)

Rossomme, S.; Hopfgartner, J.; Vynckier, S.; Palmans, H.

2016-06-01

To investigate the linear energy transfer (LET) dependence of the response of a PTW-60019 Freiburg microDiamond detector, its response was compared to the response of a plane-parallel Markus chamber in a 62 MeV/n mono-energetic carbon ion beam. Results obtained with two different experimental setups are in agreement. As recommended by IAEA TRS-398, the response of the Markus chamber was corrected for temperature, pressure, polarity effects and ion recombination. No correction was applied to the response of the microDiamond detector. The ratio of the response of the Markus chamber to the response of the microDiamond is close to unity in the plateau region. In the Bragg peak region, a significant increase of the ratio is observed, which increases to 1.2 in the distal edge region. Results indicate a correlation between the under-response of the microDiamond detector and high LET values. The combined relative standard uncertainty of the results is estimated to be 2.38% in the plateau region and 12% in the distal edge region. These values are dominated by the uncertainty of alignment in the non-uniform beam and the uncertainty of range determination.

Diagnostic system for profiling micro-beams

DOEpatents

Elmer, John W.; Palmer, Todd A.; Teruya, Alan T.; Walton, Chris C.

2007-10-30

An apparatus for characterization of a micro beam comprising a micro modified Faraday cup assembly including a first layer of material, a second layer of material operatively connected to the first layer of material, a third layer of material operatively connected to the second layer of material, and a fourth layer of material operatively connected to the third layer of material. The first layer of material comprises an electrical conducting material and has at least one first layer radial slit extending through the first layer. An electrical ground is connected to the first layer. The second layer of material comprises an insulating material and has at least one second layer radial slit corresponding to the first layer radial slit in the first layer of material. The second layer radial slit extends through the second layer. The third layer of material comprises a conducting material and has at least one third layer radial slit corresponding to the second layer radial slit in the second layer of material. The third layer radial slit extends through the third layer. The fourth layer of material comprises an electrical conducting material but does not have slits. An electrical measuring device is connected to the fourth layer. The micro modified Faraday cup assembly is positioned to be swept by the micro beam.

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

Bonding of contemporary glass ionomer cements to dentin.

PubMed

Yip, H K; Tay, F R; Ngo, H C; Smales, R J; Pashley, D H

2001-09-01

The objective of this study was to investigate the microtensile bond strength (microTBS) of contemporary glass ionomer cements (GIC) to sound coronal dentin. Three specimen teeth were prepared for each material tested: Fuji IX GP (GC), ChemFlex (Dentsply) and Ketac-Molar Aplicap (ESPE). GIC buildups were made according to the manufacturers' instructions. After being stored at 37 degrees C, 100% humidity for 24h, the teeth were vertically sectioned into 1x1mm beams for microTBS evaluation. Representative fractured beams were prepared for scanning (SEM) and transmission electron microscopic (TEM) examination. Results of the microTBS test were: Fuji IX GP (12.4+/-8.6MPa), ChemFlex (15.0+/-9.3MPa) and Ketac-Molar Aplicap (11.4+/-7.7MPa). One-way ANOVA and a multiple comparison test showed that ChemFlex had a statistically higher microTBS (p<0.05). SEM fractographic analysis showed that the predominant failure modes were interfacial and mixed failures. The GIC side of the fractured beams revealed dehydration cracks, a high level of porosity, and voids with an eggshell-like crust. TEM analysis of the demineralized dentin sides of the fractured beams revealed the presence of an intermediate layer along the GIC-dentin interface. This zone was present on the fractured dentin surface in the case of interfacial failure, and beneath GIC remnants in specimens that exhibited a mixed failure mode. The findings suggest that the bonding of GIC to dentin is not weak and that the microTBS values probably represent the weak yield strengths of GICs under tension.

Mathematical model of mass transfer at electron beam treatment

NASA Astrophysics Data System (ADS)

Konovalov, Sergey V.; Sarychev, Vladimir D.; Nevskii, Sergey A.; Kobzareva, Tatyana Yu.; Gromov, Victor E.; Semin, Alexander P.

2017-01-01

The paper proposes a model of convective mass transfer at electron beam treatment with beams in titanium alloys subjected to electro-explosion alloying by titanium diboride powder. The proposed model is based on the concept that treatment with concentrated flows of energy results in the initiation of vortices in the melted layer. The formation mechanism of these vortices rooted in the idea that the availability of temperature drop leads to the initiation of the thermo-capillary convection. For the melted layer of metal the equations of the convective heat transfer and boundary conditions in terms of the evaporated material are written. The finite element solution of these equations showed that electron-beam treatment results in the formation of multi-vortex structure that in developing captures all new areas of material. It leads to the fact that the strengthening particles are observed at the depth increasing many times the depth of their penetration according to the diffusion mechanism. The distribution of micro-hardness at depth and the thickness of strengthening zone determined from these data supported the view that proposed model of the convective mass transfer describes adequately the processes going on in the treatment with low-energy high-current electron beam.

The effect of isoenzyme-selective PDE inhibitors on methacholine-induced contraction of guinea-pig and rat ileum.

PubMed Central

Tomkinson, A.; Raeburn, D.

1996-01-01

1. We have examined the effects of the isoenzyme-selective phosphodiesterase (PDE) inhibitors, vinpocetine (type 1), siguazodan (type 3), rolipram (type 4) and zaprinast (type 5) and the non-selective PDE inhibitor enprofylline on methacholine (MCh) contractile concentration-response curves on guinea-pig and rat isolated ileum. 2. In guinea-pig ileum, vinpocetine (10-300 microM), zaprinast (1-300 microM) and enprofylline (100-1000 microM) produced a concentration-dependent depression of the maximum response (Emax) to MCh only without effect on the MCh EC50 values (rank order of potency: zaprinast > vinpocetine > enprofylline). In contrast, siguazodan (10-300 microM) and rolipram (10-300 microM) produced a rightward displacement of the MCh concentration-response curve (increase in EC50: rank order; rolipram > siguazodan), with effects on the MCh maximum seen only at higher concentrations. 3. In the rat ileum, vinpocetine (10-300 microM), zaprinast (0.1-300 microM) and enprofylline (100-1000 microM) caused depression of the MCh maximum contraction (rank order: zaprinast > vinpocetine > enprofylline). Low concentrations of rolipram and siguazodan had no significant effect on the MCh maximum. In the presence of higher concentrations (> 100 microM) of rolipram and siguazodan, a maximum response was not achieved at the highest concentration of MCh tested. As in the guinea-pig ileum, only rolipram (10-300 microM) and siguazodan (10-300 microM) produced a significant, concentration-dependent, rightward displacement of the MCh concentration-response curve (increase in EC50: rank order: rolipram > siguazodan). 4. In the guinea-pig ileum, isoprenaline (0.1 microM) produced a rightward displacement (approximately 3 fold) of the MCh concentration-response curve, accompanied by a significant depression of the maximum response. Increasing the isoprenaline concentration (1 microM) had no further effect on either parameter. Sodium nitroprusside (SNP, > or = 10 microM) produced a concentration-dependent depression of the MCh maximum without an effect on the EC50. 5. In the rat ileum, isoprenaline (1 microM) produced a concentration-dependent rightward displacement (approximately 2.8 fold) of the MCh concentration-response curve with depression of the MCh maximum at higher (> or = 100 microM) concentrations. SNP produced depression of the MCh maximum at a concentration of 10 microM and above. Effects on the MCh EC50 were seen only at 100 and 300 microM. 6. In guinea-pig ileum, isoprenaline (0.1 microM) in combination with rolipram (10 microM) further increased the MCh EC50 and reduced the MCh maximum. The combination of SNP (10 microM) with zaprinast (0.1 microM) produced no further significant effect than SNP alone. 7. In rat ileum, isoprenaline (1 microM) in combination with rolipram (10 microM) further increased the EC50 and reduced the maximum. SNP (10 microM) had no significant effect on either the MCh maximum or EC50. A combination with zaprinast (1 microM) had no further effect. 8. In conclusion, all the PDE inhibitors tested produced a concentration-dependent inhibition of the MCh concentration-response curve, indicating a modulator role for the PDE isoenzymes in gastrointestinal smooth muscle contractility. The PDE inhibitors that elevate cyclic GMP produced a depression of the MCh maximum response only, whilst those that elevate cyclic AMP produced a rightward displacement of the MCh concentration-response curve. This was confirmed by the use of isoprenaline and SNP. This difference in the type of inhibition produced by these PDE isoenzyme inhibitors may reflect a different intracellular site/mechanism by which the cyclic AMP- and cyclic GMP-activated kinases act functionally to antagonize the contractile response. PMID:8864552

[Physiopathology of cAMP/PKA signaling in neurons].

PubMed

Castro, Liliana; Yapo, Cedric; Vincent, Pierre

2016-01-01

Cyclic adenosine monophosphate (cAMP) and the cyclic-AMP dependent protein kinase (PKA) regulate a plethora of cellular functions in virtually all eukaryotic cells. In neurons, the cAMP/PKA signaling cascade controls a number of biological properties such as axonal growth, synaptic transmission, regulation of excitability or long term changes in the nucleus. Genetically-encoded optical biosensors for cAMP or PKA considerably improved our understanding of these processes by providing a real-time measurement in living neurons. In this review, we describe the recent progresses made in the creation of biosensors for cAMP or PKA activity. These biosensors revealed profound differences in the amplitude of the cAMP signal evoked by neuromodulators between various neuronal preparations. These responses can be resolved at the level of individual neurons, also revealing differences related to the neuronal type. At the subcellular level, biosensors reported different signal dynamics in domains like dendrites, cell body, nucleus and axon. Combining this imaging approach with pharmacology or genetical models points at phosphodiesterases and phosphatases as critical regulatory proteins. Biosensor imaging will certainly help understand the mechanism of action of current drugs as well as help in devising novel therapeutic strategies for neuropsychiatric diseases. © Société de Biologie, 2017.

Effects of Ohmic Resistance on Dynamic Characteristics and Impedance of Micro/Nano Cantilever Beam resonators

NASA Astrophysics Data System (ADS)

Rezazadeh, Ghader; Keyvani, Aliasghar; Sadeghi, Morteza H.; Bahrami, Manouchehr

2013-06-01

Effects of Ohmic resistance on MEMS/NEMS vibrating structures that have always been dismissed in some situations may cause important changes in resonance properties and impedance parameters of the MEMS/NEMS based circuits. In this paper it is aimed to present a theoretical model to precisely investigate the problem on a simple cantilever-substrate resonator. In this favor the Ohm's current law and charge conservation law have been merged to find a differential Equation for voltage propagation on the beam and because mostly nano structures are expected as the scope of the problem, modified couple stress theory is used to formulate the dynamic motion of the beam. The two governing equations were coupled and both nonlinear that have been solved simultaneously using a Galerkin based state space formulation. The obtained results that are in exact agreement with previous works show that dynamic pull-in voltage, switching time, and impedance of structure as a MEMS capacitor especially in frequencies higher than natural resonance frequency strongly relay on electrical resistance of the beam and substrate material.

Ceramic micro-injection molded nozzles for serial femtosecond crystallography sample delivery

NASA Astrophysics Data System (ADS)

Beyerlein, K. R.; Adriano, L.; Heymann, M.; Kirian, R.; Knoška, J.; Wilde, F.; Chapman, H. N.; Bajt, S.

2015-12-01

Serial femtosecond crystallography (SFX) using X-ray Free-Electron Lasers (XFELs) allows for room temperature protein structure determination without evidence of conventional radiation damage. In this method, a liquid suspension of protein microcrystals can be delivered to the X-ray beam in vacuum as a micro-jet, which replenishes the crystals at a rate that exceeds the current XFEL pulse repetition rate. Gas dynamic virtual nozzles produce the required micrometer-sized streams by the focusing action of a coaxial sheath gas and have been shown to be effective for SFX experiments. Here, we describe the design and characterization of such nozzles assembled from ceramic micro-injection molded outer gas-focusing capillaries. Trends of the emitted jet diameter and jet length as a function of supplied liquid and gas flow rates are measured by a fast imaging system. The observed trends are explained by derived relationships considering choked gas flow and liquid flow conservation. Finally, the performance of these nozzles in a SFX experiment is presented, including an analysis of the observed background.

Tests of neutrino interaction models with the MicroBooNE detector

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

Rafique, Aleena

2018-01-01

I measure a large set of observables in inclusive charged current muon neutrino scattering on argon with the MicroBooNE liquid argon time projection chamber operating at Fermilab. I evaluate three neutrino interaction models based on the widely used GENIE event generator using these observables. The measurement uses a data set consisting of neutrino interactions with a final state muon candidate fully contained within the MicroBooNE detector. These data were collected in 2016 with the Fermilab Booster Neutrino Beam, which has an average neutrino energy ofmore » $800$ MeV, using an exposure corresponding to $$5.0\\times10^{19}$$ protons-on-target. The analysis employs fully automatic event selection and charged particle track reconstruction and uses a data-driven technique to separate neutrino interactions from cosmic ray background events. I find that GENIE models consistently describe the shapes of a large number of kinematic distributions for fixed observed multiplicity, but I show an indication that the observed multiplicity fractions deviate from GENIE expectations.« less

Automated segmentation of the lamina cribrosa using Frangi's filter: a novel approach for rapid identification of tissue volume fraction and beam orientation in a trabeculated structure in the eye

PubMed Central

Campbell, Ian C.; Coudrillier, Baptiste; Mensah, Johanne; Abel, Richard L.; Ethier, C. Ross

2015-01-01

The lamina cribrosa (LC) is a tissue in the posterior eye with a complex trabecular microstructure. This tissue is of great research interest, as it is likely the initial site of retinal ganglion cell axonal damage in glaucoma. Unfortunately, the LC is difficult to access experimentally, and thus imaging techniques in tandem with image processing have emerged as powerful tools to study the microstructure and biomechanics of this tissue. Here, we present a staining approach to enhance the contrast of the microstructure in micro-computed tomography (micro-CT) imaging as well as a comparison between tissues imaged with micro-CT and second harmonic generation (SHG) microscopy. We then apply a modified version of Frangi's vesselness filter to automatically segment the connective tissue beams of the LC and determine the orientation of each beam. This approach successfully segmented the beams of a porcine optic nerve head from micro-CT in three dimensions and SHG microscopy in two dimensions. As an application of this filter, we present finite-element modelling of the posterior eye that suggests that connective tissue volume fraction is the major driving factor of LC biomechanics. We conclude that segmentation with Frangi's filter is a powerful tool for future image-driven studies of LC biomechanics. PMID:25589572

Manipulation of the micro and macro-structure of beams extracted from cyclotrons

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

Laxdal, R.E.

1995-09-01

It is standard practice in cyclotrons to alter the extracted micro-pulse width by using center-region slits and/or by chopping the beam before injection. The macro-structure can also be varied by means of pulsed or sinusoidal deflection devices before injection and/or after extraction. All above methods, however, involve cutting away the unwanted beam, thus reducing the time-averaged intensity. This paper will focus on some methods used to alter the time structure of extracted beams without significant beam loss. For example radial gradients in the accelerating fields from rf cavities can be utilized to compress, expand or even split longitudinally the circulatingmore » particle bunches. The macro-structure of the extracted beam can be altered by employing resonant extraction methods and replacing the static magnetic bump with either a pulsed or a sinusoidal transverse perturbation. The methods are most suitable for H cyclotrons but may also be considered in a limited scope for cyclotrons using direct extraction. Results of computer simulations and beam tests on the TRIUMF 500 MeV H{sup {minus}} cyclotron will be presented.« less

Running-specific prostheses permit energy cost similar to nonamputees.

PubMed

Brown, Mary Beth; Millard-Stafford, Mindy L; Allison, Andrew R

2009-05-01

Improvements in prosthesis design have facilitated participation in competitive running for persons with lower limb loss (AMP). The purpose of this study was to examine the physiological responses of AMP using a run-specific prosthesis (RP) versus a traditional prosthesis (P) and cross-referenced with nonamputee controls (C) matched by training status, age, gender, and body composition during level treadmill running (TM). Twelve trained runners completed a multistage submaximal TM exercise during which HR and oxygen uptake (VO(2)) were obtained. Steady state measures at 134 m x min(-1) were compared between RP and P in AMP. AMP using RP (AMP-RP) and C also performed a continuous speed-incremented maximal TM test until volitional fatigue. RP elicited lower HR and VO(2) compared with P in AMP. Using RP, AMP achieved similar VO(2max) and peak TM speed compared with C but with higher HR(max). Relative HR (%HR(max)) and oxygen uptake (%VO(2max)), the regression intercept, slope, SEE, and Pearson's r correlation were not different between AMP-RP and C. %HR(max) calculated with the published equation, %HR(max) = 0.73(%VO(2max)) + 30, was not significantly different from actual %HR(max) for AMP-RP or C in any stage. RP permits AMP to attain peak TM speed and aerobic capacity similar to trained nonamputees and significantly attenuates HR and energy cost of submaximal running compared with a P. Use of RP confers no physiological advantage compared with nonamputee runners because energy cost at the set speed was not significantly different for AMP-RP. Current equations on the basis of the relative HR-VO(2) relationship seem appropriate to prescribe exercise intensity for persons with transtibial amputations using RP.

3D micro-lenses for free space intra-chip coupling in photonic-integrated circuits (Conference Presentation)

NASA Astrophysics Data System (ADS)

Thomas, Robert; Williams, Gwilym I.; Ladak, Sam; Smowton, Peter M.

2017-02-01

The integration of multiple optical elements on a common substrate to create photonic integrated circuits (PIC) has been successfully applied in: fibre-optic communications, photonic computing and optical sensing. The push towards III-Vs on silicon promises a new generation of integrated devices that combine the advantages of both integrated electronics and optics in a single substrate. III-V edge emitting laser diodes offer high efficiency and low threshold currents making them ideal candidates for the optically active elements of the next generation of PICs. Nevertheless, the highly divergent and asymmetric beam shapes intrinsic to these devices limits the efficiency with which optical elements can be free space coupled intra-chip; a capability particularly desirable for optical sensing applications e.g. [1]. Furthermore, the monolithic nature of the integrated approach prohibits the use of macroscopic lenses to improve coupling. However, with the advent of 3D direct laser writing, three dimensional lenses can now be manufactured on a microscopic-scale [2], making the use of micro-lens technology for enhanced free space coupling of integrated optical elements feasible. Here we demonstrate the first use of 3D micro-lenses to improve the coupling efficiency of monolithically integrated lasers. Fabricated from IP-dip photoresist using a Nanoscribe GmbH 3D lithography tool, the lenses are embedded directly onto a structured GaInP/AlGaInP substrate containing arrays of ridge lasers free space coupled to one another via a 200 μm air gap. We compare the coupling efficiency of these lasers with and without micro-lenses through photo-voltage and beam profile measurements and discuss optimisation of lens design.

Development of Functional Surfaces on High-Density Polyethylene (HDPE) via Gas-Assisted Etching (GAE) Using Focused Ion Beams.

PubMed

Sezen, Meltem; Bakan, Feray

2015-12-01

Irradiation damage, caused by the use of beams in electron and ion microscopes, leads to undesired physical/chemical material property changes or uncontrollable modification of structures. Particularly, soft matter such as polymers or biological materials is highly susceptible and very much prone to react on electron/ion beam irradiation. Nevertheless, it is possible to turn degradation-dependent physical/chemical changes from negative to positive use when materials are intentionally exposed to beams. Especially, controllable surface modification allows tuning of surface properties for targeted purposes and thus provides the use of ultimate materials and their systems at the micro/nanoscale for creating functional surfaces. In this work, XeF2 and I2 gases were used in the focused ion beam scanning electron microscope instrument in combination with gallium ion etching of high-density polyethylene surfaces with different beam currents and accordingly different gas exposure times resulting at the same ion dose to optimize and develop new polymer surface properties and to create functional polymer surfaces. Alterations in the surface morphologies and surface chemistry due to gas-assisted etching-based nanostructuring with various processing parameters were tracked using high-resolution SEM imaging, complementary energy-dispersive spectroscopic analyses, and atomic force microscopic investigations.

On the Nonlinear Dynamics of a Tunable Shock Micro-switch

NASA Astrophysics Data System (ADS)

Azizi, Saber; Javaheri, Hamid; Ghanati, Parisa

2016-12-01

A tunable shock micro-switch based on piezoelectric excitation is proposed in this study. This model includes a clamped-clamped micro-beam sandwiched with two piezoelectric layers throughout the entire length. Actuation of the piezoelectric layers via a DC voltage leads to an initial axial force in the micro-beam and directly affects on its overall bending stiffness; accordingly enables two-side tuning of both the trigger time and threshold shock. The governing motion equation, in the presence of an electrostatic actuation and a shock wave, is derived using Hamilton's principle. We employ the finite element method based on the Galerkin technique to obtain the temporal and phase responses subjected to three different shock waves including half sine, triangular and rectangular forms. Subsequently, we investigate the effect of the piezoelectric excitations on the threshold shock amplitude and trigger time.

MicroCT imaging dose to mouse organs using a validated Monte Carlo model of the small animal radiation research platform (SARRP)

NASA Astrophysics Data System (ADS)

Johnstone, Christopher Daniel; Bazalova-Carter, Magdalena

2018-06-01

The goal of this work was to establish imaging dose to mouse organs with a validated Monte Carlo (MC) model of the image-guided Small Animal Radiation Research Platform (SARRP) and to investigate the effect of scatter from the internal walls on animal therapy dose determination. A MC model of the SARRP was built in the BEAMnrc code and validated with a series of homogeneous and heterogeneous phantom measurements. A segmented microCT scan of a mouse was used in DOSXYZnrc to determine mouse organ microCT imaging doses to 15–35 g mice for the SARRP pancake (mouse lying on couch) and standard (mouse standing on couch) imaging geometries for 40–80 kVp tube voltages. Imaging dose for off-center positioning shifts and maintaining image noise across tube voltages were also calculated. Half-value layer (HVL) measurements for the 220 kVp therapy beam in the presence of the SARRP shielding cabinet were modeled in BEAMnrc and compared to the 100 cm source-to-detector distance (SDD) in the scatter free, narrow-beam geometry recommended by the American Association of Physicists in Medicine Task Group 61 (AAPM TG-61). For a 60 kVp, 0.8 mA, and 60 s scan protocol, maximum mean organ imaging doses to boney and non-boney structures were 10.5 cGy and 3.5 cGy, respectively, for an average size 20 g mouse. Current-exposure combinations above 323, 203, 147, 116, and 95 mAs for 40–80 kVp tube voltages, respectively, will increase body doses above 10 cGy. MicroCT mean body dose was 18% lower in pancake compared to standard imaging geometry. An 11% difference in measured HVL at a 50 cm SDD was found compared to MC simulated HVL for the AAPM TG-61 recommended scatter free geometry at a 100 cm SDD. This change in HVL resulted in a 0.5% change in absorbed dose to water calculations for the treatment beam.

SU-E-I-85: Absorbed Dose Estimation for a Commercially Available MicroCT Scanner

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

Lau, A; Ahmad, S; Chen, Y

2015-06-15

Purpose: To quantify the simulated absorbed dose delivered for a typical scan from a commercially available microCT scanner in order to aid in the dose estimation. Methods: The simulations were conducted using the Geant4 Monte Carlo Toolkit (version 10) with the standard electromagnetic classes. The Quantum FX microCT scanner (PerkinElmer, Waltham, MA) was modeled incorporating the energy fluence and angular distributions of generated photons, spatial dimensions of nominal source-to-object and source-to-detector distances. The energy distribution was measured using a spectrometer (X-123CdTe, Amptek Inc., Bedford, USA) with a 300 angular spread from the source for the 90 kVp X-ray beams withmore » no additional filtration. The nominal distances from the source to object consisted of three setups: 154.0 mm, 104.0 mm, and 51.96 mm. Our simulations recorded the dose absorbed in a cylindrical phantom of PMMA with a fixed length of 2 cm and varying radii (10, 20, 30 and 40 mm) using 100 million incident photons. The averaged absorbed dose in the object was then quantified for all setups. An exposure measurement of 417 mR was taken using a Radcal 9095 system utilizing 10×9–180 ion chamber with the given technique of 90 kVp, 63 μA, and 12 s. The exposure rate was also simulated with same setup to calculate the conversion factor of the beam current and the number of incident photons. Results: For a typical cone-beam scan with non-filtered 90kVp, the dose coefficients (the absorbed dose per mAs) were 2.614, 2.549 and 2.467 μGy/mAs under source to object distance of 104 mm for the object diameters of 10 mm, 20 mm and 30 mm, respectively. Conclusion: A look-up table was developed where an investigator can estimate the delivered dose using this particular microCT given the scanning protocol (kVp and mAs) as well as the size of the scanned object.« less

Continuous and pulsed laser high power beam combiner for additive manufacturing applications

NASA Astrophysics Data System (ADS)

Bassignana, Marta; Califano, Alessio; Pescarmona, Francesco; Braglia, Andrea; Perrone, Guido

2018-02-01

Laser-based additive manufacturing (AM) from metal powders is emerging as the new industrial revolution, although current fabrication approaches still require long mechanical post-processing to improve the final surface quality and meet the design tolerances. To overcome this limitation, the next generation machines are expected to complement laser AM with laser ablation (LA) to implement surface finishing and micro texturing already during the device growth process. With this aim, a new beam combiner to allow the real-time interchange of additive and subtractive processes using the same scanner head has been designed. Extensive tests have been carried out using a 6 kW continuous-wave laser similar to that used for the metal powder fusion and a nanosecond 100W pulsed source similar to that used for laser ablation.

Development of a new in-air micro-PIXE set-up with in-vacuum charge measurements in Atomki

NASA Astrophysics Data System (ADS)

Török, Zs.; Huszánk, R.; Csedreki, L.; Dani, J.; Szoboszlai, Z.; Kertész, Zs.

2015-11-01

A new external microbeam set-up has recently been installed as the extension of the existing microprobe system at the Laboratory of Ion Beam Applications of Atomki, Debrecen, Hungary. The external beam set-up, based on the system of Oxford Microbeams (OM), is equipped with two X-ray detectors for PIXE analysis, a digital microscope, two alignment lasers and a precision XYZ stage for easy and reproducible positioning of the sample. Exit windows with different thicknesses and of different materials can be used according to the actual demands, currently silicon-nitride (Si3N4) film with 200 nm thickness is employed in our laboratory. The first application was demonstrated in the field of archaeometry, on Bronze Age hoards from Hungary.

Note: A portable Raman analyzer for microfluidic chips based on a dichroic beam splitter for integration of imaging and signal collection light paths

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

Geng, Yijia; Xu, Shuping; Xu, Weiqing, E-mail: xuwq@jlu.edu.cn

An integrated and portable Raman analyzer featuring an inverted probe fixed on a motor-driving adjustable optical module was designed for the combination of a microfluidic system. It possesses a micro-imaging function. The inverted configuration is advantageous to locate and focus microfluidic channels. Different from commercial micro-imaging Raman spectrometers using manual switchable light path, this analyzer adopts a dichroic beam splitter for both imaging and signal collection light paths, which avoids movable parts and improves the integration and stability of optics. Combined with surface-enhanced Raman scattering technique, this portable Raman micro-analyzer is promising as a powerful tool for microfluidic analytics.

