Hydrogen peroxide release and acid-base status in exhaled breath condensate at rest and after maximal exercise in young, healthy subjects.

PubMed

Marek, E; Platen, P; Volke, J; Mückenhoff, K; Marek, W

2009-12-07

Exhaled breath condensate (EBC) contains among a large number of mediators hydrogen peroxide (H2O2) as a marker of airway inflammation and oxidative stress. Similarly EBC pH also changes in respiratory diseases. It was the aim of our investigation to prove if hydrogen peroxide release and changes in pH of EBC changes with exercise. EBC was collected from 100 litres exhaled air along with samples of arterialized blood of 16 healthy subjects (9 males, 7 females, age 23 +/- 1 years). EBC hydrogen peroxide was analyzed with EcoCheck amperometer (FILT, Berlin). The rate of H(2)O(2) release was calculated from the concentration and collection time. pH and PCO(2) in blood and in EBC were measured with the Radiometer blood gas analyzer, EBC was equilibrated with a gas mixture (5% CO(2) in O(2)). The bicarbonate concentration was calculated according to the law of mass action for CO(2) and HCO(3)(-) (pK = 6.1). H(2)O(2) concentration in EBC was 190 +/- 109 nmol/l, and H (2)O(2) release at rest was 31.0 +/- 18.3 pmol/min. At maximal exercise, the H(2)O(2) concentration in EBC increased to 250 +/- 120 nmol/l, and H(2)O(2) release significantly increased at maximal exercise to 84.4 +/- 39.9 pmol/min (P<0.01). At rest pH of the CO(2) equilibrated EBC was at 6.08 +/- 0.23 and the [HCO(3)(-)] was 1.03 +/- 0.40 mmol/l. At maximum exercise, pH 6.18 +/- 0.17 and [HCO(3)(-)] 1.23 +/- 0.30 mmol/l remained almost unaltered. The rate of H(2)O(2) release in EBC increased during exhausting exercise (external load: 300 Watt) by a factor of 2, whereas the pH and the bicarbonate concentration of the EBC, equilibrated with 5% CO(2) at 37 degrees C were not significantly altered. It has to be proven by further experiments whether there is a linear relationship between the rates of H(2)O(2) release in EBC in graded submaximal exercise.

Effects of hemicholinium and bretylium on the release of autonomic transmitters in the isolated sino-atrial node

PubMed Central

Appel, W. C.; Vincenzi, F. F.

1970-01-01

1. In the isolated, spontaneously beating, sino-atrial node of the rabbit selective electrical excitation of intranodal autonomic nerve fibres results in a biphasic chronotropic response. This chronotropic response (negative followed by positive chronotropism) is due to the release of the autonomic transmitters (acetylcholine and noradrenaline, respectively) from intranodal nerve fibres. 2. In the presence of 2 × 10-4 g/ml hemicholinium, the negative chronotropic (cholinergic) response is abolished while the positive chronotropic (adrenergic) response is unaltered. 3. In the presence of 5 × 10-6 g/ml bretylium, the positive chronotropic response is abolished while the negative chronotropic response is little affected. 4. After blockade of the negative chronotropic response by hemicholinium, bretylium abolishes the remaining positive chronotropic response. The effect of bretylium is not altered in the presence of hemicholinium. 5. Considering currently accepted mechanisms of action for hemicholinium and bretylium, the results of these experiments do not lend support to the cholinergic link hypothesis of adrenergic neuro-effector transmission. PMID:5492897

Effects of hemicholinium and bretylium on the release of autonomic transmitters in the isolated sino-atrial node.

PubMed

Appel, W C; Vincenzi, F F

1970-10-01

1. In the isolated, spontaneously beating, sino-atrial node of the rabbit selective electrical excitation of intranodal autonomic nerve fibres results in a biphasic chronotropic response. This chronotropic response (negative followed by positive chronotropism) is due to the release of the autonomic transmitters (acetylcholine and noradrenaline, respectively) from intranodal nerve fibres.2. In the presence of 2 x 10(-4) g/ml hemicholinium, the negative chronotropic (cholinergic) response is abolished while the positive chronotropic (adrenergic) response is unaltered.3. In the presence of 5 x 10(-6) g/ml bretylium, the positive chronotropic response is abolished while the negative chronotropic response is little affected.4. After blockade of the negative chronotropic response by hemicholinium, bretylium abolishes the remaining positive chronotropic response. The effect of bretylium is not altered in the presence of hemicholinium.5. Considering currently accepted mechanisms of action for hemicholinium and bretylium, the results of these experiments do not lend support to the cholinergic link hypothesis of adrenergic neuro-effector transmission.

Investigation of drug loading and in vitro release mechanisms of insulin-lauryl sulfate complex loaded PLGA nanoparticles.

PubMed

Shi, K; Cui, F; Yamamoto, H; Kawashima, Y

2008-12-01

Insulin, a water soluble peptide hormone, was hydrophobically ion-paired with sodium lauryl sulfate (SDS) at the stoichiometric molar ratio of 6:1. The obtained insulin-SDS complex precipitation was subsequently formulated in biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles by a modified spontaneous emulsion solvent diffusion method. Compared with a conventional method for free insulin encapsulation, direct dissolution of SDS-paired insulin in the non-aqueous organic phase led to an increase in drug recovery from 42.5% to 89.6%. The more hydrophobic complex contributes to the improved affinity of insulin to the polymer matrix, resulting in a higher drug content in the nanoparticles. The drug loading was investigated by determining initial burst release at the first 30 min. The results showed that 64.8% of recovered drug were preferentially surface bound on complex loaded nanoparticles. The in vitro drug release was characterized by an initial burst and subsequent delayed release in dissolution media of deionized water and phosphate buffer saline (PBS). Compared with that in PBS, nanoparticles in deionized water medium presented very low initial burst release (15% vs. 65%) and incomplete cumulative release (25% vs. 90%) of the drug. In addition, dialysis experiments were performed to clarify the form of the released insulin in the dissolution media. The results suggested that the ion-pair complex was sensitive to ionic strength, insulin was released from the particular matrix as complex form and subsequently suffered dissociation from SDS in buffer saline. Moreover, the in vivo bioactivity of the SDS-paired insulin and nanoparticulate formulations were evaluated in mice by estimation of their blood sugar levels. The results showed that the bioactivity of insulin was unaltered after the ion-pairing process.

Effects of igneous intrusion on microporosity and gas adsorption capacity of coals in the Haizi Mine, China.

PubMed

Jiang, Jingyu; Cheng, Yuanping

2014-01-01

This paper describes the effects of igneous intrusions on pore structure and adsorption capacity of the Permian coals in the Huaibei Coalfield, China. Twelve coal samples were obtained at different distances from a ~120 m extremely thick sill. Comparisons were made between unaltered and heat-affected coals using geochemical data, pore-fracture characteristics, and adsorption properties. Thermal alteration occurs down to ~1.3 × sill thickness. Approaching the sill, the vitrinite reflectance (R(o)) increased from 2.30% to 2.78%, forming devolatilization vacuoles and a fine mosaic texture. Volatile matter (VM) decreased from 17.6% to 10.0% and the moisture decreased from 3.0% to 1.6%. With decreasing distance to the sill, the micropore volumes initially increased from 0.0054 cm(3)/g to a maximum of 0.0146 cm(3)/g and then decreased to 0.0079 cm(3)/g. The results show that the thermal evolution of the sill obviously changed the coal geochemistry and increased the micropore volume and adsorption capacity of heat-affected coal (60-160 m from the sill) compared with the unaltered coals. The trap effect of the sill prevented the high-pressure gas from being released, forming gas pocket. Mining activities near the sill created a low pressure zone leading to the rapid accumulation of methane and gas outbursts in the Haizi Mine.

Studies on the role of dopamine in the degeneration of 5-HT nerve endings in the brain of Dark Agouti rats following 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy') administration

PubMed Central

Colado, M I; O'Shea, E; Granados, R; Esteban, B; Martín, A B; Green, A R

1999-01-01

We investigated whether dopamine plays a role in the neurodegeneration of 5-hydroxytryptamine (5-HT) nerve endings occurring in Dark Agouti rat brain after 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy') administration. Haloperidol (2 mg kg−1 i.p.) injected 5 min prior and 55 min post MDMA (15 mg kg−1 i.p.) abolished the acute MDMA-induced hyperthermia and attenuated the neurotoxic loss of 5-HT 7 days later. When the rectal temperature of MDMA+haloperidol treated rats was kept elevated, this protective effect was marginal. MDMA (15 mg kg−1) increased the dopamine concentration in the dialysate from a striatal microdialysis probe by 800%. L-DOPA (25 mg kg−1 i.p., plus benserazide, 6.25 mg kg−1 i.p.) injected 2 h after MDMA (15 mg kg−1) enhanced the increase in dopamine in the dialysate, but subsequent neurodegeneration was unaltered. L-DOPA (25 mg kg−1) injected before a sub-toxic dose of MDMA (5 mg kg−1) failed to induce neurodegeneration. The MDMA-induced increase in free radical formation in the hippocampus (indicated by increased 2,3- and 2,5-dihydroxybenzoic acid in a microdialysis probe perfused with salicylic acid) was unaltered by L-DOPA. The neuroprotective drug clomethiazole (50 mg kg−1 i.p.) did not influence the MDMA-induced increase in extracellular dopamine. These data suggest that previous observations on the protective effect of haloperidol and potentiating effect of L-DOPA on MDMA-induced neurodegeneration may have resulted from effects on MDMA-induced hyperthermia. The increased extracellular dopamine concentration following MDMA may result from effects of MDMA on dopamine re-uptake, monoamine oxidase and 5-HT release rather than an ‘amphetamine-like' action on dopamine release, thus explaining why the drug does not induce degeneration of dopamine nerve endings. PMID:10193771

Effects of incorporation of nano-fluorapatite or nano-fluorohydroxyapatite on a resin-modified glass ionomer cement.

PubMed

Lin, Jun; Zhu, Jiajun; Gu, Xiaoxia; Wen, Wenjian; Li, Qingshan; Fischer-Brandies, Helge; Wang, Huiming; Mehl, Christian

2011-03-01

This study aimed to investigate the fluoride release properties and the effect on bond strength of two experimental adhesive cements. Synthesized particles of nano-fluorapatite (nano-FA) or nano-fluorohydroxyapatite (nano-FHA) were incorporated into a resin-modified glass ionomer cement (Fuji Ortho LC) and characterized using X-ray diffraction and scanning electron microscopy. Blocks with six different concentrations of nano-FA or nano-FHA were manufactured and their fluoride release properties evaluated by ultraviolet spectrophotometry. The unaltered glass ionomer cement Fuji Ortho LC (GC, control) and the two experimental cements with the highest fluoride release capacities (nano-FA+Fuji Ortho LC (GFA) and nano-FHA+Fuji Ortho LC (GFHA)) were used to bond composite blocks and orthodontic brackets to human enamel. After 24 h water storage all specimens were debonded, measuring the micro-tensile bond strength (μTBS) and the shear bond strength (SBS), respectively. The optimal concentration of added nano-FA and nano-FHA for maximum fluoride release was 25 wt.%, which nearly tripled fluoride release after 70 days compared with the control group. GC exhibited a significantly higher SBS than GFHA/GFA, with GFHA and GFA not differing significantly (P>0.05). The μTBS of GC and GFA were significantly higher than that of GFHA (P≤0.05). The results seem to indicate that the fluoride release properties of Fuji Ortho LC are improved by incorporating nano-FA or nano-FHA, simultaneously maintaining a clinically sufficient bond strength when nano-FA was added. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Presynaptic inhibition of transmitter release from rat sympathetic neurons by bradykinin.

PubMed

Edelbauer, Hannah; Lechner, Stefan G; Mayer, Martina; Scholze, Thomas; Boehm, Stefan

2005-06-01

Bradykinin is known to stimulate neurons in rat sympathetic ganglia and to enhance transmitter release from their axons by interfering with the autoinhibitory feedback, actions that involve protein kinase C. Here, bradykinin caused a transient increase in the release of previously incorporated [3H] noradrenaline from primary cultures of dissociated rat sympathetic neurons. When this effect was abolished by tetrodotoxin, bradykinin caused an inhibition of tritium overflow triggered by depolarizing K+ concentrations. This inhibition was additive to that caused by the alpha2-adrenergic agonist UK 14304, desensitized within 12 min, was insensitive to pertussis toxin, and was enhanced when protein kinase C was inactivated. The effect was half maximal at 4 nm and antagonized competitively by the B2 receptor antagonist Hoe 140. The cyclooxygenase inhibitor indomethacin and the angiotensin converting enzyme inhibitor captopril did not alter the inhibition by bradykinin. The M-type K+ channel opener retigabine attenuated the secretagogue action of bradykinin, but left its inhibitory action unaltered. In whole-cell patch-clamp recordings, bradykinin reduced voltage-activated Ca2+ currents in a pertussis toxin-insensitive manner, and this action was additive to the inhibition by UK 14304. These results demonstrate that bradykinin inhibits noradrenaline release from rat sympathetic neurons via presynaptic B2 receptors. This effect does not involve cyclooxygenase products, M-type K+ channels, or protein kinase C, but rather an inhibition of voltage-gated Ca2+ channels.

Ghrelin Causes a Decline in GABA Release by Reducing Fatty Acid Oxidation in Cortex.

PubMed

Mir, Joan Francesc; Zagmutt, Sebastián; Lichtenstein, Mathieu P; García-Villoria, Judit; Weber, Minéia; Gracia, Ana; Fabriàs, Gemma; Casas, Josefina; López, Miguel; Casals, Núria; Ribes, Antònia; Suñol, Cristina; Herrero, Laura; Serra, Dolors

2018-02-02

Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system.

Preparation and characterization of protein-loaded poly(epsilon-caprolactone) microparticles for oral vaccine delivery.

PubMed

Benoit, M A; Baras, B; Gillard, J

1999-07-05

This paper describes the conditions of preparation of poly(epsilon-caprolactone) (PCL) microparticles with a mean size between 5 and 10 microm, obtained by a double emulsion-solvent evaporation technique, suitable for oral vaccine delivery. Bovine serum albumin (BSA) was used as water-soluble model antigen for encapsulation. Different parameters influencing the microparticle size, the BSA loading and entrapment efficiency were investigated. Spherical, smooth and homogeneously distributed microparticles were produced with a BSA loading and entrapment efficiency reaching, respectively, 5% (w/w) and 30%. Polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF) analyses of BSA released from these particles confirmed that the entrapped protein seemed to remain unaltered by the protein encapsulation process. Copyright.

Dissolution of biogenic ooze over basement edifices in the equatorial Pacific with implications for hydrothermal ventilation of the oceanic crust

USGS Publications Warehouse

Bekins, B.A.; Spivack, A.J.; Davis, E.E.; Mayer, L.A.

2007-01-01

Recent observations indicate that curious closed depressions in carbonate sediments overlying basement edifices are widespread in the equatorial Pacific. A possible mechanism for their creation is dissolution by fluids exiting basement vents from off-axis hydrothermal flow. Quantitative analysis based on the retrograde solubility of calcium carbonate and cooling of basement fluids during ascent provides an estimate for the dissolution capacity of the venting fluids. Comparison of the dissolution capacity and fluid flux with typical equatorial Pacific carbonate mass accumulation rates shows that this mechanism is feasible. By maintaining sediment-free basement outcrops, the process may promote widespread circulation of relatively unaltered seawater in the basement in an area where average sediment thicknesses are 300-500 m. The enhanced ventilation can explain several previously puzzling observations in this region, including anomalously low heat flux, relatively unaltered seawater in the basement, and aerobic and nitrate-reducing microbial activity at the base of the sediments. ?? 2007 The Geological Society of America.

Activation of M1 muscarinic receptors triggers transmitter release from rat sympathetic neurons through an inhibition of M-type K+ channels.

PubMed

Lechner, Stefan G; Mayer, Martina; Boehm, Stefan

2003-12-15

Acetylcholine has long been known to excite sympathetic neurons via M1 muscarinic receptors through an inhibition of M-currents. Nevertheless, it remained controversial whether activation of muscarinic receptors is also sufficient to trigger noradrenaline release from sympathetic neurons. In primary cultures of rat superior cervical ganglia, the muscarinic agonist oxotremorine M inhibited M-currents with half-maximal effects at 1 microM and induced the release of previously incorporated [3H]noradrenaline with half-maximal effects at 10 microM. This latter action was not affected by the nicotinic antagonist mecamylamine which, however, abolished currents through nicotinic receptors elicited by high oxotremorine M concentrations. Ablation of the signalling cascades linked to inhibitory G proteins by pertussis toxin potentiated the release stimulating effect of oxotremorine M, and the half-maximal concentration required to stimulate noradrenaline release was decreased to 3 microM. Pirenzepine antagonized the inhibition of M-currents and the induction of release by oxotremorine M with identical apparent affinity, and both effects were abolished by the muscarinic toxin 7. These results indicate that one muscarinic receptor subtype, namely M1, mediates these two effects. Retigabine, which enhances M-currents, abolished the release induced by oxotremorine M, but left electrically induced release unaltered. Moreover, retigabine shifted the voltage-dependent activation of M-currents by about 20 mV to more negative potentials and caused 20 mV hyperpolarisations of the membrane potential. In the absence of retigabine, oxotremorine M depolarised the neurons and elicited action potential discharges in 8 of 23 neurons; in its presence, oxotremorine M still caused equal depolarisations, but always failed to trigger action potentials. Action potential waveforms caused by current injection were not affected by retigabine. These results indicate that the inhibition of M-currents is the basis for the stimulation of transmitter release from sympathetic neurons via M1 muscarinic receptors.

32 CFR 807.1 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION SALE TO THE PUBLIC § 807.1 General requirements. (a) Unaltered Air Force publications and forms will be made available to the public with or without charge, subject to the requirements of this part. Base Chiefs of...

Comparison of the relaxing actions of acetylcholine and substance P in smooth muscle of the guinea-pig aorta.

PubMed

Hozumi, T; Fukuta, H; Suzuki, H

1997-04-01

The relationship between relaxation produced by acetylcholine (ACh) or substance P (SP) and tissue cyclic GMP content was investigated in the isolated guinea-pig aorta. ACh and SP relaxed aortic rings precontracted with noradrenaline (NA) or high-K solution ([K+]o = 38.8 mM), in an endothelium-dependent manner. The amplitude of relaxation was larger for SP than for ACh. Nitroarginine inhibited ACh-induced but not SP-induced relaxation in NA-contraction, while this chemical inhibited both ACh- and SP-induced relaxations in high-K contraction. The tissue cyclic GMP content was not changed by nitroarginine or by removal of endothelial cells, but was elevated by stimulation with NA, ACh or SP by a factor of about 3, 5 or 11 times, respectively. These actions of ACh or SP were endothelium-dependent, and were inhibited by nitroarginine and remained unaltered by high-K solution. Thus, ACh and SP relax muscles indirectly by releasing endothelial factors, and the former by releasing mainly an endothelium-derived relaxing factor (EDRF), and the latter by releasing EDRF and other unidentified factors. As the relaxing actions of the latter factors are inhibited by high-K solution with no relation to the production of cyclic GMP, an involvement of hyperpolarizing factor, possibly EDHF, is suggested.

Effects of hydrothermal alteration on the magnetic mineralogy of mid-ocean ridge basalts, IODP Site 1301B, Juan de Fuca Ridge

NASA Astrophysics Data System (ADS)

Linville, L. M.; Housen, B.; Sager, W.

2005-12-01

Pairs of young (3.5 Ma) altered and unaltered MORB from the Juan de Fuca Ridge collected from IODP Expedition 301, Hole 1301B were studied to better understand how hydrothermal alteration affects the magnetization of oceanic crust. Thermomagnetic analysis (performed with both a VSM and Kappabridge) revealed characteristically different Curie temperatures and degree of non-reversibility between altered and unaltered samples. Magnetic contributions outlined by these methods, in addition to IRM and hysteresis parameters, indicate that samples are dominated by single domain titanomagnetite and titanomaghemite, with a titanium content of approximately TM45. Petrological analysis with a SEM confirmed the presence of abundant Fe-Ti oxides. Despite the preponderance of titanomagnetite in unaltered samples, shrinkage cracks, which offer direct evidence of maghemitization, were seen in both altered and unaltered samples, indicating (as do irreversible cooling curves for all samples) that even supposedly unaltered samples have undergone some degree of low temperature oxidation. Preliminary paleomagnetic data in related samples indicates normal polarity and inclinations that are approximately what is expected for this site. The samples also exhibit both streaked and well defined, non-streaked magnetizations. This study intends to utilize the information obtained by procedures described above to test for correlations between characteristic magnetization directions and degree of oxidation, in order to further our understanding of the effect maghemitization has on the paleomagnetism of oceanic rocks.

Effects of Igneous Intrusion on Microporosity and Gas Adsorption Capacity of Coals in the Haizi Mine, China

PubMed Central

2014-01-01

This paper describes the effects of igneous intrusions on pore structure and adsorption capacity of the Permian coals in the Huaibei Coalfield, China. Twelve coal samples were obtained at different distances from a ~120 m extremely thick sill. Comparisons were made between unaltered and heat-affected coals using geochemical data, pore-fracture characteristics, and adsorption properties. Thermal alteration occurs down to ~1.3 × sill thickness. Approaching the sill, the vitrinite reflectance (R o) increased from 2.30% to 2.78%, forming devolatilization vacuoles and a fine mosaic texture. Volatile matter (VM) decreased from 17.6% to 10.0% and the moisture decreased from 3.0% to 1.6%. With decreasing distance to the sill, the micropore volumes initially increased from 0.0054 cm3/g to a maximum of 0.0146 cm3/g and then decreased to 0.0079 cm3/g. The results show that the thermal evolution of the sill obviously changed the coal geochemistry and increased the micropore volume and adsorption capacity of heat-affected coal (60–160 m from the sill) compared with the unaltered coals. The trap effect of the sill prevented the high-pressure gas from being released, forming gas pocket. Mining activities near the sill created a low pressure zone leading to the rapid accumulation of methane and gas outbursts in the Haizi Mine. PMID:24723841

Solar, planetary, and other inert gases in two sieve fractions of a disaggregated Allende sample - A study by stepwise heating extraction

NASA Technical Reports Server (NTRS)

Palma, R. L.; Heymann, D.

1988-01-01

Inert gases released by stepwise heating of unaltered, strongly magnetic, and weakly magnetic samples from the 0-64 micron and the 105-250 micron fractions of a disaggregated and sieved sample of the Allende meteorite reveal the occurrence of both solar and planetary neon. The origin of the solar neon is thought to be implantation of solar wind ions. The origin of the planetary neon remains unresolved. Heavy isotope enriched components of krypton and xenon have been detected and there are some indications that a light krypton component may also be present. Other than a larger concentration of Xe-129 in the weakly magnetic samples, the signatures of the magnetic separates are isotopically very similar.

Diagenesis Along Fractures in an Eolian Sandstone, Gale Crater, Mars

NASA Technical Reports Server (NTRS)

Ming, D. W.; Yen, A. S.; Rampe, E. B.; Grotzinger, J. P.; Blake, D. F.; Bristow, T. F.; Chipera, S. J.; Downs, R.; Morris, R. V.; Morrison, S. M.;

Composable Distributed Access Control and Integrity Policies for Query-Based Wireless Sensor Networks

DTIC Science & Technology

2008-03-01

unaltered during transmission and verified with data authentication. Data Freshness describes the ordering and currency of data. Strong freshness is a total...Advances in Cryptology — Crypto ’97, volume 1294 of Lecture Notes in Computer Science, pages 180–197. Springer-Verlag, Berlin, 1997. GS04. Saurabh

Virus-mediated swapping of zolpidem-insensitive with zolpidem-sensitive GABA(A) receptors in cortical pyramidal cells.