A Plasma Window for Transmission of Radiation and Particle Beams from Vacuum to Atmosphere for Various Applications

NASA Astrophysics Data System (ADS)

Hershcovitch, Ady

1997-11-01

Many industrial and scientific processes like electron beam melting and welding, material modification by ion implantation, dry etching, and micro-fabrication, as well as generation of synchrotron radiation are performed almost exclusively in vacuum nowadays, since the electron and ion guns and their extractors must be kept at a reasonably high vacuum. Consequently, there are numerous drawbacks, among which are low production rates due to required pumping time, limits the vacuum volume sets on the size of target objects. In a small number of applications like non-vacuum electron beam welding, and various processes involving UV and x-ray radiation, thin vacuum walls or long stages of differential pumping are used. But, the resultant degradations of particle and radiation beams severely limit those applications. A novel apparatus, which utilized a short plasma arc, was successfully used to maintain a pressure of 7.6 x exp(-6) Torr in a vacuum chamber with a 2.36mm aperture to atmosphere, i.e., a plasma was successfully used to "plug" a hole to atmosphere while maintaining a reasonably high vacuum in the chamber. Successful transmission of charged particle beams from a vacuum through the plasma to atmosphere was accomplished. More details can be found in A. Hershcovitch, J. Appl. Physics 78, p. 5283 (1995). In addition to sustaining a vacuum atmosphere interface, the plasma has very strong lensing effect on charged particles. The plasma current generates an azimuthal magnetic field which exerts a radial Lorentz on charged particles moving parallel to the current channel. With proper orientation of the current direction, the Lorentz force is radially inward. This feature can be used to focus in beams to a very small spot size, and to overcome beam dispersion due to scattering by atmospheric atoms and molecules. Relatively hot plasma at the atmosphere boundary rarefies the atmospheric gases to further enhance particle beam propagation to the materials to target. Recent experimental results, with a plasma window coupled to a venturi, show a factor of three further enhancement in vacuum-atmosphere separation.

Analysis of ESBL- and AmpC-positive Enterobacteriaceae at the Department of Neonatology, University Hospital Olomouc.

PubMed

Husičková, Vendula; Chromá, Magdaléna; Kolář, Milan; Hricová, Kristýna; Stosová, Taťána; Kantor, Lumír; Dubrava, Lubomír

2011-06-01

Bacterial infections are an important issue in current clinical medicine. The severity of infectious diseases has increased dramatically in recent years, which is also due to increasing numbers of resistant bacteria, including strains producing broad-spectrum beta-lactamases. The study aimed at determining the prevalence of ESBL- and AmpC-positive Enterobacteriaceae at the Department of Neonatology, University Hospital Olomouc. Enterobacteriaceae were isolated from clinical samples from infants hospitalized at the Department of Neonatology, University Hospital Olomouc over a period of 2 years. ESBL- and AmpC-positive isolates were subjected to basic genetic analysis. In the study period, a total of 1,526 isolates of the Enterobacteriaceae family were identified, including 55 (3.6%) cases of the ESBL phenotype and 17 (1.1%) AmpC-positive isolates. Genetic analysis of ESBL-positive isolates revealed a majority of CTX-M enzymes. Among AmpC beta-lactamases, the EBC, CIT, DHA, and MOX types were detected. An Escherichia coli strain was isolated with mutations in the promoter region of the ampC chromosomal gene that are associated with overproduction of the relevant enzyme.

History and modern applications of nano-composite materials carrying GA/cm2 current density due to a Bose-Einstein Condensate at room temperature produced by Focused Electron Beam Induced Processing for many extraordinary novel technical applications

NASA Astrophysics Data System (ADS)

Koops, Hans W. P.

2015-12-01

The discovery of Focused Electron Beam Induced Processing and early applications of this technology led to the possible use of a novel nanogranular material “Koops-GranMat®” using Pt/C and Au/C material. which carries at room temperature a current density > 50 times the current density which high TC superconductors can carry. The explanation for the characteristics of this novel material is given. This fact allows producing novel products for many applications using Dual Beam system having a gas supply and X.Y.T stream data programming and not using GDSII layout pattern control software. Novel products are possible for energy transportation. -distribution.-switching, photon-detection above 65 meV energy for very efficient energy harvesting, for bright field emission electron sources used for vacuum electronic devices like amplifiers for HF electronics, micro-tubes, 30 GHz to 6 THz switching amplifiers with signal to noise ratio >10(!), THz power sources up to 1 Watt, in combination with miniaturized vacuum pumps, vacuum gauges, IR to THz detectors, EUV- and X-Ray sources. Since focusing electron beam induced deposition works also at low energy, selfcloning multibeam-production machines for field emitter lamps, displays, multi-beam - lithography, - imaging, and - inspection, energy harvesting, and power distribution with switches controlling field-emitter arrays for KA of currents but with < 100 V switching voltage are possible. Finally the replacement of HTC superconductors and its applications by the Koops-GranMat® having Koops-Pairs at room temperature will allow the investigation devices similar to Josephson Junctions and its applications now called QUIDART (Quantum interference devices at Room Temperature). All these possibilities will support a revolution in the optical, electric, power, and electronic technology.

D0 Solenoid Upgrade Project: D0 Solenoid Current Leads

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

Rucinski, R.; /Fermilab

This engineering note documents information gathered and design decisions made regarding the vapor cooled current leads for the D-Zero Solenoid. The decision was made during design group meetings that the D-Zero Solenoid, rated at 4825 amps, should use vapor cooled current leads rated at 6000 amps. CDF uses 6000 amp leads from American Magnetics Inc. (AMI) and has two spares in their storage lockers. Because of the spares situation and AMI's reputation, AMI would be the natural choice of vendor. The manufacturer's listed helium consumption is 19.2 liters/hr. From experience with these types of leads, more stable operation is acheivedmore » at an increased gas flow. See attached E-Mail message from RLS. We have decided to list the design flow rate at 28.8 liquid liters/hr in the design report. This corresponds to COFs operating point. A question was raised regarding how long the current leads could last at full current should the vapor cooling flow was stopped. This issue was discussed with Scott Smith from AMI. We do not feel that there is a problem for this failure scenario.« less

A micro-machined source transducer for a parametric array in air.

PubMed

Lee, Haksue; Kang, Daesil; Moon, Wonkyu

2009-04-01

Parametric array applications in air, such as highly directional parametric loudspeaker systems, usually rely on large radiators to generate the high-intensity primary beams required for nonlinear interactions. However, a conventional transducer, as a primary wave projector, requires a great deal of electrical power because its electroacoustic efficiency is very low due to the large characteristic mechanical impedance in air. The feasibility of a micro-machined ultrasonic transducer as an efficient finite-amplitude wave projector was studied. A piezoelectric micro-machined ultrasonic transducer array consisting of lead zirconate titanate uni-morph elements was designed and fabricated for this purpose. Theoretical and experimental evaluations showed that a micro-machined ultrasonic transducer array can be used as an efficient source transducer for a parametric array in air. The beam patterns and propagation curves of the difference frequency wave and the primary wave generated by the micro-machined ultrasonic transducer array were measured. Although the theoretical results were based on ideal parametric array models, the theoretical data explained the experimental results reasonably well. These experiments demonstrated the potential of micro-machined primary wave projector.

High-precision micro-displacement optical-fiber sensor based on surface plasmon resonance.

PubMed

Zhu, Zongda; Liu, Lu; Liu, Zhihai; Zhang, Yu; Zhang, Yaxun

2017-05-15

We propose and demonstrate a novel optical-fiber micro-displacement sensor based on surface plasmon resonance (SPR) by fabricating a Kretschmann configuration on graded-index multimode fiber (GIMMF). We employ a single-mode fiber to change the radial position of the incident beam as the displacement. In the GIMMF, the angle between the light beam and fiber axis, which is closely related to the resonance angle, is changed by the displacement; thus, the resonance wavelength of the fiber SPR shifts. This micro-displacement fiber sensor has a wide detection range of 0-25 μm, a high sensitivity with maximum up to 10.32 nm/μm, and a nanometer resolution with minimum to 2 nm, which transcends almost all of other optical-fiber micro-displacement sensors. In addition, we also research that increasing the fiber polishing angle or medium refractive index can improve the sensitivity. This micro-displacement sensor will have a great significance in many industrial applications and provide a neoteric, rapid, and accurate optical measurement method in micro-displacement.

Extracellular nucleotides potentiate the cytosolic Ca2+, but not cyclic adenosine 3', 5'-monophosphate response to parathyroid hormone in rat osteoblastic cells.

PubMed

Kaplan, A D; Reimer, W J; Feldman, R D; Dixon, S J

1995-04-01

Binding to PTH to its cell surface receptor activates both adenylyl cyclase and phospholipase-C, leading to elevation of cytosolic cAMP and free Ca2+. We have shown previously that extracellular nucleotides interact with P2U and P2Y subtypes of purinoceptor on osteoblastic cells, both linked to Ca2+ mobilization. In the present study, we investigated possible interactions between nucleotide and PTH signaling pathways in osteoblastic cells. The cytosolic free Ca2+ concentration ([Ca2+]i) of UMR-106 osteoblastic cells was monitored by fluorescence spectrophotometry. PTH (0.01-1 microM; bovine 1-84 or human 1-34) induced a small transient elevation of [Ca2+]i, lasting less than 1 min. A number of nucleotides, including ATP, UTP, and UDP, induced transient elevation of [Ca2+]i and potentiated the subsequent Ca2+ response to PTH. Of the nucleotides tested, UDP was the most effective at potentiating the PTH-induced Ca2+ transient. Treatment of cells with UDP (100 microM for 2.5 min), but not inorganic phosphate or uridine, reversibly potentiated the Ca2+ response to PTH (0.1 microM) by 11 +/- 2-fold (mean +/- SEM; n = 39). In contrast, UDP did not affect the cAMP response to PTH, indicating a selective action on Ca2+ signaling. Potentiation of the Ca2+ signal was still observed in the absence of extracellular Ca2+, establishing that nucleotides enhance PTH-induced release of Ca2+ from intracellular stores. Studies using selective purinoceptor agonists suggest that potentiation of PTH signaling is mediated by the P2U receptor subtype. In vivo, nucleotides released during trauma or inflammation may modulate PTH-induced Ca2+ signaling in osteoblasts.

Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities

PubMed Central

Pulito, Claudio; Mori, Federica; Sacconi, Andrea; Goeman, Frauke; Ferraiuolo, Maria; Pasanisi, Patrizia; Campagnoli, Carlo; Berrino, Franco; Fanciulli, Maurizio; Ford, Rebecca J; Levrero, Massimo; Pediconi, Natalia; Ciuffreda, Ludovica; Milella, Michele; Steinberg, Gregory R; Cioce, Mario; Muti, Paola; Strano, Sabrina; Blandino, Giovanni

2017-01-01

Metformin is a commonly prescribed type II diabetes medication that exhibits promising anticancer effects. Recently, these effects were found to be associated, at least in part, with a modulation of microRNA expression. However, the mechanisms by which single modulated microRNAs mediate the anticancer effects of metformin are not entirely clear and knowledge of such a process could be vital to maximize the potential therapeutic benefits of this safe and well-tolerated therapy. Our analysis here revealed that the expression of miR-21-5p was downregulated in multiple breast cancer cell lines treated with pharmacologically relevant doses of metformin. Interestingly, the inhibition of miR-21-5p following metformin treatment was also observed in mouse breast cancer xenografts and in sera from 96 breast cancer patients. This modulation occurred at the levels of both pri-miR-21 and pre-miR-21, suggesting transcriptional modulation. Antagomir-mediated ablation of miR-21-5p phenocopied the effects of metformin on both the clonogenicity and migration of the treated cells, while ectopic expression of miR-21-5p had the opposite effect. Mechanistically, this reduction in miR-21-5p enhanced the expression of critical upstream activators of the AMP-activated protein kinase, calcium-binding protein 39-like and Sestrin-1, leading to AMP-activated protein kinase activation and inhibition of mammalian target of rapamycin signaling. Importantly, these effects of metformin were synergistic with those of everolimus, a clinically relevant mammalian target of rapamycin inhibitor, and were independent of the phosphatase and tensin homolog status. This highlights the potential relevance of metformin in combinatorial settings for the treatment of breast cancer. PMID:28698800

Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities.

PubMed

Pulito, Claudio; Mori, Federica; Sacconi, Andrea; Goeman, Frauke; Ferraiuolo, Maria; Pasanisi, Patrizia; Campagnoli, Carlo; Berrino, Franco; Fanciulli, Maurizio; Ford, Rebecca J; Levrero, Massimo; Pediconi, Natalia; Ciuffreda, Ludovica; Milella, Michele; Steinberg, Gregory R; Cioce, Mario; Muti, Paola; Strano, Sabrina; Blandino, Giovanni

2017-01-01

Metformin is a commonly prescribed type II diabetes medication that exhibits promising anticancer effects. Recently, these effects were found to be associated, at least in part, with a modulation of microRNA expression. However, the mechanisms by which single modulated microRNAs mediate the anticancer effects of metformin are not entirely clear and knowledge of such a process could be vital to maximize the potential therapeutic benefits of this safe and well-tolerated therapy. Our analysis here revealed that the expression of miR-21-5p was downregulated in multiple breast cancer cell lines treated with pharmacologically relevant doses of metformin. Interestingly, the inhibition of miR-21-5p following metformin treatment was also observed in mouse breast cancer xenografts and in sera from 96 breast cancer patients. This modulation occurred at the levels of both pri-miR-21 and pre-miR-21, suggesting transcriptional modulation. Antagomir-mediated ablation of miR-21-5p phenocopied the effects of metformin on both the clonogenicity and migration of the treated cells, while ectopic expression of miR-21-5p had the opposite effect. Mechanistically, this reduction in miR-21-5p enhanced the expression of critical upstream activators of the AMP-activated protein kinase, calcium-binding protein 39-like and Sestrin-1, leading to AMP-activated protein kinase activation and inhibition of mammalian target of rapamycin signaling. Importantly, these effects of metformin were synergistic with those of everolimus, a clinically relevant mammalian target of rapamycin inhibitor, and were independent of the phosphatase and tensin homolog status. This highlights the potential relevance of metformin in combinatorial settings for the treatment of breast cancer.

Silicon microfabricated beam expander

NASA Astrophysics Data System (ADS)

Othman, A.; Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A.; Ain, M. F.

2015-03-01

The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed.

Photon mass attenuation coefficients of a silicon resin loaded with WO3, PbO, and Bi2O3 Micro and Nano-particles for radiation shielding

NASA Astrophysics Data System (ADS)

Verdipoor, Khatibeh; Alemi, Abdolali; Mesbahi, Asghar

2018-06-01

Novel shielding materials for photons based on silicon resin and WO3, PbO, and Bi2O3 Micro and Nano-particles were designed and their mass attenuation coefficients were calculated using Monte Carlo (MC) method. Using lattice cards in MCNPX code, micro and nanoparticles with sizes of 100 nm and 1 μm was designed inside a silicon resin matrix. Narrow beam geometry was simulated to calculate the attenuation coefficients of samples against mono-energetic beams of Co60 (1.17 and 1.33 MeV), Cs137 (663.8 KeV), and Ba133 (355.9 KeV). The shielding samples made of nanoparticles had higher mass attenuation coefficients, up to 17% relative to those made of microparticles. The superiority of nano-shields relative to micro-shields was dependent on the filler concentration and the energy of photons. PbO, and Bi2O3 nanoparticles showed higher attenuation compared to WO3 nanoparticles in studied energies. Fabrication of novel shielding materials using PbO, and Bi2O3 nanoparticles is recommended for application in radiation protection against photon beams.

Phloretin differentially inhibits volume-sensitive and cyclic AMP-activated, but not Ca-activated, Cl− channels

PubMed Central

Fan, Hai-Tian; Morishima, Shigeru; Kida, Hajime; Okada, Yasunobu

2001-01-01

Some phenol derivatives are known to block volume-sensitive Cl− channels. However, effects on the channel of the bisphenol phloretin, which is a known blocker of glucose uniport and anion antiport, have not been examined. In the present study, we investigated the effects of phloretin on volume-sensitive Cl− channels in comparison with cyclic AMP-activated CFTR Cl− channels and Ca2+-activated Cl− channels using the whole-cell patch-clamp technique.Extracellular application of phloretin (over 10 μM) voltage-independently, and in a concentration-dependent manner (IC50 ∼30 μM), inhibited the Cl− current activated by a hypotonic challenge in human epithelial T84, Intestine 407 cells and mouse mammary C127/CFTR cells.In contrast, at 30 μM phloretin failed to inhibit cyclic AMP-activated Cl− currents in T84 and C127/CFTR cells. Higher concentrations (over 100 μM) of phloretin, however, partially inhibited the CFTR Cl− currents in a voltage-dependent manner.At 30 and 300 μM, phloretin showed no inhibitory effect on Ca2+-dependent Cl− currents induced by ionomycin in T84 cells.It is concluded that phloretin preferentially blocks volume-sensitive Cl− channels at low concentrations (below 100 μM) and also inhibits cyclic AMP-activated Cl− channels at higher concentrations, whereas phloretin does not inhibit Ca2+-activated Cl− channels in epithelial cells. PMID:11487521

All-optical optoacoustic microscopy based on probe beam deflection technique.

PubMed

Maswadi, Saher M; Ibey, Bennett L; Roth, Caleb C; Tsyboulski, Dmitri A; Beier, Hope T; Glickman, Randolph D; Oraevsky, Alexander A

2016-09-01

Optoacoustic (OA) microscopy using an all-optical system based on the probe beam deflection technique (PBDT) for detection of laser-induced acoustic signals was investigated as an alternative to conventional piezoelectric transducers. PBDT provides a number of advantages for OA microscopy including (i) efficient coupling of laser excitation energy to the samples being imaged through the probing laser beam, (ii) undistorted coupling of acoustic waves to the detector without the need for separation of the optical and acoustic paths, (iii) high sensitivity and (iv) ultrawide bandwidth. Because of the unimpeded optical path in PBDT, diffraction-limited lateral resolution can be readily achieved. The sensitivity of the current PBDT sensor of 22 μV/Pa and its noise equivalent pressure (NEP) of 11.4 Pa are comparable with these parameters of the optical micro-ring resonator and commercial piezoelectric ultrasonic transducers. Benefits of the present prototype OA microscope were demonstrated by successfully resolving micron-size details in histological sections of cardiac muscle.

Numerical Study of Electrostatic Field Distortion on LPTPC End-Plates based on Bulk Micromegas Modules

NASA Astrophysics Data System (ADS)

Bhattacharya, Purba; Bhattacharya, Deb Sankar; Mukhopadhyay, Supratik; Majumdar, Nayana; Bhattacharya, Sudeb; Colas, Paul; Attié, David

2018-02-01

The R&D activities for the linear collider TPC (LC-TPC) are currently working on the adoption of the micro pattern devices for the gaseous amplification stage. Several beam tests have been carried out at DESY with a 5 GeV electron beam in a 1 T superconducting magnet. We worked on a large prototype TPC with an end-plate that was built, for the first time, using seven resistive bulk Micromegas modules. During experiments, reduced signal sensitivity was observed at the boundary of these modules. Electrostatic field distortion near the module boundaries was considered to be the possible major reason behind these observations. In the present work, we will explore this hypothesis through numerical simulation. Our aim has been to understand the origin of distortions observed close to the edges of the test beam modules and to explore the possibility of using the Garfield simulation framework for investigating a phenomenon as complex as distortion.

Optimizing laser beam profiles using micro-lens arrays for efficient material processing: applications to solar cells

NASA Astrophysics Data System (ADS)

Hauschild, Dirk; Homburg, Oliver; Mitra, Thomas; Ivanenko, Mikhail; Jarczynski, Manfred; Meinschien, Jens; Bayer, Andreas; Lissotschenko, Vitalij

2009-02-01

High power laser sources are used in various production tools for microelectronic products and solar cells, including the applications annealing, lithography, edge isolation as well as dicing and patterning. Besides the right choice of the laser source suitable high performance optics for generating the appropriate beam profile and intensity distribution are of high importance for the right processing speed, quality and yield. For industrial applications equally important is an adequate understanding of the physics of the light-matter interaction behind the process. In advance simulations of the tool performance can minimize technical and financial risk as well as lead times for prototyping and introduction into series production. LIMO has developed its own software founded on the Maxwell equations taking into account all important physical aspects of the laser based process: the light source, the beam shaping optical system and the light-matter interaction. Based on this knowledge together with a unique free-form micro-lens array production technology and patented micro-optics beam shaping designs a number of novel solar cell production tool sub-systems have been built. The basic functionalities, design principles and performance results are presented with a special emphasis on resilience, cost reduction and process reliability.

Knudsen torque on heated micro beams

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

Li, Qi; Liang, Tengfei; Ye, Wenjing

Thermally induced mechanical loading has been shown to have significant effects on micro/nano objects immersed in a gas with a non-uniform temperature field. While the majority of existing studies and related applications focus on forces, we investigate the torque, and thus the rotational motion, produced by such a mechanism. Using the asymptotic analysis in the near continuum regime, the Knudsen torque acting on an asymmetrically located uniformly heated microbeam in a cold enclosure is investigated. The existence of a non-zero net torque is demonstrated. In addition, it has been found that by manipulating the system configuration, the rotational direction ofmore » the torque can be changed. Two types of rotational motion of the microbeam have been identified: the pendulum motion of a rectangular beam, and the unidirectional rotation of a cylindrical beam. A rotational frequency of 4 rpm can be achieved for the cylindrical beam with a diameter of 3μm at Kn = 0.005. Illustrated by the simulations using the direct simulation of Monte Carlo, the Knudsen torque can be much increased in the transition regime, demonstrating the potential of Knudsen torque serving as a rotation engine for micro/nano objects.« less

A laboratory based system for laue micro x-ray diffraction.

PubMed

Lynch, P A; Stevenson, A W; Liang, D; Parry, D; Wilkins, S; Tamura, N

2007-02-01

A laboratory diffraction system capable of illuminating individual grains in a polycrystalline matrix is described. Using a microfocus x-ray source equipped with a tungsten anode and prefigured monocapillary optic, a micro-x-ray diffraction system with a 10 microm beam was developed. The beam profile generated by the ellipsoidal capillary was determined using the "knife edge" approach. Measurement of the capillary performance, indicated a beam divergence of 14 mrad and a useable energy bandpass from 5.5 to 19 keV. Utilizing the polychromatic nature of the incident x-ray beam and application of the Laue indexing software package X-Ray Micro-Diffraction Analysis Software, the orientation and deviatoric strain of single grains in a polycrystalline material can be studied. To highlight the system potential the grain orientation and strain distribution of individual grains in a polycrystalline magnesium alloy (Mg 0.2 wt % Nd) was mapped before and after tensile loading. A basal (0002) orientation was identified in the as-rolled annealed alloy; after tensile loading some grains were observed to undergo an orientation change of 30 degrees with respect to (0002). The applied uniaxial load was measured as an increase in the deviatoric tensile strain parallel to the load axis.

A high bandwidth three-axis out-of-plane motion measurement system based on optical beam deflection

NASA Astrophysics Data System (ADS)

Piyush, P.; Giridhar, M. S.; Jayanth, G. R.

2018-03-01

Multi-axis measurement of motion is indispensable for characterization of dynamic systems and control of motion stages. This paper presents an optical beam deflection-based measurement system to simultaneously measure three-axis out-of-plane motion of both micro- and macro-scale targets. Novel strategies are proposed to calibrate the sensitivities of the measurement system. Subsequently the measurement system is experimentally realized and calibrated. The system is employed to characterize coupled linear and angular motion of a piezo-actuated stage. The measured motion is shown to be in agreement with theoretical expectation. Next, the high bandwidth of the measurement system has been showcased by utilizing it to measure coupled two-axis transient motion of a Radio Frequency Micro-Electro-Mechanical System switch with a rise time of about 60 μs. Finally, the ability of the system to measure out-of-plane angular motion about the second axis has been demonstrated by measuring the deformation of a micro-cantilever beam.

Fabrication of single crystalline stripe in Si and Ge film on rolled flexible glass substrate by UV cw micro-chevron laser beam

NASA Astrophysics Data System (ADS)

Yeh, Wenchang

2017-08-01

Micro chevron laser beam annealing (μCLBA) of Si film and Ge film were introduced. Single crystal stripe with a dimension of several tens to hundreds μm in length and 3-8μm in width was formed in Si film or Ge film by scanning μCLBA over the film. Main boundaries in the c-Si stripe were Σ3 CSL twin boundary. Scanning speed of micro linear laser beam annealing (μLLBA) was varied from 0.05 m/s to 8m/s to investigate its influence to crystallinity. Even at 8m/s lateral growth taken place, however, crystal quality was better for slower lateral growth. Crystallization area per energy (APE) of μLLBA was evaluated and compared with other methods. It was found APE of μLLBA was larger than other method, especially for a display with low fill factor of TFT, APE can be several orders of magnitude larger.

Perfectionism and Depressive Symptoms in Early Adolescence

ERIC Educational Resources Information Center

Rice, Kenneth G.; Leever, Brooke A.; Noggle, Chad A.; Lapsley, Daniel K.

2007-01-01

The "Adaptive/Maladaptive Perfectionism Scale" (AMPS; K.G. Rice & K.J. Preusser, 2002) was developed on samples of 9- to 11-year-old children. A primary purpose of the current research was to examine whether the AMPS could be useful in studies of adolescents, and in particular, studies of adolescent depression. This study of 145 early adolescents…

New kids on the block: The Popeye domain containing (POPDC) protein family acting as a novel class of cAMP effector proteins in striated muscle.

PubMed

Brand, Thomas; Schindler, Roland

2017-12-01

The cyclic 3',5'-adenosine monophosphate (cAMP) signalling pathway constitutes an ancient signal transduction pathway present in prokaryotes and eukaryotes. Previously, it was thought that in eukaryotes three effector proteins mediate cAMP signalling, namely protein kinase A (PKA), exchange factor directly activated by cAMP (EPAC) and the cyclic-nucleotide gated channels. However, recently a novel family of cAMP effector proteins emerged and was termed the Popeye domain containing (POPDC) family, which consists of three members POPDC1, POPDC2 and POPDC3. POPDC proteins are transmembrane proteins, which are abundantly present in striated and smooth muscle cells. POPDC proteins bind cAMP with high affinity comparable to PKA. Presently, their biochemical activity is poorly understood. However, mutational analysis in animal models as well as the disease phenotype observed in patients carrying missense mutations suggests that POPDC proteins are acting by modulating membrane trafficking of interacting proteins. In this review, we will describe the current knowledge about this gene family and also outline the apparent gaps in our understanding of their role in cAMP signalling and beyond. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

cAMP Regulation of Airway Smooth Muscle Function

PubMed Central

Billington, Charlotte K.; Ojo, Oluwaseun O.; Penn, Raymond B.; Ito, Satoru

2013-01-01

Agonists activating β2-adrenoceptors (β2ARs) on airway smooth muscle (ASM) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease (COPD). Moreover, the use of long-acting β-agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases. β-Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction. The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as prostaglandin E2 and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration. Therefore, β2ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling. However, limitations of β-agonist therapy due to drug tachyphylaxis related to β2AR desensitization, and recent findings regarding the manner in which β2ARs and cAMP signal, have raised new and interesting questions about these well-studied molecules. In this review we discuss current concepts regarding β2ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD. PMID:22634112

The effects of Chinese medicines on cAMP/PKA signaling in central nervous system dysfunction.

PubMed

Li, Lin; Fan, Xiang; Zhang, Xi-Ting; Yue, Shao-Qian; Sun, Zuo-Yan; Zhu, Jin-Qiang; Zhang, Jun-Hua; Gao, Xiu-Mei; Zhang, Han

2017-06-01

Neuropathological injury in the mammalian adult central nervous system (CNS) may cause axon disruption, neuronal death and lasting neurological deficits. Failure of axon regeneration is one of the major challenges for CNS functional recovery. Recently, the cAMP/PKA signaling pathway has been proven to be a critical regulator for neuronal regeneration, neuroplasticity, learning and memory. Also, previous studies have shown the effects of Chinese medicines on the prevention and treatment of CNS dysfunction mediated in part by cAMP/PKA signaling. In this review, the authors discuss current knowledge of the role of cAMP/PKA signaling pathway in neuronal regeneration and provide an overview of the Chinese medicines that may enable CNS functional recovery via this signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

An overview of the facilities, activities, and developments at the University of North Texas Ion Beam Modification and Analysis Laboratory (IBMAL)

NASA Astrophysics Data System (ADS)

Rout, Bibhudutta; Dhoubhadel, Mangal S.; Poudel, Prakash R.; Kummari, Venkata C.; Pandey, Bimal; Deoli, Naresh T.; Lakshantha, Wickramaarachchige J.; Mulware, Stephen J.; Baxley, Jacob; Manuel, Jack E.; Pacheco, Jose L.; Szilasi, Szabolcs; Weathers, Duncan L.; Reinert, Tilo; Glass, Gary A.; Duggan, Jerry L.; McDaniel, Floyd D.

2013-07-01

The Ion Beam Modification and Analysis Laboratory (IBMAL) at the University of North Texas includes several accelerator facilities with capabilities of producing a variety of ion beams from tens of keV to several MeV in energy. The four accelerators are used for research, graduate and undergraduate education, and industrial applications. The NEC 3MV Pelletron tandem accelerator has three ion sources for negative ions: He Alphatross and two different SNICS-type sputter ion sources. Presently, the tandem accelerator has four high-energy beam transport lines and one low-energy beam transport line directly taken from the negative ion sources for different research experiments. For the low-energy beam line, the ion energy can be varied from ˜20 to 80 keV for ion implantation/modification of materials. The four post-acceleration beam lines include a heavy-ion nuclear microprobe; multi-purpose PIXE, RBS, ERD, NRA, and broad-beam single-event upset; high-energy ion implantation line; and trace-element accelerator mass spectrometry. The NEC 3MV single-ended Pelletron accelerator has an RF ion source mainly for hydrogen, helium and heavier inert gases. We recently installed a capacitive liner to the terminal potential stabilization system for high terminal voltage stability and high-resolution microprobe analysis. The accelerator serves a beam line for standard RBS and RBS/C. Another beamline for high energy focused ion beam application using a magnetic quadrupole lens system is currently under construction. This beam line will also serve for developmental work on an electrostatic lens system. The third accelerator is a 200 kV Cockcroft-Walton accelerator with an RF ion source. The fourth accelerator is a 2.5 MV Van de Graaff accelerator, which was in operation for last several decades is currently planned to be used mainly for educational purpose. Research projects that will be briefly discussed include materials synthesis/modification for photonic, electronic, and magnetic applications, surface sputtering and micro-fabrication of materials, development of high-energy ion microprobe systems, and educational and outreach activities.

An overview of the facilities, activities, and developments at the University of North Texas Ion Beam Modification and Analysis Laboratory (IBMAL)

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

Rout, Bibhudutta; Dhoubhadel, Mangal S.; Poudel, Prakash R.

2013-07-03

The Ion Beam Modification and Analysis Laboratory (IBMAL) at the University of North Texas includes several accelerator facilities with capabilities of producing a variety of ion beams from tens of keV to several MeV in energy. The four accelerators are used for research, graduate and undergraduate education, and industrial applications. The NEC 3MV Pelletron tandem accelerator has three ion sources for negative ions: He Alphatross and two different SNICS-type sputter ion sources. Presently, the tandem accelerator has four high-energy beam transport lines and one low-energy beam transport line directly taken from the negative ion sources for different research experiments. Formore » the low-energy beam line, the ion energy can be varied from {approx}20 to 80 keV for ion implantation/modification of materials. The four post-acceleration beam lines include a heavy-ion nuclear microprobe; multi-purpose PIXE, RBS, ERD, NRA, and broad-beam single-event upset; high-energy ion implantation line; and trace-element accelerator mass spectrometry. The NEC 3MV single-ended Pelletron accelerator has an RF ion source mainly for hydrogen, helium and heavier inert gases. We recently installed a capacitive liner to the terminal potential stabilization system for high terminal voltage stability and high-resolution microprobe analysis. The accelerator serves a beam line for standard RBS and RBS/C. Another beamline for high energy focused ion beam application using a magnetic quadrupole lens system is currently under construction. This beam line will also serve for developmental work on an electrostatic lens system. The third accelerator is a 200 kV Cockcroft-Walton accelerator with an RF ion source. The fourth accelerator is a 2.5 MV Van de Graaff accelerator, which was in operation for last several decades is currently planned to be used mainly for educational purpose. Research projects that will be briefly discussed include materials synthesis/modification for photonic, electronic, and magnetic applications, surface sputtering and micro-fabrication of materials, development of high-energy ion microprobe systems, and educational and outreach activities.« less

High energy micro electron beam generation using chirped laser pulse in the presence of an axial magnetic field

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

Akou, H., E-mail: h.akou@nit.ac.ir; Hamedi, M.

2015-10-15

In this paper, the generation of high-quality and high-energy micro electron beam in vacuum by a chirped Gaussian laser pulse in the presence of an axial magnetic field is numerically investigated. The features of energy and angular spectra, emittances, and position distribution of electron beam are compared in two cases, i.e., in the presence and absence of an external magnetic field. The electron beam is accelerated with higher energy and qualified in spatial distribution in the presence of the magnetic field. The presence of an axial magnetic field improves electron beam spatial quality as well as its gained energy throughmore » keeping the electron motion parallel to the direction of propagation for longer distances. It has been found that a 64 μm electron bunch with about MeV initial energy becomes a 20 μm electron beam with high energy of the order of GeV, after interacting with a laser pulse in the presence of an external magnetic field.« less

Design of collimating and rearrangement systems of laser diode array beam

NASA Astrophysics Data System (ADS)

Gao, Runmei; Fang, Tao; Fu, Rulian; Yao, Jianquan

2015-10-01

To improve the laser diode output beam quality, micro-cylindrical lens and the step-type lens combination are designed. The former is used to collimate beam in fast-axis direction, while the latter plays a role in the slow-axis of splitting and the rearrangement. The micro-column semi-elliptical lens is made with the drops of spherical zoom lensin electric field and with the help of the material properties of light-cured production, which can reduce the reflection of the front surface and total reflection loss of the after. The divergence angle in the fast axis is compressed to roughly the same as that in the slow-axis direction; Stepped lens splits compressed long strip beam in the slow axis, with parallelogram style of level equidistant and rearrange in the fast axis direction. The spot in the slow axis gets smaller and the spot becomes larger in the fast axis. At last divergence angle and the beam spot achieve balanced in the fast axis and slow axis, optical parameters BPP integrates approximate the same, and beam quality can be improved.

Raman microspectroscopy of optically trapped micro- and nanoobjects

NASA Astrophysics Data System (ADS)

Jonáš, Alexandr; Ježek, Jan; Šerý, Mojmír; Zemánek, Pavel

2008-12-01

We describe and characterize an experimental system for Raman microspectroscopy of micro- and nanoobjects optically trapped in aqueous suspensions with the use of a single-beam gradient optical trap (Raman tweezers). This system features two separate lasers providing light for the optical trapping and excitation of the Raman scattering spectra from the trapped specimen, respectively. Using independent laser beams for trapping and spectroscopy enables optimizing the parameters of both beams for their respective purposes. Moreover, it is possible to modulate the position of the trapped object relative to the Raman beam focus for maximizing the detected Raman signal and obtaining spatially resolved images of the trapped specimen. Using this experimental system, we have obtained Raman scattering spectra of individual optically confined micron and sub-micron sized polystyrene beads and baker's yeast cells. Sufficiently high signal-to-noise ratio of the spectra could be achieved using a few tens of milliwatts of the Raman beam power and detector integration times on the order of seconds.

3-dimensional free standing micro-structures by proton beam writing of Su 8-silver nanoParticle polymeric composite

NASA Astrophysics Data System (ADS)

Igbenehi, H.; Jiguet, S.

2012-09-01

Proton beam lithography a maskless direct-write lithographic technique (well suited for producing 3-Dimensional microstructures in a range of resist and semiconductor materials) is demonstrated as an effective tool in the creation of electrically conductive freestanding micro-structures in an Su 8 + Nano Silver polymer composite. The structures produced show non-ohmic conductivity and fit the percolation theory conduction model of tunneling of separated nanoparticles. Measurements show threshold switching and a change in conductivity of at least 4 orders of magnitude. The predictable range of protons in materials at a given energy is exploited in the creation of high aspect ratio, free standing micro-structures, made from a commercially available SU8 Silver nano-composite (GMC3060 form Gersteltec Inc. a negative tone photo-epoxy with added metallic nano-particles(Silver)) to create films with enhanced electrical properties when exposed and cured. Nano-composite films are directly written on with a finely focused MeV accelerated Proton particle beam. The energy loss of the incident proton beams in the target polymer nano- composite film is concentrated at the end of its range, where damage occurs; changing the chemistry of the nano-composite film via an acid initiated polymerization - creating conduction paths. Changing the energy of the incident beams provide exposed regions with different penetration and damage depth - exploited in the demonstrated cantilever microstructure.

Test Report - Fault Current Through Graphite Filament Reinforced Plastic

NASA Technical Reports Server (NTRS)

Evans, R. W.

1997-01-01

Tests were performed to determine the damage to samples of composite material when a current carrying wire is shorted to the surface of the composite material, and to determine whether enough current can flow through the material to blow a fuse before damage can occur. Fault current tests were performed on samples of graphite epoxy materials. Samples consisted of six layers of IM7 graphite fiber mat in Hercules 8552 epoxy resin. A variable power supply provided up to 35 amps of current. The high voltage side of the power supply was attached to a wire at the end of a hinged arm, and the low side was attached to the edge of the sample. To test joints, the return was connected to the edge of one sample, and the high side was shorted to the top of the other sample. Tests show that when current exceeds approximately 5 amps, the graphite glows, and the epoxy melts out at the shorted contact. At higher current levels the epoxy burns. At voltages above 15 volts the epoxy outer coat is easily broken, and fire, flame, and a rise in current occur suddenly. When joints are introduced, resistance is increased, and the maximum current resulting from a short circuit to the graphite epoxy is reduced. This condition can easily result in fault current lower than the circuit breaker limit and higher than the 5 amp ignition level. The shorting contact and the joint become hot spots with melting epoxy, smoke, and fire.

Development of high temperature gallium phosphide rectifiers

NASA Technical Reports Server (NTRS)

Craford, M. G.; Keune, D. L.

1972-01-01

Large area high performance, GaP rectifiers were fabricated by means of Zn diffusion into vapor phase epitaxial GaP. Devices with an active area of 0.01 sq cm typically exhibit forward voltages of 3 volts for a bias current of 1 ampere and have reverse breakdown voltages of 300 volts for temperatures from 27 C to 400 C. Typical device reverse saturation current at a reverse bias of 150 volts is less than 10 to the minus 9th power amp at 27 C and less than 0.000050 amp at 400 C.

Antimicrobial peptides as a possible interlink between periodontal diseases and its risk factors: A systematic review.

PubMed

Li, S; Schmalz, G; Schmidt, J; Krause, F; Haak, R; Ziebolz, D

2018-04-01

Antimicrobial peptides (AMPs) play a critical role in controlling innate and acquired immune responses. Local dysregulation of AMP is implicated in the pathogenesis of periodontal diseases as a response to periodontal pathogen challenge. Changes in AMP expression also characterize tobacco smoking, diabetes mellitus, obesity and rheumatoid arthritis, which are established risk factors of periodontal diseases, suggesting AMP may act as putative mechanistic links between these. The aim was to evaluate and summarize critically the current evidence pertaining to interrelationships between AMPs, periodontal diseases and selected periodontal disease risk factors. General and theme specific keywords were used to search the PUBMED database for studies relevant to AMP, periodontal diseases, smoking, diabetes mellitus, obesity and rheumatoid arthritis and critically reviewed. A total of 131 abstracts and 119 full text articles were screened for relevance; 13 studies were selected for inclusion after critical review. Local AMP dysregulation characteristic to periodontal diseases appears to occur within a broader landscape of complex systemic immune perturbations independently induced by smoking, metabolic and rheumatoid disease. The nature of these interactions and mechanistic pathways involved are inadequately understood. AMPs could be possible mechanistic interlinks between periodontal diseases and its risk factors. However, such evidence is very limited and more in vivo and in vitro studies are necessary to clarify the nature of such relationships. A greater understanding of AMPs as shared mediators is essential for unraveling their value as therapeutic or biomarker candidates. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Developmental Decline in the MicroRNA 199a (miR-199a)/miR-214 Cluster in Human Fetal Lung Promotes Type II Cell Differentiation by Upregulating Key Transcription Factors.

PubMed

Mishra, Ritu; Benlhabib, Houda; Guo, Wei; Lerma Cervantes, Connie B; Mendelson, Carole R

2018-06-01

The major surfactant protein, SP-A (a product of the SFTPA gene), serves as a marker of type II pneumocyte differentiation and surfactant synthesis. SFTPA expression in cultured human fetal lung (HFL) epithelial cells is upregulated by hormones that increase cyclic AMP (cAMP) and activate TTF-1/NKX2.1 and NF-κB. To further define mechanisms for type II cell differentiation and induction of SP-A, we investigated roles of microRNAs (miRNAs). Using microarray to identify differentially expressed miRNAs in HFL epithelial cells during type II cell differentiation in culture, we observed that members of the miRNA 199a (miR-199a)/miR-214 cluster were significantly downregulated during differentiation. Validated and predicted targets of miR-199a-3p/miR-199a-5p and miR-214, which serve roles in type II cell differentiation (COX-2, NF-κB p50/p65, and CREB1), and the CREB1 target, C/EBPβ, were coordinately upregulated. Accordingly, overexpression of miR-199a-5p, miR-199a-3p, or miR-214 mimics in cultured HFL epithelial cells decreased COX-2, NF-κB p50/p65, CREB1, and C/EBPβ proteins, with an associated inhibition of SP-A expression. Interestingly, overexpression of the EMT factor, ZEB1, which declines during cAMP-induced type II cell differentiation, increased pri-miR-199a and reduced the expression of the targets NF-κB/p50 and COX-2. Collectively, these findings suggest that the developmental decline in miR-199a/miR-214 in HFL causes increased expression of critical targets that enhance type II cell differentiation and SP-A expression. Copyright © 2018 American Society for Microbiology.

Micro-particle manipulation by single beam acoustic tweezers based on hydrothermal PZT thick film.

PubMed

Zhu, Benpeng; Xu, Jiong; Li, Ying; Wang, Tian; Xiong, Ke; Lee, Changyang; Yang, Xiaofei; Shiiba, Michihisa; Takeuchi, Shinichi; Zhou, Qifa; Shung, K Kirk

2016-03-01

Single-beam acoustic tweezers (SBAT), used in laboratory-on-a-chip (LOC) device has promising implications for an individual micro-particle contactless manipulation. In this study, a freestanding hydrothermal PZT thick film with excellent piezoelectric property (d 33 = 270pC/N and k t = 0.51) was employed for SBAT applications and a press-focusing technology was introduced. The obtained SBAT, acting at an operational frequency of 50MHz, a low f-number (∼0.9), demonstrated the capability to trap and manipulate a micro-particle sized 10μm in the distilled water. These results suggest that such a device has great potential as a manipulator for a wide range of biomedical and chemical science applications.

Micro-cone targets for producing high energy and low divergence particle beams

DOEpatents

Le Galloudec, Nathalie

2013-09-10

The present invention relates to micro-cone targets for producing high energy and low divergence particle beams. In one embodiment, the micro-cone target includes a substantially cone-shaped body including an outer surface, an inner surface, a generally flat and round, open-ended base, and a tip defining an apex. The cone-shaped body tapers along its length from the generally flat and round, open-ended base to the tip defining the apex. In addition, the outer surface and the inner surface connect the base to the tip, and the tip curves inwardly to define an outer surface that is concave, which is bounded by a rim formed at a juncture where the outer surface meets the tip.

Stabilities of lead(II) complexes formed in aqueous solution with methyl thiophosphate (MeOPS(2-)), uridine 5'- O-thiomonophosphate (UMPS(2-)) or adenosine 5'- O-thiomonophosphate (AMPS(2-)).

PubMed

Da Costa, Carla P; Krajewska, Danuta; Okruszek, Andrzej; Stec, Wojciech J; Sigel, Helmut

2002-04-01

The acidity constants of twofold protonated methyl thiophosphate (MeOPS(2-)) and of monoprotonated uridine 5'- O-thiomonophosphate (UMPS(2-)) have been determined in aqueous solution (25 degrees C; I= 0.1 M, NaNO(3)) by potentiometric pH titration. The stability constants of their 1:1 complexes formed with Pb(2+), i.e. Pb(MeOPS) and Pb(UMPS), have also been measured. The results show that replacement of a phosphate oxygen by a sulfur atom increases the acidity by about 1.4 p K units. On the basis of recently established log versus plots ( = simple phosphate or phosphonate ligands where R is a non-coordinating residue), it is shown that the stability of the Pb(thiophosphate) complexes is by log Delta= 2.43+/-0.09 larger than expected for a Pb(2+)-phosphate interaction. The identity of the stability increase (log Delta) observed for Pb(MeOPS) and Pb(UMPS) shows that the nucleobase residue in the Pb(UMPS) complex has no influence on complex formation. To be able to carry out the mentioned comparisons, we have also determined the stability constant of the complex formed between Pb(2+) and methyl phosphate; the corresponding data for Pb(UMP) were already known from our earlier studies. The present results allow an evaluation of other Pb(2+) complexes formed with thiophosphate derivatives and they are applied now to the Pb(2+) complexes of adenosine 5'- O-thiomonophosphate (AMPS(2-)). The stability constants of the Pb(H;AMPS)(+) and Pb(AMPS) complexes were measured and it is shown that, within the error limits, the stability of the Pb(AMPS) complex is determined by the basicity of the thiophosphate group of AMPS(2-); in other words, no hint for macrochelate formation involving N7 was observed. More important, with the aid of micro-stability-constant considerations it is concluded that the structure of the dominating isomer of the Pb(H;AMPS)(+) species is the one where the proton is located at the N1 site of the adenine residue and Pb(2+) is coordinated to the deprotonated thiophosphate group. The insights gained from this study with regard to thiophosphate-altered single-stranded nucleic acids and their affinity towards Pb(2+) are discussed.

Caffeine accelerates recovery from general anesthesia via multiple pathways.

PubMed

Fong, Robert; Khokhar, Suhail; Chowdhury, Atif N; Xie, Kelvin G; Wong, Josiah Hiu-Yuen; Fox, Aaron P; Xie, Zheng

2017-09-01

Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A 2a adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP] i )-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A 2A receptor blockade and [cAMP] i elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP] i and adenosine receptor blockade play a role in this response. NEW & NOTEWORTHY Currently, there is no method to accelerate emergence from anesthesia. Patients "wake" when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that caffeine is effective even at high levels of anesthetic. We also show that caffeine operates by both elevating intracellular cAMP levels and by blocking adenosine receptors. This complicated pharmacology makes caffeine especially effective in accelerating emergence from anesthesia. Copyright © 2017 the American Physiological Society.

Two-dimensional ultrahigh-density X-ray optical memory.

PubMed

Bezirganyan, Hakob P; Bezirganyan, Siranush E; Bezirganyan, Hayk H; Bezirganyan, Petros H

2007-01-01

Most important aspect of nanotechnology applications in the information ultrahigh storage is the miniaturization of data carrier elements of the storage media with emphasis on the long-term stability. Proposed two-dimensional ultrahigh-density X-ray optical memory, named X-ROM, with long-term stability is an information carrier basically destined for digital data archiving. X-ROM is a semiconductor wafer, in which the high-reflectivity nanosized X-ray mirrors are embedded. Data are encoded due to certain positions of the mirrors. Ultrahigh-density data recording procedure can e.g., be performed via mask-less zone-plate-array lithography (ZPAL), spatial-phase-locked electron-beam lithography (SPLEBL), or focused ion-beam lithography (FIB). X-ROM manufactured by nanolithography technique is a write-once memory useful for terabit-scale memory applications, if the surface area of the smallest recording pits is less than 100 nm2. In this case the X-ROM surface-storage capacity of a square centimetre becomes by two orders of magnitude higher than the volumetric data density really achieved for three-dimensional optical data storage medium. Digital data read-out procedure from proposed X-ROM can e.g., be performed via glancing-angle incident X-ray micro beam (GIX) using the well-developed X-ray reflectometry technique. In presented theoretical paper the crystal-analyser operating like an image magnifier is added to the set-up of X-ROM data handling system for the purpose analogous to case of application the higher numerical aperture objective in optical data read-out system. We also propose the set-up of the X-ROM readout system based on more the one incident X-ray micro beam. Presented scheme of two-beam data handling system, which operates on two mutually perpendicular well-collimated monochromatic incident X-ray micro beams, essentially increases the reliability of the digital information read-out procedure. According the graphs of characteristic functions presented in paper, one may choose optimally the incident radiation wavelength, as well as the angle of incidence of X-ray micro beams, appropriate for proposed digital data read-out procedure.

Self-bunching electron guns

NASA Astrophysics Data System (ADS)

Mako, Frederick M.; Len, L. K.

1999-05-01

We report on three electron gun projects that are aimed at power tube and injector applications. The purpose of the work is to develop robust electron guns which produce self-bunched, high-current-density beams. We have demonstrated, in a microwave cavity, self-bunching, cold electron emission, long life, and tolerance to contamination. The cold process is based on secondary electron emission. FMT has studied using simulation codes the resonant bunching process which gives rise to high current densities (0.01-5 kA/cm2), high charge bunches (up to 500 nC/bunch), and short pulses (1-100 ps) for frequencies from 1 to 12 GHz. The beam pulse width is nominally ˜5% of the rf period. The first project is the L-Band Micro-Pulse Gun (MPG). Measurements show ˜40 ps long micro-bunches at ˜20 A/cm2 without contamination due to air exposure. Lifetime testing has been carried out for about 18 months operating at 1.25 GHz for almost 24 hours per day at a repetition rate of 300 Hz and 5 μs-long macro-pulses. Approximately 5.8×1013 micro-bunches or 62,000 coulombs have passed through this gun and it is still working fine. The second project, the S-Band MPG, is now operational. It is functioning at a frequency of 2.85 GHz, a repetition rate of 30 Hz, with a 2 μs-long macro-pulse. It produces about 45 A in the macro-pulse. The third project is a 34.2 GHz frequency-multiplied source driven by an X-Band MPG. A point design was performed at an rf output power of 150 MW at 34.2 GHz. The resulting system efficiency is 53% and the gain is 60 dB. The system efficiency includes the input cavity efficiency, input driver efficiency (a 50 MW klystron at 11.4 GHz), output cavity efficiency, and the post-acceleration efficiency.

DE 1 observations of type 1 counterstreaming electrons and field-aligned currents

NASA Technical Reports Server (NTRS)

Lin, C. S.; Burch, J. L.; Barfield, J. N.; Sugiura, M.; Nielsen, E.

1984-01-01

Dynamics Explorer 1 satellite observations of plasma and magnetic fields during type one counterstreaming electron events are presented. Counterstreaming electrons are observed at high altitudes in the region of field-aligned current. The total current density computed from the plasma data in the 18-10,000 eV energy range is generally about 1-2 micro-A/sq m. For the downward current, low-energy electrons contribute more than 40 percent of the total plasma current density integrated above 18 eV. For the upward current, such electrons contribute less than 50 percent of that current density. Electron beams in the field-aligned direction are occasionally detected. The pitch angle distributions of counterstreaming electrons are generally enhanced at both small and large pitch angles. STARE simultaneous observations for one DE 1 pass indicated that the field-aligned current was closed through Pedersen currents in the ionosphere. The directions of the ionospheric current systems are consistent with the DE 1 observations at high altitudes.

InGaN based micro light emitting diodes featuring a buried GaN tunnel junction

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

Malinverni, M., E-mail: marco.malinverni@epfl.ch; Martin, D.; Grandjean, N.

GaN tunnel junctions (TJs) are grown by ammonia molecular beam epitaxy. High doping levels are achieved with a net acceptor concentration close to ∼10{sup 20 }cm{sup −3}, thanks to the low growth temperature. This allows for the realization of p-n junctions with ultrathin depletion width enabling efficient interband tunneling. n-p-n structures featuring such a TJ exhibit low leakage current densities, e.g., <5 × 10{sup −5} A cm{sup −2} at reverse bias of 10 V. Under forward bias, the voltage is 3.3 V and 4.8 V for current densities of 20 A cm{sup −2} and 2000 A cm{sup −2}, respectively. The specific series resistance of the whole device ismore » 3.7 × 10{sup −4} Ω cm{sup 2}. Then micro-light emitting diodes (μ-LEDs) featuring buried TJs are fabricated. Excellent current confinement is demonstrated together with homogeneous electrical injection, as seen on electroluminescence mapping. Finally, the I-V characteristics of μ-LEDs with various diameters point out the role of the access resistance at the current aperture edge.« less

The dynamic micro computed tomography at SSRF

NASA Astrophysics Data System (ADS)

Chen, R.; Xu, L.; Du, G.; Deng, B.; Xie, H.; Xiao, T.