PubMed

Sumegi, Mate; Fukazawa, Yugo; Matsui, Ko; Lorincz, Andrea; Eyre, Mark D; Nusser, Zoltan; Shigemoto, Ryuichi

2012-04-01

Recently developed pharmacogenetic and optogenetic approaches, with their own advantages and disadvantages, have become indispensable tools in modern neuroscience. Here, we employed a previously described knock-in mouse line (GABA(A)Rγ2(77I)lox) in which the γ2 subunit of the GABA(A) receptor (GABA(A)R) was mutated to become zolpidem insensitive (γ2(77I)) and used viral vectors to swap γ2(77I) with wild-type, zolpidem-sensitive γ2 subunits (γ2(77F)). The verification of unaltered density and subcellular distribution of the virally introduced γ2 subunits requires their selective labelling. For this we generated six N- and six C-terminal-tagged γ2 subunits, with which cortical cultures of GABA(A)Rγ2(−/−) mice were transduced using lentiviruses. We found that the N-terminal AU1 tag resulted in excellent immunodetection and unimpaired synaptic localization. Unaltered kinetic properties of the AU1-tagged γ2 ((AU1)γ2(77F)) channels were demonstrated with whole-cell patch-clamp recordings of spontaneous IPSCs from cultured cells. Next, we carried out stereotaxic injections of lenti- and adeno-associated viruses containing Cre-recombinase and the (AU1)γ2(77F) subunit (Cre-2A-(AU1)γ2(77F)) into the neocortex of GABA(A)Rγ2(77I)lox mice. Light microscopic immunofluorescence and electron microscopic freeze-fracture replica immunogold labelling demonstrated the efficient immunodetection of the AU1 tag and the normal enrichment of the (AU1)γ2(77F) subunits in perisomatic GABAergic synapses. In line with this,miniature and action potential-evoked IPSCs whole-cell recorded from transduced cells had unaltered amplitudes, kinetics and restored zolpidem sensitivity. Our results obtained with a wide range of structural and functional verification methods reveal unaltered subcellular distributions and functional properties of γ2(77I) and (AU1)γ2(77F) GABA(A)Rs in cortical pyramidal cells. This transgenic–viral pharmacogenetic approach has the advantage that it does not require any extrinsic protein that might endow some unforeseen alterations of the genetically modified cells. In addition, this virus-based approach opens up the possibility of modifying multiple cell types in distinct brain regions and performing alternative recombination-based intersectional genetic manipulations.

Adipokines induce catabolism of newly synthesized matrix in cartilage and meniscus tissues.

PubMed

Nishimuta, James F; Levenston, Marc E

Altered synovial levels of various adipokines (factors secreted by fat as well as other tissues) have been associated with osteoarthritis (OA) onset and progression. However, the metabolic effects of adipokines on joint tissues, in particular the fibrocartilaginous menisci, are not well understood. This study investigated effects of several adipokines on release of recently synthesized extracellular matrix in bovine cartilage and meniscus tissue explants. After labeling newly synthesized proteins and sulfated glycosaminoglycans (sGAGs) with 3 H-proline and 35 S-sulfate, respectively; bovine cartilage and meniscus tissue explants were cultured for 6 days in basal medium (control) or media supplemented with adipokines (1 µg/ml of leptin, visfatin, adiponectin, or resistin) or 20 ng/ml interleukin-1 (IL-1). Release of radiolabel and sGAG to the media during culture and the final explant water, DNA, sGAG, and retained radiolabel were measured. Matrix metalloproteinase (MMP-2) and MMP-3 activities were assessed using gelatin and casein zymography, respectively. Water and DNA contents were not significantly altered by any treatment. Visfatin, adiponectin, resistin, and IL-1 stimulated sGAG release from meniscus, whereas only IL-1 stimulated sGAG release from cartilage. Release of 3 H and 35 S was stimulated not only by resistin and IL-1 in meniscus but also by IL-1 in cartilage. Retained 3 H was unaltered by any treatment, while retained 35 S was reduced by visfatin, resistin, and IL-1 in meniscus and by only IL-1 in cartilage. Resistin and IL-1 elevated active MMP-2 and total MMP-3 in meniscus, whereas cartilage MMP-3 activity was elevated by only IL-1. Resistin stimulated rapid and extensive catabolism of meniscus tissue, similar to IL-1, whereas adipokines minimally affected cartilage. Release of newly synthesized matrix was similar to overall release in both tissues. These observations provide further indications that meniscal tissue is more sensitive to pro-inflammatory factors than cartilage and also suggest further study of resistin's role in OA.

Blunted non-nitric oxide vasodilatory neurotransmission in penile arteries from renal hypertensive rats.

PubMed

Martínez, Ana Cristina; Stankevicius, Edgaras; Jakobsen, Preben; Simonsen, Ulf

2006-05-01

The present study was designed to explore whether there are any effects on neurogenic responses in penile small arteries during the development of hypertension in a one-kidney, one-clip (1K1C) model, a non-renin-dependent model of renovascular hypertension. Five weeks after surgery, male Sprague-Dawley rats were given vehicle, bendroflumethiazide (7.5 mg/kg/day), or L-arginine (2 g/kg/day) in their drinking water for five weeks. Experiments were performed on penile small artery rings (150-200 microm) mounted on microvascular myographs for electrical field stimulation (EFS), and erectile tissue was processed for immunohistochemistry. Maximal neurogenic contractions were unmodified in penile preparations. Relaxations induced by EFS were reduced in the presence of ADMA. In 1K1C rats, neurogenic vasorelaxation mediated by nitric oxide (NO) was unaltered, while relaxation resistant to NO synthase inhibition was blunted. L-arginine and bendroflumethiazide lowered blood pressure in 1K1C rats, but vasodilation was still blunted in the penile arteries. Immunoreactivity for factor VIII and neuronal NO synthase was unaltered in penile arteries from 1K1C animals. Endothelium-dependent vasorelaxation evoked by acetylcholine was also blunted in preparations from 1K1C rats, while exogenous NO relaxation was unaffected. Plasma concentrations and urinary excretion of ADMA did not differ among the experimental animals. Our findings indicate that the reduced release of a non-NO vasodilatory neurotransmitter accounts for the impaired neurogenic vasodilation of the penile arteries. Although ADMA inhibits penile vasorelaxation, it is unlikely to affect erectile function in 1K1C rats.

The effect of food on gastrointestinal (GI) transit of sustained-release ibuprofen tablets as evaluated by gamma scintigraphy

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

Borin, M.T.; Khare, S.; Beihn, R.M.

1990-03-01

The GI transit of radiolabeled sustained-release ibuprofen 800-mg tablets in eight healthy, fed volunteers was monitored using external gamma scintigraphy. Ibuprofen serum concentrations were determined from blood samples drawn over 36 hr following dosing. Sustained-release ibuprofen tablets containing 0.18% of 170Er2O3 (greater than 96% 170Er) in the bulk formulation were manufactured under pilot-scale conditions and were radiolabeled utilizing a neutron activation procedure which converted stable 170Er to radioactive 171Er (t1/2 = 7.5 hr). At the time of dosing, each tablet contained 50 mu Ci of 171Er. Dosage form position were reported at various time intervals. In five subjects the sustained-releasemore » tablet remained in the stomach and eroded slowly over 7-12 hr, resulting in gradual increases in small bowel radioactivity. In the remaining three subjects, the intact tablet was ejected from the stomach and a gastric residence time of approximately 4 hr was measured. This is in marked contrast to a previous study conducted in fasted volunteers in which gastric retention time ranged from 10 to 60 min. Differences in GI transit between fed and fasted volunteers had little effect on ibuprofen bioavailability. AUC and Tmax were unaltered and Cmax was increased by 24%, which is in agreement with results from a previous, crossover-design food effect study.« less

Use for Teachers and Students | Galaxy of Images

Science.gov Websites

the website. Some Frequently Asked Questions by Students and Teachers May I put unaltered images, text Libraries (http://www.sil.si.edu). May I put unaltered images, text or content from this website on my should include a link back to Smithsonian Libraries (http://www.sil.si.edu). May I put images, text or

A First Look at Airborne Imaging Spectrometer (AIS) Data in an Area of Altered Volcanic Rocks and Carbonate Formations, Hot Creek Range, South Central Nevada

NASA Technical Reports Server (NTRS)

Feldman, S. C.; Taranik, J. V.; Mouat, D. A.

1985-01-01

Three flight lines of Airborne Imaging Spectrometer (AIS) data were collected in 128 bands between 1.2 and 2.4 microns in the Hot Creek Range, Nevada on July 25, 1984. The flight lines are underlain by hydrothermally altered and unaltered Paleozoic carbonates and Tertiary rhyolitic to latitic volcanics in the Tybo mining district. The original project objectives were to discriminate carbonate rocks from other rock types, to distinguish limestone from dolomite, and to discriminate carbonate units from each other using AIS imagery. Because of high cloud cover over the prime carbonate flight line and because of the acquisition of another flight line in altered and unaltered volcanics, the study has been extended to the discrimination of alteration products. In an area of altered and unaltered rhyolites and latites in Red Rock Canyon, altered and unaltered rock could be discriminated from each other using spectral features in the 1.16 to 2.34 micron range. The altered spectral signatures resembled montmorillonite and kaolinite. Field samples were gathered and the presence of montmorillonite was confirmed by X-ray analysis.

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

Allison, N.; Finch, A.A.; Tudhope, A.W.

The Sr/Ca of coral skeletons demonstrates potential as an indicator of sea surface temperatures (SSTs). However, the glacial-interglacial SST ranges predicted from Sr/Ca of fossil corals are usually higher than from other marine proxies. We observed infilling of secondary aragonite, characterized by high Sr/Ca ratios, along intraskeletal pores of a fossil coral from Papua New Guinea that grew during the penultimate deglaciation (130 {+-} 2 ka). Selective microanalysis of unaltered areas of the fossil coral indicates that SSTs at {approx}130 ka were {le} 1 C cooler than at present in contrast with bulk measurements (combining infilled and unaltered areas) whichmore » indicate a difference of 6-7 C. The analysis of unaltered areas of fossil skeletons by microprobe techniques may offer a route to more accurate reconstruction of past SSTs.« less

Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3

NASA Technical Reports Server (NTRS)

Clancy, J. S.; Takeshima, H.; Hamilton, S. L.; Reid, M. B.

1999-01-01

Skeletal muscle expresses at least two isoforms of the calcium release channel in the sarcoplasmic reticulum (RyR1 and RyR3). Whereas the function of RyR1 is well defined, the physiological significance of RyR3 is unclear. Some authors have suggested that RyR3 participates in excitation-contraction coupling and that RyR3 may specifically confer resistance to fatigue. To test this hypothesis, we measured contractile function of diaphragm strips from adult RyR3-deficient mice (exon 2-targeted mutation) and their heterozygous and wild-type littermates. In unfatigued diaphragm, there were no differences in isometric contractile properties (twitch characteristics, force-frequency relationships, maximal force) among the three groups. Our fatigue protocol (30 Hz, 0.25 duty cycle, 37 degrees C) depressed force to 25% of the initial force; however, lack of RyR3 did not accelerate the decline in force production. The force-frequency relationship was shifted to higher frequencies and was depressed in fatigued diaphragm; lack of RyR3 did not exaggerate these changes. We therefore provide evidence that RyR3 deficiency does not alter contractile function of adult muscle before, during, or after fatigue.

Charcoal as a capture material for silver nanoparticles in the aquatic environment

NASA Astrophysics Data System (ADS)

McGillicuddy, Eoin; Morrison, Liam; Cormican, Martin; Morris, Dearbháile

2017-04-01

Background: The reported antibacterial activity of silver nanoparticles (AgNPs) has led to their incorporation into numerous consumer products including; textiles, domestic appliances, food containers, cosmetics, paints, medical and medicinal products. The AgNPs incorporated into these products can be released into the environment and aquatic system during their production, use and end of life disposal. In the aquatic environment, uncertainties surround the concentration, fate and effects of AgNPs. The aim of this project is to examine charcoal as a potential material for capture of silver nanoparticles from the aquatic environment. Material/methods: Activated charcoal is a commonly used filter material and was selected for this project to determine its suitability as a capture material for AgNPs in water samples. Activated charcoal (Norit® CA1 (Sigma-Aldrich)) was exposed to 100 ppb, 25 nm PVP coated AgNPs (nanoComposix) prepared in Milli-Q water. These solutions were exposed to unaltered charcoal granules for 20 hours after which the decrease of silver in the solution was measured using ICP-MS. In order to improve the removal, the surface area of the charcoal was increased firstly by grinding with a pestle and mortar and secondly by milling the charcoal. The milled charcoal was prepared using an agate ball mill running at 500 rpm for 5 minutes. The activated charcoal was then exposed to samples containing 10 ppb AgNPs. Results: In the initial tests, approximately 10% of the silver was removed from the water samples using the unaltered activated charcoal granules. Further experiments were carried out to compare the unaltered granules with the ground and milled charcoal. These tests were carried out similarly to the previous test however lower concentration of 10 ppb was used. After 20 hours of exposure the granule samples, as previously, showed approximately a 10% reduction in silver content with the ground charcoal giving approximately 30% reduction in silver concentration and in the sample exposed to milled charcoal, approximately 60% reduction in silver concentration was observed. These tests found that increasing the surface area of the charcoal increased the silver reduction in the solution. Conclusions: Data suggest that charcoal may be a suitable material for use in the capture of AgNPs from water samples

Modified overdentures for the management of oligodontia and developmental defects.

PubMed

Abadi, B J; Kimmel, N A; Falace, D A

1982-01-01

A technique for the construction of complete dentures over unaltered natural teeth has been described and illustrated for three different situations. The procedure is straightforward and simple and varies only slightly from conventional overdenture construction. The technique offers several advantages for a patient who wishes to keep the remaining natural teeth unaltered but who requires significant functional or esthetic improvement. Since the teeth are unaltered, any type of future treatment may be considered at any time without being compromised. This is an important factor to consider for the young patient. The cost, when compared to the fabrication of a fixed or cast removable prosthesis, is significantly less, while still providing acceptable esthetics and function. The versatility of this procedure allows its use in a number of situations which are not amenable to more complicated treatment methods.

Compositional variation of glauconites in Upper Cretaceous-Paleogene sedimentary iron-ore deposits in South-eastern Western Siberia

NASA Astrophysics Data System (ADS)

Rudmin, Maxim; Banerjee, Santanu; Mazurov, Aleksey

2017-06-01

Glauconite occurs either as unaltered greenish or as altered brownish variety in Upper Cretaceous-Palaeocene sediments in the southeastern corner of Western Siberia. Studied section within the Bakchar iron-ore deposit includes Ipatovo, Slavgorod, Gan'kino and Lyulinvor formations, which are represented by sandstones, siltstones, claystones and oolitic ironstones of coastal-marine facies. The origin of unaltered glauconite is explained by the ;verdissement theory;. Transgressions during Lower Coniacian, Santonian and Campanian favored the formation of unaltered glauconites in dysoxic to anoxic conditions. Subaerial exposure of glauconite resulted in leaching of potassium, oxidation of iron and formation of iron hydroxides in Upper Coniacian, Maastrichtian and Palaeocene. Glauconite ultimately converts to leptochlorite and hydrogoethite by this alteration. Abundant microscopic gold inclusions, besides sulphides, sulphates, oxides and silicates characterize this glauconite. Mineral inclusions include precious, rare metals and non-ferrous metals. The concentration of gold in glauconite may be as high as 42.9 ppb. Abundant inclusions of various compositions in glauconites indicate enrichment of marine sediments in precious and non-precious metals. While major element composition of glauconites is affected by subaerial exposure, the broadly similar micro-inclusions in both altered and unaltered varieties are possibly related to the comparatively immobile nature of REE and trace elements.

Moving house: long-term dynamics of corticosterone secretion are unaltered in translocated populations of a rare reptile (the tuatara, Sphenodon punctatus).

PubMed

Anderson, Lindsay E; Cree, Alison; Towns, David R; Nelson, Nicola J

2015-01-01

Translocations are an important conservation tool used to restore at-risk species to their historical range. Unavoidable procedures during translocations, such as habitat disturbance, capture, handling, processing, captivity, transport and release to a novel environment, have the potential to be stressful for most species. In this study, we examined acute and chronic stress (through the measurement of the glucocorticoid corticosterone) in a rare reptile (the tuatara, Sphenodon punctatus). We found that: (i) the acute corticosterone response remains elevated during the initial translocation process but is not amplified by cumulative stressors; and (ii) the long-term dynamics of corticosterone secretion are similar in translocated and source populations. Taken together, our results show that translocated tuatara are generally resistant to cumulative acute stressors and show no hormonal sign of chronic stress. Translocation efforts in tuatara afford the potential to reduce extinction risk and restore natural ecosystems.

Role of the satiety factor oleoylethanolamide in alcoholism.

PubMed

Bilbao, Ainhoa; Serrano, Antonia; Cippitelli, Andrea; Pavón, Francisco J; Giuffrida, Andrea; Suárez, Juan; García-Marchena, Nuria; Baixeras, Elena; Gómez de Heras, Raquel; Orio, Laura; Alén, Francisco; Ciccocioppo, Roberto; Cravatt, Benjamin F; Parsons, Loren H; Piomelli, Daniele; Rodríguez de Fonseca, Fernando

2016-07-01

Oleoylethanolamide (OEA) is a satiety factor that controls motivational responses to dietary fat. Here we show that alcohol administration causes the release of OEA in rodents, which in turn reduces alcohol consumption by engaging peroxisome proliferator-activated receptor-alpha (PPAR-α). This effect appears to rely on peripheral signaling mechanisms as alcohol self-administration is unaltered by intracerebral PPAR-α agonist administration, and the lesion of sensory afferent fibers (by capsaicin) abrogates the effect of systemically administered OEA on alcohol intake. Additionally, OEA is shown to block cue-induced reinstatement of alcohol-seeking behavior (an animal model of relapse) and reduce the severity of somatic withdrawal symptoms in alcohol-dependent animals. Collectively, these findings demonstrate a homeostatic role for OEA signaling in the behavioral effects of alcohol exposure and highlight OEA as a novel therapeutic target for alcohol use disorders and alcoholism. © 2015 Society for the Study of Addiction.

Cascade Bioassay Evidence for the Existence of Urothelium-Derived Inhibitory Factor in Guinea Pig Urinary Bladder

PubMed Central

Guan, Na N.; Thor, Anna; Hallén, Katarina; Wiklund, N. Peter; Gustafsson, Lars E.

2014-01-01

Our aim was to investigate whether guinea pig urothelium-derived bioactivities compatible with the existence of urothelium-derived inhibitory factor could be demonstrated by in vitro serial bioassay and whether purinergic P1 receptor agonists, nitric oxide, nitrite or prostaglandins might explain observed activities. In a cascade superfusion system, urothelium-denuded guinea pig ureters were used as bioassay tissues, recording their spontaneous rhythmic contractions in presence of scopolamine. Urothelium-intact or -denuded guinea pig urinary bladders were used as donor tissues, stimulated by intermittent application of carbachol before or during the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the adenosine/P1 nucleoside receptor antagonist 8-(p-sulfophenyl)theophylline (8-PST) or the cyclo-oxygenase inhibitor diclofenac infused to bath donor and bioassay tissues. The spontaneous contractions of bioassay ureters were unaltered by application of carbachol 1–5 µM in the presence of scopolamine 5–30 µM. When carbachol was applied over the urothelium-denuded bladder, the assay ureter contraction rate was unaltered. Introducing carbachol over the everted urothelium-intact bladder significantly inhibited the contraction frequency of the assay ureter, suggesting the transfer of an inhibitory activity from the bladder to the assay ureter. The transmissible inhibitory activity was not markedly antagonized by L-NAME, 8-PST or diclofenac, while L-NAME nearly abolished nitrite release from the urothelium-intact bladder preparations. We suggest that urothelium-derived inhibitory factor is a transmissible entity over a significant distance as demonstrated in this novel cascade superfusion assay and seems less likely to be nitric oxide, nitrite, an adenosine receptor agonist or subject to inhibition by administration of a cyclo-oxygenase inhibitor. PMID:25084114

Cascade bioassay evidence for the existence of urothelium-derived inhibitory factor in Guinea pig urinary bladder.

PubMed

Guan, Na N; Thor, Anna; Hallén, Katarina; Wiklund, N Peter; Gustafsson, Lars E

2014-01-01

Our aim was to investigate whether guinea pig urothelium-derived bioactivities compatible with the existence of urothelium-derived inhibitory factor could be demonstrated by in vitro serial bioassay and whether purinergic P1 receptor agonists, nitric oxide, nitrite or prostaglandins might explain observed activities. In a cascade superfusion system, urothelium-denuded guinea pig ureters were used as bioassay tissues, recording their spontaneous rhythmic contractions in presence of scopolamine. Urothelium-intact or -denuded guinea pig urinary bladders were used as donor tissues, stimulated by intermittent application of carbachol before or during the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the adenosine/P1 nucleoside receptor antagonist 8-(p-sulfophenyl)theophylline (8-PST) or the cyclo-oxygenase inhibitor diclofenac infused to bath donor and bioassay tissues. The spontaneous contractions of bioassay ureters were unaltered by application of carbachol 1-5 µM in the presence of scopolamine 5-30 µM. When carbachol was applied over the urothelium-denuded bladder, the assay ureter contraction rate was unaltered. Introducing carbachol over the everted urothelium-intact bladder significantly inhibited the contraction frequency of the assay ureter, suggesting the transfer of an inhibitory activity from the bladder to the assay ureter. The transmissible inhibitory activity was not markedly antagonized by L-NAME, 8-PST or diclofenac, while L-NAME nearly abolished nitrite release from the urothelium-intact bladder preparations. We suggest that urothelium-derived inhibitory factor is a transmissible entity over a significant distance as demonstrated in this novel cascade superfusion assay and seems less likely to be nitric oxide, nitrite, an adenosine receptor agonist or subject to inhibition by administration of a cyclo-oxygenase inhibitor.

Intermediate-Depth Subduction Earthquakes Recorded by Pseudotachylyte in Dry Eclogite-Facies Oceanic Lithosphere from the Alps

NASA Astrophysics Data System (ADS)

Scambelluri, M.; Pennacchioni, G.; Gilio, M.; Bestmann, M.