2018-05-01

Synchrotron radiation micro-computed tomography (SR-μCT) is a critical technique for quantitative characterizing the 3D internal structure of samples, recently the dynamic SR-μCT has been attracting vast attention since it can evaluate the three-dimensional structure evolution of a sample. A dynamic μCT method, which is based on monochromatic beam, was developed at the X-ray Imaging and Biomedical Application Beamline at Shanghai Synchrotron Radiation Facility, by combining the compressed sensing based CT reconstruction algorithm and hardware upgrade. The monochromatic beam based method can achieve quantitative information, and lower dose than the white beam base method in which the lower energy beam is absorbed by the sample rather than contribute to the final imaging signal. The developed method is successfully used to investigate the compression of the air sac during respiration in a bell cricket, providing new knowledge for further research on the insect respiratory system.

Hepatic gene expression profiling of 5'-AMP-induced hypometabolism in mice.

PubMed

Zhao, Zhaoyang; Miki, Takao; Van Oort-Jansen, Anita; Matsumoto, Tomoko; Loose, David S; Lee, Cheng Chi

2011-04-12

There is currently much interest in clinical applications of therapeutic hypothermia. Hypothermia can be a consequence of hypometabolism. We have recently established a procedure for the induction of a reversible deep hypometabolic state in mice using 5'-adenosine monophosphate (5'-AMP) in conjunction with moderate ambient temperature. The current study aims at investigating the impact of this technology at the gene expression level in a major metabolic organ, the liver. Our findings reveal that expression levels of the majority of genes in liver are not significantly altered by deep hypometabolism. However, among those affected by hypometabolism, more genes are differentially upregulated than downregulated both in a deep hypometabolic state and in the early arousal state. These altered gene expression levels during 5'-AMP induced hypometabolism are largely restored to normal levels within 2 days of the treatment. Our data also suggest that temporal control of circadian genes is largely stalled during deep hypometabolism.

Chemical micro-sensor

DOEpatents

Ruggiero, Anthony J.

2005-05-03

An integrated optical capillary electrophoresis system for analyzing an analyte. A modulated optical pump beam impinges on an capillary containing the analyte/buffer solution which is separated by electrophoresis. The thermally-induced change in the index of refraction of light in said electrophoresis capillary is monitored using an integrated micro-interferometer. The interferometer includes a first interferometer arm intersecting the electrophoresis capillary proximate the excitation beam and a second, reference interferometer arm. Changes in index of refraction in the analyte measured by interrogating the interferometer state using white light interferometry and a phase-generated carrier demodulation technique. Background thermo-optical activity in the buffer solution is cancelled by splitting the pump beam and exciting pure buffer solution in a second section of capillary where it crosses the reference arm of the interferometer.

Role of exchange protein directly activated by cAMP (EPAC1) in breast cancer cell migration and apoptosis.

PubMed

Kumar, Naveen; Gupta, Sonal; Dabral, Surbhi; Singh, Shailja; Sehrawat, Seema

2017-06-01

Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death. Herein, we performed the analysis of the Cancer Genome Atlas (TCGA) dataset to evaluate the essential role of cAMP molecular network in breast cancer. We report that EPAC1, PKA, and AKAP9 along with other molecular partners are amplified in breast cancer patients, indicating the importance of this signaling network. To evaluate the functional role of few of these proteins, we used pharmacological modulators and analyzed their effect on cell migration and cell death in breast cancer cells. Hence, we report that inhibition of EPAC1 activity using pharmacological modulators leads to inhibition of cell migration and induces cell death. Additionally, we also observed that the inhibition of EPAC1 resulted in disruption of its association with the microtubule cytoskeleton and delocalization of AKAP9 from the centrosome as analyzed by in vitro imaging. Finally, this study suggests for the first time the mechanistic insights of mode of action of a primary cAMP-dependent sensor, Exchange protein activated by cAMP 1 (EPAC1), via its interaction with A-kinase anchoring protein 9 (AKAP9). This study provides a new cell signaling cAMP-EPAC1-AKAP9 direction to the development of additional biotherapeutics for breast cancer.

High frequency characteristic of a monolithic 500 °C OpAmp-RC integrator in SiC bipolar IC technology

NASA Astrophysics Data System (ADS)

Tian, Ye; Zetterling, Carl-Mikael

2017-09-01

This paper presents a comprehensive investigation of the frequency response of a monolithic OpAmp-RC integrator implemented in a 4H-SiC bipolar IC technology. The circuits and devices have been measured and characterized from 27 to 500 °C. The devices have been modelled to identify that the substrate capacitance is a dominant factor affecting the OpAmp's high-frequency response. Large Miller compensation capacitors of more than 540 pF are required to ensure stability of the internal OpAmp. The measured unit-gain-bandwidth product of the OpAmp is ∼1.1 MHz at 27 °C, and decreases to ∼0.5 MHz at 500 °C mainly due to the reduction of the transistor's current gain. On the other hand, it is not necessary to compensate the integrator in a relatively wide bandwidth ∼0.7 MHz over the investigated temperature range. At higher frequencies, the integrator's frequency response has been identified to be significantly affected by that of the OpAmp and load impedance. This work demonstrates the potential of this technology for high temperature applications requiring bandwidths of several megahertz.

Flavonoid Regulation of HCN2 Channels*

PubMed Central

Carlson, Anne E.; Rosenbaum, Joel C.; Brelidze, Tinatin I.; Klevit, Rachel E.; Zagotta, William N.

2013-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are pacemaker channels whose currents contribute to rhythmic activity in the heart and brain. HCN channels open in response to hyperpolarizing voltages, and the binding of cAMP to their cyclic nucleotide-binding domain (CNBD) facilitates channel opening. Here, we report that, like cAMP, the flavonoid fisetin potentiates HCN2 channel gating. Fisetin sped HCN2 activation and shifted the conductance-voltage relationship to more depolarizing potentials with a half-maximal effective concentration (EC50) of 1.8 μm. When applied together, fisetin and cAMP regulated HCN2 gating in a nonadditive fashion. Fisetin did not potentiate HCN2 channels lacking their CNBD, and two independent fluorescence-based binding assays reported that fisetin bound to the purified CNBD. These data suggest that the CNBD mediates the fisetin potentiation of HCN2 channels. Moreover, binding assays suggest that fisetin and cAMP partially compete for binding to the CNBD. NMR experiments demonstrated that fisetin binds within the cAMP-binding pocket, interacting with some of the same residues as cAMP. Together, these data indicate that fisetin is a partial agonist for HCN2 channels. PMID:24085296

[Occurrence of AmpC-positive Klebsiella pneumoniae strains in patients with haematological malignancies].

PubMed

Chromá, Magdaléna; Kolár, Milan; Sauer, Pavel; Faber, Edgar; Stosová, Tatána; Koukalová, Dagmar; Indrák, Karel

2008-10-01

Currently, important bacterial beta-lactamases of increasing clinical significance include AmpC enzymes. The aim was to assess their occurrence in Klebsiella pneumoniae strains isolated from patients with haematological malignancies in a prospective study. Over a 2-month period, strains of the species were isolated from clinical material obtained from patients hospitalized at the Department of Haemato-Oncology of the University Hospital Olomouc. The strains were identified using standard microbiological techniques and the Vitek 2 automated system. Production of AmpC beta-lactamases was roughly determined by phenotypic tests and subsequently confirmed by PCR detection of genes encoding these enzymes. During the above-mentioned period, a total of 35 K. pneumoniae isolates were collected. In 7 of them, production of AmpC beta-lactamases was preliminarily detected by phenotypic test. The multiplex PCR method confirmed phenotyping and determined DHA types in all the isolates. All AmpC-positive isolates were false-susceptible to at least one of the tested third-generation cephalosporins. In one patient, clinically apparent infection caused by this strain was documented. The reported results suggest the possibility of occurrence of AmpC-beta-lactamases in K. pneumoniae strains with clinical significance.

Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents.

PubMed

Mani, Bharath K; Robakowski, Christina; Brueggemann, Lyubov I; Cribbs, Leanne L; Tripathi, Abhishek; Majetschak, Matthias; Byron, Kenneth L

2016-03-01

Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K(+) currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 > Kv7.4/Kv7.5 > Kv7.4. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents

PubMed Central

Mani, Bharath K.; Robakowski, Christina; Brueggemann, Lyubov I.; Cribbs, Leanne L.; Tripathi, Abhishek; Majetschak, Matthias

2016-01-01

Kv7 (KCNQ) channels, formed as homo- or heterotetramers of Kv7.4 and Kv7.5 α-subunits, are important regulators of vascular smooth muscle cell (VSMC) membrane voltage. Recent studies demonstrate that direct pharmacological modulation of VSMC Kv7 channel activity can influence blood vessel contractility and diameter. However, the physiologic regulation of Kv7 channel activity is still poorly understood. Here, we study the effect of cAMP/protein kinase A (PKA) activation on whole cell K+ currents through endogenous Kv7.5 channels in A7r5 rat aortic smooth muscle cells or through Kv7.4/Kv7.5 heteromeric channels natively expressed in rat mesenteric artery smooth muscle cells. The contributions of specific α-subunits are further dissected using exogenously expressed human Kv7.4 and Kv7.5 homo- or heterotetrameric channels in A7r5 cells. Stimulation of Gαs-coupled β-adrenergic receptors with isoproterenol induced PKA-dependent activation of endogenous Kv7.5 currents in A7r5 cells. The receptor-mediated enhancement of Kv7.5 currents was mimicked by pharmacological agents that increase [cAMP] (forskolin, rolipram, 3-isobutyl-1-methylxanthine, and papaverine) or mimic cAMP (8-bromo-cAMP); the 2- to 4-fold PKA-dependent enhancement of currents was also observed with exogenously expressed Kv7.5 channels. In contrast, exogenously-expressed heterotetrameric Kv7.4/7.5 channels in A7r5 cells or native mesenteric artery smooth muscle Kv7.4/7.5 channels were only modestly enhanced, and homo-tetrameric Kv7.4 channels were insensitive to this regulatory pathway. Correspondingly, proximity ligation assays indicated that isoproterenol induced PKA-dependent phosphorylation of exogenously expressed Kv7.5 channel subunits, but not of Kv7.4 subunits. These results suggest that signal transduction-mediated responsiveness of vascular smooth muscle Kv7 channel subunits to cAMP/PKA activation follows the order of Kv7.5 >> Kv7.4/Kv7.5 > Kv7.4. PMID:26700561

Plasma Shield for In-Air and Under-Water Beam Processes

NASA Astrophysics Data System (ADS)

Hershcovitch, Ady

2007-11-01

As the name suggests, the Plasma Shield is designed to chemically and thermally shield a target object by engulfing an area subjected to beam treatment with inert plasma. The shield consists of a vortex-stabilized arc that is employed to shield beams and workpiece area of interaction from atmospheric or liquid environment. A vortex-stabilized arc is established between a beam generating device (laser, ion or electron gun) and the target object. The arc, which is composed of a pure noble gas (chemically inert), engulfs the interaction region and shields it from any surrounding liquids like water or reactive gases. The vortex is composed of a sacrificial gas or liquid that swirls around and stabilizes the arc. In current art, many industrial processes like ion material modification by ion implantation, dry etching, and micro-fabrication, as well as, electron beam processing, like electron beam machining and electron beam melting is performed exclusively in vacuum, since electron guns, ion guns, their extractors and accelerators must be kept at a reasonably high vacuum, and since chemical interactions with atmospheric gases adversely affect numerous processes. Various processes involving electron ion and laser beams can, with the Plasma Shield be performed in practically any environment. For example, electron beam and laser welding can be performed under water, as well as, in situ repair of ship and nuclear reactor components. The plasma shield results in both thermal (since the plasma is hotter than the environment) and chemical shielding. The latter feature brings about in-vacuum process purity out of vacuum, and the thermal shielding aspect results in higher production rates. Recently plasma shielded electron beam welding experiments were performed resulting in the expected high quality in-air electron beam welding. Principle of operation and experimental results are to be discussed.

Single cell adhesion force measurement for cell viability identification using an AFM cantilever-based micro putter

NASA Astrophysics Data System (ADS)

Shen, Yajing; Nakajima, Masahiro; Kojima, Seiji; Homma, Michio; Kojima, Masaru; Fukuda, Toshio

2011-11-01

Fast and sensitive cell viability identification is a key point for single cell analysis. To address this issue, this paper reports a novel single cell viability identification method based on the measurement of single cell shear adhesion force using an atomic force microscopy (AFM) cantilever-based micro putter. Viable and nonviable yeast cells are prepared and put onto three kinds of substrate surfaces, i.e. tungsten probe, gold and ITO substrate surfaces. A micro putter is fabricated from the AFM cantilever by focused ion beam etching technique. The spring constant of the micro putter is calibrated using the nanomanipulation approach. The shear adhesion force between the single viable or nonviable cell and each substrate is measured using the micro putter based on the nanorobotic manipulation system inside an environmental scanning electron microscope. The adhesion force is calculated based on the deflection of the micro putter beam. The results show that the adhesion force of the viable cell to the substrate is much larger than that of the nonviable cell. This identification method is label free, fast, sensitive and can give quantitative results at the single cell level.

Analysis of copper mixed kerosene servotherm in EDM of Monel 400™

NASA Astrophysics Data System (ADS)

Anandakumar, P. A.; Molla, Baya; Biruke, Fisha; Aravind, S.

2017-05-01

Powder mixed electro discharge machine process (PMEDM) is a hybrid machine process where a conductive powders is mixed to the dielectric fluid to facilitate effective machining of advanced material. This present study focused on performance of copper mixed kerosene servotherm as dielectric medium in EDM of Monel 400TM. The ratio of kerosene sevothermis 75 : 25. The copper powder was mixed with dielectric medium of kerosene servothem of 6g, 8g and 10 g respectively. This mixture was analyzed using different current rate of 8 amps, 10 amps and 12 amps to know the performance characteristics by using material removal rate, tool wear rate, diameter overcut, surface finish and dimensional accuracy. Based on the experimental investigation it is concluded that copper powder of 10g with 10 amps performed well than that of all other parameters.

Complexities of Focused Ion Beam Preparation of Electron-Transparent Sections for Meteorite Studies

NASA Astrophysics Data System (ADS)

Ishii, H. A.; Bradley, J. P.; Teslich, N.

2012-09-01

Focused Ion Beam is increasingly used to prepare site-specific, electron-transparent sections for meteorite micro-texture and -chemistry studies. We discuss technical challenges and frequently-overlooked FIB artifacts relevant to meteorite analyses.

Polarized deuterium internal target at AmPS (NIKHEF)

NASA Astrophysics Data System (ADS)

Ferro-Luzzi, M.; Zhou, Z.-L.; van den Brand, J. F. J.; Bulten, H. J.; Alarcon, R.; van Bakel, N.; Botto, T.; Bouwhuis, M.; van Buuren, L.; Comfort, J.; Doets, M.; Dolfini, S.; Ent, R.; Geurts, D.; Heimberg, P.; Higinbotham, D. W.; de Jager, C. W.; Lang, J.; de Lange, D. J.; Norum, B.; Passchier, I.; Poolman, H. R.; Six, E.; Steijger, J.; Szczerba, D.; Unal, O.; de Vries, H.

1998-01-01

We describe the polarized deuterium target internal to the NIKHEF medium-energy electron storage ring. Tensor polarized deuterium was produced in an atomic beam source and injected into a storage cell target. A Breit-Rabi polarimeter was used to monitor the injected atomic beam intensity and polarization. An electrostatic ion-extraction system and a Wien filter were utilized to measure on-line the atomic fraction of the target gas in the storage cell. This device was supplemented with a tensor polarization analyzer using the neutron anisotropy of the 3H(d,n)α reaction at 60 keV. This method allows determining the density-averaged nuclear polarization of the target gas, independent of spatial and temporal variations. We address issues important for polarized hydrogen/deuterium internal targets, such as the effects of spin-exchange collisions and resonant transitions induced by the RF fields of the charged particle beam.

Polarized deuterium internal target at AmPS (NIKHEF)

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

Norum, Blaine; De Jager, Cornelis; Geurts, D.

1997-08-01

We describe the polarized deuterium target internal to the NIKHEF medium-energy electron storage ring. Tensor polarized deuterium was produced in an atomic beam source and injected into a storage cell target. A Breit-Rabi polarimeter was used to monitor the injected atomic beam intensity and polarization. An electrostatic ion-extraction system and a Wien filter were utilized to measure on-line the atomic fraction of the target gas in the storage cell. This device was supplemented with a tensor polarization analyzer using the neutron anisotropy of the 3H(d,n)sigma reaction at 60 keV. This method allows determining the density-averaged nuclear polarization of the targetmore » gas, independent of spatial and temporal variations. We address issues important for polarized hydrogen/deuterium internal targets, such as the effects of spin-exchange collisions and resonant transitions induced by the RF fields of the charged particle beam.« less

Polarized deuterium internal target at AmPS (NIKHEF)

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

Ferro-Luzzi, M.; NIKHEF, P.O. Box 41882, 1009 DB Amsterdam; Zhou, Z.-L.

1998-01-20

We describe the polarized deuterium target internal to the NIKHEF medium-energy electron storage ring. Tensor polarized deuterium was produced in an atomic beam source and injected into a storage cell target. A Breit-Rabi polarimeter was used to monitor the injected atomic beam intensity and polarization. An electrostatic ion-extraction system and a Wien filter were utilized to measure on-line the atomic fraction of the target gas in the storage cell. This device was supplemented with a tensor polarization analyzer using the neutron anisotropy of the {sup 3}H(d,n){alpha} reaction at 60 keV. This method allows determining the density-averaged nuclear polarization of themore » target gas, independent of spatial and temporal variations. We address issues important for polarized hydrogen/deuterium internal targets, such as the effects of spin-exchange collisions and resonant transitions induced by the RF fields of the charged particle beam.« less

Trapped buckyball turns up the amp

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

Hellemans, A.

1997-02-21

Since their discovery in 1985, the soccer-ball shaped molecules of 60 or more carbon atoms known as fullerenes have displayed a dazzling variety of tricks, coaxed by researchers to become superconductors at low temperature, light and carbon ion beam emittors. Two European researchers have added something to this list: they have created an electronic-mechanical amplifier from a single buckyball. This article describes the circumstances of the discovery and future directions of the research.

Aurintricarboxylic acid is a potent inhibitor of phosphofructokinase.

PubMed Central

McCune, S A; Foe, L G; Kemp, R G; Jurin, R R

1989-01-01

Aurintricarboxylic acid (ATA) was found to be a very potent inhibitor of purified rabbit liver phosphofructokinase (PFK), giving 50% inhibition at 0.2 microM. The inhibition was in a manner consistent with interaction at the citrate-inhibitory site of the enzyme. The data suggest that inhibition of PFK by ATA was not due to denaturation of the enzyme or the irreversible binding of inhibitor, since the inhibition could be reversed by addition of allosteric activators of PFK, i.e. fructose 2,6-bisphosphate or AMP. Two other tricarboxylic acids, agaric acid and (-)-hydroxycitrate, were found to inhibit PFK. ATA at much higher concentrations (500 microM) was shown to inhibit fatty acid synthesis from endogenous glycogen in rat hepatocytes; however, protein synthesis was not altered. PMID:2525029

Efficient protocols for Stirling heat engines at the micro-scale

NASA Astrophysics Data System (ADS)

Muratore-Ginanneschi, Paolo; Schwieger, Kay

2015-10-01

We investigate the thermodynamic efficiency of sub-micro-scale Stirling heat engines operating under the conditions described by overdamped stochastic thermodynamics. We show how to construct optimal protocols such that at maximum power the efficiency attains for constant isotropic mobility the universal law η=2 ηC/(4-ηC) , where ηC is the efficiency of an ideal Carnot cycle. We show that these protocols are specified by the solution of an optimal mass transport problem. Such solution can be determined explicitly using well-known Monge-Ampère-Kantorovich reconstruction algorithms. Furthermore, we show that the same law describes the efficiency of heat engines operating at maximum work over short time periods. Finally, we illustrate the straightforward extension of these results to cases when the mobility is anisotropic and temperature dependent.

Optical characterization of magnesium incorporation in p-GaN layers for core–shell nanorod light-emitting diodes

NASA Astrophysics Data System (ADS)

Gîrgel, I.; Šatka, A.; Priesol, J.; Coulon, P.-M.; Le Boulbar, E. D.; Batten, T.; Allsopp, D. W. E.; Shields, P. A.

2018-04-01

III-nitride nanostructures are of interest for a new generation of light-emitting diodes (LEDs). However, the characterization of doping incorporation in nanorod (NR) structures, which is essential for creating the p-n junction diodes, is extremely challenging. This is because the established electrical measurement techniques (such as capacitance–voltage or Hall-effect methods) require a simple sample geometry and reliable ohmic contacts, both of which are difficult to achieve in nanoscale devices. The need for homogenous, conformal n-type or p-type layers in core–shell nanostructures magnifies these challenges. Consequently, we demonstrate how a combination of non-contact methods (micro-photoluminescence, micro-Raman and cathodoluminescence), as well as electron-beam-induced-current, can be used to analyze the uniformity of magnesium incorporation in core–shell NRs and make a first estimate of doping levels by the evolution of band transitions, strain and current mapping. These techniques have been used to optimize the growth of core–shell nanostructures for electrical carrier injection, a significant milestone for their use in LEDs.

Capacitive charge generation apparatus and method for testing circuits

DOEpatents

Cole, E.I. Jr.; Peterson, K.A.; Barton, D.L.

1998-07-14

An electron beam apparatus and method for testing a circuit are disclosed. The electron beam apparatus comprises an electron beam incident on an outer surface of an insulating layer overlying one or more electrical conductors of the circuit for generating a time varying or alternating current electrical potential on the surface; and a measurement unit connected to the circuit for measuring an electrical signal capacitively coupled to the electrical conductors to identify and map a conduction state of each of the electrical conductors, with or without an electrical bias signal being applied to the circuit. The electron beam apparatus can further include a secondary electron detector for forming a secondary electron image for registration with a map of the conduction state of the electrical conductors. The apparatus and method are useful for failure analysis or qualification testing to determine the presence of any open-circuits or short-circuits, and to verify the continuity or integrity of electrical conductors buried below an insulating layer thickness of 1-100 {micro}m or more without damaging or breaking down the insulating layer. The types of electrical circuits that can be tested include integrated circuits, multi-chip modules, printed circuit boards and flexible printed circuits. 7 figs.

Micro-/nanosized cantilever beams and mass sensors under applied axial tensile/compressive force vibrating in vacuum and viscous fluid

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

Stachiv, Ivo, E-mail: stachiv@fzu.cz; Institute of Physics, Czech Academy of Sciences, Prague; Fang, Te-Hua

2015-11-15

Vibrating micro-/nanosized cantilever beams under an applied axial force are the key components of various devices used in nanotechnology. In this study, we perform a complete theoretical investigation of the cantilever beams under an arbitrary value of the axial force vibrating in a specific environment such as vacuum, air or viscous fluid. Based on the results easy accessible expressions enabling one the fast and highly accurate estimations of changes in the Q-factor and resonant frequencies of beam oscillating in viscous fluid caused by the applied axial force are derived and analyzed. It has been also shown that for beam-to-string andmore » string vibrational regimes the mode shape starts to significantly deviate from the one known for a beam without axial force. Moreover, a linear dependency of the vibrational amplitude in resonance on the dimensionless tension parameter has been found. We revealed that only a large axial force, i.e. the string vibrational regime, significantly improves the Q-factor of beams submerged in fluid, while an increase of the axial force in beam and beam-to-string transition regimes has a negligibly small impact on the Q-factor enhancement. Experiments carried out on the carbon nanotubes and nanowires are in a good agreement with present theoretical predictions.« less

Diode magnetic-field influence on radiographic spot size

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

Ekdahl, Carl A. Jr.

2012-09-04

Flash radiography of hydrodynamic experiments driven by high explosives is a well-known diagnostic technique in use at many laboratories. The Dual-Axis Radiography for Hydrodynamic Testing (DARHT) facility at Los Alamos was developed for flash radiography of large hydrodynamic experiments. Two linear induction accelerators (LIAs) produce the bremsstrahlung radiographic source spots for orthogonal views of each experiment ('hydrotest'). The 2-kA, 20-MeV Axis-I LIA creates a single 60-ns radiography pulse. For time resolution of the hydrotest dynamics, the 1.7-kA, 16.5-MeV Axis-II LIA creates up to four radiography pulses by slicing them out of a longer pulse that has a 1.6-{micro}s flattop. Bothmore » axes now routinely produce radiographic source spot sizes having full-width at half-maximum (FWHM) less than 1 mm. To further improve on the radiographic resolution, one must consider the major factors influencing the spot size: (1) Beam convergence at the final focus; (2) Beam emittance; (3) Beam canonical angular momentum; (4) Beam-motion blur; and (5) Beam-target interactions. Beam emittance growth and motion in the accelerators have been addressed by careful tuning. Defocusing by beam-target interactions has been minimized through tuning of the final focus solenoid for optimum convergence and other means. Finally, the beam canonical angular momentum is minimized by using a 'shielded source' of electrons. An ideal shielded source creates the beam in a region where the axial magnetic field is zero, thus the canonical momentum zero, since the beam is born with no mechanical angular momentum. It then follows from Busch's conservation theorem that the canonical angular momentum is minimized at the target, at least in principal. In the DARHT accelerators, the axial magnetic field at the cathode is minmized by using a 'bucking coil' solenoid with reverse polarity to cancel out whatever solenoidal beam transport field exists there. This is imperfect in practice, because of radial variation of the total field across the cathode surface, solenoid misalignments, and long-term variability of solenoid fields for given currents. Therefore, it is useful to quantify the relative importance of canonical momentum in determining the focal spot, and to establish a systematic methodology for tuning the bucking coils for minimum spot size. That is the purpose of this article. Section II provides a theoretical foundation for understanding the relative importance of the canonical momentum. Section III describes the results of simulations used to quantify beam parameters, including the momentum, for each of the accelerators. Section IV compares the two accelerators, especially with respect to mis-tuned bucking coils. Finally, Section IV concludes with a methodology for optimizing the bucking coil settings.« less

cAMP regulation of airway smooth muscle function.

PubMed

Billington, Charlotte K; Ojo, Oluwaseun O; Penn, Raymond B; Ito, Satoru

2013-02-01

Agonists activating β(2)-adrenoceptors (β(2)ARs) on airway smooth muscle (ASM) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease (COPD). Moreover, the use of long-acting β-agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases. β-Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction. The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as prostaglandin E(2) and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration. Therefore, β(2)ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling. However, limitations of β-agonist therapy due to drug tachyphylaxis related to β(2)AR desensitization, and recent findings regarding the manner in which β(2)ARs and cAMP signal, have raised new and interesting questions about these well-studied molecules. In this review we discuss current concepts regarding β(2)ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Decoding spatial and temporal features of neuronal cAMP/PKA signaling with FRET biosensors.

PubMed

Castro, Liliana R V; Guiot, Elvire; Polito, Marina; Paupardin-Tritsch, Daniéle; Vincent, Pierre

2014-02-01

Cyclic adenosine monophosphate (cAMP) and the cyclic-AMP-dependent protein kinase (PKA) regulate a plethora of cellular functions in virtually all eukaryotic cells. In neurons, the cAMP/PKA signaling cascade controls a number of biological properties such as axonal growth, pathfinding, efficacy of synaptic transmission, regulation of excitability, or long term changes. Genetically encoded optical biosensors for cAMP or PKA are considerably improving our understanding of these processes by providing a real-time measurement in living neurons. In this review, we describe the recent progress made in the creation of biosensors for cAMP or PKA activity. These biosensors revealed profound differences in the amplitude of the cAMP signal evoked by neuromodulators between various neuronal preparations. These responses can be resolved at the level of individual neurons, also revealing differences related to the neuronal type. At the sub-cellular level, biosensors reported different signal dynamics in domains like dendrites, cell body, nucleus, and axon. Combining this imaging approach with pharmacology or genetic models points at phosphodiesterases and phosphatases as critical regulatory proteins. Biosensor imaging will certainly emerge as a forefront tool to decipher the subtle mechanics of intracellular signaling. This will certainly help us to understand the mechanism of action of current drugs and foster the development of novel molecules for neuropsychiatric diseases. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels*♦

PubMed Central

VanSchouwen, Bryan; Akimoto, Madoka; Sayadi, Maryam; Fogolari, Federico; Melacini, Giuseppe

2015-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP allosterically modulates HCN through the cAMP-dependent formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN, to which cAMP binds. Although the apo versus holo conformational changes of the cAMP-binding domain (CBD) have been previously mapped, only limited information is currently available on the HCN IR dynamics, which have been hypothesized to play a critical role in the cAMP-dependent gating of HCN. Here, using molecular dynamics simulations validated and complemented by experimental NMR and CD data, we comparatively analyze HCN IR dynamics in the four states of the thermodynamic cycle arising from the coupling between cAMP binding and tetramerization equilibria. This extensive set of molecular dynamics trajectories captures the active-to-inactive transition that had remained elusive for other CBDs, and it provides unprecedented insight on the role of IR dynamics in HCN autoinhibition and its release by cAMP. Specifically, the IR tetramerization domain becomes more flexible in the monomeric states, removing steric clashes that the apo-CDB structure would otherwise impose. Furthermore, the simulations reveal that the active/inactive structural transition for the apo-monomeric CBD occurs through a manifold of pathways that are more divergent than previously anticipated. Upon cAMP binding, these pathways become disallowed, pre-confining the CBD conformational ensemble to a tetramer-compatible state. This conformational confinement primes the IR for tetramerization and thus provides a model of how cAMP controls HCN channel gating. PMID:25944904

An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis.

PubMed

Kamath, Vidyulata; Moberg, Paul J; Calkins, Monica E; Borgmann-Winter, Karin; Conroy, Catherine G; Gur, Raquel E; Kohler, Christian G; Turetsky, Bruce I

2012-07-01

While olfactory deficits have been reported in schizophrenia and youths at-risk for psychosis, few studies have linked these deficits to current pathophysiological models of the illness. There is evidence that disrupted cyclic adenosine 3',5'-monophosphate (cAMP) signaling may contribute to schizophrenia pathology. As cAMP mediates olfactory signal transduction, the degree to which this disruption could manifest in olfactory impairment was ascertained. Odor-detection thresholds to two odorants that differ in the degree to which they activate intracellular cAMP were assessed in clinical risk and low-risk participants. Birhinal assessments of odor-detection threshold sensitivity to lyral and citralva were acquired in youths experiencing prodromal symptoms (n=17) and controls at low risk for developing psychosis (n=15). Citralva and lyral are odorants that differ in cAMP activation; citralva is a strong cAMP activator and lyral is a weak cAMP activator. The overall group-by-odor interaction was statistically significant. At-risk youths showed significantly reduced odor detection thresholds for lyral, but showed intact detection thresholds for citralva. This odor-specific threshold deficit was uncorrelated with deficits in odor identification or discrimination, which were also present. ROC curve analysis revealed that olfactory performance correctly classified at-risk and low-risk youths with greater than 97% accuracy. This study extends prior findings of an odor-specific hyposmia implicating cAMP-mediated signal transduction in schizophrenia and unaffected first-degree relatives to include youths at clinical risk for developing the disorder. These results suggest that dysregulation of cAMP signaling may be present during the psychosis prodrome. Copyright © 2012 Elsevier B.V. All rights reserved.

An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis

PubMed Central

Kamath, Vidyulata; Moberg, Paul J.; Calkins, Monica E.; Borgmann-Winter, Karin; Conroy, Catherine G.; Gur, Raquel E.; Kohler, Christian G.; Turetsky, Bruce I.

2012-01-01

Background While olfactory deficits have been reported in schizophrenia and youths at-risk for psychosis, few studies have linked these deficits to current pathophysiological models of the illness. There is evidence that disrupted cyclic adenosine 3’,5’-monophosphate (cAMP) signaling may contribute to schizophrenia pathology. As cAMP mediates olfactory signal transduction, the degree to which this disruption could manifest in olfactory impairment was ascertained. Odor-detection thresholds to two odorants that differ in the degree to which they activate intracellular cAMP were assessed in clinical risk and low-risk participants. Method Birhinal assessments of odor-detection threshold sensitivity to lyral and citralva were acquired in youths experiencing prodromal symptoms (n = 17) and controls at low risk for developing psychosis (n = 15). Citralva and lyral are odorants that differ in cAMP activation; citralva is a strong cAMP activator and lyral is a weak cAMP activator. Results The overall group-by-odor interaction was statistically significant. At-risk youths showed significantly reduced odor detection thresholds for lyral, but showed intact detection thresholds for citralva. This odor-specific threshold deficit was uncorrelated with deficits in odor identification or discrimination, which were also present. ROC curve analysis revealed that olfactory performance correctly classified at-risk and low-risk youths with greater than 97% accuracy. Conclusions This study extends prior findings of an odor-specific hyposmia implicating cAMP-mediated signal transduction in schizophrenia and unaffected first-degree relatives to include youths at clinical risk for developing the disorder. These results suggest that dysregulation of cAMP signaling may be present during the psychosis prodrome. PMID:22537567

Lifetime experimental study of graphite cathode for relativistic backward wave oscillator

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

Wu, Ping; Science and Technology on High Power Microwave Laboratory, Northwest Institute of Nuclear Technology, Xi'an 710024; Sun, Jun

2016-07-21

Graphite cathodes are widely used due to their good emission properties, especially their long lifetime. Some previous papers have researched their lifetime under certain conditions and uncovered some important phenomena. This paper is dedicated to research the lifetime of the graphite cathode under higher power. In the lifetime test, the voltage and current amplitudes are about 970 kV and 9.7 kA, respectively. The repetition rate is 20 Hz. An X-band relativistic backward wave oscillator is used to generate high power microwave by utilizing the electron beam energy. The experimental results demonstrate that the emission property of the graphite cathode remains quite stable duringmore » 10{sup 5} pulses, despite some slight deteriorations regarding the beam and microwave parameters. The macroscopic morphology change of the cathode blade due to material evaporation is observed by a laser microscope. The mass loss of the graphite cathode is about 60 μg/C. Meanwhile, the observation by a scanning electron microscope uncovers that the original numerous flaky micro-structures are totally replaced by a relatively smooth surface at the mid region of the cathode blade and a large number of new micro-protrusions at the blade edges during the lifetime test.« less

Ultrasonic Micro-Blades for the Rapid Extraction of Impact Tracks from Aerogel

NASA Technical Reports Server (NTRS)

Ishii, H. A.; Graham, G. A.; Kearsley, A. T.; Grant, P. G.; Snead, C. J.; Bradley, J. P.

2005-01-01

The science return of NASA's Stardust Mission with its valuable cargo of cometary debris hinges on the ability to efficiently extract particles from silica aerogel collectors. The current method for extracting cosmic dust impact tracks is a mature procedure involving sequential perforation of the aerogel with glass needles on computer controlled micromanipulators. This method is highly successful at removing well-defined aerogel fragments of reasonable optical clarity while causing minimal damage to the surrounding aerogel collector tile. Such a system will be adopted by the JSC Astromaterials Curation Facility in anticipation of Stardust s arrival in early 2006. In addition to Stardust, aerogel is a possible collector for future sample return missions and is used for capture of hypervelocity ejecta in high power laser experiments of interest to LLNL. Researchers will be eager to obtain Stardust samples for study as quickly as possible, and rapid extraction tools requiring little construction, training, or investment would be an attractive asset. To this end, we have experimented with micro-blades for the Stardust impact track extraction process. Our ultimate goal is a rapid extraction system in a clean electron beam environment, such as an SEM or dual-beam FIB, for in situ sample preparation, mounting and analysis.

BBU and Corkscrew Growth Predictions for the Darht Second Axis Accelerator

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

Chen, Y.J.; Fawley, W.M.

2001-06-12

The second axis accelerator of the Dual Axis Radiographic Hydrodynamic Test (DARHT-II) facility will produce a 2-kA, 20-MeV, 2-{micro}s output electron beam with a design goal of less than 1000 {pi} mm-mrad normalized transverse emittance. In order to meet this goal, both the beam breakup instability (BBJ) and transverse corkscrew motion (due to chromatic phase advance) must be limited in growth. Using data from recent experimental measurements of the transverse impedance of actual DARHT-II accelerator cells by Briggs et al. [2], they have used the LLNL BREAKUP code to predict BBU and corkscrew growth in DARHT-II. The results suggest thatmore » BBU growth should not seriously degrade the final achievable spot size at the x-ray converter, presuming the initial excitation level is of the order 100 microns or smaller. For control of corkscrew growth, a major concern is the number of tuning shots needed to utilize effectively the tuning-V algorithm [3]. Presuming that the solenoid magnet alignment falls within spec, they believe that possibly as few as 50-100 shots will be necessary to set the dipole corrector magnet currents. They give some specific examples of tune determination for a hypothetical set of alignment errors.« less

BBU and Corkscrew Growth Predictions for the DARHT Second Axis Accelerator

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

Chen, Y J; Fawley, W M

2001-06-12

The second axis accelerator of the Dual Axis Radiographic Hydrodynamic Test (DARHT-II) facility will produce a 2-kA, 20-MeV, 2-{micro}s output electron beam with a design goal of less than 1000 {pi} mm-mrad normalized transverse emittance. In order to meet this goal, both the beam breakup instability (BBU) and transverse ''corkscrew'' motion (due to chromatic phase advance) must be limited in growth. Using data from recent experimental measurements of the transverse impedance of actual DARHT-II accelerator cells by Briggs et al., they have used the LLNL BREAKUP code to predict BBU and corkscrew growth in DARHT-II. The results suggest that BBUmore » growth should not seriously degrade the final achievable spot size at the x-ray converter, presuming the initial excitation level is of the order 100 microns or smaller. For control of corkscrew growth, a major concern is the number of ''tuning'' shots needed to utilize effectively the ''tuning-V'' algorithm. Presuming that the solenoid magnet alignment falls within spec, they believe that possibly as few as 50-100 shots will be necessary to set the dipole corrector magnet currents. They give some specific examples of tune determination for a hypothetical set of alignment errors.« less

Ceramic micro-injection molded nozzles for serial femtosecond crystallography sample delivery

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

Beyerlein, K. R.; Adriano, L.; Heymann, M.

Serial femtosecond crystallography (SFX) using X-ray Free-Electron Lasers (XFELs) allows for room temperature protein structure determination without evidence of conventional radiation damage. In this method, a liquid suspension of protein microcrystals can be delivered to the X-ray beam in vacuum as a micro-jet, which replenishes the crystals at a rate that exceeds the current XFEL pulse repetition rate. Gas dynamic virtual nozzles produce the required micrometer-sized streams by the focusing action of a coaxial sheath gas and have been shown to be effective for SFX experiments. Here, we describe the design and characterization of such nozzles assembled from ceramic micro-injectionmore » molded outer gas-focusing capillaries. Trends of the emitted jet diameter and jet length as a function of supplied liquid and gas flow rates are measured by a fast imaging system. The observed trends are explained by derived relationships considering choked gas flow and liquidflow conservation. In conclusion, the performance of these nozzles in a SFX experiment is presented, including an analysis of the observed background.« less

Ceramic micro-injection molded nozzles for serial femtosecond crystallography sample delivery

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

Beyerlein, K. R.; Heymann, M.; Kirian, R.

Serial femtosecond crystallography (SFX) using X-ray Free-Electron Lasers (XFELs) allows for room temperature protein structure determination without evidence of conventional radiation damage. In this method, a liquid suspension of protein microcrystals can be delivered to the X-ray beam in vacuum as a micro-jet, which replenishes the crystals at a rate that exceeds the current XFEL pulse repetition rate. Gas dynamic virtual nozzles produce the required micrometer-sized streams by the focusing action of a coaxial sheath gas and have been shown to be effective for SFX experiments. Here, we describe the design and characterization of such nozzles assembled from ceramic micro-injectionmore » molded outer gas-focusing capillaries. Trends of the emitted jet diameter and jet length as a function of supplied liquid and gas flow rates are measured by a fast imaging system. The observed trends are explained by derived relationships considering choked gas flow and liquid flow conservation. Finally, the performance of these nozzles in a SFX experiment is presented, including an analysis of the observed background.« less

Ceramic micro-injection molded nozzles for serial femtosecond crystallography sample delivery

DOE PAGES

Beyerlein, K. R.; Adriano, L.; Heymann, M.; ...

2015-12-08

Serial femtosecond crystallography (SFX) using X-ray Free-Electron Lasers (XFELs) allows for room temperature protein structure determination without evidence of conventional radiation damage. In this method, a liquid suspension of protein microcrystals can be delivered to the X-ray beam in vacuum as a micro-jet, which replenishes the crystals at a rate that exceeds the current XFEL pulse repetition rate. Gas dynamic virtual nozzles produce the required micrometer-sized streams by the focusing action of a coaxial sheath gas and have been shown to be effective for SFX experiments. Here, we describe the design and characterization of such nozzles assembled from ceramic micro-injectionmore » molded outer gas-focusing capillaries. Trends of the emitted jet diameter and jet length as a function of supplied liquid and gas flow rates are measured by a fast imaging system. The observed trends are explained by derived relationships considering choked gas flow and liquidflow conservation. In conclusion, the performance of these nozzles in a SFX experiment is presented, including an analysis of the observed background.« less

Progress in ultrafast laser processing and future prospects

NASA Astrophysics Data System (ADS)

Sugioka, Koji

2017-03-01

The unique characteristics of ultrafast lasers have rapidly revolutionized materials processing after their first demonstration in 1987. The ultrashort pulse width of the laser suppresses heat diffusion to the surroundings of the processed region, which minimizes the formation of a heat-affected zone and thereby enables ultrahigh precision micro- and nanofabrication of various materials. In addition, the extremely high peak intensity can induce nonlinear multiphoton absorption, which extends the diversity of materials that can be processed to transparent materials such as glass. Nonlinear multiphoton absorption enables three-dimensional (3D) micro- and nanofabrication by irradiation with tightly focused femtosecond laser pulses inside transparent materials. Thus, ultrafast lasers are currently widely used for both fundamental research and practical applications. This review presents progress in ultrafast laser processing, including micromachining, surface micro- and nanostructuring, nanoablation, and 3D and volume processing. Advanced technologies that promise to enhance the performance of ultrafast laser processing, such as hybrid additive and subtractive processing, and shaped beam processing are discussed. Commercial and industrial applications of ultrafast laser processing are also introduced. Finally, future prospects of the technology are given with a summary.

Measuring Micro-Friction Torque in MEMS Gas Bearings

PubMed Central

Fang, Xudong; Liu, Huan

2016-01-01

An in situ measurement of micro-friction torque in MEMS gas bearings, which has been a challenging research topic for years, is realized by a system designed in this paper. In the system, a high accuracy micro-force sensor and an electronically-driven table are designed, fabricated and utilized. With appropriate installation of the sensor and bearings on the table, the engine rotor can be driven to rotate with the sensor using a silicon lever beam. One end of the beam is fixed to the shaft of the gas bearing, while the other end is free and in contact with the sensor probe tip. When the sensor begins to rotate with the table, the beam is pushed by the sensor probe to rotate in the same direction. For the beam, the friction torque from the gas bearing is balanced by the torque induced by pushing force from the sensor probe. Thus, the friction torque can be calculated as a product of the pushing force measured by the sensor and the lever arm, which is defined as the distance from the sensor probe tip to the centerline of the bearing. Experimental results demonstrate the feasibility of this system, with a sensitivity of 1.285 mV/μN·m in a range of 0 to 11.76 μN·m when the lever arm is 20 mm long. The measuring range can be modified by varying the length of the lever arm. Thus, this system has wide potential applications in measuring the micro-friction torque of gas bearings in rotating MEMS machines. PMID:27213377

An Inexpensive Toroidal Solenoid for an Investigative Student Lab

NASA Astrophysics Data System (ADS)

Ferstl, Andrew; Broberg, John

2008-09-01

Magnetism and Ampère's law is a common subject in most calculus-based introductory physics courses. Many textbooks offer examples to calculate the magnetic field produced by a symmetric current by using Ampère's law. These examples include the solenoid and the toroidal solenoid (sometimes called a torus; see Fig. 1), which are used in many applications, including the study of plasmas.

Micro-resonator-based electric field sensors with long durations of sensitivity

NASA Astrophysics Data System (ADS)

Ali, Amir R.

2017-05-01

In this paper, we present a new fabrication method for the whispering gallery mode (WGM) micro-sphere based electric field sensor that which allows for longer time periods of sensitivity. Recently, a WGM-based photonic electric field sensor was proposed using a coupled dielectric microsphere-beam. The external electric field imposes an electrtrostriction force on the dielectric beam, deflecting it. The beam, in turn compresses the sphere causing a shift in its WGM. As part of the fabrication process, the PDMS micro-beams and the spheres are curied at high-temperature (100oC) and subsequently poled by exposing to strong external electric field ( 8 MV/m) for two hours. The poling process allows for the deposition of surface charges thereby increasing the electrostriction effect. This methodology is called curing-then-poling (CTP). Although the sensors do become sufficiently sensitive to electric field, they start de-poling after a short period (within 10 minutes) after poling, hence losing sensitivity. In an attempt to mitigate this problem and to lock the polarization for a longer period, we use an alternate methodology whereby the beam is poled and cured simultaneously (curing-while-poling or CWP). The new fabrication method allows for the retention of polarization (and hence, sensitivity to electric field) longer ( 1500 minutes). An analysis is carried out along with preliminary experiments. Results show that electric fields as small as 100 V/m can be detected with a 300 μm diameter sphere sensor a day after poling.

A contribution to the expansion of the applicability of electrostatic forces in micro transducers

NASA Astrophysics Data System (ADS)

Schenk, Harald; Conrad, Holger; Gaudet, Matthieu; Uhlig, Sebastian; Kaiser, Bert; Langa, Sergiu; Stolz, Michael; Schimmanz, Klaus

2017-02-01

Electrostatic actuation is highly efficient at micro and nanoscale. However, large deflection in common electrostatically driven MEMS requires large electrode separation and thus high driving voltages. To offer a solution to this problem we developed a novel electrostatic actuator class, which is based on a force-to-stress transformation in the periodically patterned upper layer of a silicon cantilever beam. We report on advances in the development of such electrostatic bending actuators. Several variants of a CMOS compatible and RoHS-directive compliant fabrication processes to fabricate vertical deflecting beams with a thickness of 30 μm are presented. A concept to extend the actuation space towards lateral deflecting elements is introduced. The fabricated and characterized vertical deflecting cantilever beam variants make use of a 0.2 μm electrode gap and achieve deflections of up to multiples of this value. Simulation results based on an FE-model applied to calculate the voltage dependent curvature for various actuator cell designs are presented. The calculated values show very good agreement with the experimentally determined voltage controlled actuation curvatures. Particular attention was paid to parasitic effects induced by small, sub micrometer, electrode gaps. This includes parasitic currents between the two electrode layers. No experimental hint was found that such effects significantly influence the curvature for a control voltage up to 45 V. The paper provides an outlook for the applicability of the technology based on specifically designed and fabricated actuators which allow for a large variety of motion patterns including out-of-plane and in-plane motion as well as membrane deformation and linear motion.

Self-organized microstructures induced by MeV ion beam on silicon surface

NASA Astrophysics Data System (ADS)

Ahmad, Muthanna

2017-02-01

Micro patterning of self organized structure on silicon surface is induced by ion implantation of energetic (MeV) copper ions. This work reports for the first time the ability of using energetic ions for producing highly ordered ripples and dots of micro sizes. The experiments are realized at the Tandem ion beam accelerator (3 MV) at the IBA laboratory of the Atomic Energy Commission of Syria. Similarly to nano patterning formed by slow ions, the formation of micro patterned structures dots and ripples is observed to be depending on the angle of ion beam incidence, energy and ion fluence. The observation of such microstructures formation is limited to a range of ion energies (few MeV) at fluence higher than 1.75 × 1017 ion cm-2. The patterned surface layer is completely amorphousized by the ion implantation. Shadowing effect is observed in the formation of microripples and superstructures in the top of ripples. The superstructure develops new morphology that is not observed before. This morphology has butterfly shape with symmetry in its structure.

Tunable plasmonic toroidal terahertz metamodulator

NASA Astrophysics Data System (ADS)

Gerislioglu, Burak; Ahmadivand, Arash; Pala, Nezih

2018-04-01

Optical modulators are essential and strategic parts of micro- and nanophotonic circuits to encode electro-optical signals in the optical domain. Here, by using arrays of multipixel toroidal plasmonic terahertz (THz) metamolecules, we developed a functional plasmonic metamodulator with high efficiency and tunability. Technically, the dynamic toroidal dipole induces nonradiating charge-current arrangements leading to have an exquisite role in defining the inherent spectral features of various materials. By categorizing in a different family of multipoles far from the traditional electromagnetic multipoles, the toroidal dipole corresponds to poloidal currents flowing on the surface of a closed-loop torus. Utilizing the sensitivity of the optically driven toroidal momentum to the incident THz beam power and by employing both numerical tools and experimental analysis, we systematically studied the spectral response of the proposed THz plasmonic metadevice. In this Rapid Communication, we uncover a correlation between the existence and the excitation of the toroidal response and the incident beam power. This mechanism is employed to develop THz toroidal metamodulators with a strong potential to be employed for practical advanced and next-generation communication, filtering, and routing applications.

Diffractive micro-optical element with nonpoint response

NASA Astrophysics Data System (ADS)

Soifer, Victor A.; Golub, Michael A.

1993-01-01

Common-use diffractive lenses have microrelief zones in the form of simple rings that provide only an optical power but do not contain any image information. They have a point-image response under point-source illumination. We must use a more complicated non-point response to focus a light beam into different light marks, letter-type images as well as for optical pattern recognition. The current presentation describes computer generation of diffractive micro- optical elements with complicated curvilinear zones of a regular piecewise-smooth structure and grey-level or staircase phase microrelief. The manufacture of non-point response elements uses the steps of phase-transfer calculation and orthogonal-scan masks generation or lithographic glass etching. Ray-tracing method is shown to be applicable in this task. Several working samples of focusing optical elements generated by computer and photolithography are presented. Using the experimental results we discuss here such applications as laser branding.

Efficient fabrication of carbon nanotube micro tip arrays by tailoring cross-stacked carbon nanotube sheets.

PubMed

Wei, Yang; Liu, Peng; Zhu, Feng; Jiang, Kaili; Li, Qunqing; Fan, Shoushan

2012-04-11

Carbon nanotube (CNT) micro tip arrays with hairpin structures on patterned silicon wafers were efficiently fabricated by tailoring the cross-stacked CNT sheet with laser. A blade-like structure was formed at the laser-cut edges of the CNT sheet. CNT field emitters, pulled out from the end of the hairpin by an adhesive tape, can provide 150 μA intrinsic emission currents with low beam noise. The nice field emission is ascribed to the Joule-heating-induced desorption of the emitter surface by the hairpin structure, the high temperature annealing effect, and the surface morphology. The CNT emitters with hairpin structures will greatly promote the applications of CNTs in vacuum electronic devices and hold the promises to be used as the hot tips for thermochemical nanolithography. More CNT-based structures and devices can be fabricated on a large scale by this versatile method. © 2012 American Chemical Society

Microbeam complex at TIARA: Technologies to meet a wide range of applications

NASA Astrophysics Data System (ADS)

Kamiya, T.; Takano, K.; Satoh, T.; Ishii, Y.; Nishikawa, H.; Seki, S.; Sugimoto, M.; Okumura, S.; Fukuda, M.

2011-10-01

Since 1990 R&Ds of microbeam technology has been progressed at the TIARA facility of JAEA Takasaki. In order to meet a wide variety of ion beam applications, analysis, radiation effect studies, or fabrication in regions of micro- or nano-structures, three different types of ion microbeam systems were developed. In these systems, high-spatial resolutions have been achieved and techniques of micro-PIXE, single ion hit and particle beam writing (PBW) were also developed for these applications. Microbeams, on the other hand, require the highest quality of beams from the accelerators, the cyclotron in particular, which was an important part of the microbeam technology of TIARA. In this paper, the latest progress of the ion microbeam technology and applications are summarized and a future prospect of them is discussed.

Electrophysiological Evidence for the Presence of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Mouse Sperm

PubMed Central

Dulce, Figueiras Fierro; José, Acevedo Juan; Pablo, Martínez; Escoffier, Jessica; Sepúlveda, Francisco V.; Enrique, Balderas; Gerardo, Orta; Pablo, Visconti; Alberto, Darszon

2014-01-01

Mammalian sperm must undergo a maturational process, named capacitation, in the female reproductive tract to fertilize the egg. Sperm capacitation is regulated by a cAMP/PKA pathway and involves increases in intracellular Ca2+, pH, Cl−, protein tyrosine phosphorylation, and in mouse and some other mammals a membrane potential hyperpolarization. The cystic fibrosis transmembrane conductance regulator (CFTR), a Cl− channel modulated by cAMP/PKA and ATP, was detected in mammalian sperm and proposed to modulate capacitation. Our whole-cell patch-clamp recordings from testicular mouse sperm now reveal a Cl− selective component to membrane current that is ATP-dependent, stimulated by cAMP, cGMP and genistein (a CFTR agonist, at low concentrations), and inhibited by DPC and CFTRinh-172, two well-known CFTR antagonists. Furthermore, the Cl− current component activated by cAMP and inhibited by CFTRinh-172 is absent in recordings on testicular sperm from mice possessing the CFTR ΔF508 loss-of-function mutation, indicating that CFTR is responsible for this component. A Cl− selective like current component displaying CFTR characteristics was also found in wild type epididymal sperm bearing the cytoplasmatic droplet. Capacitated sperm treated with CFTRinh-172 undergo a shape change, suggesting that CFTR is involved in cell volume regulation. These findings indicate that functional CFTR channels are present in mouse sperm and their biophysical properties are consistent with their proposed participation in capacitation. PMID:22833409

cAMP controls rod photoreceptor sensitivity via multiple targets in the phototransduction cascade

PubMed Central

Astakhova, Luba A.; Samoiliuk, Evgeniia V.; Govardovskii, Victor I.