2016-12-01

While geophysical studies and laboratory experiments provide much information on subduction earthquakes, field studies identifying the rock types for earthquake development and the deep seismogenic environments are still scarce. To date, fluid overpressure and volume decrease during hydrous mineral breakdown the widely favoured trigger of subduction earthquakes in serpentinized lithospheric mantle and hydrated low-velocity layers atop slabs. Here we document up to 40 cm-thick pseudotachylyte (PST) in Alpine oceanic gabbro and peridotite (2-2.5 GPa-550-620°C), the analogue of a modern cold subducting oceanic lithosphere. These rocks mostly remained unaltered dry systems; only very minor domains (<1%) record partial hydration and static eclogitic metamorphism. Meta-peridotite shows high-pressure olivine + antigorite (garnet + zoisite + chlorite after mantle plagioclase); meta-gabbro develops omphacite + zoisite + talc + chloritoid + garnet. Abundant syn-eclogitic pseudotachylyte cut the dry gabbro-peridotite and the eclogitized domains. In meta-peridotite, PST shows olivine, orthopyroxene, spinel microliths and clasts of high-pressure olivine + antigorite and garnet + zoisite + chlorite aggregates. In metagabbro, microfaults in damage zones near PST cut brecciated igneous pyroxene cemented by omphacite. In unaltered gabbro, glassy PST contains micron-scale garnet replacing plagioclase microliths during, or soon after, PST cooling. In the host rock, garnet coronas between igneous olivine and plagioclase only occur near PST and between closely spaced PST veins. Absence of garnet away from PST indicates that garnet growth was triggered by mineral seeds and by heat released by PST. The above evidence shows that pseudotachylyte formed at eclogite-facies conditions. In such setting, strong, dry, metastable gabbro-peridotite concentrate stress to generate large intermediate depth subduction earthquakes without much involvement of free fluid.

Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells.

PubMed

Aguilar, Edenil C; Santos, Lana Claudinez Dos; Leonel, Alda J; de Oliveira, Jamil Silvano; Santos, Elândia Aparecida; Navia-Pelaez, Juliana M; da Silva, Josiane Fernandes; Mendes, Bárbara Pinheiro; Capettini, Luciano S A; Teixeira, Lilian G; Lemos, Virginia S; Alvarez-Leite, Jacqueline I

2016-08-01

Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied. We investigated the influence of butyrate on oxidative status, reactive oxygen species (ROS) release and oxidative enzymes (NADPH oxidase and iNOS) in atherosclerotic lesions of ApoE(-/-) mice and in oxLDL-stimulated peritoneal macrophages and endothelial cells (EA.hy926). The lesion area in aorta was reduced while in the aortic valve, although lesion area was unaltered, superoxide production and protein nitrosylation were reduced in butyrate-supplemented mice. Peritoneal macrophages from the butyrate group presented a lower free radical release after zymosan stimulus. When endothelial cells were pretreated with butyrate before oxLDL stimulus, the CCL-2 and superoxide ion productions and NADPH oxidase subunit p22phox were reduced. In macrophage cultures, in addition to a reduction in ROS release, nitric oxide and iNOS expression were down-regulated. The data suggest that one mechanism related to the effect of butyrate on atherosclerotic development is the reduction of oxidative stress in the lesion site. The reduction of oxidative stress related to NADPH oxidase and iNOS expression levels associated to butyrate supplementation attenuates endothelium dysfunction and macrophage migration and activation in the lesion site. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurotransmitter alteration in a testosterone propionate-induced polycystic ovarian syndrome rat model.

PubMed

Chaudhari, Nirja K; Nampoothiri, Laxmipriya P

2017-02-01

Polycystic ovarian syndrome (PCOS), one of the leading causes of infertility seen in women, is characterized by anovulation and hyperandrogenism, resulting in ovarian dysfunction. In addition, associations of several metabolic complications like insulin resistance, obesity, dyslipidemia and psychological co-morbidities are well known in PCOS. One of the major factors influencing mood and the emotional state of mind is neurotransmitters. Also, these neurotransmitters are very crucial for GnRH release. Hence, the current study investigates the status of neurotransmitters in PCOS. A PCOS rat model was developed using testosterone. Twenty-one-day-old rats were subcutaneously injected with 10 mg/kg body weight of testosterone propionate (TP) for 35 days. The animals were validated for PCOS characteristics by monitoring estrus cyclicity, serum testosterone and estradiol levels and by histological examination of ovarian sections. Neurotransmitter estimation was carried out using fluorometric and spectrophotometric methods. TP-treated animals demonstrated increased serum testosterone levels with unaltered estradiol content, disturbed estrus cyclicity and many peripheral cysts in the ovary compared to control rats mimicking human PCOS. Norepinephrine (NE), dopamine, serotonin, γ-amino butyric acid (GABA) and epinephrine levels were significantly low in TP-induced PCOS rats compared to control ones, whereas the activity of acetylcholinesterase in the PCOS brain was markedly elevated. Neurotransmitter alteration could be one of the reasons for disturbed gonadotropin-releasing hormone (GnRH) release, consequently directing the ovarian dysfunction in PCOS. Also, decrease in neurotransmitters, mainly NE, serotonin and dopamine (DA) attributes to mood disorders like depression and anxiety in PCOS.

Mineral chemistry and shrimp U-Pb Geochronology of mesoproterozoic polycrase-titanite veins in the sullivan Pb-Zn-Ag Deposit, British Columbia

USGS Publications Warehouse

Slack, J.F.; Aleinikoff, J.N.; Belkin, H.E.; Fanning, C.M.; Ransom, P.W.

2008-01-01

Small polycrase-titanite veins 0.1-2 mm thick cut the tourmalinite feeder zone in the deep footwall of the Sullivan Pb-Zn-Ag deposit, southeastern British Columbia. Unaltered, euhedral crystals of polycrase and titanite 50-100 ??m in diameter are variably replaced by a finer-grained alteration-induced assemblage composed of anhedral polycrase and titanite with local calcite, albite, epidote, allanite, and thorite or uranothorite (or both). Average compositions of the unaltered and altered polycrase, as determined by electron-microprobe analysis, are (Y0.38 REE0.49 Th0.10 Ca0.04 Pb0.03 Fe0.01U0.01) (Ti1.48 Nb0.54 W0.04 Ta0.02)O6 and (Y0.42 REE0.32 Th0.15 U0.06 Ca0.04 Pb0.01 Fe0.01) (Ti1.57 Nb0.44 W0.04 Ta0.02)O6, respectively. The unaltered titanite has, in some areas, appreciable F (to 0.15 apfu), Y (to 0.40 apfu), and Nb (to 0.13 apfu). SHRIMP U-Pb geochronology of eight grains of unaltered polycrase yields a weighted 207Pb/206Pb age of 1413 ?? 4 Ma (2??) that is interpreted to be the age of vein formation. This age is 50-60 m.y. younger than the ca. 1470 Ma age of synsedimentary Pb-Zn-Ag mineralization in the Sullivan deposit, which is based on combined geological and geochronological data. SHRIMP ages for altered polycrase and titanite suggest later growth of minerals during the ???1370-1320 Ma East Kootenay and ???1150-1050 Ma Grenvillian orogenies. The 1413 ?? 4 Ma age for the unaltered polycrase in the veins records a previously unrecognized post-ore (1370 Ma) mineralizing event in the Sullivan deposit and vicinity. The SHRIMP U-Pb age of the polycrase and high concentrations of REE, Y, Ti, Nb, and Th in the veins, together with elevated F in titanite and the absence of associated sulfides, suggest transport of these high-field-strength elements (HFSE) by F-rich and S-poor hydrothermal fluids unrelated to the fluids that formed the older Fe-Pb-Zn-Ag sulfide ores of the Sullivan deposit. Fluids containing abundant REE, HFSE, and F may have been derived from a geochemically specialized magma such as those that form alkaline granites, pegmatites, or carbonatites. In an alternative model. preferred here, these fluids were associated with a rift-related, crustal metasomatic event in the region. Determination of a Mesoproterozoic age for the polycrase-titanite veins establishes the first known occurrence of pre-Grenvillian REE-rich mineralization in the Belt-Purcell basin.

Effect of Fluoride-Releasing Adhesive Systems on the Mechanical Properties of Eroded Dentin.

PubMed

Guedes, Ana Paula Albuquerque; Moda, Mariana Dias; Suzuki, Thaís Yumi Umeda; Godas, André Gustavo de Lima; Sundfeld, Renato Herman; Briso, André Luiz Fraga; Santos, Paulo Henrique dos

2016-01-01

The aim of the study was to evaluate the effect of erosive pH cycling with solutions that simulate dental erosion on Martens hardness (HMV) and elastic modulus (Eit) of dentin restored with fluoride-releasing adhesive systems. Twenty-seven bovine dentin slabs were restored with three adhesive systems: Adper Single Bond 2 total-etch adhesive system, One Up Bond F and Clearfil SE Protect fluoride-containing self-etching adhesive systems. The restorations were made with Filtek Z250. The HMV and Eit values at distances of 10, 30, 50 and 70 µm from the interface were evaluated using a dynamic ultra microhardness tester before and after immersion in deionized water, citric acid and hydrochloric acid (n=9). Data were submitted to repeated-measures ANOVA and Fisher's PLSD tests (=0.05). After erosive cycling, HMV values of dentin decreased in all groups. For dentin restored with Adper Single Bond 2, the lowest values were found closer to the hybrid layer, while for One Up Bond F and Clearfil SE Protect, the values remained unaltered at all distances. For dentin restored with fluoride-releasing adhesive systems, a decrease in Eit was found, but after 30 µm this difference was not significant. The acid substances were able to alter HMV and Eit of the underlying dentin. For fluoride-releasing adhesives, the greater the distance from bonded interface, the lower the Eit values. The fluoride in One Up Bond F and Clearfil SE Protect was able to protect the underlying dentin closer to the materials. In this way, the fluoride from adhesive systems could have some positive effect in the early stages of erosive lesions.

Prenatal glucocorticoid programming of brain corticosteroid receptors and corticotrophin-releasing hormone: possible implications for behaviour.

PubMed

Welberg, L A; Seckl, J R; Holmes, M C

2001-01-01

Glucocorticoids may underlie the association between low birth weight and adult disorders such as hypertension, type 2 diabetes and affective dysfunction. We investigated the behavioural and molecular consequences of two paradigms of prenatal dexamethasone administration in rats. Rats received dexamethasone (100 microg/kg per day) throughout pregnancy (DEX1-3), in the last third of pregnancy only (DEX3) or vehicle. Both dexamethasone treatments reduced birth weight, only DEX1-3 offspring had reduced body weight in adulthood. In adult offspring, both prenatal dexamethasone paradigms reduced exploratory behaviour in an open field. In contrast, only DEX3 reduced exploration in an elevated plus-maze and impaired behavioural responses and learning in a forced-swim test. This behavioural inhibition may reflect increased baseline corticotrophin-releasing hormone mRNA levels (30% higher) in the central nucleus of the amygdala in both dexamethasone-exposed groups. Adult DEX3 offspring also showed increased corticotrophin-releasing hormone mRNA with unaltered glucocorticoid receptor mRNA in the hypothalamic paraventricular nucleus and reduced hippocampal glucocorticoid- and mineralocorticoid receptor mRNA expression, suggesting reduced hippocampal sensitivity to glucocorticoid suppression of the stress axis. In contrast, DEX1-3 rats had no changes in hippocampal corticosteroid receptors, but showed increased mRNA levels for both receptors in the basolateral nucleus of the amygdala. From this data we suggest that prenatal glucocorticoid exposure programs behavioural inhibition perhaps via increased amygdalar corticotrophin-releasing hormone levels, while DEX3 also impairs coping and learning in aversive situations, possibly via altered hippocampal corticosteroid receptor levels. Overexposure to glucocorticoids, especially late in gestation, may explain the link between reduced early growth and adult affective dysfunction.

Biocompatibility and bond degradation of poly-acrylic acid coated copper iodide-adhesives.

PubMed

ALGhanem, Adi; Fernandes, Gabriela; Visser, Michelle; Dziak, Rosemary; Renné, Walter G; Sabatini, Camila

2017-09-01

To investigate the effect of poly-acrylic acid (PAA) copper iodide (CuI) adhesives on bond degradation, tensile strength, and biocompatibility. PAA-CuI particles were incorporated into Optibond XTR, Optibond Solo and XP Bond in 0.1 and 0.5mg/ml. Clearfil SE Protect, an MDPB-containing adhesive, was used as control. The adhesives were applied to human dentin, polymerized and restored with composite in 2mm-increments. Resin-dentin beams (0.9±0.1mm 2 ) were evaluated for micro-tensile bond strength after 24h, 6 months and 1year. Hourglass specimens (10×2×1mm) were evaluated for ultimate tensile strength (UTS). Cell metabolic function of human gingival fibroblast cells exposed to adhesive discs (8×1mm) was assessed with MTT assay. Copper release from adhesive discs (5×1mm) was evaluated with UV-vis spectrophotometer after immersion in 0.9% NaCl for 1, 3, 5, 7, 10, 14, 21 and 30 days. SEM, EDX and XRF were conducted for microstructure characterization. XTR and Solo did not show degradation when modified with PAA-CuI regardless of the concentration. The UTS for adhesives containing PAA-CuI remained unaltered relative to the controls. The percent viable cells were reduced for Solo 0.5mg/ml and XP 0.1 or 0.5mg/ml PAA-CuI. XP demonstrated the highest ion release. For all groups, the highest release was observed at days 1 and 14. PAA-CuI particles prevented the bond degradation of XTR and Solo after 1year without an effect on the UTS for any adhesive. Cell viability was affected for some adhesives. A similar pattern of copper release was demonstrated for all adhesives. Copyright © 2017. Published by Elsevier Ltd.

Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine.

PubMed

Baldwin, H A; Colado, M I; Murray, T K; De Souza, R J; Green, A R

1993-03-01

1. Administration to rats of methamphetamine (15 mg kg-1, i.p.) every 2 h to a total of 4 doses resulted in a neurotoxic loss of striatal dopamine of 36% and of 5-hydroxytryptamine (5-HT) in the cortex (43%) and hippocampus (47%) 3 days later. 2. Administration of chlormethiazole (50 mg kg-1, i.p.) 15 min before each dose of methamphetamine provided complete protection against the neurotoxic loss of monoamines while administration of dizocilpine (1 mg kg-1, i.p.) using the same dose schedule provided substantial protection. 3. Measurement of dopamine release in the striatum by in vivo microdialysis revealed that methamphetamine produced an approximate 7000% increase in dopamine release after the first injection. The enhanced release response was somewhat diminished after the third injection but still around 4000% above baseline. Dizocilpine (1 mg kg-1, i.p.) did not alter this response but chlormethiazole (50 mg kg-1, i.p.) attenuated the methamphetamine-induced release by approximately 40%. 4. Dizocilpine pretreatment did not influence the decrease in the dialysate concentration of the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) produced by administration of methamphetamine while chlormethiazole pretreatment decreased the dialysate concentration of these metabolites still further. 5. The concentration of dopamine in the dialysate during basal conditions increased modestly during the course of the experiment. This increase did not occur in chlormethiazole-treated rats. HVA concentrations were unaltered by chlormethiazole administration. 6. Chlormethiazole (100-1000 microM) did not alter methamphetamine (100 microM) or K+ (35 mM)-evoked release of endogenous dopamine from striatal prisms in vitro. 7. Several NMDA antagonists prevent methamphetamine-induced neurotoxicity; however chlormethiazole is not an NMDA antagonist. Inhibition of striatal dopamine function prevents methamphetamine-induced toxicity of both dopamine and 5-HT pathways. Therefore the attenuation of the enhanced dopamine release which occurs in animals given chlormethiazole may be associated with the protective action of this drug against methamphetamine-induced neurotoxicity.

Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione.

PubMed

Marchionatti, Ana M; Perez, Adriana V; Diaz de Barboza, Gabriela E; Pereira, Beatriz M; Tolosa de Talamoni, Nori G

2008-02-01

Menadione (MEN) inhibits intestinal calcium absorption by a mechanism not completely understood. The aim of this work was to find out the role of mitochondria in this inhibitory mechanism. Hence, normal chicks treated with one i.p. dose of MEN were studied in comparison with controls. Intestinal calcium absorption was measured by the in situ ligated intestinal segment technique. GSH, oxidoreductase activities from the Krebs cycle and enzymes of the antioxidant system were measured in isolated mitochondria. Mitochondrial membrane potential was measured by a flow cytometer technique. DNA fragmentation and cytochrome c localization were determined by immunocytochemistry. Data indicate that in 30 min, MEN decreases intestinal Ca(2+) absorption, which returns to the control values after 10 h. GSH was only decreased for half an hour, while the activity of malate dehydrogenase and alpha-ketoglutarate dehydrogenase was diminished for 48 h. Mn(2+)-superoxide dismutase activity was increased in 30 min, whereas the activity of catalase and glutathione peroxidase remained unaltered. DNA fragmentation and cytochrome c release were maximal in 30 min, but were recovered after 15 h. In conclusion, MEN inhibits intestinal Ca(2+) absorption by mitochondrial dysfunction as revealed by GSH depletion and alteration of the permeability triggering the release of cytochrome c and DNA fragmentation.

Parkin promotes proteasomal degradation of synaptotagmin IV by accelerating polyubiquitination.

PubMed

Kabayama, Hiroyuki; Tokushige, Naoko; Takeuchi, Makoto; Kabayama, Miyuki; Fukuda, Mitsunori; Mikoshiba, Katsuhiko

2017-04-01

Parkin is an E3 ubiquitin ligase whose mutations cause autosomal recessive juvenile Parkinson's disease (PD). Unlike the human phenotype, parkin knockout (KO) mice show no apparent dopamine neuron degeneration, although they demonstrate reduced expression and activity of striatal mitochondrial proteins believed to be necessary for neuronal survival. Instead, parkin-KO mice show reduced striatal evoked dopamine release, abnormal synaptic plasticity, and non-motor symptoms, all of which appear to mimic the preclinical features of Parkinson's disease. Extensive studies have screened candidate synaptic proteins responsible for reduced evoked dopamine release, and synaptotagmin XI (Syt XI), an isoform of Syt family regulating membrane trafficking, has been identified as a substrate of parkin in humans. However, its expression level is unaltered in the striatum of parkin-KO mice. Thus, the target(s) of parkin and the molecular mechanisms underlying the impaired dopamine release in parkin-KO mice remain unknown. In this study, we focused on Syt IV because of its highly homology to Syt XI, and because they share an evolutionarily conserved lack of Ca 2+ -binding capacity; thus, Syt IV plays an inhibitory role in Ca 2+ -dependent neurotransmitter release in PC12 cells and neurons in various brain regions. We found that a proteasome inhibitor increased Syt IV protein, but not Syt XI protein, in neuron-like, differentiated PC12 cells, and that parkin interacted with and polyubiquitinated Syt IV, thereby accelerating its protein turnover. Parkin overexpression selectively degraded Syt IV protein, but not Syt I protein (indispensable for Ca 2+ -dependent exocytosis), thus enhancing depolarization-dependent exocytosis. Furthermore, in parkin-KO mice, the level of striatal Syt IV protein was increased. Our data indicate a crucial role for parkin in the proteasomal degradation of Syt IV, and provide a potential mechanism of parkin-regulated, evoked neurotransmitter release. Copyright © 2017 Elsevier Inc. All rights reserved.

Using Silica Sol as a Nanoglue to Prepare Nanoscale Mesoporous Composite Gel and Aerogels

DTIC Science & Technology

2000-03-31

solution-phase reactants remain unaltered. Furthermore, the composite constitutes a rigid solid architecture, such that the silica aerogel structure...nm) was immobilized in a silica aerogel structure according to the method of the present invention. The optical properties of 9 these materials...Aerogel Preparation. Acid- and base-catalyzed silica aerogels were prepared by procedures similarto those previously published in Russo et al.J.Non

Comparison of species composition and richness of fish assemblages in altered and unaltered littoral habitats

USGS Publications Warehouse

Poe, T.P.; Hatcher, C.O.; Brown, C.L.; Schloesser, D.W.

1986-01-01

Species composition and richness of fish assemblages in altered and unaltered littoral habitats in Lake St. Clair, Michigan, differed between areas. A percid-cyprinid-cyprinodontid assemblage dominated in the unaltered area, Muscamoot Bay, which has a natural shoreline (with almost no alteration due to dredging or bulkheading), high water quality, and high species richness of aquatic macrophytes. A centrarchid assemblage dominated in the altered area, Belvidere Bay, which has a bulkheaded shoreline, many dredged areas, reduced water quality due to inputs of nutrients from a nearby river, and relatively low species richness of aquatic macrophytes. Habitat factors, species richness and abundance of aquatic macrophytes, had the most influence on fish community structure in both areas. The percid-cyprinid-cyprinodontid assemblage was significantly correlated with six species of macrophytes whereas the centrarchid assemblage was significantly correlated with only four. These patterns suggest that preference for diverse habitats was higher, and tolerance to habitat alteration lower, in percid-cyprinid-cyprinodontid assemblages than in centrarchid assemblages.

Discrimination of hydrothermally altered rocks along the Battle Mountain-Eureka, Nevada, mineral belt using Landsat images

USGS Publications Warehouse

Krohn, M. Dennis; Abrams, Michael J.; Rowan, Lawrence C.

1978-01-01

Landsat Multispectral Scanner (MSS) images of the northwestern part of the Battle Mountain-Eureki, Nevada mineral belt were evaluated for distinguishing hydrothermally altered rocks associated with porphyry copper and disseminated gold deposits. Detection of altered rocks from Landsat is based on the distinctive spectral reflectance of limonite present at coatings on weathered surfaces Some altered rocks are visible as bleached areas in individual MSS bands; however, they cannot be consistently distinguished from unaltered rocks with high albedo nor from bright areas resulting .from topographic slope. Black-and-white ratio images were generated to subdue .topographic effects, and three ratio images were composited in color to portray spectral radiance differences, forming an image known as a color-ratio composite (CRC). The optimum CRC image for this area has MSS 4/5 as blue, MSS 4/6 as yellow, and MSS 6/7 as magenta, and differs in two respects from most CRC images of arid areas. First, as a result of the increased vegetation cover in the study area, MSS 5/6 was replaced by MSS 4/6 as the yellow layer. Second, 70 mm positive transparencies were replaced by large format images (64 cm), thereby improving the internal registration of the CRC image and the effective spatial resolution. The pattern of limonitic rocks depicted in the CRC closely agrees with the mapped pattern of the alteration zones at the Copper Canyon and Copper Basin porphyry copper deposits. Certain west-facing topographic slopes in the altered areas are depicted as unaltered in the CRC, apparently due to atmospheric scattering, and illustrate the need for atmospheric correction. The disseminated gold deposits at Gold Acres and Tenabo are poorly represented in the CRC because of the general absence of limonite on these deposits. The presence of unaltered limonitic sedimentary and volcanic rocks is the largest obstacle to discriminating altered areas within the mineral belt. Reflectance spectra, made in situ and in the laboratory indicate differences between altered and unaltered rocks in the Spectra region between 1.1 ?m and 2.5 ?m. Such differences may be detectable by a remote scanner with a longer wavelength range than current Landsat MSS (0.6 ?m-1.1 ?m).