2012-01-01

In early studies, both cyclic AMP (cAMP) and cGMP were considered as potential secondary messengers regulating the conductivity of the vertebrate photoreceptor plasma membrane. Later discovery of the cGMP specificity of cyclic nucleotide–gated channels has shifted attention to cGMP as the only secondary messenger in the phototransduction cascade, and cAMP is not considered in modern schemes of phototransduction. Here, we report evidence that cAMP may also be involved in regulation of the phototransduction cascade. Using a suction pipette technique, we recorded light responses of isolated solitary rods from the frog retina in normal solution and in the medium containing 2 µM of adenylate cyclase activator forskolin. Under forskolin action, flash sensitivity rose more than twofold because of a retarded photoresponse turn-off. The same concentration of forskolin lead to a 2.5-fold increase in the rod outer segment cAMP, which is close to earlier reported natural day/night cAMP variations. Detailed analysis of cAMP action on the phototransduction cascade suggests that several targets are affected by cAMP increase: (a) basal dark phosphodiesterase (PDE) activity decreases; (b) at the same intensity of light background, steady background-induced PDE activity increases; (c) at light backgrounds, guanylate cyclase activity at a given fraction of open channels is reduced; and (d) the magnitude of the Ca2+ exchanger current rises 1.6-fold, which would correspond to a 1.6-fold elevation of [Ca2+]in. Analysis by a complete model of rod phototransduction suggests that an increase of [Ca2+]in might also explain effects (b) and (c). The mechanism(s) by which cAMP could regulate [Ca2+]in and PDE basal activity is unclear. We suggest that these regulations may have adaptive significance and improve the performance of the visual system when it switches between day and night light conditions. PMID:23008435

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

Kandlakunta, P; Pham, R; Zhang, T

Purpose: To develop and characterize a high brightness multiple-pixel thermionic emission x-ray (MPTEX) source. Methods: Multiple-pixel x-ray sources allow for designs of novel x-ray imaging techniques, such as fixed gantry CT, digital tomosynthesis, tetrahedron beam computed tomography, etc. We are developing a high-brightness multiple-pixel thermionic emission x-ray (MPTEX) source based on oxide coated cathodes. Oxide cathode is chosen as the electron source due to its high emission current density and low operating temperature. A MPTEX prototype has been developed which may contain up to 41 micro-rectangular oxide cathodes in 4 mm pixel spacing. Electronics hardware was developed for source controlmore » and switching. The cathode emission current was evaluated and x-ray measurements were performed to estimate the focal spot size. Results: The oxide cathodes were able to produce ∼110 mA cathode current in pulse mode which corresponds to an emission current density of 0.55 A/cm{sup 2}. The maximum kVp of the MPTEX prototype currently is limited to 100 kV due to the rating of high voltage feedthrough. Preliminary x-ray measurements estimated the focal spot size as 1.5 × 1.3 mm{sup 2}. Conclusion: A MPTEX source was developed with thermionic oxide coated cathodes and preliminary source characterization was successfully performed. The MPTEX source is able to produce an array of high brightness x-ray beams with a fast switching speed.« less

New multichannel kinetic spectrophotometer-fluorimeter with pulsed measuring beam for photosynthesis research.

PubMed

Bína, David; Litvín, Radek; Vácha, Frantisek; Siffel, Pavel

2006-06-01

A multichannel kinetic spectrophotometer-fluorimeter with pulsed measuring beam and differential optics has been constructed for measurements of light-induced absorbance and fluorescence yield changes in isolated chlorophyll-proteins, thylakoids and intact cells including algae and photosynthetic bacteria. The measuring beam, provided by a short (2 micros) pulse from a xenon flash lamp, is divided into a sample and reference channel by a broad band beam splitter. The spectrum in each channel is analyzed separately by a photodiode array. The use of flash measuring beam and differential detection yields high signal-to-noise ratio (noise level of 2 x 10(-4) in absorbance units per single flash) with negligible actinic effect. The instrument covers a spectral range between 300 and 1050 nm with a spectral resolution of 2.1, 6.4 or 12.8 nm dependent on the type of grating used. The optical design of the instrument enables measuring of the difference spectra during an actinic irradiation of samples with continuous light and/or saturation flashes. The time resolution of the spectrophotometer is limited by the length of Xe flash lamp pulses to 2 micros.

Enhanced optical alignment of a digital micro mirror device through Bayesian adaptive exploration

NASA Astrophysics Data System (ADS)

Wynne, Kevin B.; Knuth, Kevin H.; Petruccelli, Jonathan

2017-12-01

As the use of Digital Micro Mirror Devices (DMDs) becomes more prevalent in optics research, the ability to precisely locate the Fourier "footprint" of an image beam at the Fourier plane becomes a pressing need. In this approach, Bayesian adaptive exploration techniques were employed to characterize the size and position of the beam on a DMD located at the Fourier plane. It couples a Bayesian inference engine with an inquiry engine to implement the search. The inquiry engine explores the DMD by engaging mirrors and recording light intensity values based on the maximization of the expected information gain. Using the data collected from this exploration, the Bayesian inference engine updates the posterior probability describing the beam's characteristics. The process is iterated until the beam is located to within the desired precision. This methodology not only locates the center and radius of the beam with remarkable precision but accomplishes the task in far less time than a brute force search. The employed approach has applications to system alignment for both Fourier processing and coded aperture design.

Animal Venom Peptides: Potential for New Antimicrobial Agents.

PubMed

Primon-Barros, Muriel; José Macedo, Alexandre

2017-01-01

Microbial infections affect people worldwide, causing diseases with significant impact on public health, indicating the need for research and development of new antimicrobial agents. Animal venoms represent a vast and largely unexploited source of biologically active molecules with attractive candidates for the development of novel therapeutics. Venoms consist of complex mixtures of molecules, including antimicrobial peptides (AMPs). Since the discovery of AMPs, they have been studied as promising new antimicrobial drugs. Amongst the remarkable sources of AMPs with known antimicrobial activities are ants, bees, centipedes, cone snails, scorpions, snakes, spiders, and wasps. The antimicrobial tests against bacteria, protozoans, fungi and viruses using 170 different peptides isolated directly from crude venoms or cDNA libraries of venom glands are listed and discussed in this review, as well as hemolytic ativity. The potential of venoms as source of new compounds, including AMPs, is extensively discussed. Currently, there are six FDA-approved drugs and many others are undergoing preclinical and clinical trials. The search for antimicrobial "weapons" makes the AMPs from venoms promising candidates. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides in the Fight against Neglected Tropical Diseases.

PubMed

Lewies, Angélique; Wentzel, Johannes F; Jacobs, Garmi; Du Plessis, Lissinda H; Angélique, Lewies; Frederik, Wentzel Johannes; Garmi, Jacobs; Hester, Du Plessis Lissinda

2015-08-24

Recently, research into the development of new antimicrobial agents has been driven by the increase in resistance to traditional antibiotics and Emerging Infectious Diseases. Antimicrobial peptides (AMPs) are promising candidates as alternatives to current antibiotics in the treatment and prevention of microbial infections. AMPs are produced by all known living species, displaying direct antimicrobial killing activity and playing an important role in innate immunity. To date, more than 2000 AMPs have been discovered and many of these exhibit broad-spectrum antibacterial, antiviral and anti-parasitic activity. Neglected tropical diseases (NTDs) are caused by a variety of pathogens and are particularly wide-spread in low-income and developing regions of the world. Alternative, cost effective treatments are desperately needed to effectively battle these medically diverse diseases. AMPs have been shown to be effective against a variety of NTDs, including African trypanosomes, leishmaniosis and Chagas disease, trachoma and leprosy. In this review, the potential of selected AMPs to successfully treat a variety of NTD infections will be critically evaluated.

Archetypal tryptophan-rich antimicrobial peptides: properties and applications.

PubMed

Shagaghi, Nadin; Palombo, Enzo A; Clayton, Andrew H A; Bhave, Mrinal

2016-02-01

Drug-resistant microorganisms ('superbugs') present a serious challenge to the success of antimicrobial treatments. Subsequently, there is a crucial need for novel bio-control agents. Many antimicrobial peptides (AMPs) show a broad-spectrum activity against bacteria, fungi or viruses and are strong candidates to complement or substitute current antimicrobial agents. Some AMPs are also effective against protozoa or cancer cells. The tryptophan (Trp)-rich peptides (TRPs) are a subset of AMPs that display potent antimicrobial activity, credited to the unique biochemical properties of tryptophan that allow it to insert into biological membranes. Further, many Trp-rich AMPs cross bacterial membranes without compromising their integrity and act intracellularly, suggesting interactions with nucleic acids and enzymes. In this work, we overview some archetypal TRPs derived from natural sources, i.e., indolicidin, tritrpticin and lactoferricin, summarising their biochemical properties, structures, antimicrobial activities, mechanistic studies and potential applications.

Applications of X-Ray Micro-Beam for Data Collection.

PubMed

Sanishvili, Ruslan; Fischetti, Robert F

2017-01-01

Micro-diffraction tools for macromolecular crystallography, first developed at the end of 1990s and now an integral part of many synchrotron beamlines, enable some of the experiments which were not feasible just a decade or so ago. These include data collection from very small samples, just a few micrometers in size; from larger, but severely inhomogeneous samples; and from samples which are optically invisible. Improved micro-diffraction tools led to improved signal-to-noise ratio, to mitigation of radiation damage in some cases, and to better-designed diffraction experiments. Small, micron-scale beams can be attained in different ways and knowing the details of the implementation is important in order to design the diffraction experiment properly. Similarly, precision, reproducibility and stability of the goniometry, and caveats of detection systems need to be taken into account. Lastly, to make micro-diffraction widely applicable, the sophistication, robustness, and user-friendliness of these tools are just as important as the technical capabilities.

Fabrication of nanobeads from nanocups by controlling scission/crosslinking in organic polymer materials.

PubMed

Oyama, Tomoko Gowa; Oshima, Akihiro; Washio, Masakazu; Tagawa, Seiichi

2012-12-14

The development of several kinds of micro/nanofabrication techniques has resulted in many innovations in the micro/nanodevices that support today's science and technology. With feature miniaturization, the fabrication tools have shifted from light to ionizing radiation. Here, we propose a simple micro/nanofabrication technique for organic materials using a scanning beam (SB) of ionizing radiation. By controlling the scission/crosslinking of the material via three-dimensional energy-deposition distribution of the SB, appropriate solvents can easily peel off only the crosslinked region from the bulk material. The technique was demonstrated using a focused ion beam and a chlorinated organic polymer. The polymer underwent main-chain scission upon irradiation, but it crosslinked after high-dose irradiation. Appropriate solvents could easily peel off only the crosslinked region from the bulk material. The technique, 'nanobead from nanocup', enabled the production of desired structures such as nanowires and nanomembranes. It can be also applied to the micro/nanofabrication of functional materials.

Nucleotides, micro- and macro-nutrients, limonoids, flavonoids, and hydroxycinnamates composition in the phloem sap of sweet orange

PubMed Central

Hijaz, Faraj; Manthey, John A.; Van der Merwe, Deon; Killiny, Nabil

2016-01-01

ABSTRACT Currently, the global citrus production is declining due to the spread of Huanglongbing (HLB). HLB, otherwise known as citrus greening, is caused by Candidatus Liberibacter asiaticus (CLas) and is transmitted by the Asian citrus psyllids (ACP), Diaphorina citri Kuwayama. ACP transmits CLas bacterium while feeding on the citrus phloem sap. Multiplication of CLas in the phloem of citrus indicates that the sap contains all the essential nutrients needed for CLas. In this study, we investigated the micro- and macro-nutrients, nucleotides, and others secondary metabolites of phloem sap from pineapple sweet orange. The micro- and macro-nutrients were analyzed using inductively coupled plasma-mass spectroscopy (ICP-MS) and inductively coupled plasma-optical emission spectroscopy (ICP-OES). Nucleotides and other secondary metabolites analysis was accomplished by reversed phase HPLC coupled with UV, fluorescence detection, or negative mode electrospray ionization mass spectrometry (ESI-MS). Calcium (89 mM) was the highest element followed by potassium (38.8 mM) and phosphorous (24 mM). Magnesium and sulfur were also abundant and their concentrations were 15 and 9 mM, respectively. The rest of the elements were found in low amounts (< 2mM). The concentrations of ATP, ADP, and AMP were 16, 31, and 3 µ mole/Kg fwt, respectively. GTP, GMP. NAD, FMN, FAD, and riboflavin were found at concentrations below (3 µ mole/Kg fwt). The phloem was rich in nomilin 124 mM and limonin 176 µ mole/Kg fwt. Hesperidin, vicenin-2, sinensetin, and nobiletin were the most predominant flavonoids. In addition, several hydroxycinnamates were detected. The results of this study will increase our knowledge about the nature and the chemical composition of citrus phloem sap. PMID:27171979

Nucleotides, micro- and macro-nutrients, limonoids, flavonoids, and hydroxycinnamates composition in the phloem sap of sweet orange.

PubMed

Hijaz, Faraj; Manthey, John A; Van der Merwe, Deon; Killiny, Nabil

2016-06-02

Currently, the global citrus production is declining due to the spread of Huanglongbing (HLB). HLB, otherwise known as citrus greening, is caused by Candidatus Liberibacter asiaticus (CLas) and is transmitted by the Asian citrus psyllids (ACP), Diaphorina citri Kuwayama. ACP transmits CLas bacterium while feeding on the citrus phloem sap. Multiplication of CLas in the phloem of citrus indicates that the sap contains all the essential nutrients needed for CLas. In this study, we investigated the micro- and macro-nutrients, nucleotides, and others secondary metabolites of phloem sap from pineapple sweet orange. The micro- and macro-nutrients were analyzed using inductively coupled plasma-mass spectroscopy (ICP-MS) and inductively coupled plasma-optical emission spectroscopy (ICP-OES). Nucleotides and other secondary metabolites analysis was accomplished by reversed phase HPLC coupled with UV, fluorescence detection, or negative mode electrospray ionization mass spectrometry (ESI-MS). Calcium (89 mM) was the highest element followed by potassium (38.8 mM) and phosphorous (24 mM). Magnesium and sulfur were also abundant and their concentrations were 15 and 9 mM, respectively. The rest of the elements were found in low amounts (< 2mM). The concentrations of ATP, ADP, and AMP were 16, 31, and 3 µ mole/Kg fwt, respectively. GTP, GMP. NAD, FMN, FAD, and riboflavin were found at concentrations below (3 µ mole/Kg fwt). The phloem was rich in nomilin 124 mM and limonin 176 µ mole/Kg fwt. Hesperidin, vicenin-2, sinensetin, and nobiletin were the most predominant flavonoids. In addition, several hydroxycinnamates were detected. The results of this study will increase our knowledge about the nature and the chemical composition of citrus phloem sap.

Modeling and measurement of a micro-optic beam deflector

NASA Technical Reports Server (NTRS)

Milster, Tom D.; Wong, J. Nan

1992-01-01

The use is studied of a unity-magnification micro-optic beam deflector. The defelector consists of two arrays of positively powered lenslets. The lenslets on each array are arranged in a square grid. Design criteria are based on usefulness in optical data storage devices. The deflector is designed to operate over a + or - 1.6 range of deflection angles. Modeling results are compared with interferometric analysis of the wavefront from a single lenslet pair. The results indicate that the device is nearly diffraction limited, but there are substantial wavefront errors at the edges and corners of the lenslets.

Opioid agonists binding and responses in SH-SY5Y cells

NASA Technical Reports Server (NTRS)

Costa, E. M.; Hoffmann, B. B.; Loew, G. H.

1992-01-01

SH-SY5Y (human neuroblastoma) cultured cells, known to have mu-opioid receptors, have been used to assess and compare the ability of eight representative mu-selective compounds from diverse opioid families to recognize and activate these receptors. A wide range of receptor affinities spanning a factor of 10,000 was found between the highest affinity fentanyl analogs (Ki = 0.1nM) and the lowest affinity analog, meperidine (Ki = 1 microM). A similar range was found for inhibition of PGE1-stimulated cAMP accumulation with a rank order of activities that closely paralleled binding affinities. Maximum inhibition of cAMP accumulation by each compound was about 80%. Maximum stimulation of GTPase activity (approximately 50%) was also similar for all compounds except the lowest affinity meperidine. Both effects were naloxone reversible. These results provide further evidence that mu-receptors are coupled to inhibition of adenylate cyclase and that the SH-SY5Y cell line is a good system for assessment of mu-agonists functional responses.

Mega-Amp Opening Switch with Nested Electrodes/Pulsed Generator of Ion and Ion Cluster Beams.

DTIC Science & Technology

1985-07-01

i.e., noncollisiona].) resistivity which controls the "~switch opening" function (specifically, the rate of disintergration of the PF pinch where...unaffected the pinch field Be and then disassemble in a light (D) component and other heavy components. Production and propagation of-neutrals (from...emission, production and - evaporation would imply a distorsion of the pinholeimage-because of B -which is not p.-.. observed (our pinhole resolution is 150

Coupling to protein kinases A and C of adenosine A2B receptors involved in the facilitation of noradrenaline release in the prostatic portion of rat vas deferens.

PubMed

Queiroz, Glória; Quintas, Clara; Talaia, Carlos; Gonçalves, Jorge

2004-08-01

In the prostatic portion of rat vas deferens, the non-selective adenosine receptor agonist NECA (0.1-30 microM), but not the A(2A) agonist CGS 21680 (0.001-10 microM), caused a facilitation of electrically evoked noradrenaline release (up to 43 +/- 4%), when inhibitory adenosine A(1) receptors were blocked. NECA-elicited facilitation of noradrenaline release was prevented by the A(2B) receptor-antagonist MRS 1754, enhanced by preventing cyclic-AMP degradation with rolipram, abolished by the protein kinase A inhibitors H-89, KT 5720 and cyclic-AMPS-Rp and attenuated by the protein kinase C inhibitors Ro 32-0432 and calphostin C. The adenosine uptake inhibitor NBTI also elicited a facilitation of noradrenaline release; an effect that was abolished by adenosine deaminase and attenuated by MRS 1754, by inhibitors of the extracellular nucleotide metabolism and by blockade of alpha(1)-adrenoceptors and P2X receptors with prazosin and NF023, respectively. It was concluded that adenosine A(2B) receptors are involved in a facilitation of noradrenaline release in the prostatic portion of rat vas deferens that can be activated by adenosine formed by extracellular catabolism of nucleotides. The receptors seem to be coupled to the adenylyl cyclase-protein kinase A pathway but activation of the protein kinase C by protein kinase A, may also contribute to the adenosine A(2B) receptor-mediated facilitation of noradrenaline release.

X-ray tomography of powder injection moulded micro parts using synchrotron radiation

NASA Astrophysics Data System (ADS)

Heldele, R.; Rath, S.; Merz, L.; Butzbach, R.; Hagelstein, M.; Haußelt, J.

2006-05-01

Powder injection moulding is one of the most promising replication methods for the mass production of metal and ceramic micro parts. The material for injection moulding, a so-called feedstock, consists of thermoplastic binder components and inorganic filler with approximately equal volume fractions. Injection moulding of the feedstock leads to a green part that can be processed to a dense metal or ceramic micro part by debinding and sintering. During the injection moulding process extremely high shear rates are applied. This promotes the separation of powder and binder leading to a particle density variation in the green part causing anisotropic shrinkage during post-processing. The knowledge of introducing density gradients and defects would consequently allow the optimization of the feedstock, the moulding parameters and the validation of a simulation tool based on the Dissipative Particle Dynamics which is currently under development, as well. To determine the particle density and defect distribution in micro parts synchrotron radiation tomography in absorption mode was used. Due to its parallel and monochromatic character a quantitative reconstruction, free of beam hardening artifacts, is possible. For the measurement, bending bars consisting of dispersed fused silica particles in a polymeric matrix were used. The presented results using this set-up show that crucial defects and density variations can be detected.

Distributed source model for the full-wave electromagnetic simulation of nonlinear terahertz generation.

PubMed

Fumeaux, Christophe; Lin, Hungyen; Serita, Kazunori; Withayachumnankul, Withawat; Kaufmann, Thomas; Tonouchi, Masayoshi; Abbott, Derek

2012-07-30

The process of terahertz generation through optical rectification in a nonlinear crystal is modeled using discretized equivalent current sources. The equivalent terahertz sources are distributed in the active volume and computed based on a separately modeled near-infrared pump beam. This approach can be used to define an appropriate excitation for full-wave electromagnetic numerical simulations of the generated terahertz radiation. This enables predictive modeling of the near-field interactions of the terahertz beam with micro-structured samples, e.g. in a near-field time-resolved microscopy system. The distributed source model is described in detail, and an implementation in a particular full-wave simulation tool is presented. The numerical results are then validated through a series of measurements on square apertures. The general principle can be applied to other nonlinear processes with possible implementation in any full-wave numerical electromagnetic solver.

Reduction of 1/f noise in graphene after electron-beam irradiation

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

Zahid Hossain, Md.; Rumyantsev, Sergey; Ioffe Physical-Technical Institute, The Russian Academy of Sciences, St. Petersburg 194021

2013-04-15

We investigated experimentally the effect of the electron-beam irradiation on the level of the low-frequency 1/f noise in graphene devices. It was found that 1/f noise in graphene reduces with increasing concentration of defects induced by irradiation. The increased amount of structural disorder in graphene under irradiation was verified with micro-Raman spectroscopy. The bombardment of graphene devices with 20-keV electrons reduced the noise spectral density, S{sub I}/I{sup 2} (I is the source-drain current) by an order-of magnitude at the radiation dose of 10{sup 4} {mu}C/cm{sup 2}. We analyzed the observed noise reduction in the limiting cases of the mobility andmore » carrier number fluctuation mechanisms. The obtained results are important for the proposed graphene applications in analog, mixed-signal, and radio-frequency systems, integrated circuits and sensors.« less

An automated BPM characterization system for LEDA

NASA Astrophysics Data System (ADS)

Shurter, R. B.; Gilpatrick, J. D.; Ledford, J.; O'Hara, J.; Power, J.

1998-12-01

An automated and highly accurate system for "mapping" 5 cm-diameter beam position monitors (BPMs) used in the Low Energy Demonstrator Accelerator (LEDA) at Los Alamos is described. Two-dimensional data is accumulated from the four micro-stripline electrodes in the probe by sweeping an antenna driven at the LEDA bunching frequency of 350 MHz in discrete steps across the aperture. These data are then used to determine the centroid, first- and third-order sensitivities of the BPM. These probe response coefficients are then embedded in the LEDA control system database to provide normalized beam position information to the operators. A short summary of previous systems we have fielded is given, along with their attributes and deficiencies that had a bearing on this latest design. Lessons learned from this system will, in turn, be used on the next mappers that are currently being designed for 15 cm and 2.5 cm BPMs.

Large patternable metal nanoparticle sheets by photo/e-beam lithography

NASA Astrophysics Data System (ADS)

Saito, Noboru; Wang, Pangpang; Okamoto, Koichi; Ryuzaki, Sou; Tamada, Kaoru

2017-10-01

Techniques for micro/nano-scale patterning of large metal nanoparticle sheets can potentially be used to realize high-performance photoelectronic devices because the sheets provide greatly enhanced electrical fields around the nanoparticles due to localized surface plasmon resonances. However, no single metal nanoparticle sheet currently exists with sufficient durability for conventional lithographical processes. Here, we report large photo and/or e-beam lithographic patternable metal nanoparticle sheets with improved durability by incorporating molecular cross-linked structures between nanoparticles. The cross-linked structures were easily formed by a one-step chemical reaction; immersing a single nanoparticle sheet consisting of core metals, to which capping molecules ionically bond, in a dithiol ethanol solution. The ligand exchange reaction processes were discussed in detail, and we demonstrated 20 μm wide line and space patterns, and a 170 nm wide line of the silver nanoparticle sheets.

Simulation of a cascaded longitudinal space charge amplifier for coherent radiation generation

DOE PAGES

Halavanau, A.; Piot, P.

2016-03-03

Longitudinal space charge (LSC) effects are generally considered as harmful in free-electron lasers as they can seed unfavorable energy modulations that can result in density modulations with associated emittance dilution. It was pointed out, however, that such \\micro-bunching instabilities" could be potentially useful to support the generation of broadband coherent radiation. Therefore there has been an increasing interest in devising accelerator beam lines capable of controlling LSC induced density modulations. In the present paper we augment these previous investigations by combining a grid-less space charge algorithm with the popular particle-tracking program elegant. This high-fidelity model of the space charge ismore » used to benchmark conventional LSC models. We then employ the developed model to optimize the performance of a cascaded longitudinal space charge amplifier using beam parameters comparable to the ones achievable at Fermilab Accelerator Science & Technology (FAST) facility currently under commissioning at Fermilab.« less

Study of nanoscale structural biology using advanced particle beam microscopy

NASA Astrophysics Data System (ADS)

Boseman, Adam J.

This work investigates developmental and structural biology at the nanoscale using current advancements in particle beam microscopy. Typically the examination of micro- and nanoscale features is performed using scanning electron microscopy (SEM), but in order to decrease surface charging, and increase resolution, an obscuring conductive layer is applied to the sample surface. As magnification increases, this layer begins to limit the ability to identify nanoscale surface structures. A new technology, Helium Ion Microscopy (HIM), is used to examine uncoated surface structures on the cuticle of wild type and mutant fruit flies. Corneal nanostructures observed with HIM are further investigated by FIB/SEM to provide detailed three dimensional information about internal events occurring during early structural development. These techniques are also used to reconstruct a mosquito germarium in order to characterize unknown events in early oogenesis. Findings from these studies, and many more like them, will soon unravel many of the mysteries surrounding the world of developmental biology.

A future, intense source of negative hydrogen ions

NASA Technical Reports Server (NTRS)

Siefken, Hugh; Stein, Charles

1994-01-01

By directly heating lithium hydride in a vacuum, up to 18 micro-A/sq cm of negative hydrogen has been obtained from the crystal lattice. The amount of ion current extracted and analyzed is closely related to the temperature of the sample and to the rate at which the temperature is changed. The ion current appears to be emission limited and saturates with extraction voltage. For a fixed extraction voltage, the ion current could be maximized by placing a grid between the sample surface and the extraction electrode. Electrons accompanying the negative ions were removed by a magnetic trap. A Wein velocity filter was designed and built to provide definitive mass analysis of the extracted ion species. This technique when applied to other alkali hydrides may produce even higher intensity beams possessing low values of emittance.

Activation of protein kinase A in the amygdala modulates anxiety-like behaviors in social defeat exposed mice.