Benefit Assessment of the Precision Departure Release Capability Concept

NASA Technical Reports Server (NTRS)

Palopo, Kee; Chatterji, Gano B.; Lee, Hak-Tae

2011-01-01

A Precision Departure Release Capability concept is being evaluated by both the National Aeronautics and Space Administration and the Federal Aviation Administration as part of a larger goal of improving throughput, efficiency and capacity in integrated departure, arrival and surface operations. The concept is believed to have the potential of increasing flight efficiency and throughput by avoiding missing assigned slots and minimizing speed increase or path stretch to recover the slot. The main thrust of the paper is determining the impact of early and late departures from the departure runway when an aircraft has a slot assigned either at a meter fix or at the arrival airport. Results reported in the paper are for two scenarios. The first scenario considers flights out of Dallas/Fort Worth destined for Hartsfield-Jackson International Airport in Atlanta flying through the Meridian meter-fix in the Memphis Center with miles-in-trail constraints. The second scenario considers flights destined to George Bush Intercontinental/Houston Airport with specified airport arrival rate constraint. Results show that delay reduction can be achieved by allowing reasonable speed changes in scheduling. It was determined that the traffic volume between Dallas/Fort Worth and Atlanta via the Meridian fix is low and the departures times are spread enough that large departure schedule uncertainty can be tolerated. Flights can depart early or late within 90 minutes without accruing much more delay due to miles-in-trail constraint at the Meridian fix. In the Houston scenario, 808 arrivals from 174 airports were considered. Results show that delay experienced by the 16 Dallas/Fort Worth departures is higher if initial schedules of the remaining 792 flights are kept unaltered while they are rescheduled. Analysis shows that the probability of getting the initially assigned slot back after perturbation and rescheduling decreases with increasing standard deviation of the departure delay distributions. Results show that most Houston arrivals can be expected to be on time based on the assumed zero-mean Normal departure delay distributions achievable by Precision Departure Release Capability. In the current system, airport-departure delay, which is the sum of gate-departure delay and taxi-out delay, is observed at the airports. This delay acts as a bias, which can be reduced by Precision Departure Release Capability.

Biomarkers of oxidative stress and inflammation after wood smoke exposure in a reconstructed Viking Age house.

PubMed

Jensen, Annie; Karottki, Dorina Gabriela; Christensen, Jannie Marie; Bønløkke, Jakob Hjort; Sigsgaard, Torben; Glasius, Marianne; Loft, Steffen; Møller, Peter

2014-10-01

Exposure to particles from combustion of wood is associated with respiratory symptoms, whereas there is limited knowledge about systemic effects. We investigated effects on systemic inflammation, oxidative stress and DNA damage in humans who lived in a reconstructed Viking Age house, with indoor combustion of wood for heating and cooking. The subjects were exposed to high indoor concentrations of PM2.5 (700-3,600 µg/m(3)), CO (10.7-15.3 ppm) and NO2 (140-154 µg/m(3)) during a 1-week stay. Nevertheless, there were unaltered levels of genotoxicity, determined as DNA strand breaks and formamidopyrimidine DNA glycosylase and oxoguanine DNA glycosylase 1 sensitive sites in peripheral blood mononuclear cells. There were also unaltered expression levels of OGG1, HMOX1, CCL2, IL8, and TNF levels in leukocytes. In serum, there were unaltered levels of C-reactive protein, IL6, IL8, TNF, lactate dehydrogenase, cholesterol, triglycerides, and high-density lipoproteins. The wood smoke exposure was associated with decreased serum levels of sICAM-1, and a tendency to decreased sVCAM-1 levels. There was a minor increase in the levels of circulating monocytes expressing CD31, whereas there were unaltered expression levels of CD11b, CD49d, and CD62L on monocytes after the stay in the house. In conclusion, even a high inhalation exposure to wood smoke was associated with limited systemic effects on markers of oxidative stress, DNA damage, inflammation, and monocyte activation. © 2014 Wiley Periodicals, Inc.

Thermoresponsive Polymers with Lower Critical Solution Temperature- or Upper Critical Solution Temperature-Type Phase Behaviour Do Not Induce Toxicity to Human Endothelial Cells.

PubMed

Ji, Yuejia; Zhu, Mengxiang; Gong, Yu; Tang, Haoyu; Li, Juan; Cao, Yi

2017-01-01

Thermoresponsive polymers have gained extensive attention as biomedical materials especially for targeted drug delivery systems. We have recently developed water-soluble polypeptide-based thermoresponsive polymers that exhibit lower critical solution temperature (LCST)- or upper critical solution temperature (UCST)-type phase behaviours. In this study, the toxicity of these polymers to human umbilical vein endothelial cells (HUVECs) was investigated to assess the safety and biocompatibility. Up to 100 μg/ml, thermoresponsive polymers did not induce cytotoxicity to HUVECs, showing as unaltered mitochondrial viability assessed as cell counting kit-8 (CCK-8) assay and membrane integrity assessed as lactate dehydrogenase (LDH) assay. Inflammatory response, assessed as the release of chemokine-soluble monocyte chemotactic protein 1 (sMCP-1) and interleukin-8 (IL-8) as well as cytokine IL-6, was not significantly affected by the polymers. In addition, 1 μM thapsigargin (TG), an endoplasmic reticulum (ER) stress inducer, significantly decreased mitochondrial viability, but did not affect membrane integrity or inflammatory response. The presence of thermoresponsive polymers with LCST-type phase behaviour did not further affect the effects of TG. In conclusion, the thermoresponsive polymers used in this study are not toxic to endothelial cells and therefore could be further considered as safe materials for biomedical applications. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Neocortical concentrations of neuropeptides in senile dementia of the Alzheimer and Lewy body type: comparison with Parkinson's disease and severity correlations.

PubMed

Leake, A; Perry, E K; Perry, R H; Jabeen, S; Fairbairn, A F; McKeith, I G; Ferrier, I N

1991-02-15

Corticotropin releasing hormone (CRH), somatostatin (SRIF), and arginine vasopressin (AVP) concentrations were estimated using radioimmunoassay in the temporal and occipital cortices in postmortem brain from patients clinically and neuropathologically diagnosed as senile dementia of the Lewy body type (SDLT), senile dementia of the Alzheimer type (SDAT), and Parkinson's disease (PD) and from neurologically normal controls. The concentration of temporal and occipital neocortical CRH was diminished in both SDAT and SDLT compared to control values, whereas SRIF was reduced only in temporal cortex in both these conditions. In contrast, the concentrations of both CRH and SRIF were unaltered in PD. The concentrations of AVP in SDLT, SDAT, and PD were similar to those found in the control groups. The decrement in SRIF, but not CRH, was found to be correlated with some indices of severity of illness in SDAT; a similar but nonsignificant trend for SRIF was observed in SDLT.

Remarkable preservation of terpenoids and record of volatile signalling in plant-animal interactions from Miocene amber.

PubMed

Dutta, Suryendu; Mehrotra, Rakesh C; Paul, Swagata; Tiwari, R P; Bhattacharya, Sharmila; Srivastava, Gaurav; Ralte, V Z; Zoramthara, C

2017-09-08

Plants produce and release a large array of volatile organic compounds that play many ecological functions. These volatile plant metabolites serve as pollinator attractants, herbivore and pathogen repellents and protect plants from abiotic stresses. To date, the geological evolution of these organic compounds remains unknown. The preservation potential of these metabolites in the fossil record is very poor due to their low boiling points. Here we report a series of volatile sesquiterpenoids, including δ-elemene, α-copaene, β-elemene, β-caryophyllene, α-humulene, germacrene D, δ-cadiene and spathunenol, from early Miocene (~17 million year) amber from eastern India. The survival of these unaltered bioterpenoids can be attributed to the existence of extraordinary taphonomic conditions conducive to the preservation of volatile biomolecules through deep time. Furthermore, the occurrence of these volatiles in the early Miocene amber suggests that the plants from this period had evolved metabolic pathways to synthesize these organic molecules to play an active role in forest ecology, especially in plant-animal interactions.

Use of imaging in the 0.46-2.36 [micrometers] spectral region for alteration mapping in the Cuprite mining district, Nevada

USGS Publications Warehouse

Abrams, Michael J.; Ashley, R.P.; Rowan, L.C.; Goetz, A.F.H.; Kahle, A.B.

1977-01-01

Color composites of Landsat MSS ratio images that display variations in the intensity of ferric-iron absorption bands are highly effective for mapping limonitic altered rocks, but ineffective for mapping nonlimonitic altered rocks. Analysis of 0.45-2.5 ?m field and laboratory spectra shows that iron-deficient opalites in the Cuprite mining district, Nevada, have an intense OH-absorption band near 2.2 ?m owing to their clay mineral and alunite contents and that this spectral feature is absent or weak in adjacent unaltered tuff and basalt. To evaluate the usefulness of this spectral feature for discriminating between altered and unaltered rocks, we generated color-ratio composite images from multispectral (0.46-2.36 ?m) aircraft data. The altered rocks in the district can be discriminated from unaltered rocks with few ambiguities; in addition, some effects of mineralogical zoning can be discriminated within the altered area. Only variations in amounts of limonite can be discerned in shorter wavelength aircraft data, Landsat MSS bands, and color aerial photographs.

Food, gastrointestinal pH, and models of oral drug absorption.

PubMed

Abuhelwa, Ahmad Y; Williams, Desmond B; Upton, Richard N; Foster, David J R

2017-03-01

This article reviews the major physiological and physicochemical principles of the effect of food and gastrointestinal (GI) pH on the absorption and bioavailability of oral drugs, and the various absorption models that are used to describe/predict oral drug absorption. The rate and extent of oral drug absorption is determined by a complex interaction between a drug's physicochemical properties, GI physiologic factors, and the nature of the formulation administered. GI pH is an important factor that can markedly affect oral drug absorption and bioavailability as it may have significant influence on drug dissolution & solubility, drug release, drug stability, and intestinal permeability. Different regions of the GI tract have different drug absorptive properties. Thus, the transit time in each GI region and its variability between subjects may contribute to the variability in the rate and/or extent of drug absorption. Food-drug interactions can result in delayed, decreased, increased, and sometimes un-altered drug absorption. Food effects on oral absorption can be achieved by direct and indirect mechanisms. Various models have been proposed to describe oral absorption ranging from empirical models to the more sophisticated "mechanism-based" models. Through understanding of the physicochemical and physiological rate-limiting factors affecting oral absorption, modellers can implement simplified population-based modelling approaches that are less complex than whole-body physiologically-based models but still capture the essential elements in a physiological way and hence will be more suited for population modelling of large clinical data sets. It will also help formulation scientists to better predict formulation performance and to develop formulations that maximize oral bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

Poly(ethylene glycol) layered silicate nanocomposites for retarded drug release prepared by hot-melt extrusion.

PubMed

Campbell, Kayleen; Craig, Duncan Q M; McNally, Tony

2008-11-03

Composites of paracetamol loaded poly(ethylene glycol) (PEG) with a naturally derived and partially synthetic layered silicate (nanoclay) were prepared using hot-melt extrusion. The extent of dispersion and distribution of the paracetamol and nanoclay in the PEG matrix was examined using a combination of field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and wide-angle X-ray diffraction (WAXD). The paracetamol polymorph was shown to be well dispersed in the PEG matrix and the nanocomposite to have a predominately intercalated and partially exfoliated morphology. The form 1 monoclinic polymorph of the paracetamol was unaltered after the melt mixing process. The crystalline behaviour of the PEG on addition of both paracetamol and nanoclay was investigated using differential scanning calorimetry (DSC) and polarised hot-stage optical microscopy. The crystalline content of PEG decreased by up to 20% when both drug and nanoclay were melt blended with PEG, but the average PEG spherulite size increased by a factor of 4. The time taken for 100% release of paracetamol from the PEG matrix and corresponding diffusion coefficients were significantly retarded on addition of low loadings of both naturally occurring and partially synthetic nanoclays. The dispersed layered silicate platelets encase the paracetamol molecules, retarding diffusion and altering the dissolution behaviour of the drug molecule in the PEG matrix.

[Psychosocial profile and family support perception in adults].

PubMed

Landeros-Herrera, Jesús Ernesto; Simental-Mendía, Luis E; Rodríguez-Durán, Juan Luis

2015-01-01

Psychosocial profile disturbances are the basis of personality disorders, which are frequent in México. Thus, the objective of this study was to determine if the family support perception is associated with the psychosocial profile in adults. A total of 450 men and non-pregnant women aged 18 to 60 years were enrolled in a population-based cross-sectional study. According psychosocial profile individuals were allocated into groups altered and unaltered. The presences of psychiatric illness, renal, hepatic, and cardiovascular disease, malignancy or any kind of disability were exclusion criteria. The family support perception was determined by family APGAR and the psychosocial profile using the Dr. Víctor Chávez test. A logistic regression analysis was used to compute the association between family support perception and psychosocial profile. A total of 344 (76.4 %) and 106 (23.5 %) subjects were included into the groups with altered and unaltered psychosocial profile, respectively. Both, moderate family dysfunction (OR = 1.80 95 % CI 1.01-3.23 p = 0.04), and high family dysfunction (OR = 3.88 95 % CI 1.09-12.09 p = 0.02) were significantly associated with altered psychosocial profile. Both, moderate and high family dysfunctions are associated with altered psychosocial profile in adults.

Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats.

PubMed

Goswami, Ananda Raj; Dutta, Goutam; Ghosh, Tusharkanti

2016-06-01

Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS.

Could the Mantle Under Island Arcs Contribute to Long Wavelength Magnetic Anomalies?

NASA Astrophysics Data System (ADS)

Friedman, S. A.; Ferre, E. C.; Martin-Hernandez, F.; Feinberg, J. M.; Conder, J. A.

2016-12-01

Some island arcs show significant long-wavelength positive magnetic anomalies with potential sources in the mantle wedge while others do not. Here we compare the magnetic properties of mantle xenoliths form metasomatized mantle wedges with counterparts from pristine unaltered mantle and we discuss the role mantle processes may play in producing these anomalies. Samples for this study originate from four localities displaying different degrees of metasomatism, as evidenced by the presence of phlogophite, pargasite, and secondary minerals (olv, cpx, opx): a) Five samples from Ichinomegata crater, Megata volcano, in NE Japan are characteristically lherzolitic with metasomatic pargasite present; b) Six samples from Kurose, SW Japan are mainly harzburgites that contain rare, late stage metasomatic sulfides; c) Ten samples from the Iraya volcano, Batan Island, in the Philippines are lherzolites, harzburgites, and dunites that contain metasomatic olivine, orthopyroxene, clinopyroxene and pargasite; and d) Ten samples from Avacha and Shiveluch volcanoes in Kamchatka, consists of unaltered harzburgites supported by an LOI <1%. Sample localities come from subduction zones of the western Pacific Ocean, where the angle of subduction varies (from 10° in SW Japan to 55° in the Kamchatka and Taiwan-Luzon arcs). When present, ferromagnetic minerals include stoichiometric magnetite with occasional pyrrhotite only in metasomatized samples. Ultimately, metasomatized mantle material has a Koenigsberger ratio less than 1.0 indicating it would not primarily contribute to satellite-altitude magnetic anomalies. While unaltered mantle material may produce a Koenigsberger ratio greater than 1.0, and would thus, contribute to long wavelength magnetic anomalies. The presence of both metasomatized and unaltered mantle material beneath island arcs would be supportive of the positive magnetic anomaly found in some subduction zones.

Cross-modal enhancement of speech detection in young and older adults: does signal content matter?

PubMed

Tye-Murray, Nancy; Spehar, Brent; Myerson, Joel; Sommers, Mitchell S; Hale, Sandra

2011-01-01

The purpose of the present study was to examine the effects of age and visual content on cross-modal enhancement of auditory speech detection. Visual content consisted of three clearly distinct types of visual information: an unaltered video clip of a talker's face, a low-contrast version of the same clip, and a mouth-like Lissajous figure. It was hypothesized that both young and older adults would exhibit reduced enhancement as visual content diverged from the original clip of the talker's face, but that the decrease would be greater for older participants. Nineteen young adults and 19 older adults were asked to detect a single spoken syllable (/ba/) in speech-shaped noise, and the level of the signal was adaptively varied to establish the signal-to-noise ratio (SNR) at threshold. There was an auditory-only baseline condition and three audiovisual conditions in which the syllable was accompanied by one of the three visual signals (the unaltered clip of the talker's face, the low-contrast version of that clip, or the Lissajous figure). For each audiovisual condition, the SNR at threshold was compared with the SNR at threshold for the auditory-only condition to measure the amount of cross-modal enhancement. Young adults exhibited significant cross-modal enhancement with all three types of visual stimuli, with the greatest amount of enhancement observed for the unaltered clip of the talker's face. Older adults, in contrast, exhibited significant cross-modal enhancement only with the unaltered face. Results of this study suggest that visual signal content affects cross-modal enhancement of speech detection in both young and older adults. They also support a hypothesized age-related deficit in processing low-contrast visual speech stimuli, even in older adults with normal contrast sensitivity.

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

PubMed

Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

2016-06-01

Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

Unaltered Angiogenesis-Regulating Activities of Platelets in Mild Type 2 Diabetes Mellitus despite a Marked Platelet Hyperreactivity.

PubMed

Miao, Xinyan; Zhang, Wei; Huang, Zhangsen; Li, Nailin

2016-01-01

Type 2 diabetes mellitus (T2DM) is associated with platelet dysfunction and impaired angiogenesis. Aim of the study is to investigate if platelet dysfunction might hamper platelet angiogenic activities in T2DM patients. Sixteen T2DM patients and gender/age-matched non-diabetic controls were studied. Flow cytometry and endothelial colony forming cell (ECFC) tube formation on matrigel were used to assess platelet reactivity and angiogenic activity, respectively. Thrombin receptor PAR1-activating peptide (PAR1-AP) induced higher platelet P-selectin expression, and evoked more rapid and intense platelet annexin V binding in T2DM patients, seen as a more rapid increase of annexin V+ platelets (24.3±6.4% vs 12.6±3.8% in control at 2 min) and a higher elevation (30.9±5.1% vs 24.3±3.0% at 8 min). However, PAR1-AP and PAR4-AP induced similar releases of angiogenic regulators from platelets, and both stimuli evoked platelet release of platelet angiogenic regulators to similar extents in T2DM and control subjects. Thus, PAR1-stimulated platelet releasate (PAR1-PR) and PAR4-PR similarly enhanced capillary-like network/tube formation of ECFCs, and the enhancements did not differ between T2DM and control subjects. Direct supplementation of platelets to ECFCs at the ratio of 1:200 enhanced ECFC tube formation even more markedly, leading to approximately 100% increases of the total branch points of ECFC tube formation, for which the enhancements were also similar between patients and controls. In conclusion, platelets from T2DM subjects are hyperreactive. Platelet activation induced by high doses of PAR1-AP, however, results in similar releases of angiogenic regulators in mild T2DM and control subjects. Platelets from T2DM and control subjects also demonstrate similar enhancements on ECFC angiogenic activities.

Short-time dissolution mechanisms of kaolinitic tropical soils

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

Malengreau, N.; Sposito, Garrison

1996-03-01

Previous research on the short-time dissolution behavior of kaolinitic Oxisols suggested pH-dependent kinetics involving ligand-promoted dissolution, metal readsorption, and colloidal dispersion, with soil organic matter conjectured to play a decisive role. A novel combination of spectroscopy, lightscattering, and batch dissolution experiments, conducted at controlled pH and ionic strength over five dissolution periods ranging from 1 to 12 h, was applied to evaluate this mechanism for samples of a representative kaolinitic Oxisol; collected at both forested and cultivated field sites (leading to significant differences in organic matter content and field soil pH). The overall characteristics of the pH-dependent net release kineticsmore » of Al, Fe, and Si by the soil samples, for any dissolution period in the range investigated, were determined by the pH value at which colloid dispersion commenced, which decreased significantly as the soil organic matter content increased. Plots of log(Si/Al released) (or Si/Fe released) vs. -log [H+] ([H+] is proton concentration) were superimposable for all dissolution periods studied, rising to a plateau value above the point of zero net charge of the soils (pH 3.2). Light-scattering and X-ray diffraction data showed conclusively that this plateau represented the release of siliceous colloids containing kaolinite and X-ray amorphous material. X-ray diffraction, UV-visible diffuse reflectance spectroscopy, and electron spin resonance spectroscopy, applied to the soil samples before and after dissolution, and after conventional chemical extractions to remove Al, C, Fe, and Si, showed that kaolinite and iron oxide phases (the latter being highly Al-substituted and present in both coatings and occlusions) were essentially unaltered by dissolution, even at -log [H+] = 2, whereas substantial dissolution loss of soil quartz occurred. Diffuse reflectance spectroscopy gave strong evidence that C in these soils occurs principally in discrete solid phases, not as a reactive coating on mineral surfaces.« less

Adenosine receptors and muscarinic receptors cooperate in acetylcholine release modulation in the neuromuscular synapse.

PubMed

Santafe, M M; Priego, M; Obis, T; Garcia, N; Tomàs, M; Lanuza, M A; Tomàs, J

2015-07-01

Adenosine receptors (ARs) are present in the motor terminals at the mouse neuromuscular junction. ARs and the presynaptic muscarinic acetylcholine receptors (mAChRs) share the functional control of the neuromuscular junction. We analysed their mutual interaction in transmitter release modulation. In electrophysiological experiments with unaltered synaptic transmission (muscles paralysed by blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB), we found that: (i) a collaborative action between different AR subtypes reduced synaptic depression at a moderate activity level (40 Hz); (ii) at high activity levels (100 Hz), endogenous adenosine production in the synaptic cleft was sufficient to reduce depression through A1 -type receptors (A1 Rs) and A2 A-type receptors (A2 A Rs); (iii) when the non-metabolizable 2-chloroadenosine (CADO) agonist was used, both the quantal content and depression were reduced; (iv) the protective effect of CADO on depression was mediated by A1 Rs, whereas A2 A Rs seemed to modulate A1 Rs; (v) ARs and mAChRs absolutely depended upon each other for the modulation of evoked and spontaneous acetylcholine release in basal conditions and in experimental conditions with CADO stimulation; (vi) the purinergic and muscarinic mechanisms cooperated in the control of depression by sharing a common pathway although the purinergic control was more powerful than the muscarinic control; and (vii) the imbalance of the ARs created by using subtype-selective and non-selective inhibitory and stimulatory agents uncoupled protein kinase C from evoked transmitter release. In summary, ARs (A1 Rs, A2 A Rs) and mAChRs (M1 , M2 ) cooperated in the control of activity-dependent synaptic depression and may share a common protein kinase C pathway. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Effect of clomiphene on Ca(2+) movement in human prostate cancer cells.

PubMed

Jiann, Bang-Ping; Lu, Yih-Chau; Chang, Hong-Tai; Huang, Jong-Khing; Jan, Chung-Ren

2002-05-17

The effect of clomiphene, an ovulation-inducing agent, on cytosolic free Ca(2+) levels ([Ca(2+)](i)) in populations of PC3 human prostate cancer cells was explored by using fura-2 as a Ca(2+) indicator. Clomiphene at concentrations between 10-50 microM increased [Ca(2+)](i) in a concentration-dependent manner. The [Ca(2+)](i) signal was biphasic with an initial rise and a slow decay. Ca(2+) removal inhibited the Ca(2+) signal by 41%. Adding 3 mM Ca(2+) increased [Ca(2+)](i) in cells pretreated with clomiphene in Ca(2+)-free medium, confirming that clomiphene induced Ca(2+) entry. In Ca(2+)-free medium, pretreatment with 50 microM brefeldin A (to permeabilize the Golgi complex), 1 microM thapsigargin (to inhibit the endoplasmic reticulum Ca(2+) pump), and 2 microM carbonylcyanide m-chlorophenylhydrazone (to uncouple mitochondria) inhibited 25% of 50 microM clomiphene-induced store Ca(2+) release. Conversely, pretreatment with 50 microM clomiphene in Ca(2+)-free medium abolished the [Ca(2+)](i) increase induced by brefeldin A, thapsigargin or carbonylcyanide m-chlorophenylhydrazone. The 50 microM clomiphene-induced Ca(2+)release was unaltered by inhibiting phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). Trypan blue exclusion assay suggested that incubation with clomiphene (50 microM) for 2-15 min induced time-dependent decrease in cell viability by 10-50%. Collectively, the results suggest that clomiphene induced [Ca(2+)](i) increases in PC3 cells by releasing store Ca(2+) from multiple stores in an phospholipase C-independent manner, and by activating Ca(2+) influx; and clomiphene was of mild cytotoxicity.

Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2.

PubMed

Grubb, Søren; Aistrup, Gary L; Koivumäki, Jussi T; Speerschneider, Tobias; Gottlieb, Lisa A; Mutsaers, Nancy A M; Olesen, Søren-Peter; Calloe, Kirstine; Thomsen, Morten B

2015-08-01

Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast-recovering transient outward K(+) current (Ito,f) and with CaV1.2 to mediate the inward L-type Ca(2+) current (ICa,L). Anesthetized KChIP2(-/-) mice have normal cardiac contraction despite the lower ICa,L, and we hypothesized that the delayed repolarization could contribute to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ₂ protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby augmenting Ca(2+)-induced Ca(2+) release. Ca(2+) transients in disaggregated KChIP2(-/-) cardiomyocytes are indeed comparable to wild-type transients, corroborating the preserved contractile function and suggesting that the compensatory mechanism lies in the Ca(2+)-induced Ca(2+) release event. We next functionally probed dyad structure, ryanodine receptor Ca(2+) sensitivity, and sarcoplasmic reticulum Ca(2+) load and found that increased temporal synchronicity of the Ca(2+) release in KChIP2(-/-) cardiomyocytes may reflect improved dyad structure aiding the compensatory mechanisms in preserving cardiac contractile force. Thus the bimodal effect of KChIP2 on Ito,f and ICa,L constitutes an important regulatory effect of KChIP2 on cardiac contractility, and we conclude that delayed repolarization and improved dyad structure function together to preserve cardiac contraction in KChIP2(-/-) mice. Copyright © 2015 the American Physiological Society.

Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

PubMed Central

Vendelbo, Mikkel Holm; Møller, Andreas Buch; Christensen, Britt; Nellemann, Birgitte; Clasen, Berthil Frederik Forrest; Nair, K. Sreekumaran; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels

2014-01-01

Aim Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth. Methods Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days. Results Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation. Conclusions Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth. PMID:25020061

In Vivo and In Vitro Arsenic Exposition Induces Oxidative Stress in Anterior Pituitary Gland.

PubMed

Ronchetti, Sonia A; Bianchi, María S; Duvilanski, Beatriz H; Cabilla, Jimena P

2016-07-01

Inorganic arsenic (iAs) is at the top of toxic metalloids. Inorganic arsenic-contaminated water consumption is one of the greatest environmental health threats worldwide. Human iAs exposure has been associated with cancers of several organs, neurological disorders, and reproductive problems. Nevertheless, there are no reports describing how iAs affects the anterior pituitary gland. The aim of this study was to investigate the mechanisms involved in iAs-mediated anterior pituitary toxicity both in vivo and in vitro. We showed that iAs administration (from 5 to 100 ppm) to male rats through drinking water increased messenger RNA expression of several oxidative stress-responsive genes in the anterior pituitary gland. Serum prolactin levels diminished, whereas luteinizing hormone (LH) levels were only affected at the higher dose tested. In anterior pituitary cells in culture, 25 µmol/L iAs significantly decreased prolactin release in a time-dependent fashion, whereas LH levels remained unaltered. Cell viability was significantly reduced mainly by apoptosis evidenced by morphological and phosphatidylserine externalization studies. This process is characterized by early depolarization of mitochondrial membrane potential and increased levels of reactive oxygen species. Expression of some key oxidative stress-responsive genes, such as heme oxygenase-1 and metallothionein-1, was also stimulated by iAs exposure. The antioxidant N-acetyl cysteine prevented iAs-induced effects on the expression of oxidative stress markers, prolactin release, and apoptosis. In summary, the present work demonstrates for the first time that iAs reduces prolactin release both in vivo and in vitro and induces apoptosis in anterior pituitary cells, possibly resulting from imbalanced cellular redox status. © The Author(s) 2016.

Effect of inhibitors of prostaglandin synthesis on gonadotropin release in the rat.

PubMed

Ojeda, S R; Harms, P G; McCann, S M

1975-10-01

To study the effect of blockade of prostaglandin (PG) synthesis on gonadotropin release in the rat, inhibitors of PG synthesis were injected by various routes in various experimental conditions. The injection of 5-, 8-, 11-, 14-eicosatetraynoic acid (TYA) into the third ventricle (3rd V) significantly decreased plasma LH of ovariectomized (OVX) rats 1, 2, and 4 h following its injection; however, TYA failed to alter plasma LH in OVX rats when administered as a single sc injection and also failed to prevent the post-castration rise in plasma LH when administered sc once daily for 4 days to short-term OVX rats. None of these treatments altered plasma FSH concentrations. Indomethacin (Id) injected into the 3rd V or implanted into the medial basal hypothalamus (MBH) of OVX rats depressed plasma LH 1--6 h later. This effect was no longer observed 24--72 h following its implantation in the MBH. When different doses of Id were administered as single sc injections to OVX rats, plasma LH titers were depressed 24--32 h later, whereas plasma FSH remained either unaltered or was slightly increased. Similarly, the post-castration rise of plasma LH but not that of FSH in male rats was suppressed by a single sc injection of Id given 6 h before orchidectomy. Id administered acutely iv failed to modify the pulsatile release of LH in OVX rats, but it effectively inhibited this release when injected sc 20--30 h before the initiation of blood collection. Moreover, Id blocked the progesterone-induced LH and FSH release in OVX estrogen-primed rats when given sc 24 h before progesterone, but not when it was injected either sc or iv shortly (2 h) before or shortly after (1--3 h) progesterone treatment. Rats treated with Id showed a decrease in BW 24--32 h afters its sc injection. However, the effects of Id on LH release could not be explained by lack of food intake since fasted controls showed LH titers similar to fed rats. Id did not significantly inhibit the LH release in response to synthetic LH-releasing hormone (LHRH) in OVX rats, but partially blocked the response in OVX estrogen, progesterone-treated (OEP) rats. Surprisingly, in OEP rats, Id appeared to potentiate the FSH release in response to LHRH. The results of this study indicate that inhibitors of PG synthesis administered at high doses can inhibit LH release in the rat and that this effect is mainly due to a direct effect of the drug or drugs on the central nervous systen. Consequently, the results of this study give further support to the hypothesis that PGs play a physiological role in the control of gonadotropin secretion.

Soil-plant-microbial relations in hydrothermally altered soils of Northern California

USGS Publications Warehouse

Blecker, S.W.; Stillings, L.L.; DeCrappeo, N.M.; Ippolito, J.A.

2014-01-01

Soils developed on relict hydrothermally altered soils throughout the Western USA present unique opportunities to study the role of geology on above and belowground biotic activity and composition. Soil and vegetation samples were taken at three unaltered andesite and three hydrothermally altered (acid-sulfate) sites located in and around Lassen VolcanicNational Park in northeastern California. In addition, three different types of disturbed areas (clearcut, thinned, and pipeline) were sampled in acid-sulfate altered sites. Soils were sampled (0–15 cm) in mid-summer 2010 from both under-canopy and between-canopy areas within each of the sites. Soils were analyzed for numerous physical and chemical properties along with soil enzyme assays, C and N mineralization potential, microbial biomass-C and C-substrate utilization. Field vegetation measurements consisted of canopy cover by life form (tree, shrub, forb, and grass), tree and shrub density, and above-ground net primary productivity of the understory. Overall, parameters at the clearcut sites were more similar to the unaltered sites, while parameters at the thinned and pipeline sites were more similar to the altered sites. We employed principal components analysis (PCA) to develop two soil quality indices (SQI) to help quantify the differences among the sites: one based on the correlation between soil parameters and canopy cover, and the second based on six sub-indices. Soil quality indices developed in these systems could provide a means for monitoring and identifying key relations between the vegetation, soils, and microorganisms.

Hydrothermal alteration of a rhyolitic hyaloclastite from Ponza Island, Italy

NASA Astrophysics Data System (ADS)

Ylagan, Robert F.; Altaner, Stephen P.; Pozzuoli, Antonio

1996-12-01

A rhyolitic hyaloclastite from Ponza island, Italy, has been hydrothermally altered producing four distinct alteration zones based on XRD and field textures: (1) non-pervasive argillic zone; (2) propylitic zone; (3) silicic zone; and (4) sericitic zone. The unaltered hyaloclastite is a volcanic breccia with clasts of vesiculated obsidian in a matrix of predominantly pumice lapilli. Incomplete alteration of the hyaloclastite resulted in the non pervasive argillic zone, characterized by smectite and disordered opal-CT. Obsidian clasts, some pumice lapilli, and pyrogenic plagioclase and biotite are unaltered. Smectite has an irregular flakey morphology, although euhedral particles are occasionally observed. The propylitic zone is characterized by mixed-layer illite/smectite (I/S) with 10 to 85% illite (I), mordenite, opal-C and authigenic K-feldspar (akspar). The matrix of the hyaloclastite is completely altered and obsidian clasts are silicified; however, plagioclase and biotite phenocrysts remain unaltered. Flakey I/S replaces pumice, and mordenite, akspar and silica line and fill pores. I/S particles are composed predominantly of subequant plates and euhedral laths. The silicic zone is characterized by highly illitic I/S with ≥ 90% I, quartz, akspar and occasional albite. In this zone the matrix and clasts are completely altered, and pyrogenic plagioclase shows significant alteration. Illitic I/S has a euhedral lath-like morphology. In the sericitic zone the hyaloclastite altered primarily to illitic I/S with ≥ 66% I, quartz, and minor akspar and pyrite. Clay minerals completely replace pyrogenic feldspars and little evidence remains of the original hyaloclastite texture. Unlike other zones, illitic I/S is fibrous and pure illite samples are composed of euhedral laths and hexagonal plates. The temperatures of hydrothermal alteration likely ranged from 30 to 90 °C for the argillic zone, from 110 to 160 °C for the propylitic zone, from 160 to 270 °C for the silicic zone, and were possibly as high as 300 °C for the sericitic zone. The four zones occur as linear bands that increase in intensity north of the bentonite mine at Cala dell'Acqua. The alteration zones have two orientations and may be structurally controlled by E-W- and NE-SW-trending faulting which is consistent with the dominant structural trends of the Pontine archipelago. Finally, hydrothermal alteration most likely involved seawater based on the geologic evolution of Ponza.

Estimation of unaltered daily mean streamflow at ungaged streams of New York, excluding Long Island, water years 1961-2010

USGS Publications Warehouse

Gazoorian, Christopher L.

2015-01-01

A graphical user interface, with an integrated spreadsheet summary report, has been developed to estimate and display the daily mean streamflows and statistics and to evaluate different water management or water withdrawal scenarios with the estimated monthly data. This package of regression equations, U.S. Geological Survey streamgage data, and spreadsheet application produces an interactive tool to estimate an unaltered daily streamflow hydrograph and streamflow statistics at ungaged sites in New York. Among other uses, the New York Streamflow Estimation Tool can assist water managers with permitting water withdrawals, implementing habitat protection, estimating contaminant loads, or determining the potential affect from chemical spills.

Pectin Biosynthesis Is Critical for Cell Wall Integrity and Immunity in Arabidopsis thaliana

PubMed Central

Bethke, Gerit; Thao, Amanda; Xiong, Guangyan; Hatsugai, Noriyuki; Katagiri, Fumiaki; Pauly, Markus

2016-01-01

Plant cell walls are important barriers against microbial pathogens. Cell walls of Arabidopsis thaliana leaves contain three major types of polysaccharides: cellulose, various hemicelluloses, and pectins. UDP-d-galacturonic acid, the key building block of pectins, is produced from the precursor UDP-d-glucuronic acid by the action of glucuronate 4-epimerases (GAEs). Pseudomonas syringae pv maculicola ES4326 (Pma ES4326) repressed expression of GAE1 and GAE6 in Arabidopsis, and immunity to Pma ES4326 was compromised in gae6 and gae1 gae6 mutant plants. These plants had brittle leaves and cell walls of leaves had less galacturonic acid. Resistance to specific Botrytis cinerea isolates was also compromised in gae1 gae6 double mutant plants. Although oligogalacturonide (OG)-induced immune signaling was unaltered in gae1 gae6 mutant plants, immune signaling induced by a commercial pectinase, macerozyme, was reduced. Macerozyme treatment or infection with B. cinerea released less soluble uronic acid, likely reflecting fewer OGs, from gae1 gae6 cell walls than from wild-type Col-0. Although both OGs and macerozyme-induced immunity to B. cinerea in Col-0, only OGs also induced immunity in gae1 gae6. Pectin is thus an important contributor to plant immunity, and this is due at least in part to the induction of immune responses by soluble pectin, likely OGs, that are released during plant-pathogen interactions. PMID:26813622

The Role of Dopamine Receptors in the Neurobehavioral Syndrome Provoked by Activation of L-Type Calcium Channels in Rodents

PubMed Central

Kasim, Suhail; Blake, Bonita L.; Fan, Xueliang; Chartoff, Elena; Egami, Kiyoshi; Breese, George R.; Hess, Ellen J.; Jinnah, H.A.

2010-01-01

In rodents, activation of L-type calcium channels with ± BayK 8644 causes an unusual behavioral syndrome that includes dystonia and self-biting. Prior studies have linked both of these behaviors to dysfunction of dopaminergic transmission in the striatum. The current studies were designed to further elucidate the relationship between ± BayK 8644 and dopaminergic transmission in the expression of the behavioral syndrome. The drug does not appear to release presynaptic dopamine stores, since microdialysis of the striatum revealed dopamine release was unaltered by ± BayK 8644. In addition, the behaviors were preserved or even exaggerated in mice or rats with virtually complete dopamine depletion. On the other hand, pretreatment of mice with D3 or D1/5 dopamine receptor antagonists attenuated the behavioral effects of ± BayK 8644, while pretreatment with D2 or D4 antagonists had no effect. In D3 receptor knockout mice, ± BayK 8644 elicited both dystonia and self-biting, but these behaviors were less severe than in matched controls. In D1 receptor knockout mice, behavioral responses to ± BayK 8644 appeared exaggerated. These results argue that the behavioral effects of ± BayK 8644 are not mediated by a presynaptic influence. Instead, the behaviors appear to result from a postsynaptic activation of the drug, which does not require but can be modified by D3 or D1/5 receptors. PMID:17028428

Unaltered repopulation properties of mouse hematopoietic stem cells transduced with lentiviral vectors

PubMed Central

Gonzalez-Murillo, Africa; Lozano, M. Luz; Montini, Eugenio; Bueren, Juan A.

2008-01-01

Recent studies of retroviral-mediated gene transfer have shown that retroviral integrations themselves may trigger nonmalignant clonal expansion of hematopoietic stem cells (HSCs) in transplant recipients. These observations suggested that previous conclusions of HSC dynamics based on gamma-retroviral gene marking should be confirmed with improved vectors having a more limited capacity to transactivate endogenous genes. Because of the low trans-activation activity of self-inactivating lentiviral vectors (LVs), we have investigated whether the LV marking of mouse HSCs induces a competitive repopulation advantage in recipients of serially transplants. As deduced from analyses conducted in primary and secondary recipients, we concluded that lentivirally transduced HSCs have no competitive repopulation advantages over untransduced HSCs. By linear amplification-mediated polymerase chain reaction (LAM-PCR) analysis, we characterized LV-targeted genes in HSC clones that engrafted up to quaternary recipients. Although 9 clones harbored integrations close to defined retroviral insertion sites, none was characterized as a common integration site, and none was present in HSC clones repopulating quaternary recipients. Taken together, our results show unaltered repopulation properties of HSCs transduced with LVs, and confirm early studies suggesting the natural capacity of a few HSC clones to generate a monoclonal or oligoclonal hematopoiesis in transplant recipients. PMID:18684860

Mechanistic insight into ultrasound induced enhancement of simultaneous saccharification and fermentation of Parthenium hysterophorus for ethanol production.

PubMed

Singh, Shuchi; Agarwal, Mayank; Sarma, Shyamali; Goyal, Arun; Moholkar, Vijayanand S

2015-09-01

This paper presents investigations into mechanism of ultrasound assisted bioethanol synthesis using Parthenium hysterophorus biomass through simultaneous saccharification and fermentation (SSF) mode. Approach of coupling experimental results to mathematical model for SSF using Genetic Algorithm based optimization has been adopted. Comparison of model parameters for experiments with mechanical shaking and sonication (10% duty cycle) give an interesting mechanistic account of influence of ultrasound on SSF system. A 4-fold rise in ethanol and cell mass productivity is seen with ultrasound. The analysis reveals following facets of influence of ultrasound on SSF: increase in Monod constant for glucose for cell growth, maximal specific growth rate and inhibition constant of cell growth by glucose and reduction in specific cell death rate. Values of inhibition constant of cell growth by ethanol (K3E), and constants for growth associated (a) and non-growth associated (b) ethanol production remained unaltered with sonication. Beneficial effects of ultrasound are attributed to enhanced cellulose hydrolysis, enhanced trans-membrane transport of substrate and products as well as dilution of the toxic substances due to micro-convection induced by ultrasound. Intrinsic physiological functioning of cells remained unaffected by ultrasound as indicated by unaltered values of K3E, a and b. Copyright © 2015 Elsevier B.V. All rights reserved.

Nlrp3-dependent IL-1β inhibits CD103+ dendritic cell differentiation in the gut.

PubMed

Mak'Anyengo, Rachel; Duewell, Peter; Reichl, Cornelia; Hörth, Christine; Lehr, Hans-Anton; Fischer, Sandra; Clavel, Thomas; Denk, Gerald; Hohenester, Simon; Kobold, Sebastian; Endres, Stefan; Schnurr, Max; Bauer, Christian

2018-03-08

Inflammatory bowel disease (IBD) is associated with enhanced levels of the IL-1 family cytokines IL-1β and IL-18, which are activated by the Nlrp3 inflammasome. Here, we investigated the role of inflammasome-driven cytokine release on T cell polarization and DC differentiation in steady state and T cell transfer colitis. In vitro and in vivo data showed that IL-1β induces Th17 polarization and increases GM‑CSF production by T cells. Reduced IL-1β levels in Nlrp3-/- mice correlated with enhanced FLT3L levels and increased frequency of tolerogenic CD103+ DC. In the T cell transfer colitis model, Nlrp3 deficiency resulted in lower IL‑1β levels, reduced Th17 immunity, and less severe colitis. Unaltered IL-18 levels in both mouse strains pointed toward Nlrp3-independent processing. Importantly, cohousing revealed that the gut microbiome had no impact on the observed Nlrp3-/- phenotype. This study demonstrates that NLRP3 acts as a molecular switch of intestinal homeostasis by shifting local immune cells toward an inflammatory phenotype via IL-1β.

Antipyretic Effects of Citral and Possible Mechanisms of Action.

PubMed

Emílio-Silva, Maycon T; Mota, Clarissa M D; Hiruma-Lima, Clélia A; Antunes-Rodrigues, José; Cárnio, Evelin C; Branco, Luiz G S

2017-10-01

Citral is a mixture of the two monoterpenoid isomers (neral and geranial) widely used as a health-promoting food additive safe for human and animal (approved by the US Food and Drug Administration). In vitro studies have reported on the capability of citral to reduce inflammation. Here, we report antipyretic effects of citral in vivo using the most well-accepted model of sickness syndrome, i.e., systemic administration of lipopolysaccharide ( LPS ) to rats. Citral given by gavage caused no change in control euthermic rats (treated with saline) but blunted most of the assessed parameters related to the sickness syndrome [fever (hallmark of infection), plasma cytokines (IL-1β, IL-6, and TNF-α) release, and prostaglandin E 2 (PGE 2 ) synthesis (both peripherally and hypothalamic)]. Moreover, LPS caused a sharp increase in plasma corticosterone levels that was unaltered by citral. These data are consistent with the notion that citral has a corticosterone-independent potent antipyretic effect, acting on the peripheral febrigenic signaling (plasma levels of IL-1β, IL-6, TNF-α, and PGE 2 ), eventually down-modulating hypothalamic PGE 2 production.

Impact of α-amylase during breadmaking on in vitro kinetics of starch hydrolysis and glycaemic index of enriched bread with bran.

PubMed

Sanz-Penella, Juan Mario; Laparra, José Moisés; Haros, Monika

2014-09-01

Nowadays, the use of enzymes has become a common practice in the bakery industry, as they can improve dough quality and texture of final product. However, the use of α-amylases could have a negative effect in the glycaemic load of product, due to the released sugars from the starch hydrolysis that are not used by yeasts during the fermentation process. This study evaluated the effect of the addition of α-amylase in bakery products with bran on in vitro kinetics of starch hydrolysis. The use of flour with a high degree of extraction or high bran amount could decrease the GI even with the inclusion of α-amylase in the formulation. It should be taken into account the amount of bran and α-amylase when formulating breads in order to obtain products with lower GI than white bread. However, the fact that kinetics of starch hydrolysis remained unaltered indicates that the use of α-amylase in bread-making processes could provide technological advantages improving quality of breads without markedly changes in their glycaemic index.

FAA Pilot Knowledge Tests: Learning or Rote Memorization?

NASA Technical Reports Server (NTRS)

Casner, Stephen M.; Jones, Karen M.; Puentes, Antonio; Irani, Homi

2004-01-01

The FAA pilot knowledge test is a multiple-choice assessment tool designed to measure the extent to which applicants for FAA pilot certificates and ratings have mastered a corpus of required aeronautical knowledge. All questions that appear on the test are drawn from a database of questions that is made available to the public. The FAA and others are concerned that releasing test questions may encourage students to focus their study on memorizing test questions. To investigate this concern, we created our own database of questions that differed from FAA questions in four different ways. Our first three question types were derived by modifying existing FAA questions: (1) rewording questions and answers; (2) shuffling answers; and (3) substituting different figures for problems that used figures. Our last question type posed a question about required knowledge for which no FAA question currently exists. Forty-eight student pilots completed one of two paper-and-pencil knowledge tests that contained a mix of these experimental questions. The results indicate significantly lower scores for some question types when compared to unaltered FAA questions to which participants had prior access.

Biomechanical comparison between bicortical pin and monocortical screw/polymethylmethacrylate constructs in the cadaveric canine cervical vertebral column.

PubMed

Hettlich, Bianca F; Allen, Matthew J; Pascetta, Daniel; Fosgate, Geoffrey T; Litsky, Alan S

2013-08-01

To compare biomechanical stiffness of cadaveric canine cervical spine constructs stabilized with bicortical stainless steel pins and polymethylmethacrylate (PMMA), monocortical stainless steel screws with PMMA, or monocortical titanium screws with PMMA. Biomechanical cadaver study. Eighteen canine cervical vertebral columns (C2-C7) were collected from skeletally mature dogs (weighing 22-32 kg). Specimens were radiographed and examined by dual energy X-ray absorptiometry. Stiffness of the unaltered C4-C5 intervertebral motion unit was measured in extension, flexion and lateral bending using non-destructive 4-point bend testing. Specimens were then stabilized by (1) bicortical stainless steel pins/PMMA, (2) monocortical stainless steel screws/PMMA, or (3) monocortical titanium screws/PMMA. Mechanical testing was repeated and stiffness data from unaltered specimens and the 3 treatment groups were compared. All 3 surgical methods significantly increased stiffness of the C4-C5 motion unit compared with the unaltered specimen (P < .001 for all treatments), but stiffness was not significantly different among the 3 fixation groups (P = .578). In this model, monocortical screw fixation (with stainless steel or titanium screws) was biomechanically equivalent to bicortical fixation. © Copyright 2013 by The American College of Veterinary Surgeons.

Supercritical Carbon Dioxide Extraction of Coronene in the Presence of Perchlorate for In Situ Chemical Analysis of Martian Regolith.

PubMed

McCaig, Heather C; Stockton, Amanda; Crilly, Candice; Chung, Shirley; Kanik, Isik; Lin, Ying; Zhong, Fang

2016-09-01

The analysis of the organic compounds present in the martian regolith is essential for understanding the history and habitability of Mars, as well as studying the signs of possible extant or extinct life. To date, pyrolysis, the only technique that has been used to extract organic compounds from the martian regolith, has not enabled the detection of unaltered native martian organics. The elevated temperatures required for pyrolysis extraction can cause native martian organics to react with perchlorate salts in the regolith and possibly result in the chlorohydrocarbons that have been detected by in situ instruments. Supercritical carbon dioxide (SCCO2) extraction is an alternative to pyrolysis that may be capable of delivering unaltered native organic species to an in situ detector. In this study, we report the SCCO2 extraction of unaltered coronene, a representative polycyclic aromatic hydrocarbon (PAH), from martian regolith simulants, in the presence of 3 parts per thousand (ppth) sodium perchlorate. PAHs are a class of nonpolar molecules of astrobiological interest and are delivered to the martian surface by meteoritic infall. We also determined that the extraction efficiency of coronene was unaffected by the presence of perchlorate on the regolith simulant, and that no sodium perchlorate was extracted by SCCO2. This indicates that SCCO2 extraction can provide de-salted samples that could be directly delivered to a variety of in situ detectors. SCCO2 was also used to extract trace native fluorescent organic compounds from the martian regolith simulant JSC Mars-1, providing further evidence that SCCO2 extraction may provide an alternative to pyrolysis to enable the delivery of unaltered native organic compounds to an in situ detector on a future Mars rover. Biomarkers-Carbon dioxide-In situ measurement-Mars-Search for Mars' organics. Astrobiology 16, 703-714.

Graphene-Based Interfaces Do Not Alter Target Nerve Cells.

PubMed

Fabbro, Alessandra; Scaini, Denis; León, Verónica; Vázquez, Ester; Cellot, Giada; Privitera, Giulia; Lombardi, Lucia; Torrisi, Felice; Tomarchio, Flavia; Bonaccorso, Francesco; Bosi, Susanna; Ferrari, Andrea C; Ballerini, Laura; Prato, Maurizio

2016-01-26

Neural-interfaces rely on the ability of electrodes to transduce stimuli into electrical patterns delivered to the brain. In addition to sensitivity to the stimuli, stability in the operating conditions and efficient charge transfer to neurons, the electrodes should not alter the physiological properties of the target tissue. Graphene is emerging as a promising material for neuro-interfacing applications, given its outstanding physico-chemical properties. Here, we use graphene-based substrates (GBSs) to interface neuronal growth. We test our GBSs on brain cell cultures by measuring functional and synaptic integrity of the emerging neuronal networks. We show that GBSs are permissive interfaces, even when uncoated by cell adhesion layers, retaining unaltered neuronal signaling properties, thus being suitable for carbon-based neural prosthetic devices.

Peroxidized mineral oil increases the oxidant status of culture media and inhibits in vitro porcine embryo development.

PubMed

Martinez, C A; Nohalez, A; Ceron, J J; Rubio, C P; Roca, J; Cuello, C; Rodriguez-Martinez, H; Martinez, E A; Gil, M A

2017-11-01

The use of oils with undetected alterations is a long-recognized problem for in vitro embryo production systems. Since peroxides in oils have been associated with reduced embryo production outcomes, our goals were (1) to evaluate the effects of a batch of mineral oil (MO) that was suspected to be altered on the in vitro production of pig embryos and (2) to determine oil peroxide values throughout culture and the transfer of oxidant agents from oil to culture media. Sunflower oil, which has a completely different chemical composition than MO but a higher oxidative status, and unaltered MO were used as controls. Oocyte maturation, fertilization and embryo development were affected differently depending on the oil overlay used. While the suspected MO was not able to sustain in vitro maturation and fertilization, the oocytes incubated in the presence of sunflower oil were matured and fertilized similarly to those of the unaltered MO group. Moreover, the cleavage rate of presumed zygotes cultured under the suspected MO was severely reduced compared with those cultured under the other oils, and none of the cleaved embryos developed to the blastocyst stage. Although the cleavage rates in the sunflower oil and unaltered MO groups were similar, embryos cultured under sunflower oil also failed to develop to the blastocyst stage. Our results revealed that the suspected MO and sunflower oil had similar levels of peroxides and that these levels were much higher than those of the unaltered MO. The total oxidant status was higher in media incubated under peroxidized oils than in fresh media or media incubated without an oil overlay or under unaltered MO, indicating that oxidant agents were transferred to the incubation media. However, unlike the sunflower oil group, the culture media incubated under the suspected MO had high levels of total oxidant status and low levels of hydrogen peroxide and reactive oxygen species, suggesting the presence of other unknown oxidant agents in that oil. These results indicate that a peroxidized MO overlay dramatically decreases embryo production outcomes. This decrease could be associated with the higher peroxide values of the oil but cannot be explained by the levels of hydrogen peroxide and reactive oxygen species transferred from the oil to the culture media. It is likely that different oxidant agent(s) and/or other toxic compounds present in the peroxidized MO are responsible for its damaging effects on oocytes and embryos. Copyright © 2017 Elsevier Inc. All rights reserved.

Lead nitrate induced unallied expression of liver and kidney functions in male albino rats.

PubMed

Chougule, Priti; Patil, Bhagyashree; Kanase, Aruna

2005-06-01

To determine the effects of lead where lead accumulates maximum (liver followed by kidney), liver and kidney functions were studied using low oral dose of lead nitrate for prolonged duration. Dose of 20 mg lead nitrate/kg body wt/day was used in male albino rats. AST and ALT levels altered independently. When ALT remained unaltered after 7 and 21 days of treatment, it is decreased by 13.21% after 14 days treatment. AST was marginally lowered after 7 days, increased after 14 days and increased marginally after 21 days. Bilirubin (conjugated, unconjugated and total) decreased after 7 and 14 days and increased after 21 days. Urea increase was directly proportional to duration. Creatinine remained unaltered.

Acoustic Constraints and Musical Consequences: Exploring Composers' Use of Cues for Musical Emotion

PubMed Central

Schutz, Michael

2017-01-01

Emotional communication in music is based in part on the use of pitch and timing, two cues effective in emotional speech. Corpus analyses of natural speech illustrate that happy utterances tend to be higher and faster than sad. Although manipulations altering melodies show that passages changed to be higher and faster sound happier, corpus analyses of unaltered music paralleling those of natural speech have proven challenging. This partly reflects the importance of modality (i.e., major/minor), a powerful musical cue whose use is decidedly imbalanced in Western music. This imbalance poses challenges for creating musical corpora analogous to existing speech corpora for purposes of analyzing emotion. However, a novel examination of music by Bach and Chopin balanced in modality illustrates that, consistent with predictions from speech, their major key (nominally “happy”) pieces are approximately a major second higher and 29% faster than their minor key pieces (Poon and Schutz, 2015). Although this provides useful evidence for parallels in use of emotional cues between these domains, it raises questions about how composers “trade off” cue differentiation in music, suggesting interesting new potential research directions. This Focused Review places those results in a broader context, highlighting their connections with previous work on the natural use of cues for musical emotion. Together, these observational findings based on unaltered music—widely recognized for its artistic significance—complement previous experimental work systematically manipulating specific parameters. In doing so, they also provide a useful musical counterpart to fruitful studies of the acoustic cues for emotion found in natural speech. PMID:29249997

Acoustic Constraints and Musical Consequences: Exploring Composers' Use of Cues for Musical Emotion.

PubMed

Schutz, Michael

2017-01-01

Emotional communication in music is based in part on the use of pitch and timing, two cues effective in emotional speech. Corpus analyses of natural speech illustrate that happy utterances tend to be higher and faster than sad. Although manipulations altering melodies show that passages changed to be higher and faster sound happier, corpus analyses of unaltered music paralleling those of natural speech have proven challenging. This partly reflects the importance of modality (i.e., major/minor), a powerful musical cue whose use is decidedly imbalanced in Western music. This imbalance poses challenges for creating musical corpora analogous to existing speech corpora for purposes of analyzing emotion. However, a novel examination of music by Bach and Chopin balanced in modality illustrates that, consistent with predictions from speech, their major key (nominally "happy") pieces are approximately a major second higher and 29% faster than their minor key pieces (Poon and Schutz, 2015). Although this provides useful evidence for parallels in use of emotional cues between these domains, it raises questions about how composers "trade off" cue differentiation in music, suggesting interesting new potential research directions. This Focused Review places those results in a broader context, highlighting their connections with previous work on the natural use of cues for musical emotion. Together, these observational findings based on unaltered music-widely recognized for its artistic significance-complement previous experimental work systematically manipulating specific parameters. In doing so, they also provide a useful musical counterpart to fruitful studies of the acoustic cues for emotion found in natural speech.

Interaction of a chick skin collagen fragment (alpha1-CB5) with human platelets. Biochemical studies during the aggregation and release reaction.

PubMed

Chiang, T M; Beachey, E H; Kang, A H

1975-09-10

The denatured alpha1(I) chain and the cyanogen bromide peptide, alpha1(I)-CB5, of chick skin collagen cause the release of serotonin and leakage of lactic dehydrogenase from human platelets in a manner similar to the release reaction mediated by adenosine diphosphate and native collagen. These peptides also cause a decrease in the level of adenosine 3':5'-monophosphate (cAMP) in platelets. Adenylate cyclase activity of platelets is partially inhibited by these peptides as well as by native collagen, ADP, and epinephrine, but cAMP phosphodiesterase activity is unaltered by these substances. In contrast, the level of platelet guanosine 3':5'-monophosphate (cGMP) is increased by the collagen peptides as well as the other aggregating agents. The increase is associated with increased guanylate cyclase, but normal cGMP phosphodiesterase activities of platelets. Optical rotatory and viscometric measurements of the alpha1 chains and alpha1-CB5 of chick skin in 0.01 M phosphate/0.15 M sodium chloride, pH 7.4, at various temperatures as a function of time indicate that no detectable renaturation occurs at 37 degrees for at least 30 min of observation. Molecular sieve chromatography of alpha1-CB5 in the phosphate buffer at 37 degrees shows that its elution position is identical to that performed under denaturing conditions (at 45 degrees) with no evidence of higher molecular weight aggregates, and the alpha1-CB5 glycopeptide fraction eluting from the column at the position of its monomer retains the platelet aggregating activity. Additionally, electron microscopic examination of the platelet-rich plasma that had been reacted with these peptides fail to show any ordered collagen structures. These data indicate that the denatured alpha1 chain and alpha1-CB5 glycopeptide of chick skin collagen mediate platelet aggregation through the "physiologic" release reaction in a manner similar to that induced by other aggregating agents such as ADP, epinephrine, or native collagen, and support the conclusion that the aggregating activity of the alpha1 chain and alpha1-CB5 is not likely to be due to the formation of polymerized products.

AGR-3/4 Irradiation Test Predictions using PARFUME

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

Skerjanc, William Frances; Collin, Blaise Paul

2016-03-01

PARFUME, a fuel performance modeling code used for high temperature gas reactors, was used to model the AGR-3/4 irradiation test using as-run physics and thermal hydraulics data. The AGR-3/4 test is the combined third and fourth planned irradiations of the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. The AGR-3/4 test train consists of twelve separate and independently controlled and monitored capsules. Each capsule contains four compacts filled with both uranium oxycarbide (UCO) unaltered “driver” fuel particles and UCO designed-to-fail (DTF) fuel particles. The DTF fraction was specified to be 1×10-2. This report documents the calculations performed to predictmore » failure probability of TRISO-coated fuel particles during the AGR-3/4 experiment. In addition, this report documents the calculated source term from both the driver fuel and DTF particles. The calculations include the modeling of the AGR-3/4 irradiation that occurred from December 2011 to April 2014 in the Advanced Test Reactor (ATR) over a total of ten ATR cycles including seven normal cycles, one low power cycle, one unplanned outage cycle, and one Power Axial Locator Mechanism cycle. Results show that failure probabilities are predicted to be low, resulting in zero fuel particle failures per capsule. The primary fuel particle failure mechanism occurred as a result of localized stresses induced by the calculated IPyC cracking. Assuming 1,872 driver fuel particles per compact, failure probability calculated by PARFUME leads to no predicted particle failure in the AGR-3/4 driver fuel. In addition, the release fraction of fission products Ag, Cs, and Sr were calculated to vary depending on capsule location and irradiation temperature. The maximum release fraction of Ag occurs in Capsule 7 reaching up to 56% for the driver fuel and 100% for the DTF fuel. The release fraction of the other two fission products, Cs and Sr, are much smaller and in most cases less than 1% for the driver fuel. The notable exception occurs in Capsule 7 where the release fraction for Cs and Sr reach up to 0.73% and 2.4%, respectively, for the driver fuel. For the DTF fuel in Capsule 7, the release fraction for Cs and Sr are estimated to be 100% and 5%, respectively.« less

Liability and ophthalmic drug use.

PubMed

Classé, J G

1992-01-01

Ophthalmic drug use has been an aspect of optometry for more than two decades. Although utilization of these drugs has produced significant changes in the clinical and legal responsibilities of optometrists, the liability posture of the profession has remained unaltered. Studies of malpractice claims against optometrists and ophthalmologists have demonstrated that ophthalmologists are much more likely to be charged with negligence for adverse drug reactions and that drug-related malpractice claims are not a liability issue for optometrists. Based on the experiences of both professions, this paper describes the adverse effects of common ophthalmic drugs, with emphasis on those drug reactions that have resulted in litigation.

Chronic adriamycin treatment impairs CGRP-mediated functions of meningeal sensory nerves.

PubMed

Deák, Éva; Rosta, Judit; Boros, Krisztina; Kis, Gyöngyi; Sántha, Péter; Messlinger, Karl; Jancsó, Gábor; Dux, Mária

2018-06-01

Adriamycin is a potent anthracycline-type antitumor agent, but it also exerts potentially serious side effects due to its cardiotoxic and neurotoxic propensity. Multiple impairments in sensory nerve functions have been recently reported in various rat models. The present experiments were initiated in an attempt to reveal adriamycin-induced changes in sensory effector functions of chemosensitive meningeal afferents. Meningeal blood flow was measured with laser Doppler flowmetry in the parietal dura mater of adult male Wistar rats. The dura mater was repeatedly stimulated by topical applications of capsaicin, a transient receptor potential vanilloid 1 (TRPV1) receptor agonist, or acrolein, a transient receptor potential ankyrin 1 (TRPA1) receptor agonist, which induce the release of calcitonin gene-related peptide (CGRP) from meningeal afferents. The blood flow increasing effects of CGRP, histamine, acetylcholine and forskolin were also measured. Capsaicin- and acrolein-induced CGRP release was measured with enzyme-linked immunoassay in an ex vivo dura mater preparation. TRPV1 content of trigeminal ganglia and TRPV1-, CGRP- and CGRP receptor component-immunoreactive structures were examined in dura mater samples obtained from control and adriamycin-treated rats. The vasodilator effects of capsaicin, acrolein and CGRP were significantly reduced in adriamycin-treated animals while histamine-, acetylcholine- and forskolin-induced vasodilatation were unaffected. Measurements of CGRP release in an ex vivo dura mater preparation revealed an altered dynamic upon repeated stimulations of TRPV1 and TRPA1 receptors. In whole-mount dura mater preparations immunohistochemistry revealed altered CGRP receptor component protein (RCP)-immunoreactivity in adriamycin-treated animals, while CGRP receptor activity modifying protein (RAMP1)-, TRPV1- and CGRP-immunostaining were left apparently unaltered. Adriamycin-treatment slightly reduced TRPV1 protein content of trigeminal ganglia. The present findings demonstrate that adriamycin-treatment alters the function of the trigeminovascular system leading to reduced meningeal sensory neurogenic vasodilatation that may affect the local regulatory and protective mechanisms of chemosensitive afferents leading to alterations in tissue integrity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Photochemical dissolution of organic matter from resuspended sediments: Impact of source and diagenetic state on photorelease

NASA Astrophysics Data System (ADS)

Helms, J. R.; Glinski, D. A.; Mead, R. N.; Southwell, M.; Avery, G. B., Jr.; Kieber, R. J.; Skrabal, S. A.

2015-12-01

Resuspended sediments exposed to simulated solar radiation release dissolved organic carbon (DOC). However, it is unclear how the provenance of sedimentary organic matter (OM) impacts this photorelease. In the first geographically extensive study of this phenomenon, twenty three size fractionated, fine grained sediments (< ca. 10-20 μm) from a variety of drainage basins were resuspended (at suspended solid loading of 29- 255 mg/l) and exhibited a net photochemical DOC release ranging from 2 to 178 μmol/g/h. There was a logarithmic increase in photoreleased DOC vs. the proportion of sedimentary OC (%), most likely due to photon limitation at high sedimentary OC loading (i.e. high mass-specific absorption limiting light penetration). Sediment source and quality - determined using lipid biomarkers - had a significant effect on DOC photorelease. The fatty acid terrestrial aquatic ratio (TARFA) indicated that terrestrially derived sediments exhibited relatively greater DOC photorelease. The long chain carbon preference index (CPI24-34) indicated that diagenetically unaltered terrestrial OM photoreleased more DOC than diagenetically altered terrestrial OM. The short chain carbon preference index (CPI14-22) demonstrated that sediments containing diagenetically altered planktonic or algal derived OM had a greater photorelease rate of DOC than fresh algal OM. This suggests that humic substances (humus and/or adsorbed humic and fulvic acids) play an important role in the photochemical dissolution of OC regardless of whether or not they are imported from upstream (i.e. terrestrial humics) or generated within the depositional or sedimentary environment (i.e. humification of algal dissolved OM).

Adipose Triglyceride Lipase Is Implicated in Fuel- and Non-fuel-stimulated Insulin Secretion*

PubMed Central

Peyot, Marie-Line; Guay, Claudiane; Latour, Martin G.; Lamontagne, Julien; Lussier, Roxane; Pineda, Marco; Ruderman, Neil B.; Haemmerle, Guenter; Zechner, Rudolf; Joly, Érik; Madiraju, S. R. Murthy; Poitout, Vincent; Prentki, Marc

2009-01-01

Reduced lipolysis in hormone-sensitive lipase-deficient mice is associated with impaired glucose-stimulated insulin secretion (GSIS), suggesting that endogenous β-cell lipid stores provide signaling molecules for insulin release. Measurements of lipolysis and triglyceride (TG) lipase activity in islets from HSL−/− mice indicated the presence of other TG lipase(s) in the β-cell. Using real time-quantitative PCR, adipose triglyceride lipase (ATGL) was found to be the most abundant TG lipase in rat islets and INS832/13 cells. To assess its role in insulin secretion, ATGL expression was decreased in INS832/13 cells (ATGL-knockdown (KD)) by small hairpin RNA. ATGL-KD increased the esterification of free fatty acid (FFA) into TG. ATGL-KD cells showed decreased glucose- or Gln + Leu-induced insulin release, as well as reduced response to KCl or palmitate at high, but not low, glucose. The KATP-independent/amplification pathway of GSIS was considerably reduced in ATGL-KD cells. ATGL−/− mice were hypoinsulinemic and hypoglycemic and showed decreased plasma TG and FFAs. A hyperglycemic clamp revealed increased insulin sensitivity and decreased GSIS and arginine-induced insulin secretion in ATGL−/− mice. Accordingly, isolated islets from ATGL−/− mice showed reduced insulin secretion in response to glucose, glucose + palmitate, and KCl. Islet TG content and FFA esterification into TG were increased by 2-fold in ATGL−/− islets, but glucose usage and oxidation were unaltered. The results demonstrate the importance of ATGL and intracellular lipid signaling for fuel- and non-fuel-induced insulin secretion. PMID:19389712

Biological activity of the azlactone derivative EPA-35 against Trypanosoma cruzi.

PubMed

de Azeredo, Camila Maria Oliveira; Ávila, Eloah Pereira; Pinheiro, Danielle Lobo Justo; Amarante, Giovanni Wilson; Soares, Maurilio José

2017-02-01

Chagas disease, caused by Trypanosoma cruzi, affects six to seven million people worldwide. Treatment is based on benznidazole, producing several side effects and debatable efficacy, highlighting the need for new alternative drugs. We investigated the activity of four C-4 functionalized azlactone derivatives (EPA-27, EPA-35, EPA-63 and EPA-91) as potential T. cruzi inhibitors. Screening with epimastigotes indicated EPA-35 as the best compound (IC50/24 h: 33 μM). This compound was 14.1 times more potent against intracellular amastigotes (IC50/24 h: 2.34 μM). Treatment of infected Vero cells for 72 h (up to 30 μM EPA-35) resulted in a dose-dependent decrease in number of trypomastigotes and amastigotes released in the supernatant, but the amastigote/trypomastigote ratio remained constant, indicating that amastigote growth was disturbed, but cell differentiation was unaffected. Analysis of treated epimastigotes by flow cytometry indicated that the plasma membrane remained intact, but there was a significant decrease in mitochondrial membrane potential. The pattern of cell distribution in the cell cycle stages (G1, G2, M) was unaltered in treated epimastigotes, indicating a trypanocidal rather than a trypanostatic activity. Scanning electron microscopy and flow cytometry showed epimastigotes with a round shape and decrease in cell size. Taken together, our data indicate that the EPA-35 is effective against T. cruzi. Synthetic transformation of EPA-35 into other derivatives may provide promising compounds for further evaluation against this parasite. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Impairment of the reproductive potential of male fathead minnows by environmentally relevant exposures to 4-nonylphenolf

USGS Publications Warehouse

Schoenfuss, H.L.; Bartell, S.E.; Bistodeau, T.B.; Cediel, R.A.; Grove, K.J.; Zintek, Larry; Lee, K.E.; Barber, L.B.

2008-01-01

The synthetic organic compound 4-nonylphenol (NP) has been detected in many human-impacted surface waters in North America. In this study, we examined the ability of NP to alter reproductive competence in male fathead minnows after a 28 day flow-through exposure in a range of environmentally relevant concentrations bracketing the U.S. Environmental Protection Agency toxicity-based NP chronic exposure criterion of 6.1 ??g NP/L. Exposure to NP at and above the EPA chronic exposure criterion resulted in an induction of plasma vitellogenin (VTG) within 14 days. However, 7 days after the cessation of exposure, VTG concentrations had dropped more than 50% and few males expressed VTG above the detection threshold. All of the morphological endpoints, including gonadosomatic index, hepatosomatic index, secondary sexual characters, and histopathology, were unaltered by all NP treatments. However, when NP-exposed male fish were allowed to compete with control males for access to nest sites and females, most treatments altered the reproductive competence of exposed males. At lower NP concentrations, exposed males out-competed control males, possibly by being primed through the estrogenic NP exposure in a fashion similar to priming by pheromones released from female fathead minnows. At higher NP exposure concentrations, this priming effect was negated by the adverse effects of the exposure and control males out-competed treated males. Results of this study indicate the complexity of endocrine disrupting effects and the need for multiple analysis levels to assess the effects of these compounds on aquatic organisms. ?? 2007 Elsevier B.V. All rights reserved.