PubMed

Yang, Liu; Shi, Li-Jun; Yu, Jin; Zhang, Yu-Qiu

2016-01-08

Social defeat (SD) stress induces social avoidance and anxiety-like phenotypes. Amygdala is recognized as an emotion-related brain region such as fear, aversion and anxiety. It is conceivable to hypothesize that activation of amygdala is involved in SD-dependent behavioral defects. SD model was established using C57BL/6J mice that were physically defeated by different CD-1 mice for 10 days. Stressed mice exhibited decreased social interaction level in social interaction test and significant anxiety-like behaviors in elevated plus maze and open field tests. Meanwhile, a higher phosphorylation of PKA and CREB with a mutually linear correlation, and increased Fos labeled cells in the basolateral amygdala (BLA) were observed. Activation of PKA in the BLA by 8-Br-cAMP, a PKA activitor, significantly upregulated pCREB and Fos expression. To address the role of PKA activation on SD stress-induced social avoidance and anxiety-like behaviors, 8-Br-cAMP or H-89, a PKA inhibitor, was continuously administered into the bilateral BLA by a micro-osmotic pump system during the 10-day SD period. Neither H-89 nor 8-Br-cAMP affected the social behavior. Differently, 8-Br-cAMP significantly relieved anxiety-like behaviors in both general and moderate SD protocols. H-89 per se did not have anxiogenic effect in naïve mice, but aggravated moderate SD stress-induced anxiety-like behaviors. The antidepressant clomipramine reduced SD-induced anxiety and up-regulated pPKA level in the BLA. These results suggest that SD-driven PKA activation in the basolateral amygdala is actually a compensatory rather than pathogenic response in the homeostasis, and modulating amygdaloid PKA may exhibit potency in the therapy of social derived disorders.

Composite, all-ceramics, high-peak power Nd:YAG/Cr(4+):YAG monolithic micro-laser with multiple-beam output for engine ignition.

PubMed

Pavel, Nicolaie; Tsunekane, Masaki; Taira, Takunori

2011-05-09

A passively Q-switched Nd:YAG/Cr(4+):YAG micro-laser with three-beam output was realized. A single active laser source made of a composite, all-ceramics Nd:YAG/Cr(4+):YAG monolithic cavity was pumped by three independent lines. At 5 Hz repetition rate, each line delivered laser pulses with ~2.4 mJ energy and 2.8-MW peak power. The M(2) factor of a laser beam was 3.7, and stable air breakdowns were realized. The increase of pump repetition rate up to 100 Hz improved the laser pulse energy by 6% and required ~6% increase of the pump pulse energy. Pulse timing of the laser-array beams can by adjusted by less than 5% tuning of an individual line pump energy, and therefore simultaneous multi-point ignition is possible. This kind of laser can be used for multi-point ignition of an automobile engine. © 2011 Optical Society of America

Miniaturized CARS microendoscope probe design for label-free intraoperative imaging

NASA Astrophysics Data System (ADS)

Chen, Xu; Wang, Xi; Xu, Xiaoyun; Cheng, Jie; Liu, Zhengfan; Weng, Sheng; Thrall, Michael J.; Goh, Alvin C.; McCormick, Daniel T.; Wong, Kelvin; Wong, Stephen T. C.

2014-03-01

A Coherent Anti-Stokes Raman Scattering (CARS) microendoscope probe for early stage label-free prostate cancer diagnosis at single cell resolution is presented. The handheld CARS microendoscope probe includes a customized micro-electromechanical systems (MEMS) scanning mirror as well as miniature optical and mechanical components. In our design, the excitation laser (pump and stokes beams) from the fiber is collimated, reflected by the reflecting mirror, and transmitted via a 2D MEMS scanning mirror and a micro-objective system onto the sample; emission in the epi-direction is returned through the micro-objective lens, MEMS and reflecting mirror, and collimation system, and finally the emission signal is collected by a photomultiplier tube (PMT). The exit pupil diameter of the collimator system is designed to match the diameter of the MEMS mirror and the entrance pupil diameter of the micro-objective system. The back aperture diameter of the micro-objective system is designed according to the largest MEMS scanning angle and the distance between the MEMS mirror and the back aperture. To increase the numerical aperture (NA) of the micro-objective system in order to enhance the signal collection efficiency, the back aperture diameter of the micro-objective system is enlarged with an upfront achromatic wide angle Keplerian telescope beam expander. The integration of a miniaturized micro-optics probe with optical fiber CARS microscopy opens up the possibility of in vivo molecular imaging for cancer diagnosis and surgical intervention.

Integrated Circuit Design of 3 Electrode Sensing System Using Two-Stage Operational Amplifier

NASA Astrophysics Data System (ADS)

Rani, S.; Abdullah, W. F. H.; Zain, Z. M.; N, Aqmar N. Z.

2018-03-01

This paper presents the design of a two-stage operational amplifier(op amp) for 3-electrode sensing system readout circuits. The designs have been simulated using 0.13μm CMOS technology from Silterra (Malaysia) with Mentor graphics tools. The purpose of this projects is mainly to design a miniature interfacing circuit to detect the redox reaction in the form of current using standard analog modules. The potentiostat consists of several op amps combined together in order to analyse the signal coming from the 3-electrode sensing system. This op amp design will be used in potentiostat circuit device and to analyse the functionality for each module of the system.

Identification of the fatty acid activation site on human ClC-2.

PubMed

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

2017-06-01

Fatty acids (including lubiprostone and cobiprostone) are human ClC-2 (hClC-2) Cl - channel activators. Molecular and cellular mechanisms underlying this activation were examined. Role of a four-amino acid PKA activation site, RGET 691 , of hClC-2 was investigated using wild-type (WT) and mutant (AGET, RGEA, and AGAA) hClC-2 expressed in 293EBNA cells as well as involvement of PKA, intracellular cAMP concentration ([cAMP] i ), EP 2 , or EP 4 receptor agonist activity. All fatty acids [lubiprostone, cobiprostone, eicosatetraynoic acid (ETYA), oleic acid, and elaidic acid] caused significant rightward shifts in concentration-dependent Cl - current activation (increasing EC 50 s) with mutant compared with WT hClC-2 channels, without changing time and voltage dependence, current-voltage rectification, or methadone inhibition of the channel. As with lubiprostone, cobiprostone activation of hClC-2 occurred with PKA inhibitor (myristoylated protein kinase inhibitor) present or when using double PKA activation site (RRAA 655 /RGEA 691 ) mutant. Cobiprostone did not activate human CFTR. Fatty acids did not increase [cAMP] i in hClC-2/293EBNA or T84 cells. Using T84 CFTR knockdown cells, cobiprostone increased hClC-2 Cl - currents without increasing [cAMP] i, while PGE 2 and forskolin-IBMX increased both. Fatty acids were not agonists of EP 2 or EP 4 receptors. L-161,982, a supposed EP 4 -selective inhibitor, had no effect on lubiprostone-activated hClC-2 Cl - currents but significantly decreased T84 cell barrier function measured by transepithelial resistance and fluorescent dextran transepithelial movement. The present findings show that RGET 691 of hClC-2 (possible binding site) plays an important functional role in fatty acid activation of hClC-2. PKA, [cAMP] i , and EP 2 or EP 4 receptors are not involved. These studies provide the molecular basis for fatty acid regulation of hClC-2. Copyright © 2017 the American Physiological Society.

Aging management program of the reactor building concrete at Point Lepreau Generating Station

NASA Astrophysics Data System (ADS)

Aldea, C.-M.; Shenton, B.; Demerchant, M. M.; Gendron, T.

2011-04-01

In order for New Brunswick Power Nuclear (NBPN) to control the risks of degradation of the concrete reactor building at the Point Lepreau Generating Station (PLGS) the development of an aging management plan (AMP) was initiated. The intention of this plan was to determine the requirements for specific structural components of concrete of the reactor building that require regular inspection and maintenance to ensure the safe and reliable operation of the plant. The document is currently in draft form and presents an integrated methodology for the application of an AMP for the concrete of the reactor building. The current AMP addresses the reactor building structure and various components, such as joint sealant and liners that are integral to the structure. It does not include internal components housed within the structure. This paper provides background information regarding the document developed and the strategy developed to manage potential degradation of the concrete of the reactor building, as well as specific programs and preventive and corrective maintenance activities initiated.

Hepatic gene expression profiling of 5′-AMP-induced hypometabolism in mice

PubMed Central

Miki, Takao; Van Oort-Jansen, Anita; Matsumoto, Tomoko; Loose, David S.; Lee, Cheng Chi

2011-01-01

There is currently much interest in clinical applications of therapeutic hypothermia. Hypothermia can be a consequence of hypometabolism. We have recently established a procedure for the induction of a reversible deep hypometabolic state in mice using 5′-adenosine monophosphate (5′-AMP) in conjunction with moderate ambient temperature. The current study aims at investigating the impact of this technology at the gene expression level in a major metabolic organ, the liver. Our findings reveal that expression levels of the majority of genes in liver are not significantly altered by deep hypometabolism. However, among those affected by hypometabolism, more genes are differentially upregulated than downregulated both in a deep hypometabolic state and in the early arousal state. These altered gene expression levels during 5′-AMP induced hypometabolism are largely restored to normal levels within 2 days of the treatment. Our data also suggest that temporal control of circadian genes is largely stalled during deep hypometabolism. PMID:21224422

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

Morioka, A.; Misawa, H.; Obara, T.

Solar micro-type III radio bursts are elements of the so-called type III storms and are characterized by short-lived, continuous, and weak emissions. Their frequency of occurrence with respect to radiation power is quite different from that of ordinary type III bursts, suggesting that the generation process is not flare-related, but due to some recurrent acceleration processes around the active region. We examine the relationship of micro-type III radio bursts with coronal streamers. We also explore the propagation channel of bursts in the outer corona, the acceleration process, and the escape route of electron beams. It is observationally confirmed that micro-typemore » III bursts occur near the edge of coronal streamers. The magnetic field line of the escaping electron beams is tracked on the basis of the frequency drift rate of micro-type III bursts and the electron density distribution model. The results demonstrate that electron beams are trapped along closed dipolar field lines in the outer coronal region, which arise from the interface region between the active region and the coronal hole. A 22 year statistical study reveals that the apex altitude of the magnetic loop ranges from 15 to 50 R{sub S}. The distribution of the apex altitude has a sharp upper limit around 50 R{sub S} suggesting that an unknown but universal condition regulates the upper boundary of the streamer dipolar field.« less

Direct writing of micro/nano-scale patterns by means of particle lens arrays scanned by a focused diode pumped Nd:YVO4 laser

NASA Astrophysics Data System (ADS)

Pena, Ana; Wang, Zengbo; Whitehead, David; Li, Lin

2010-11-01

A practical approach to a well-known technique of laser micro/nano-patterning by optical near fields is presented. It is based on surface patterning by scanning a Gaussian laser beam through a self-assembled monolayer of silica micro-spheres on a single-crystalline silicon (Si) substrate. So far, the outcome of this kind of near-field patterning has been related to the simultaneous, parallel surface-structuring of large areas either by top hat or Gaussian laser intensity distributions. We attempt to explore the possibility of using the same technique in order to produce single, direct writing of features. This could be of advantage for applications in which only some areas need to be patterned (i.e. local area selective patterning) or single lines are required (e.g. a particular micro/nano-fluidic channel). A diode pumped Nd:YVO4 laser system (wavelength of 532 nm, pulse duration of 8 ns, repetition rate of 30 kHz) with a computer-controlled 3 axis galvanometer beam scanner was employed to write user-defined patterns through the particle lens array on the Si substrate. After laser irradiation, the obtained patterns which are in the micro-scale were composed of sub-micro/micro-holes or bumps. The micro-pattern resolution depends on the dimension of both the micro-sphere’s diameter and the beam’s spot size. The developed technique could potentially be employed to fabricate photonic crystal structures mimicking nature’s butterfly wings and anti-reflective “moth eye” arrays for photovoltaic cells.

Transcriptome changes and cAMP oscillations in an archaeal cell cycle.

PubMed

Baumann, Anke; Lange, Christian; Soppa, Jörg

2007-06-11

The cell cycle of all organisms includes mass increase by a factor of two, replication of the genetic material, segregation of the genome to different parts of the cell, and cell division into two daughter cells. It is tightly regulated and typically includes cell cycle-specific oscillations of the levels of transcripts, proteins, protein modifications, and signaling molecules. Until now cell cycle-specific transcriptome changes have been described for four eukaryotic species ranging from yeast to human, but only for two prokaryotic species. Similarly, oscillations of small signaling molecules have been identified in very few eukaryotic species, but not in any prokaryote. A synchronization procedure for the archaeon Halobacterium salinarum was optimized, so that nearly 100% of all cells divide in a time interval that is 1/4th of the generation time of exponentially growing cells. The method was used to characterize cell cycle-dependent transcriptome changes using a genome-wide DNA microarray. The transcript levels of 87 genes were found to be cell cycle-regulated, corresponding to 3% of all genes. They could be clustered into seven groups with different transcript level profiles. Cluster-specific sequence motifs were detected around the start of the genes that are predicted to be involved in cell cycle-specific transcriptional regulation. Notably, many cell cycle genes that have oscillating transcript levels in eukaryotes are not regulated on the transcriptional level in H. salinarum. Synchronized cultures were also used to identify putative small signaling molecules. H. salinarum was found to contain a basal cAMP concentration of 200 microM, considerably higher than that of yeast. The cAMP concentration is shortly induced directly prior to and after cell division, and thus cAMP probably is an important signal for cell cycle progression. The analysis of cell cycle-specific transcriptome changes of H. salinarum allowed to identify a strategy of transcript level regulation that is different from all previously characterized species. The transcript levels of only 3% of all genes are regulated, a fraction that is considerably lower than has been reported for four eukaryotic species (6%-28%) and for the bacterium C. crescentus (19%). It was shown that cAMP is present in significant concentrations in an archaeon, and the phylogenetic profile of the adenylate cyclase indicates that this signaling molecule is widely distributed in archaea. The occurrence of cell cycle-dependent oscillations of the cAMP concentration in an archaeon and in several eukaryotic species indicates that cAMP level changes might be a phylogenetically old signal for cell cycle progression.

Separating and combining single-mode and multimode optical beams

DOEpatents

Ruggiero, Anthony J; Masquelier, Donald A; Cooke, Jeffery B; Kallman, Jeffery S

2013-11-12

Techniques for combining initially separate single mode and multimode optical beams into a single "Dual Mode" fiber optic have been developed. Bi-directional propagation of two beams that are differentiated only by their mode profiles (i.e., wavefront conditions) is provided. The beams can be different wavelengths and or contain different modulation information but still share a common aperture. This method allows the use of conventional micro optics and hybrid photonic packaging techniques to produce small rugged packages suitable for use in industrial or military environments.

Geometrical E-beam proximity correction for raster scan systems

NASA Astrophysics Data System (ADS)

Belic, Nikola; Eisenmann, Hans; Hartmann, Hans; Waas, Thomas

1999-04-01

High pattern fidelity is a basic requirement for the generation of masks containing sub micro structures and for direct writing. Increasing needs mainly emerging from OPC at mask level and x-ray lithography require a correction of the e-beam proximity effect. The most part of e-beam writers are raster scan system. This paper describes a new method for geometrical pattern correction in order to provide a correction solution for e-beam system that are not able to apply variable doses.

Antimicrobial activity of broccoli (Brassica oleracea var. italica) cultivar Avenger against pathogenic bacteria, phytopathogenic filamentous fungi and yeast.

PubMed

Pacheco-Cano, R D; Salcedo-Hernández, R; López-Meza, J E; Bideshi, D K; Barboza-Corona, J E

2018-01-01

The objective of this study was to show whether the edible part of broccoli has antibacterial and antifungal activity against micro-organism of importance in human health and vegetable spoilage, and to test if this effect was partially due to antimicrobial peptides (AMPs). Crude extracts were obtained from florets and stems of broccoli cultivar Avenger and the inhibitory effect was demonstrated against pathogenic bacteria (Bacillus cereus, Staphylococcus xylosus, Staphylococcus aureus, Shigella flexneri, Shigella sonnei, Proteus vulgaris), phytopathogenic fungi (Colletotrichum gloeosporioides, Asperigillus niger) and yeasts (Candida albicans and Rhodotorula sp.). It was shown that samples treated with proteolytic enzymes had a reduction of approximately 60% in antibacterial activity against Staph. xylosus, suggesting that proteinaceous compounds might play a role in the inhibitory effect. Antimicrobial components in crude extracts were thermoresistant and the highest activity was observed under acidic conditions. It was shown that antifungal activity of broccoli's crude extracts might not be attributed to chitinases. Organic broccoli cultivar Avenger has antimicrobial activity against pathogenic bacteria, yeast and phytophatogenic fungi. Data suggest that this effect is partially due to AMPs. Broccoli's crude extracts have activity not only against pathogenic bacteria but also against phytophatogenic fungi of importance in agriculture. We suggest for first time that the inhibitory effect is probably due to AMPs. © 2017 The Society for Applied Microbiology.

Accurate electrostatic and van der Waals pull-in prediction for fully clamped nano/micro-beams using linear universal graphs of pull-in instability

NASA Astrophysics Data System (ADS)

Tahani, Masoud; Askari, Amir R.

2014-09-01

In spite of the fact that pull-in instability of electrically actuated nano/micro-beams has been investigated by many researchers to date, no explicit formula has been presented yet which can predict pull-in voltage based on a geometrically non-linear and distributed parameter model. The objective of present paper is to introduce a simple and accurate formula to predict this value for a fully clamped electrostatically actuated nano/micro-beam. To this end, a non-linear Euler-Bernoulli beam model is employed, which accounts for the axial residual stress, geometric non-linearity of mid-plane stretching, distributed electrostatic force and the van der Waals (vdW) attraction. The non-linear boundary value governing equation of equilibrium is non-dimensionalized and solved iteratively through single-term Galerkin based reduced order model (ROM). The solutions are validated thorough direct comparison with experimental and other existing results reported in previous studies. Pull-in instability under electrical and vdW loads are also investigated using universal graphs. Based on the results of these graphs, non-dimensional pull-in and vdW parameters, which are defined in the text, vary linearly versus the other dimensionless parameters of the problem. Using this fact, some linear equations are presented to predict pull-in voltage, the maximum allowable length, the so-called detachment length, and the minimum allowable gap for a nano/micro-system. These linear equations are also reduced to a couple of universal pull-in formulas for systems with small initial gap. The accuracy of the universal pull-in formulas are also validated by comparing its results with available experimental and some previous geometric linear and closed-form findings published in the literature.

Hard alpha-keratin degradation inside a tissue under high flux X-ray synchrotron micro-beam: a multi-scale time-resolved study.

PubMed

Leccia, Emilie; Gourrier, Aurélien; Doucet, Jean; Briki, Fatma

2010-04-01

X-rays interact strongly with biological organisms. Synchrotron radiation sources deliver very intense X-ray photon fluxes within micro- or submicro cross-section beams, resulting in doses larger than the MGy. The relevance of synchrotron radiation analyses of biological materials is therefore questionable since such doses, million times higher than the ones used in radiotherapy, can cause huge damages in tissues, with regard to not only DNA, but also proteic and lipid organizations. Very few data concerning the effect of very high X-ray doses in tissues are available in the literature. We present here an analysis of the structural phenomena which occur when the model tissue of human hair is irradiated by a synchrotron X-ray micro-beam. The choice of hair is supported by its hierarchical and partially ordered keratin structure which can be analysed inside the tissue by X-ray diffraction. To assess the damages caused by hard X-ray micro-beams (1 microm(2) cross-section), short exposure time scattering SAXS/WAXS patterns have been recorded at beamline ID13 (ESRF) after various irradiation times. Various modifications of the scattering patterns are observed, they provide fine insight of the radiation damages at various hierarchical levels and also unexpectedly provide information about the stability of the various hierarchical structural levels. It appears that the molecular level, i.e. the alpha helices which are stabilized by hydrogen bonds and the alpha-helical coiled coils which are stabilized by hydrophobic interactions, is more sensitive to radiation than the supramolecular architecture of the keratin filament and the filament packing within the keratin associated proteins matrix, which is stabilized by disulphide bonds. (c) 2009 Elsevier Inc. All rights reserved.

The Potential for Health Monitoring in Expandable Space Modules: The Bigelow Expandable Activity Module on the ISS

NASA Technical Reports Server (NTRS)

Wells, Nathan D.; Madaras, Eric I.

2017-01-01

Expandable modules for use in space and on the Moon or Mars offer a great opportunity for volume and mass savings in future space exploration missions. This type of module can be compressed into a relatively small shape on the ground, allowing them to fit into space vehicles with a smaller cargo/fairing size than a traditional solid, metallic structure based module would allow. In April 2016, the Bigelow Expandable Activity Module (BEAM) was berthed to the International Space Station (ISS). BEAM is the first human-rated expandable habitat/module to be deployed and crewed in space. BEAM is a NASA managed ISS payload project in partnership with Bigelow Aerospace. BEAM is intended to stay attached to ISS for an operational period of 2 years to help advance the technology readiness for future expandable modules. BEAM has been instrumented with a suite of space flight certified sensors systems which will help characterize the module's performance for thermal, radiation shielding and impact monitoring against potential Micro Meteoroid/Orbital Debris (MM/OD) providing fundamental information on the BEAM environment for potential health monitoring requirements and capabilities. This paper will provide an overview of how the sensors/instrumentation systems were developed, tested, installed and an overview of the current sensor system operations. It will also discuss how the MM/OD impact detection system referred to as the Distributed Impact Detection System (DIDS) data is being processed and reviewed on the ground by the principle investigators.

Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball'-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers

PubMed Central

Greenwald, Mark K; Lundahl, Leslie H; Steinmiller, Caren L

2010-01-01

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy. PMID:20881947

Role of Dynamics in the Autoinhibition and Activation of the Exchange Protein Directly Activated by Cyclic AMP (EPAC)*

PubMed Central

VanSchouwen, Bryan; Selvaratnam, Rajeevan; Fogolari, Federico; Melacini, Giuseppe

2011-01-01

The exchange protein directly activated by cAMP (EPAC) is a key receptor of cAMP in eukaryotes and controls critical signaling pathways. Currently, no residue resolution information is available on the full-length EPAC dynamics, which are known to be pivotal determinants of allostery. In addition, no information is presently available on the intermediates for the classical induced fit and conformational selection activation pathways. Here these questions are addressed through molecular dynamics simulations on five key states along the thermodynamic cycle for the cAMP-dependent activation of a fully functional construct of EPAC2, which includes the cAMP-binding domain and the integral catalytic region. The simulations are not only validated by the agreement with the experimental trends in cAMP-binding domain dynamics determined by NMR, but they also reveal unanticipated dynamic attributes, rationalizing previously unexplained aspects of EPAC activation and autoinhibition. Specifically, the simulations show that cAMP binding causes an extensive perturbation of dynamics in the distal catalytic region, assisting the recognition of the Rap1b substrate. In addition, analysis of the activation intermediates points to a possible hybrid mechanism of EPAC allostery incorporating elements of both the induced fit and conformational selection models. In this mechanism an entropy compensation strategy results in a low free-energy pathway of activation. Furthermore, the simulations indicate that the autoinhibitory interactions of EPAC are more dynamic than previously anticipated, leading to a revised model of autoinhibition in which dynamics fine tune the stability of the autoinhibited state, optimally sensitizing it to cAMP while avoiding constitutive activation. PMID:21873431

Micro-crystallography developments at GM/CA CAT at the APS.

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

Xu, S.; Makarov, O.; Benn, R.

2010-01-01

Recently, several important structures have been solved using micro-crystallographic techniques that previously could not have been solved with conventional crystallography. At GM/CA-CAT we continue to develop micro-crystallographic capabilities for difficult problems such as small crystals of large macromolecular complexes or membrane proteins grown in the lipidic cubic phase. This paper will describe three major upgrades to our arsenal of tools, 'mini-beam' collimators, active beamstop, and an improved goniostat. Our 'mini-beam' collimators have evolved to a new triple-collimator fabricated from molybdenum as a uni-body. This has significantly improved the robustness, ease of initial alignment, and reduction of background. More recently, twomore » prototypes of a quad-collimator have been developed and fabricated to provide a selection of mini-beams of 5, 10, 20 {mu}m and a 300 {mu}m scatter-guard on a single body. The smaller beams and samples have increased the demand on the tolerances of our goniostat. To meet these challenges we have designed and implemented a goniostat with a 1-micron peak-to-peak sphere of confusion. This is a significant improvement over the previous 6 micron sphere of confusion of the commercially available air-bearing and XY stages. Finally, an 'active beamstop' has been constructed. This will provide non-invasive, real time feedback at the sample during data collection.« less

Micro-Crystallography Developments at GM/CA-CAT at the APS

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

Xu Shenglan; Makarov, Oleg; Benn, Rich

2010-06-23

Recently, several important structures have been solved using micro-crystallographic techniques that previously could not have been solved with conventional crystallography. At GM/CA-CAT we continue to develop micro-crystallographic capabilities for difficult problems such as small crystals of large macromolecular complexes or membrane proteins grown in the lipidic cubic phase. This paper will describe three major upgrades to our arsenal of tools, 'mini-beam' collimators, active beamstop, and an improved goniostat. Our 'mini-beam' collimators have evolved to a new triple-collimator fabricated from molybdenum as a uni-body. This has significantly improved the robustness, ease of initial alignment, and reduction of background. More recently, twomore » prototypes of a quad-collimator have been developed and fabricated to provide a selection of mini-beams of 5, 10, 20 {mu}m and a 300 {mu}m scatter-guard on a single body. The smaller beams and samples have increased the demand on the tolerances of our goniostat. To meet these challenges we have designed and implemented a goniostat with a 1-micron peak-to-peak sphere of confusion. This is a significant improvement over the previous 6 micron sphere of confusion of the commercially available air-bearing and XY stages. Finally, an 'active beamstop' has been constructed. This will provide non-invasive, real time feedback at the sample during data collection.« less

Intense beam production of highly charged heavy ions by the superconducting electron cyclotron resonance ion source SECRAL.

PubMed

Zhao, H W; Sun, L T; Zhang, X Z; Guo, X H; Cao, Y; Lu, W; Zhang, Z M; Yuan, P; Song, M T; Zhao, H Y; Jin, T; Shang, Y; Zhan, W L; Wei, B W; Xie, D Z

2008-02-01

There has been increasing demand to provide higher beam intensity and high enough beam energy for heavy ion accelerator and some other applications, which has driven electron cyclotron resonance (ECR) ion source to produce higher charge state ions with higher beam intensity. One of development trends for highly charged ECR ion source is to build new generation ECR sources by utilization of superconducting magnet technology. SECRAL (superconducting ECR ion source with advanced design in Lanzhou) was successfully built to produce intense beams of highly charged ion for Heavy Ion Research Facility in Lanzhou (HIRFL). The ion source has been optimized to be operated at 28 GHz for its maximum performance. The superconducting magnet confinement configuration of the ion source consists of three axial solenoid coils and six sextupole coils with a cold iron structure as field booster and clamping. An innovative design of SECRAL is that the three axial solenoid coils are located inside of the sextupole bore in order to reduce the interaction forces between the sextupole coils and the solenoid coils. For 28 GHz operation, the magnet assembly can produce peak mirror fields on axis of 3.6 T at injection, 2.2 T at extraction, and a radial sextupole field of 2.0 T at plasma chamber wall. During the commissioning phase at 18 GHz with a stainless steel chamber, tests with various gases and some metals have been conducted with microwave power less than 3.5 kW by two 18 GHz rf generators. It demonstrates the performance is very promising. Some record ion beam intensities have been produced, for instance, 810 e microA of O(7+), 505 e microA of Xe(20+), 306 e microA of Xe(27+), and so on. The effect of the magnetic field configuration on the ion source performance has been studied experimentally. SECRAL has been put into operation to provide highly charged ion beams for HIRFL facility since May 2007.