Opioid tolerance in periaqueductal gray neurons isolated from mice chronically treated with morphine

PubMed Central

Bagley, Elena E; Chieng, Billy C H; Christie, MacDonald J; Connor, Mark

2005-01-01

The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined μ-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (ICa) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice. Mice were injected s.c. with 300 mg kg−1 of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protocol produced significant tolerance to the antinociceptive effects of morphine in a test of thermal nociception. Voltage clamp recordings were made of ICa in acutely isolated PAG neurons and GIRK in PAG slices. The MOP agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin) inhibited ICa in neurons from CMT mice (230 nM) with a similar potency to vehicle (150 nM), but with a reduced maximal effectiveness (37% inhibition in vehicle neurons, 27% in CMT neurons). Inhibition of ICa by the GABAB agonist baclofen was not altered by CMT. Met-enkephalin-activated GIRK currents recorded in PAG slices were significantly smaller in neurons from CMT mice than vehicles, while GIRK currents activated by baclofen were unaltered. These data demonstrate that CMT-induced antinociceptive tolerance is accompanied by homologous reduction in the effectiveness of MOP agonists to inhibit ICa and activate GIRK. Thus, a reduction in MOP number and/or functional coupling to G proteins accompanies the characteristic cellular adaptations to CMT previously described in PAG neurons. PMID:15980868

Opioid tolerance in periaqueductal gray neurons isolated from mice chronically treated with morphine.

PubMed

Bagley, Elena E; Chieng, Billy C H; Christie, MacDonald J; Connor, Mark

2005-09-01

The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined mu-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (I(Ca)) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice. Mice were injected s.c. with 300 mg kg(-1) of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protocol produced significant tolerance to the antinociceptive effects of morphine in a test of thermal nociception. Voltage clamp recordings were made of I(Ca) in acutely isolated PAG neurons and GIRK in PAG slices. The MOP agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin) inhibited I(Ca) in neurons from CMT mice (230 nM) with a similar potency to vehicle (150 nM), but with a reduced maximal effectiveness (37% inhibition in vehicle neurons, 27% in CMT neurons). Inhibition of I(Ca) by the GABA(B) agonist baclofen was not altered by CMT. Met-enkephalin-activated GIRK currents recorded in PAG slices were significantly smaller in neurons from CMT mice than vehicles, while GIRK currents activated by baclofen were unaltered. These data demonstrate that CMT-induced antinociceptive tolerance is accompanied by homologous reduction in the effectiveness of MOP agonists to inhibit I(Ca) and activate GIRK. Thus, a reduction in MOP number and/or functional coupling to G proteins accompanies the characteristic cellular adaptations to CMT previously described in PAG neurons.

The reactions of cytidine and 2'-deoxycytidine with SO4.- revisited. Pulse radiolysis and product studies.

PubMed

Aravindakumar, Charuvila T; Schuchmann, Man Nien; Rao, Balijepalli S; von Sonntag, Justus; von Sonntag, Clemens

2003-01-21

The reactions of SO4.- with 2'-deoxycytidine 1a and cytidine 1b lead to very different intermediates (base radicals with 1a, sugar radicals with 1b). The present study provides spectral and kinetic data for the various intermediates by pulse radiolysis as well as information on final product yields (free cytosine). Taking these and literature data into account allows us to substantiate but also modify in essential aspects the current mechanistic concept (H. Catterall, M. J. Davies and B. C. Gilbert, J. Chem. Soc., Perkin Trans. 2, 1992, 1379). SO4.- radicals have been generated radiolytically in the reaction of peroxodisulfate with the hydrated electron (and the H. atom). In the reaction of SO4.- with 1a (k = 1.6 x 10(9) dm3 mol-1 s-1), a transient (lambda max = 400 nm, shifted to 450 nm at pH 3) is observed. This absorption is due to two intermediates. The major component (lambda max approximately 385 nm) does not react with O2 and has been attributed to an N-centered radical 4a formed upon sulfate release and deprotonation at nitrogen. The minor component, rapidly wiped out by O2, must be due to C-centered OH-adduct radical(s) 6a and/or 7a suggested to be formed by a water-induced nucleophilic replacement. These radicals decay by second-order kinetics. Free cytosine is only formed in low yields (G = 0.14 x 10(-7) mol J-1 upon electron-beam irradiation). In contrast, 1b gives rise to an intermediate absorbing at lambda max = 530 nm (shifted to 600 nm in acid solution) which rapidly decays (k = 6 x 10(4) s-1). In the presence of O2, the decay is much faster (k approximately 1.3 x 10(9) dm3 mol-1 s-1) indicating that this species must be a C-centered radical. This has been attributed to the C(5)-yl radical 8 formed upon the reaction of the C(2')-OH group with the cytidine SO4(.-)-adduct radical 2b. This reaction competes very effectively with the corresponding reaction of water and the release of sulfate and a proton generating the N-centered radical. Upon the decay of 8, sugar radical 11 is formed with the release of cytosine. The latter is formed with a G value of 2.8 x 10(-7) mol J-1 (85% of primary SO4.-) at high dose rates (electron beam irradiation). At low dose rates (gamma-radiolysis) its yield is increased to 7 x 10(-7) mol J-1 due to a chain reaction involving peroxodisulfate and reducing free radicals. Phosphate buffer prevents the formation of the sugar radical at the SO4(.-)-adduct stage by enhancing the rate of sulfate release by deprotonation of 2b and also by speeding up the decay of the C(5)-yl radical into another (base) radical. Cytosine release in cytidine is mechanistically related to strand breakage in poly(C). Literature data on the effect of dioxygen on strand breakage yields in poly(C) induced by SO4.- (suppressed) and upon photoionisation (unaltered) lead us to conclude that in poly(C) and also in the present system free radical cations are not involved to a major extent. This conclusion modifies an essential aspect of the current mechanistic concept.

Predicting the biological condition of streams: Use of geospatial indicators of natural and anthropogenic characteristics of watersheds

USGS Publications Warehouse

Carlisle, D.M.; Falcone, J.; Meador, M.R.

2009-01-01

We developed and evaluated empirical models to predict biological condition of wadeable streams in a large portion of the eastern USA, with the ultimate goal of prediction for unsampled basins. Previous work had classified (i.e., altered vs. unaltered) the biological condition of 920 streams based on a biological assessment of macroinvertebrate assemblages. Predictor variables were limited to widely available geospatial data, which included land cover, topography, climate, soils, societal infrastructure, and potential hydrologic modification. We compared the accuracy of predictions of biological condition class based on models with continuous and binary responses. We also evaluated the relative importance of specific groups and individual predictor variables, as well as the relationships between the most important predictors and biological condition. Prediction accuracy and the relative importance of predictor variables were different for two subregions for which models were created. Predictive accuracy in the highlands region improved by including predictors that represented both natural and human activities. Riparian land cover and road-stream intersections were the most important predictors. In contrast, predictive accuracy in the lowlands region was best for models limited to predictors representing natural factors, including basin topography and soil properties. Partial dependence plots revealed complex and nonlinear relationships between specific predictors and the probability of biological alteration. We demonstrate a potential application of the model by predicting biological condition in 552 unsampled basins across an ecoregion in southeastern Wisconsin (USA). Estimates of the likelihood of biological condition of unsampled streams could be a valuable tool for screening large numbers of basins to focus targeted monitoring of potentially unaltered or altered stream segments. ?? Springer Science+Business Media B.V. 2008.

Effects of temperature-humidity index and chromium supplementation on antioxidant capacity, heat shock protein 72, and cytokine responses of lactating cows.

PubMed

Zhang, F J; Weng, X G; Wang, J F; Zhou, D; Zhang, W; Zhai, C C; Hou, Y X; Zhu, Y H

2014-07-01

Heat stress adversely affects the productivity and immune status of dairy cows. The temperature-humidity index (THI) is commonly used to indicate the degree of heat stress on dairy cattle. We investigated the effects of different THI and Cr supplementation on the antioxidant capacity, the levels of heat shock protein 72 (Hsp72), and cytokine responses of lactating cows. The study used a total of 24 clinically healthy uniparous midlactation Holstein cows, which were randomly divided into 2 groups (n = 12 per group), and was conducted in 3 designated THI periods: low THI period (LTHI; THI = 56.4 ± 2.5), moderate THI period (MTHI; THI = 73.9 ± 1.7), and high THI period (HTHI; THI = 80.3 ± 1.0). The 2 groups of cows were fed corn and corn silage based basal diet supplemented chromium picolinate to provide 3.5 mg of Cr/cow daily (Cr+) or basal diet with no Cr (Cr-). The experiment was a 3 × 2 factorial design. The numbers of leukocytes (P < 0.05) and serum levels of glucose (P < 0.001) were lower; however, the serum levels of blood urea nitrogen (BUN; P < 0.001) and creatinine (P < 0.001) were greater in the MTHI and HTHI than in LTHI. The total antioxidant capacity in the serum was unaltered; an increase in superoxide dismutase activity (P < 0.001) and in serum malondialdehyde concentration (P < 0.001) was observed in the MTHI and HTHI compared with the LTHI. The high THI led to increases in serum concentrations of tumor necrosis factor-α (TNF-α; P < 0.001) and IL-10 (P < 0.05). Cows supplemented with Cr had lower (P = 0.009) serum concentrations of cholesterol but greater (P < 0.001, respectively) serum levels of Hsp72 and IL-10 compared with those without Cr supplementation in the HTHI. Western blot analysis revealed that cows supplemented with Cr had greater (P = 0.038) expression of the inhibitor of nuclear factor kappa B α (IκBα) in peripheral blood mononuclear cells (PBMC) compared with those without Cr supplementation in the HTHI, whereas the expression of Hsp72 in PBMC was unaltered. Data indicate that there is a decrease in glucose and increases in BUN and creatinine in the serum of midlactation cows under hot conditions during the summer and that these cows have a lowered oxidative capacity but an elevated antioxidant capacity. In addition, Cr may play an anti-inflammatory role in lactating cows by promoting the release of Hsp72, increasing the production of IL-10, and inhibiting the degradation of IκBα under hot conditions during the summer.

Hydrologic Drought Decision Support System (HyDroDSS)

USGS Publications Warehouse

Granato, Gregory E.

2014-01-01

The hydrologic drought decision support system (HyDroDSS) was developed by the U.S. Geological Survey (USGS) in cooperation with the Rhode Island Water Resources Board (RIWRB) for use in the analysis of hydrologic variables that may indicate the risk for streamflows to be below user-defined flow targets at a designated site of interest, which is defined herein as data-collection site on a stream that may be adversely affected by pumping. Hydrologic drought is defined for this study as a period of lower than normal streamflows caused by precipitation deficits and (or) water withdrawals. The HyDroDSS is designed to provide water managers with risk-based information for balancing water-supply needs and aquatic-habitat protection goals to mitigate potential effects of hydrologic drought. This report describes the theory and methods for retrospective streamflow-depletion analysis, rank correlation analysis, and drought-projection analysis. All three methods are designed to inform decisions made by drought steering committees and decisionmakers on the basis of quantitative risk assessment. All three methods use estimates of unaltered streamflow, which is the measured or modeled flow without major withdrawals or discharges, to approximate a natural low-flow regime. Retrospective streamflow-depletion analysis can be used by water-resource managers to evaluate relations between withdrawal plans and the potential effects of withdrawal plans on streams at one or more sites of interest in an area. Retrospective streamflow-depletion analysis indicates the historical risk of being below user-defined flow targets if different pumping plans were implemented for the period of record. Retrospective streamflow-depletion analysis also indicates the risk for creating hydrologic drought conditions caused by use of a pumping plan. Retrospective streamflow-depletion analysis is done by calculating the net streamflow depletions from withdrawals and discharges and applying these depletions to a simulated record of unaltered streamflow. Rank correlation analysis in the HyDroDSS indicates the persistence of hydrologic measurements from month to month for the prediction of developing hydrologic drought conditions and quantitatively indicates which hydrologic variables may be used to indicate the onset of hydrologic drought conditions. Rank correlation analysis also indicates the potential use of each variable for estimating the monthly minimum unaltered flow at a site of interest for use in the drought-projection analysis. Rank correlation analysis in the HyDroDSS is done by calculating Spearman’s rho for paired samples and the 95-percent confidence limits of this rho value. Rank correlation analysis can be done by using precipitation, groundwater levels, measured streamflows, and estimated unaltered streamflows. Serial correlation analysis, which indicates relations between current and future values, can be done for a single site. Cross correlation analysis, which indicates relations among current values at one site and current and future values at a second site, also can be done. Drought-projection analysis in the HyDroDSS indicates the risk for being in a hydrologic drought condition during the current month and the five following months with and without pumping. Drought-projection analysis also indicates the potential effectiveness of water-conservation methods for mitigating the effect of withdrawals in the coming months on the basis of the amount of depletion caused by different pumping plans and on the risk of unaltered flows being below streamflow targets. Drought-projection analysis in the HyDroDSS is done with Monte Carlo methods by using the position analysis method. In this method the initial value of estimated unaltered streamflows is calculated by correlation to a measured hydrologic variable (monthly precipitation, groundwater levels, or streamflows from an index station identified with the rank correlation analysis). Then a pseudorandom number generator is used to create 251 six-month-long flow traces by using a bootstrap method. Serial correlation of the estimated unaltered monthly minimum streamflows determined from the rank correlation analysis is preserved within each flow trace. The sample of unaltered streamflows indicates the risk of being below flow targets in the coming months under simulated natural conditions (without historic withdrawals). The streamflow-depletion algorithms are then used to estimate risks of flow being below targets if selected pumping plans are used. This report also describes the implementation of the HyDroDSS. The HyDroDSS was developed as a Microsoft Access® database application to facilitate storage, handling, and use of hydrologic datasets with a simple graphical user interface. The program is implemented in the database by using the Visual Basic for Applications® (VBA) programming language. Program source code for the analytical techniques is provided in the HyDroDSS and in electronic text files accompanying this report. Program source code for the graphical user interface and for data-handling code, which is specific to Microsoft Access® and the HyDroDSS, is provided in the database. An installation package with a run-time version of the software is available with this report for potential users who do not have a compatible copy of Microsoft Access®. Administrative rights are needed to install this version of the HyDroDSS. A case study, to demonstrate the use of HyDroDSS and interpretation of results for a site of interest, is detailed for the USGS streamgage on the Hunt River (station 01117000) near East Greenwich in central Rhode Island. The Hunt River streamgage was used because it has a long record of streamflow and is in a well-studied basin with a substantial amount of hydrologic and water-use data including groundwater pumping for municipal water supply.

Nlrp3-dependent IL-1β inhibits CD103+ dendritic cell differentiation in the gut

PubMed Central

Mak’Anyengo, Rachel; Reichl, Cornelia; Hörth, Christine; Lehr, Hans‑Anton; Fischer, Sandra; Clavel, Thomas; Denk, Gerald; Kobold, Sebastian; Endres, Stefan; Bauer, Christian

2018-01-01

Inflammatory bowel disease (IBD) is associated with enhanced levels of the IL-1 family cytokines IL-1β and IL-18, which are activated by the Nlrp3 inflammasome. Here, we investigated the role of inflammasome-driven cytokine release on T cell polarization and DC differentiation in steady state and T cell transfer colitis. In vitro and in vivo data showed that IL-1β induces Th17 polarization and increases GM‑CSF production by T cells. Reduced IL-1β levels in Nlrp3–/– mice correlated with enhanced FLT3L levels and increased frequency of tolerogenic CD103+ DC. In the T cell transfer colitis model, Nlrp3 deficiency resulted in lower IL‑1β levels, reduced Th17 immunity, and less severe colitis. Unaltered IL-18 levels in both mouse strains pointed toward Nlrp3-independent processing. Importantly, cohousing revealed that the gut microbiome had no impact on the observed Nlrp3–/– phenotype. This study demonstrates that NLRP3 acts as a molecular switch of intestinal homeostasis by shifting local immune cells toward an inflammatory phenotype via IL-1β. PMID:29515025

Influences of prostanoids and nitric oxide on post-suspension hypotension in female Sprague-Dawley rats

NASA Technical Reports Server (NTRS)

Eatman, D.; Listhrop, R. A.; Beasley, A. S.; Socci, R. R.; Abukhalaf, I.; Bayorh, M. A.

2003-01-01

Impairment in cardiovascular functions sometimes manifested in astronauts during standing postflight, may be related to the diminished autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, using the 30 degrees head-down tilt (HDT) model, we compared the cardiovascular and biochemical effects of 7 days of suspension and a subsequent 6-h post-suspension period between suspended and non-suspended conscious female Sprague-Dawley rats. Mean arterial pressure (MAP) and heart rate were measured prior to suspension (basal), daily thereafter, and every 2h post-suspension. Following 7 days of suspension, MAP was not different from their basal values, however, upon release from suspension, MAP was significantly reduced compared to the non-suspended rats. Nitric oxide levels were elevated while thromboxane A(2) levels declined significantly in both plasma and tissue samples following post-suspension. The levels of prostacyclin following post-suspension remained unaltered in plasma and aortic rings but was significantly elevated in carotid arterial rings. Therefore, the post-suspension reduction in mean arterial pressure is due mostly to overproduction of nitric oxide and to a lesser extent prostacyclin.

Impact of vinclozolin on reproductive behavior and endocrinology in Japanese quail (Coturnix coturnix japonica)

USGS Publications Warehouse

McGary, S.; Henry, P.F.P.; Ottinger, M.A.

2001-01-01

The impact of endocrine-disrupting chemicals (EDCs) has been demonstrated in mammalian models, but less research is available for avian species. The effects of vinclozolin (VIN), an antiandrogenic fungicide, on sexual differentiation and maturation were investigated in Japanese quail (Coturnix coturnix japonica). On day 4 of incubation, embryos were exposed to no treatment, oil, or 25, 50, or 100 ppm of VIN. Endpoints measured included adult male reproductive behavior, hypothalamic gonadotropin-releasing hormone I (GnRH-I) content in hatchlings and adults, plasma steroid levels in hatchlings and adults, proctodeal gland growth during maturation, and relative testicular weight at seven weeks of age. Results showed that exposure to VIN significantly (p < 0.05) altered GnRH-I in male hatchlings, whereas GnRH-I levels in females remained unaffected. Although steroid levels were unaltered by any VIN treatment, the display of male reproductive behavior seemed delayed, with the number of mounts and the number of cloacal contacts being significantly (p < 0.05) lower in the VIN-treated males. This could have an extreme negative impact on wild avian species that are routinely exposed to similar EDCs.

Hawthorn extract inhibits human isolated neutrophil functions.

PubMed

Dalli, Ernesto; Milara, Javier; Cortijo, Julio; Morcillo, Esteban J; Cosín-Sales, Juan; Sotillo, José Francisco

2008-06-01

Hawthorn extract is a popular herbal medicine given as adjunctive treatment for chronic heart failure. In contrast to the cardiac properties of hawthorn extract, its anti-inflammatory effect has been scarcely investigated. This study examines the effects of a dry extract of leaves and flowers of Crataegus laevigata on various functional outputs of human neutrophils in vitro. Incubation of human neutrophils obtained from peripheral blood of healthy donors with C. laevigata extract (0.75-250 microg/ml) inhibited N-formyl-Met-Leu-Phe (FMLP)-induced superoxide anion generation, elastase release and chemotactic migration with potency values of 43.6, 21.9, and 31.6 microg/ml, respectively. By contrast, serum-opsonized zymosan-induced phagocytosis was unaltered by plant extract. C. laevigata extract (125 microg/ml) reduced FMLP-induced leukotriene B(4) production and lipopolysaccharide-induced generation of tumour necrosis factor-alpha and interleukin-8. Extract inhibited FMLP-induced intracellular calcium signal with potency of 17.4 microg/ml. Extract also markedly inhibited the extracellular calcium entry into calcium-depleted neutrophils, and the thapsigargin-induced intracellular calcium response. In conclusion, C. laevigata extract inhibited various functional outputs of activated human neutrophils which may be relevant to the pathophysiology of cardiac failure.

Plasticity of Astrocytic Coverage and Glutamate Transporter Expression in Adult Mouse Cortex

PubMed Central

Steiner, Pascal; Hirling, Harald; Welker, Egbert; Knott, Graham W

2006-01-01

Astrocytes play a major role in the removal of glutamate from the extracellular compartment. This clearance limits the glutamate receptor activation and affects the synaptic response. This function of the astrocyte is dependent on its positioning around the synapse, as well as on the level of expression of its high-affinity glutamate transporters, GLT1 and GLAST. Using Western blot analysis and serial section electron microscopy, we studied how a change in sensory activity affected these parameters in the adult cortex. Using mice, we found that 24 h of whisker stimulation elicited a 2-fold increase in the expression of GLT1 and GLAST in the corresponding cortical column of the barrel cortex. This returns to basal levels 4 d after the stimulation was stopped, whereas the expression of the neuronal glutamate transporter EAAC1 remained unaltered throughout. Ultrastructural analysis from the same region showed that sensory stimulation also causes a significant increase in the astrocytic envelopment of excitatory synapses on dendritic spines. We conclude that a period of modified neuronal activity and synaptic release of glutamate leads to an increased astrocytic coverage of the bouton–spine interface and an increase in glutamate transporter expression in astrocytic processes. PMID:17048987

Multiple receptors mobilize calcium through a pertussis toxin (PT) sensitive GTP-binding protein in human neutrophils (PMN's)

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

Lad, P.M.; Olson, C.V.; Grewal, I.S.

1986-03-05

Treatment of PMN's with PT causes an abolition of chemotaxis, enzyme release, superoxide generation and aggregation caused by f-met-leu-phe (FMLP),C5a and platelet activating factor (PAF). Lectin (Con-A) induced capping and receptor induced shape change are abolished, but phagocytosis is unaltered. In whole cells, calcium mobilization induced by FMLP, PAF and Con-A inhibited by PT although the FMLP-mediated effect is more susceptible to PT's effects. Treatment of PMN's with phorbol 12-myristate 13 acetate (PMA) causes an abolition of calcium mobilization by all agents in a range which also inhibits cap formation. Investigation of calcium uptake reveals PT sensitive and insensitive components.more » Reciprocal interactions between Ns and Ni proteins are also observed since pretreatment with FMLP and PAF causes a stimulation of Ns-mediated cyclic AMP enhancement while pretreatment with Ns linked receptors (PGE/sub 1/ and beta receptor agonists) inhibits calcium mobilization. Comparative peptide mapping studies indicate substantial similarity between Ni proteins in PMN's, platelets and human erythrocytes. The authors results suggest that the Ni linked calcium mobilization sensitive to PMA is important to the regulation of the human neutrophil.« less

Alkaloids in plants and root cultures of Atropa belladonna overexpressing putrescine N-methyltransferase.