High sensitive space electric field sensing based on micro fiber interferometer with field force driven gold nanofilm.

PubMed

Zhu, Tao; Zhou, Liming; Liu, Min; Zhang, Jingdong; Shi, Leilei

2015-10-28

The traditional electrical field sensing can be realized by utilizing electro-optic materials or liquid crystals, and has limitations of easy breakdown, free assembly and difficult measurement of low-frequency. Here, we propose a new method to realize safe measurement of spatial dynamic electric field by using a micro fiber interferometer integrated with gold nanofilm. The energy of the electric charge received through antenna forms the intrinsic electric field with two micro electrodes, one of which is the 120 nm gold film vibration beam micromachined by femtosecond lasers and integrated with the micro fiber. The change of the intrinsic electric field force due to the spatial electric field will cause the vibration of the film beam. By demodulating the output signal of the micro fiber interferometer, the electric field can be measured. We demonstrate the detectable frequency ranges from tens of Hz to tens of KHz, and the minimum electric field intensity is ~200 V/m at 1 KHz. Our electric field measurement technology combining optical fiber interference with gold nanostructures shows the advantages of security, high sensitivity, compact size, and multiplexed multi-point and remote detection.

High sensitive space electric field sensing based on micro fiber interferometer with field force driven gold nanofilm

PubMed Central

Zhu, Tao; Zhou, Liming; Liu, Min; Zhang, Jingdong; Shi, Leilei

2015-01-01

The traditional electrical field sensing can be realized by utilizing electro-optic materials or liquid crystals, and has limitations of easy breakdown, free assembly and difficult measurement of low-frequency. Here, we propose a new method to realize safe measurement of spatial dynamic electric field by using a micro fiber interferometer integrated with gold nanofilm. The energy of the electric charge received through antenna forms the intrinsic electric field with two micro electrodes, one of which is the 120 nm gold film vibration beam micromachined by femtosecond lasers and integrated with the micro fiber. The change of the intrinsic electric field force due to the spatial electric field will cause the vibration of the film beam. By demodulating the output signal of the micro fiber interferometer, the electric field can be measured. We demonstrate the detectable frequency ranges from tens of Hz to tens of KHz, and the minimum electric field intensity is ~200 V/m at 1 KHz. Our electric field measurement technology combining optical fiber interference with gold nanostructures shows the advantages of security, high sensitivity, compact size, and multiplexed multi-point and remote detection. PMID:26507680

Design of a bullet beam pattern of a micro ultrasound transducer (Conference Presentation)

NASA Astrophysics Data System (ADS)

Roh, Yongrae; Lee, Seongmin

2016-04-01

Ultrasonic imaging transducer is often required to compose a beam pattern of a low sidelobe level and a small beam width over a long focal region to achieve good image resolution. Normal ultrasound transducers have many channels along its azimuth, which allows easy formation of the sound beam into a desired shape. However, micro-array transducers have no control of the beam pattern along their elevation. In this work, a new method is proposed to manipulate the beam pattern by using an acoustic multifocal lens and a shaded electrode on top of the piezoelectric layer. The shading technique split an initial uniform electrode into several segments and combined those segments to compose a desired beam pattern. For a given elevation width and frequency, the optimal pattern of the split electrodes was determined by means of the OptQuest-Nonlinear Program (OQ-NLP) algorithm to achieve the lowest sidelobe level. The requirement to achieve a small beam width with a long focal region was satisfied by employing an acoustic lens of three multiple focuses. Optimal geometry of the multifocal lens such as the radius of curvature and aperture diameter for each focal point was also determined by the OQ-NLP algorithm. For the optimization, a new index was devised to evaluate the on-axis response: focal region ratio = focal region / minimum beam width. The larger was the focal region ratio, the better was the beam pattern. Validity of the design has been verified through fabricating and characterizing an experimental prototype of the transducer.

Reduction of extended-spectrum-β-lactamase- and AmpC-β-lactamase-producing Escherichia coli through processing in two broiler chicken slaughterhouses.

PubMed

Pacholewicz, Ewa; Liakopoulos, Apostolos; Swart, Arno; Gortemaker, Betty; Dierikx, Cindy; Havelaar, Arie; Schmitt, Heike

2015-12-23

Whilst broilers are recognised as a reservoir of extended-spectrum-β-lactamase (ESBL)- and AmpC-β-lactamase (AmpC)-producing Escherichia coli, there is currently limited knowledge on the effect of slaughtering on its concentrations on poultry meat. The aim of this study was to establish the concentration of ESBL/AmpC producing E. coli on broiler chicken carcasses through processing. In addition the changes in ESBL/AmpC producing E. coli concentrations were compared with generic E. coli and Campylobacter. In two slaughterhouses, the surface of the whole carcasses was sampled after 5 processing steps: bleeding, scalding, defeathering, evisceration and chilling. In total, 17 batches were sampled in two different slaughterhouses during the summers of 2012 and 2013. ESBL/AmpC producing E. coli was enumerated on MacConkey agar with 1mg/l cefotaxime, and the ESBL/AmpC phenotypes and genotypes were characterised. The ESBL/AmpC producing E. coli concentrations varied significantly between the incoming batches in both slaughterhouses. The concentrations on broiler chicken carcasses were significantly reduced during processing. In Slaughterhouse 1, all subsequent processing steps reduced the concentrations except evisceration which led to a slight increase that was statistically not significant. The changes in concentration between processing steps were relatively similar for all sampled batches in this slaughterhouse. In contrast, changes varied between batches in Slaughterhouse 2, and the overall reduction through processing was higher in Slaughterhouse 2. Changes in ESBL/AmpC producing E. coli along the processing line were similar to changes in generic E. coli in both slaughterhouses. The effect of defeathering differed between ESBL/AmpC producing E. coli and Campylobacter. ESBL/AmpC producing E. coli decreased after defeathering, whereas Campylobacter concentrations increased. The genotypes of ESBL/AmpC producing E. coli (blaCTX-M-1, blaSHV-12, blaCMY-2, blaTEM-52c, blaTEM-52cvar) from both slaughterhouses match typical poultry genotypes. Their distribution differed between batches and changed throughout processing for some batches. The concentration levels found after chilling were between 10(2) and 10(5)CFU/carcass. To conclude, changes in ESBL/AmpC producing E. coli concentrations on broiler chicken carcasses during processing are influenced by batch and slaughterhouse, pointing to the role of both primary production and process control for reducing ESBL/AmpC producing E. coli levels in final products. Due to similar changes upon processing, E. coli can be used as a process indicator of ESBL/AmpC producing E. coli, because the processing steps had similar impact on both organisms. Cross contamination may potentially explain shifts in genotypes within some batches through the processing. Copyright © 2015 Elsevier B.V. All rights reserved.

Ultra-short pulse delivery at high average power with low-loss hollow core fibers coupled to TRUMPF's TruMicro laser platforms for industrial applications

NASA Astrophysics Data System (ADS)

Baumbach, S.; Pricking, S.; Overbuschmann, J.; Nutsch, S.; Kleinbauer, J.; Gebs, R.; Tan, C.; Scelle, R.; Kahmann, M.; Budnicki, A.; Sutter, D. H.; Killi, A.

2017-02-01

Multi-megawatt ultrafast laser systems at micrometer wavelength are commonly used for material processing applications, including ablation, cutting and drilling of various materials or cleaving of display glass with excellent quality. There is a need for flexible and efficient beam guidance, avoiding free space propagation of light between the laser head and the processing unit. Solid core step index fibers are only feasible for delivering laser pulses with peak powers in the kW-regime due to the optical damage threshold in bulk silica. In contrast, hollow core fibers are capable of guiding ultra-short laser pulses with orders of magnitude higher peak powers. This is possible since a micro-structured cladding confines the light within the hollow core and therefore minimizes the spatial overlap between silica and the electro-magnetic field. We report on recent results of single-mode ultra-short pulse delivery over several meters in a lowloss hollow core fiber packaged with industrial connectors. TRUMPF's ultrafast TruMicro laser platforms equipped with advanced temperature control and precisely engineered opto-mechanical components provide excellent position and pointing stability. They are thus perfectly suited for passive coupling of ultra-short laser pulses into hollow core fibers. Neither active beam launching components nor beam trackers are necessary for a reliable beam delivery in a space and cost saving packaging. Long term tests with weeks of stable operation, excellent beam quality and an overall transmission efficiency of above 85 percent even at high average power confirm the reliability for industrial applications.

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

Ammigan, K.; Hurh, P.

The Radiation Damage In Accelerator Target Environments (RaDIATE) collaboration was founded in 2012 and currently consists of over 50 participants and 11 institutions globally. Due to the increasing power of future proton accelerator sources in target facilities, there is a critical need to further understand the physical and thermo-mechanical radiation response of target facility materials. Thus, the primary objective of the RaDIATE collaboration is to draw on existing expertise in the nuclear materials and accelerator targets fields to generate new and useful materials data for application within the accelerator and fission/fusion communities. Current research activities of the collaboration include postmore » irradiation examination (PIE) of decommissioned components from existing beamlines such as the NuMI beryllium beam window and graphite NT-02 target material. PIE of these components includes advanced microstructural analyses (SEM/TEM, EBSD, EDS) and micro-mechanics technique such as nano-indentation, to help characterize any microstructural radiation damage incurred during operation. New irradiation campaigns of various candidate materials at both low and high energy beam facilities are also being pursued. Beryllium helium implantation studies at the University of Surrey as well as high energy proton irradiation of various materials at Brookhaven National Laboratory’s BLIP facility have been initiated. The program also extends to beam-induced thermal shock experiments using high intensity beam pulses at CERN’s HiRadMat facility, followed by advanced PIE activities to evaluate thermal shock resistance of the materials. Preliminary results from ongoing research activities, as well as the future plans of the RaDIATE collaboration R&D program will be discussed.« less

A cGMP kinase mutant with increased sensitivity to the protein kinase inhibitor peptide PKI(5-24).

PubMed

Ruth, P; Kamm, S; Nau, U; Pfeifer, A; Hofmann, F

1996-01-01

Synthetic peptides corresponding to the active domain of the heat-stable inhibitor protein PKI are very potent inhibitors of cAMP-dependent protein kinase, but are extremely weak inhibitors of cGMP-dependent protein kinase. In this study, we tried to confer PKI sensitivity to cGMP kinase by site-directed mutagenesis. The molecular requirements for high affinity inhibition by PKI were deduced from the crystal structure of the cAMP kinase/PKI complex. A prominent site of interaction are residues Tyr235 and Phe239 in the catalytic subunit, which from a sandwich-like structure with Phe10 of the PKI(5-24) peptide. To increase the sensitivity for PKI, the cGMP kinase codons at the corresponding sites, Ser555 and Ser559, were changed to Tyr and Phe. The mutant cGMP kinase was stimulated half maximally by cGMP at 3-fold higher concentrations (240 nM) than the wild type (77 nM). Wild type and mutant cGMP kinase did not differ significantly in their Km and Vmax for three different substrate peptides. The PKI(5-24) peptide inhibited phosphotransferase activity of the mutant cGMP kinase with higher potency than that of wild type, with Ki values of 42 +/- .3 microM and 160 +/- .7 microM, respectively. The increased affinity of the mutant cGMP kinase was specific for the PKI(5-24) peptide. Mutation of the essential Phe10 in the PKI(5-24) sequence to an Ala yielded a peptide that inhibited mutant and wild type cGMP kinase with similar potency, with Ki values of 160 +/- 11 and 169 +/- 27 microM, respectively. These results suggest that the mutations Ser555Tyr and Ser559Phe are required, but not sufficient, for high affinity inhibition of cGMP kinase by PKI.

Optimization and validation of a fast amplification protocol for AmpFlSTR® Profiler Plus® for rapid forensic human identification.

PubMed

Laurin, Nancy; Frégeau, Chantal

2012-01-01

The goal of this work was to optimize and validate a fast amplification protocol for the multiplex amplification of the STR loci included in AmpFlSTR(®) Profiler Plus(®) to expedite human DNA identification. By modifying the cycling conditions and by combining the use of a DNA polymerase optimized for high speed PCR (SpeedSTAR™ HS) and a more efficient thermal cycler instrument (Bio-RAD C1000™), we were able to reduce the amplification process from 4h to 26 min. No modification to the commercial AmpFlSTR(®) Profiler Plus(®) primer mix was required. When compared to the current Royal Canadian Mounted Police (RCMP) amplification protocol, no differences with regards to specificity, sensitivity, heterozygote peak height ratios and overall profile balance were noted. Moreover, complete concordance was obtained with profiles previously generated with the standard amplification protocol and minor alleles in mixture samples were reliably typed. An increase in n-4 stutter ratios (2.2% on average for all loci) was observed for profiles amplified with the fast protocol compared to the current procedure. Our results document the robustness of this rapid amplification protocol for STR profiling using the AmpFlSTR(®) Profiler Plus(®) primer set and demonstrate that comparable data can be obtained in substantially less time. This new approach could provide an alternative option to current multiplex STR typing amplification protocols in order to increase throughput or expedite time-sensitive cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Advanced Energy Conversion Concept for Beamed-Energy Propulsion.

DTIC Science & Technology

1987-08-21

pulsed simultaneously at 40 HL. the thruster will operate almost iMen&1 within the infra - sonIc regime. c) Asymmetric thrust considerations During low...LSD WAVES) - / TIME I-*- INFRA - SONIC I LEVITATIUN FREQUENCY Firm U-27 .?AmpUtude-laimpd macro-pulam .5 " I A. SIDE VIEW CUNICAL TIP ,?I , i...s equal local sta ic), and the sonic velocity. Since cool air can rush in only at the speed of sound, one would want to minimize the expanded plasma

Development of economic MeV-ion microbeam technology at Chiang Mai University

NASA Astrophysics Data System (ADS)

Singkarat, S.; Puttaraksa, N.; Unai, S.; Yu, L. D.; Singkarat, K.; Pussadee, N.; Whitlow, H. J.; Natyanum, S.; Tippawan, U.

2017-08-01

Developing high technologies but in economic manners is necessary and also feasible for developing countries. At Chiang Mai University, Thailand, we have developed MeV-ion microbeam technology based on a 1.7-MV Tandetron tandem accelerator with our limited resources in a cost-effective manner. Instead of using expensive and technically complex electrostatic or magnetic quadrupole focusing lens systems, we have developed cheap MeV-ion microbeams using programmed L-shaped blade aperture and capillary techniques for MeV ion beam lithography or writing and mapping. The programmed L-shaped blade micro-aperture system consists of a pair of L-shaped movable aperture pieces which are controlled by computer to cut off the ion beam for controlling the beam size down to the micrometer order. The capillary technique utilizes our home-fabricated tapered glass capillaries to realize microbeams. Either system can be installed inside the endstation of the MeV ion beam line of the accelerator. Both systems have been applied to MeV-ion beam lithography or writing of micro-patterns for microfluidics applications to fabricate lab-on-chip devices. The capillary technique is being developed for MeV-ion beam mapping of biological samples. The paper reports details of the techniques and introduces some applications.

Wave front engineering by means of diffractive optical elements for applications in microscopy

NASA Astrophysics Data System (ADS)

Cojoc, Dan; Ferrari, Enrico; Garbin, Valeria; Cabrini, Stefano; Carpentiero, Alessandro; Prasciolu, Mauro; Businaro, Luca; Kaulich, Burchard; Di Fabrizio, Enzo

2006-05-01

We present a unified view regarding the use of diffractive optical elements (DOEs) for microscopy applications a wide range of electromagnetic spectrum. The unified treatment is realized through the design and fabrication of DOE through which wave front beam shaping is obtained. In particular we show applications ranging from micromanipulation using optical tweezers to X-ray differential interference contrast (DIC) microscopy. We report some details on the design and physical implementation of diffractive elements that beside focusing perform also other optical functions: beam splitting, beam intensity and phase redistribution or mode conversion. Laser beam splitting is used for multiple trapping and independent manipulation of spherical micro beads and for direct trapping and manipulation of biological cells with non-spherical shapes. Another application is the Gauss to Laguerre-Gaussian mode conversion, which allows to trap and transfer orbital angular momentum of light to micro particles with high refractive index and to trap and manipulate low index particles. These experiments are performed in an inverted optical microscope coupled with an infrared laser beam and a spatial light modulator for DOEs implementation. High resolution optics, fabricated by means of e-beam lithography, are demonstrated to control the intensity and the phase of the sheared beams in X-ray DIC microscopy. DIC experiments with phase objects reveal a dramatic increase in image contrast compared to bright-field X-ray microscopy.

Elegant Gaussian beams for enhanced optical manipulation

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

Alpmann, Christina, E-mail: c.alpmann@uni-muenster.de; Schöler, Christoph; Denz, Cornelia

2015-06-15

Generation of micro- and nanostructured complex light beams attains increasing impact in photonics and laser applications. In this contribution, we demonstrate the implementation and experimental realization of the relatively unknown, but highly versatile class of complex-valued Elegant Hermite- and Laguerre-Gaussian beams. These beams create higher trapping forces compared to standard Gaussian light fields due to their propagation changing properties. We demonstrate optical trapping and alignment of complex functional particles as nanocontainers with standard and Elegant Gaussian light beams. Elegant Gaussian beams will inspire manifold applications in optical manipulation, direct laser writing, or microscopy, where the design of the point-spread functionmore » is relevant.« less

Design and fabrication of continuous-profile diffractive micro-optical elements as a beam splitter.

PubMed

Feng, Di; Yan, Yingbai; Jin, Guofan; Fan, Shoushan

2004-10-10

An optimization algorithm that combines a rigorous electromagnetic computation model with an effective iterative method is utilized to design diffractive micro-optical elements that exhibit fast convergence and better design quality. The design example is a two-dimensional 1-to-2 beam splitter that can symmetrically generate two focal lines separated by 80 microm at the observation plane with a small angle separation of +/- 16 degrees. Experimental results are presented for an element with continuous profiles fabricated into a monocrystalline silicon substrate that has a width of 160 microm and a focal length of 140 microm at a free-space wavelength of 10.6 microm.

Multiocular image sensor with on-chip beam-splitter and inner meta-micro-lens for single-main-lens stereo camera.

PubMed

Koyama, Shinzo; Onozawa, Kazutoshi; Tanaka, Keisuke; Saito, Shigeru; Kourkouss, Sahim Mohamed; Kato, Yoshihisa

2016-08-08

We developed multiocular 1/3-inch 2.75-μm-pixel-size 2.1M- pixel image sensors by co-design of both on-chip beam-splitter and 100-nm-width 800-nm-depth patterned inner meta-micro-lens for single-main-lens stereo camera systems. A camera with the multiocular image sensor can capture horizontally one-dimensional light filed by both the on-chip beam-splitter horizontally dividing ray according to incident angle, and the inner meta-micro-lens collecting the divided ray into pixel with small optical loss. Cross-talks between adjacent light field images of a fabricated binocular image sensor and of a quad-ocular image sensor are as low as 6% and 7% respectively. With the selection of two images from one-dimensional light filed images, a selective baseline for stereo vision is realized to view close objects with single-main-lens. In addition, by adding multiple light field images with different ratios, baseline distance can be tuned within an aperture of a main lens. We suggest the electrically selective or tunable baseline stereo vision to reduce 3D fatigue of viewers.

A new fabrication technique for complex refractive micro-optical systems

NASA Astrophysics Data System (ADS)

Tormen, Massimo; Carpentiero, Alessandro; Ferrari, Enrico; Cabrini, Stefano; Cojoc, Dan; Di Fabrizio, Enzo

2006-01-01

We present a new method that allows to fabricate structures with tightly controlled three-dimensional profiles in the 10 nm to 100 μm scale range. This consists of a sequence of lithographic steps such as Electron Beam (EB) or Focused Ion Beam (FIB) lithography, alternated with isotropic wet etching processes performed on a quartz substrate. Morphological characterization by SEM and AFM shows that 3D structures with very accurate shape control and nanometer scale surface roughness can be realized. Quartz templates have been employed as complex system of micromirrors after metal coating of the patterned surface or used as stamps in nanoimprint, hot embossing or casting processes to shape complex plastic elements. Compared to other 3D micro and nanostructuring methods, in which a hard material is directly "sculptured" by energetic beams, our technique requires a much less intensive use of expensive lithographic equipments, for comparable volumes of structured material, resulting in dramatic increase of throughput. Refractive micro-optical elements have been fabricated and characterized in transmission and reflection modes with white and monochromatic light. The elements produce a distribution of sharp focal spots and lines in the three dimensional space, opening the route for applications of image reconstruction based on refractive optics.

Atrial corrected Fourier amplitude ratios for the scintigraphic quantitation of valvar regurgitation

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

Dae, M.W.; Botvinick, E.H.; O'Connell, J.W.

1984-01-01

Current scintigraphic methods commonly overestimate the degree of valvar regurgitation (VR), and displace normal ratios from unity, owing largely to RA contamination of the RV region of interest in the ''best septal'' LAO projection. The authors developed a method to correct for this overlap, using the Fourier amplitude (AMP) ratio. Amplitude is first ''weighted'' for phase angle using a vectorial sum, to improve assessment in patients (PTS) with contraction abnormalities. RV AMP is then corrected for underestimation by adding the product of mean LAO RA AMP times the difference between RA areas in anterior and LAO projections to the calculatedmore » RV AMP. In 15 PTS with aortic or mitral VR, corrected AMP ratios (CAR) were compared to ratios assessed angiographically and in 12 PTS without VR were compared to uncorrected AMP ratios (UAR), and to stroke volume ratios (SVR) from SV images (SVI), and ED and ES counts data (CT). CAR interobserver agreement was high (R=.97). When VR PTS ranked by CAR as mild (1.3-1.8), moderate (1.9-2.5), or severe (>2.5) were compared to similar chatheterization based ranks, there were no significant differences using the Mann Whitney test for ordinal data. CAR is a simple, objective and reproducible method of quantitating VR. It reduces the error in those without VR, allows sensitive identification of mild VR, and maintains accurate assessment of severe VR.« less

Synchrotron X-ray micro-beam studies of ancient Egyptian make-up

NASA Astrophysics Data System (ADS)

Martinetto, P.; Anne, M.; Dooryhée, E.; Drakopoulos, M.; Dubus, M.; Salomon, J.; Simionovici, A.; Walter, Ph.

2001-07-01

Vases full of make-up are most often present in the burial furniture of Egyptian tombs dated from the pharaonic period. The powdered cosmetics made of isolated grains are analysed to identify their trace element signature. From this signature we identify the provenance of the mineral ingredients in the make-up and we observe different impurities in products, which have been demonstrated as synthetic substances by previous works. Focused X-ray micro-beam ( 2×5 μm2) is successively tuned at 11 keV, below the L III absorption edge of Pb, and 31.8 keV for global characterisation of the metal impurities. The fluorescence signal integrated over each single grain is detected against the X-ray micro-diffraction pattern collected in transmission with a bi-dimensional detector. Furthermore, for galena grains rich in Zn, the XANES signal at the K-absorption edge of Zn shows its immediate nearest-neighbour environment.

A MEMS-based Air Flow Sensor with a Free-standing Micro-cantilever Structure

PubMed Central

Wang, Yu-Hsiang; Lee, Chia-Yen; Chiang, Che-Ming

2007-01-01

This paper presents a micro-scale air flow sensor based on a free-standing cantilever structure. In the fabrication process, MEMS techniques are used to deposit a silicon nitride layer on a silicon wafer. A platinum layer is deposited on the silicon nitride layer to form a piezoresistor, and the resulting structure is then etched to create a freestanding micro-cantilever. When an air flow passes over the surface of the cantilever beam, the beam deflects in the downward direction, resulting in a small variation in the resistance of the piezoelectric layer. The air flow velocity is determined by measuring the change in resistance using an external LCR meter. The experimental results indicate that the flow sensor has a high sensitivity (0.0284 Ω/ms-1), a high velocity measurement limit (45 ms-1) and a rapid response time (0.53 s). PMID:28903233

CTX-M-15 and OXA-10 beta lactamases in multi drug resistant Pseudomonas aeruginosa: First report from Pakistan.

PubMed

Ullah, Waheed; Qasim, Muhammad; Rahman, Hazir; Khan, Saadullah; Rehman, Zia Ur; Ali, Nawab; Muhammad, Noor

2017-04-01

Pseudomonas aeruginosa is an emerging threat to public health worldwide due to their rapid development of drug resistance including beta-lactamases. The present study was designed to investigate the incidence of β-lactamases and genotypic pattern of CTX and OXA in the clinical isolate of multidrug resistant P. aeruginosa. In this study a total of 102 MDR P. aeruginosa isolates obtained from Lady Reading Hospital, Peshawar, Pakistan were subjected to extended spectrum beta lactamase (ESBL), metallo beta lactamase (MBL) and plasmid mediated β-lactamase (AmpC) detection using phenotypic and molecular methods. Furthermore, sequencing of CTX and OXA gene was performed. Out of 102 MDR P. aeruginosa isolates, 71 (69.6%) were beta lactamase producers. The incidence of ESBL, MBL and AmpC in clinical isolates of P. aeruginosa was found to be 23.94%, 40.84% and 35.21% respectively. Co-production of ESBL and AmpC were also observed in some isolates. There were 14 (19.71%) CTX-M-15 harboring isolates which were ESBL (64.28%), MBL (21.42%) and AmpC (14.28%) producer. Co-production of ESBL/MBL (14.28%), ESBL/AmpC (14.28%) and MBL/AmpC (14.28%) were also observed in the CTX M-15 harboring isolates while 12.28% isolates were not ESBL, MBL or AmpC producer. OXA-10 was detected in 8 (11.26%) isolates which were ESBL (12.5%), MBL (37.5%) and AmpC (12.5%) producer. OXA 10 isolates also exhibit co-production of ESBL/AmpC (12.5%) and MBL/AmpC (12.5%). All CTX-M-15 carried the class A β-lactamase conserved domain while OXA-10 harbored conserved domain of class D β-lactamase. The current study for the first time reported and characterized the CTX-M-15 and OXA-10 among MDR P. aeruginosa isolates from Pakistan. Further efforts are needed to understand the molecular mechanism of drug resistance with CTX and OXA harboring P. aeruginosa isolates. Copyright © 2017 Elsevier Ltd. All rights reserved.