PubMed

Rothe, Grit; Hachiya, Akira; Yamada, Yasuyuki; Hashimoto, Takashi; Dräger, Birgit

2003-09-01

Putrescine N-methyltransferase (PMT) is the first alkaloid-specific enzyme for nicotine and tropane alkaloid formation. The pmt gene from Nicotiana tabacum was fused to the CaMV 35S promoter and integrated into the Atropa belladonna genome. Transgenic plants and derived root cultures were analysed for gene expression and for levels of alkaloids and their precursors. Scopolamine, hyoscyamine, tropine, pseudotropine, tropinone, and calystegines were found unaltered or somewhat decreased in pmt-overexpressing lines compared to controls. When root cultures were treated with 5% sucrose, calystegine levels were elevated in control roots, but were not affected in pmt-overexpressing roots. 1 microM auxin reduced calystegine levels in control roots, while in pmt-overexpressing roots all alkaloids remained unaltered. Expression level of pmt alone is apparently not limiting for tropane alkaloid formation in A. belladonna.

Mice Lacking the SLAM Family Member CD84 Display Unaltered Platelet Function in Hemostasis and Thrombosis

PubMed Central

Hofmann, Sebastian; Braun, Attila; Pozgaj, Rastislav; Morowski, Martina; Vögtle, Timo; Nieswandt, Bernhard

2014-01-01

Background Platelets are anuclear cell fragments derived from bone marrow megakaryocytes that safeguard vascular integrity by forming thrombi at sites of vascular injury. Although the early events of thrombus formation—platelet adhesion and aggregation—have been intensively studied, less is known about the mechanisms and receptors that stabilize platelet-platelet interactions once a thrombus has formed. One receptor that has been implicated in this process is the signaling lymphocyte activation molecule (SLAM) family member CD84, which can undergo homophilic interactions and becomes phosphorylated upon platelet aggregation. Objective The role of CD84 in platelet physiology and thrombus formation was investigated in CD84-deficient mice. Methods and Results We generated CD84-deficient mice and analyzed their platelets in vitro and in vivo. Cd84−/− platelets exhibited normal activation and aggregation responses to classical platelet agonists. Furthermore, CD84 deficiency did not affect integrin-mediated clot retraction and spreading of activated platelets on fibrinogen. Notably, also the formation of stable three-dimensional thrombi on collagen-coated surfaces under flow ex vivo was unaltered in the blood of Cd84−/− mice. In vivo, Cd84−/− mice exhibited unaltered hemostatic function and arterial thrombus formation. Conclusion These results show that CD84 is dispensable for thrombus formation and stabilization, indicating that its deficiency may be functionally compensated by other receptors or that it may be important for platelet functions different from platelet-platelet interactions. PMID:25551754

Thermal alterations of organic matter in coal wastes from Upper Silesia, Poland

NASA Astrophysics Data System (ADS)

Misz-Kennan, Magdalena

2010-01-01

Self-heating and self-combustion are currently taking place in some coal waste dumps in the Upper Silesian Coal Basin, Poland, e.g. the dumps at Rymer Cones, Starzykowiec, and the Marcel Coal Mine, all in the Rybnik area. These dumps are of similar age and self-heating and combustion have been occurring in all three for many years. The tools of organic petrography (maceral composition, rank, etc.), gas chromatography-mass spectrometry, and proximate and ultimate analysis are used to investigate the wastes. Organic matter occurs in quantities up to 85 vol.%, typically a few to several vol.%, in the wastes. All three maceral groups (vitrinite, liptinite, and inertinite) are present as unaltered and variously-altered constituents associated with newly-formed petrographic components (bitumen expulsions, pyrolytic carbon). The predominant maceral group is vitrinite with alterations reflected in the presence of irregular cracks, oxidation rims and, rarely, devolatilisation pores. In altered wastes, paler grey-vitrinite and/or coke dominates. The lack of plasticity, the presence of paler-coloured particles, isotropic massive coke, dispersed coked organic matter, and expulsions of bitumens all indicate that heating was slow and extended over a long time. Macerals belonging to other groups are present in unaltered form or with colours paler than the colours of the parent macerals. Based on the relative contents of organic compounds, the most important groups of these identified in the wastes are n-alkanes, acyclic isoprenoids, hopanes, polycyclic aromatic hydrocarbons (PAHs) and their derivatives, phenol and its derivatives. These compounds occur in all wastes except those most highly altered where they were probably destroyed by high temperatures. These compounds were generated mainly from liptinite-group macerals. Driven by evaporation and leaching, they migrated within and out of the dump. Their presence in some wastes in which microscopically visible organic matter is lacking suggests that they originated elsewhere and subsequently migrated through the dump piles. During their migration, the compounds fractionated, were adsorbed on minerals and/or interacted. The absence of alkenes, and of other unsaturated organic compounds, may reflect primary diagenetic processes that occurred in coals and coal shales during burial and/or organic matter type. Their absence may also be a consequence of heating that lasted many years, hydropyrolysis, and/or the participation of minerals in the reactions occurring within the dumps. The wastes contain compounds typical of organic matter of unaltered kerogen III type and the products of pyrolytic processes, and mixtures of both. In some wastes, organic compounds are completely absent having been destroyed by severe heating. The distributions of n-alkanes in many samples are typical of pyrolysates. In some wastes, narrow n-alkane distributions reflect their generation over small temperature ranges. In others, wider distributions point to greater temperature ranges. Other wastes contain n-alkane distributions typical of unaltered coal and high pristane content or mixtures of pyrolysates and unaltered waste material. The wastes also contain significant amounts of final αβ hopanes. Polycyclic aromatic hydrocarbons are represented only by two- to five-ring compounds as is typical of the thermal alteration of hard coal. Correlations between the degree of organic matter alteration and the relative contents of individual PAHs and hopanes and geochemical indicators of thermal alteration are generally poor. The properties of the organic matter (its composition and rank), temperature fluctuations within the dumps, migration of organic compounds and mineral involvement are probably responsible for this. The processes taking place in coal waste dumps undergoing self-heating and self-combustion are complicated; they are very difficult to estimate and define. The methods of organic petrology and geochemistry give complementary data allowing the processes to be described. However, each of the dumps investigated represents a separate challenge to be surmounted in any regional attempt to delineate the regional environmental impact of these waste dumps.

On the primordial condensation and accretion environment and the remanent magnetization of meteorites

NASA Technical Reports Server (NTRS)

Brecher, A.

1973-01-01

In the context of various models for the early evolution of a solar nebula, the possible roles assigned to ambient magnetic fields and the paleointensities required to establish the stable natural remanent magnetization observed in meteorites, are discussed. It is suggested that the record of paleofields present during condensation, growth, and accumulation of grains is likely to have been preserved as chemical or thermochemical remanence in unaltered meteoritic material. Fine particle theories appear adequate for treating meteoritic remanence, if models based on corresponding types of permanent magnet materials, e.g., powder ferrites for chondrites and diffusion hardened alloys for iron meteorites, are adopted.

5. Photograph of a photograph in possession of Rock Island ...

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

5. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. WEST ELEVATION IN UNALTERED CONDITION. ORIGINALLY PUBLISHED 1898. - Rock Island Arsenal, Building No. 280, Sylvan Drive, Rock Island, Rock Island County, IL

Assessment of the risk of solar ultraviolet radiation to amphibians. I. Dose-dependent induction of hindlimb malformations in the northern leopard frog (Rana pipiens).

PubMed

Ankley, Gerald T; Diamond, Stephen A; Tietge, Joseph E; Holcombe, Gary W; Jensen, Kathleen M; Defoe, David L; Peterson, Ryan

2002-07-01

A number of environmental stressors have been hypothesized as responsible for recent increases in limb malformations in several species of North American amphibians. The purpose of this study was to generate dose-response data suitable for assessing the potential role of solar ultraviolet (UV) radiation in causing limb malformations in a species in which this phenomenon seemingly is particularly prevalent, the northern leopard frog (Rana pipiens). Frogs were exposed from early embryonic stages through complete metamorphosis to varying natural sunlight regimes, including unaltered (100%) sunlight, sunlight subjected to neutral density filtration to achieve relative intensities of 85%, 75%, 65%, 50%, and 25% of unaltered sunlight, and sunlight filtered with glass or acrylamide to attenuate, respectively, the UVB (290-320 nm) and UVB plus UVA (290-380 nm) portions of the spectrum. The experiments were conducted in a controlled setting, with continual monitoring of UVB, UVA, and visible light to support a robust exposure assessment. Full sunlight caused approximately 50% mortality of the frogs during early larval development; no significant treatment-related mortality occurred under any of the other exposure regimes, including 100% sunlight with glass or acrylamide filtration. There was a dose-dependent (p < 0.0001) induction of hindlimb malformations in the frogs, with the percentage of affected animals ranging from about 97% under unaltered sunlight to 0% in the 25% neutral density treatment. Malformations were comprised mostly of missing or truncated digits, and generally were bilateral as well as symmetrical. Filtration of sunlight with either glass or acrylamide both significantly reduced the incidence of malformed limbs. The estimated sunlight dose resulting in a 50% limb malformation rate (ED50) was 63.5%. The limb ED50 values based on measured sunlight intensities corresponded to average daily doses of 4.5 and 100 Wh x m(-2) for UVB and UVA, respectively. Exposure to sunlight also resulted in increased eye malformations in R. pipiens, however, the dose-response relationship for this endpoint was not monotonic. The results of this study, in conjunction with measured or predicted exposure data from natural settings, provide a basis for quantitative prediction of the risk of solar UV radiation to amphibians.

Attenuated Ca(2+) release in a mouse model of limb girdle muscular dystrophy 2A.

PubMed

DiFranco, Marino; Kramerova, Irina; Vergara, Julio L; Spencer, Melissa Jan

2016-01-01

Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 knockout (C3KO) mice) leads to reduced ryanodine receptor (RyR1) expression and abnormal Ca2+/calmodulin-dependent protein kinase II (Ca-CaMKII)-mediated signaling. We previously reported that Ca(2+) release measured by fura2-FF imaging in response to single action potential stimulation was reduced in old C3KO mice; however, the use of field stimulation prevented investigation of the mechanisms underlying this impairment. Furthermore, our prior studies were conducted on older animals, whose muscles showed advanced muscular dystrophy, which prevented us from establishing whether impaired Ca(2+) handling is an early feature of disease. In the current study, we sought to overcome these matters by studying single fibers isolated from young wild-type (WT) and C3KO mice using a low affinity calcium dye and high intracellular ethylene glycol-bis(2-aminoethylether)-n,n,n',n'-tetraacetic acid (EGTA) to measure Ca(2+) fluxes. Muscles were subjected to both current and voltage clamp conditions. Standard and confocal fluorescence microscopy was used to study Ca(2+) release in single fibers enzymatically isolated from hind limb muscles of wild-type and C3KO mice. Two microelectrode amplifier and experiments were performed under current or voltage clamp conditions. Calcium concentration changes were detected with an impermeant low affinity dye in the presence of high EGTA intracellular concentrations, and fluxes were calculated with a single compartment model. Standard Western blotting analysis was used to measure the concentration of RyR1 and the α subunit of the dihydropyridine (αDHPR) receptors. Data are presented as mean ± SEM and compared with the Student's test with significance set at p < 0.05. We found that the peak value of Ca(2+) fluxes elicited by single action potentials was significantly reduced by 15-20 % in C3KO fibers, but the kinetics was unaltered. Ca(2+) release elicited by tetanic stimulation was also impaired in C3KO fibers. Confocal studies confirmed that Ca(2+) release was similarly reduced in all triads of C3KO mice. Voltage clamp experiments revealed a normal voltage dependence of Ca(2+) release in C3KO mice but reduced peak Ca(2+) fluxes as with action potential stimulation. These findings concur with biochemical observations of reduced RyR1 and αDHPR levels in C3KO muscles and reduced mechanical output. Confocal studies revealed a similar decrease in Ca(2+) release at all triads consistent with a homogenous reduction of functional voltage activated Ca(2+) release sites. Overall, these results suggest that decreased Ca(2+) release is an early defect in calpainopathy and may contribute to the observed reduction of CaMKII activation in C3KO mice.

Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet.

PubMed

Flachs, P; Mohamed-Ali, V; Horakova, O; Rossmeisl, M; Hosseinzadeh-Attar, M J; Hensler, M; Ruzickova, J; Kopecky, J

2006-02-01

Diets rich in n-3 polyunsaturated fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against insulin resistance and obesity in rodents and increase insulin sensitivity in healthy humans. We tested whether the anti-diabetic effects of EPA and DHA involve enhanced production of the endogenous insulin sensitiser, adiponectin. We studied the effects, in an obesity-promoting high-fat diet, of partial replacement of vegetable oils by EPA/DHA concentrate (6% EPA, 51% DHA) over a 5-week period in adult male C57BL/6J mice that either had free access to food or had their food intake restricted by 30%. At the end of the treatment, systemic markers of lipid and glucose metabolism and full-length adiponectin and leptin were measured. Adiponectin (Adipoq) and leptin (Lep) gene expression in dorsolumbar and epididymal white adipose tissue (WAT) and isolated adipocytes was quantified and adipokine production from WAT explants evaluated. In mice with free access to food, plasma triacylglycerols, NEFA, and insulin levels were lower in the presence of EPA/DHA, while glucose and leptin levels were not significantly altered. Food restriction decreased plasma triacylglycerols, glucose, insulin and leptin, but not adiponectin. EPA/DHA increased plasma adiponectin levels, independent of food intake, reflecting the stimulation of Adipoq expression in adipocytes and the release of adiponectin from WAT, particularly from epididymal fat. Expression of Lep and the release of leptin from WAT, while being extremely sensitive to caloric restriction, was unaltered by EPA/DHA. Intake of diets rich in EPA and DHA leads to elevated systemic concentrations of adiponectin, largely independent of food intake or adiposity and explain, to some extent, their anti-diabetic effects.

Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH.

PubMed

Acampora, D; Mazan, S; Tuorto, F; Avantaggiato, V; Tremblay, J J; Lazzaro, D; di Carlo, A; Mariano, A; Macchia, P E; Corte, G; Macchia, V; Drouin, J; Brûlet, P; Simeone, A

1998-04-01

Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1-/- mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1-/- mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.

Do Mitochondria Limit Hot Fish Hearts? Understanding the Role of Mitochondrial Function with Heat Stress in Notolabrus celidotus

PubMed Central

Iftikar, Fathima I.; Hickey, Anthony J. R.

2013-01-01

Hearts are the first organs to fail in animals exposed to heat stress. Predictions of climate change mediated increases in ocean temperatures suggest that the ectothermic heart may place tight constraints on the diversity and distribution of marine species with cardiovascular systems. For many such species, their upper temperature limits (Tmax) and respective heart failure (HF) temperature (THF) are only a few degrees from current environmental temperatures. While the ectothermic cardiovascular system acts as an “ecological thermometer,” the exact mechanism that mediates HF remains unresolved. We propose that heat-stressed cardiac mitochondria drive HF. Using a common New Zealand fish, Notolabrus celidotus, we determined the THF (27.5°C). Haemoglobin oxygen saturation appeared to be unaltered in the blood surrounding and within heat stressed hearts. Using high resolution respirometry coupled to fluorimeters, we explored temperature-mediated changes in respiration, ROS and ATP production, and overlaid these changes with THF. Even at saturating oxygen levels several mitochondrial components were compromised before THF. Importantly, the capacity to efficiently produce ATP in the heart is limited at 25°C, and this is prior to the acute THF for N. celidotus. Membrane leakiness increased significantly at 25°C, as did cytochrome c release and permeability to NADH. Maximal flux rates and the capacity for the electron transport system to uncouple were also altered at 25°C. These data indicate that mitochondrial membrane integrity is lost, depressing ATP synthesis capacity and promoting cytochrome c release, prior to THF. Mitochondria can mediate HF in heat stressed hearts in fish and play a significant role in thermal stress tolerance, and perhaps limit species distributions by contributing to HF. PMID:23724026

Do mitochondria limit hot fish hearts? Understanding the role of mitochondrial function with heat stress in Notolabrus celidotus.

PubMed

Iftikar, Fathima I; Hickey, Anthony J R

2013-01-01

Hearts are the first organs to fail in animals exposed to heat stress. Predictions of climate change mediated increases in ocean temperatures suggest that the ectothermic heart may place tight constraints on the diversity and distribution of marine species with cardiovascular systems. For many such species, their upper temperature limits (Tmax) and respective heart failure (HF) temperature (T(HF)) are only a few degrees from current environmental temperatures. While the ectothermic cardiovascular system acts as an "ecological thermometer," the exact mechanism that mediates HF remains unresolved. We propose that heat-stressed cardiac mitochondria drive HF. Using a common New Zealand fish, Notolabrus celidotus, we determined the THF (27.5°C). Haemoglobin oxygen saturation appeared to be unaltered in the blood surrounding and within heat stressed hearts. Using high resolution respirometry coupled to fluorimeters, we explored temperature-mediated changes in respiration, ROS and ATP production, and overlaid these changes with T(HF). Even at saturating oxygen levels several mitochondrial components were compromised before T(HF). Importantly, the capacity to efficiently produce ATP in the heart is limited at 25°C, and this is prior to the acute T(HF) for N. celidotus. Membrane leakiness increased significantly at 25°C, as did cytochrome c release and permeability to NADH. Maximal flux rates and the capacity for the electron transport system to uncouple were also altered at 25°C. These data indicate that mitochondrial membrane integrity is lost, depressing ATP synthesis capacity and promoting cytochrome c release, prior to T(HF). Mitochondria can mediate HF in heat stressed hearts in fish and play a significant role in thermal stress tolerance, and perhaps limit species distributions by contributing to HF.

Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S.

PubMed

Li, Xianting; Patel, Jyoti C; Wang, Jing; Avshalumov, Marat V; Nicholson, Charles; Buxbaum, Joseph D; Elder, Gregory A; Rice, Margaret E; Yue, Zhenyu

2010-02-03

PARK8/LRRK2 (leucine-rich repeat kinase 2) was recently identified as a causative gene for autosomal dominant Parkinson's disease (PD), with LRRK2 mutation G2019S linked to the most frequent familial form of PD. Emerging in vitro evidence indicates that aberrant enzymatic activity of LRRK2 protein carrying this mutation can cause neurotoxicity. However, the physiological and pathophysiological functions of LRRK2 in vivo remain elusive. Here we characterize two bacterial artificial chromosome (BAC) transgenic mouse strains overexpressing LRRK2 wild-type (Wt) or mutant G2019S. Transgenic LRRK2-Wt mice had elevated striatal dopamine (DA) release with unaltered DA uptake or tissue content. Consistent with this result, LRRK2-Wt mice were hyperactive and showed enhanced performance in motor function tests. These results suggest a role for LRRK2 in striatal DA transmission and the consequent motor function. In contrast, LRRK2-G2019S mice showed an age-dependent decrease in striatal DA content, as well as decreased striatal DA release and uptake. Despite increased brain kinase activity, LRRK2-G2019S overexpression was not associated with loss of DAergic neurons in substantia nigra or degeneration of nigrostriatal terminals at 12 months. Our results thus reveal a pivotal role for LRRK2 in regulating striatal DA transmission and consequent control of motor function. The PD-associated mutation G2019S may exert pathogenic effects by impairing these functions of LRRK2. Our LRRK2 BAC transgenic mice, therefore, could provide a useful model for understanding early PD pathological events.

Effect of resveratrol and orchidectomy on the vasorelaxing influence of perivascular adipose tissue.

PubMed

Boydens, Charlotte; Pauwels, Bart; Van de Voorde, Johan

2016-04-01

Perivascular adipose tissue (PVAT) releases several adipo(cyto)kines. Some are vasoactive substances that elicit a net beneficial anticontractile effect. Resveratrol and testosterone are known to modulate adipo(cyto)kine release from adipose tissue and could therefore influence the anticontractile effect of PVAT. In vitro tension measurements were performed using thoracic aorta segments with and without adipose tissue from sham-operated or orchidectomized male Swiss mice. Concentration-response curves to norepinephrine (NOR) were constructed in the presence and absence of resveratrol (10 μM, 15 min) or the relaxant effect of resveratrol (10-100 μM) was investigated after inducing tone with NOR (5 μM). Aortas with PVAT displayed significantly attenuated contractions to NOR compared with aortas without PVAT. In aortas without PVAT, resveratrol (10 μM) significantly decreased NOR responses and elicited concentration-dependent (10-100 µM) relaxations. However, in aortas with adherent PVAT, resveratrol (10 μM) neither decreased NOR responses, nor did resveratrol (10-100 µM) induce arterial relaxations. The anticontractile effect of PVAT was less pronounced in the presence of resveratrol and unaltered by orchidectomy. Orchidectomy did not influence contractions induced by NOR. Orchidectomy does not modulate the anticontractile capacity of PVAT, while resveratrol decreases the vasorelaxing influence of PVAT. The positive effects associated with resveratrol addition are neutralized by the presence of PVAT. This is thought to result from a dual effect of resveratrol: (1) inhibition of the influence of vasodilatory adipo(cyto)kines and (2) a direct relaxant effect on the vascular smooth muscle. Overall, the beneficial relaxing effect of resveratrol is lost in mice thoracic aorta surrounded by PVAT.

Increased radial glia quiescence, decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon.

PubMed

Edelmann, Kathrin; Glashauser, Lena; Sprungala, Susanne; Hesl, Birgit; Fritschle, Maike; Ninkovic, Jovica; Godinho, Leanne; Chapouton, Prisca

2013-09-01

The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia. Copyright © 2013 Wiley Periodicals, Inc.

Astrocyte Sodium Signalling and Panglial Spread of Sodium Signals in Brain White Matter.

PubMed

Moshrefi-Ravasdjani, Behrouz; Hammel, Evelyn L; Kafitz, Karl W; Rose, Christine R

2017-09-01

In brain grey matter, excitatory synaptic transmission activates glutamate uptake into astrocytes, inducing sodium signals which propagate into neighboring astrocytes through gap junctions. These sodium signals have been suggested to serve an important role in neuro-metabolic coupling. So far, it is unknown if astrocytes in white matter-that is in brain regions devoid of synapses-are also able to undergo such intra- and intercellular sodium signalling. In the present study, we have addressed this question by performing quantitative sodium imaging in acute tissue slices of mouse corpus callosum. Focal application of glutamate induced sodium transients in SR101-positive astrocytes. These were largely unaltered in the presence of ionotropic glutamate receptors blockers, but strongly dampened upon pharmacological inhibition of glutamate uptake. Sodium signals induced in individual astrocytes readily spread into neighboring SR101-positive cells with peak amplitudes decaying monoexponentially with distance from the stimulated cell. In addition, spread of sodium was largely unaltered during pharmacological inhibition of purinergic and glutamate receptors, indicating gap junction-mediated, passive diffusion of sodium between astrocytes. Using cell-type-specific, transgenic reporter mice, we found that sodium signals also propagated, albeit less effectively, from astrocytes to neighboring oligodendrocytes and NG2 cells. Again, panglial spread was unaltered with purinergic and glutamate receptors blocked. Taken together, our results demonstrate that activation of sodium-dependent glutamate transporters induces sodium signals in white matter astrocytes, which spread within the astrocyte syncytium. In addition, we found a panglial passage of sodium signals from astrocytes to NG2 cells and oligodendrocytes, indicating functional coupling between these macroglial cells in white matter.

Fate of Carbohydrates and Lignin during Composting and Mycelium Growth of Agaricus bisporus on Wheat Straw Based Compost

PubMed Central

Jurak, Edita; Punt, Arjen M.; Arts, Wim; Kabel, Mirjam A.; Gruppen, Harry

2015-01-01

In wheat straw based composting, enabling growth of Agaricus bisporus mushrooms, it is unknown to which extent the carbohydrate-lignin matrix changes and how much is metabolized. In this paper we report yields and remaining structures of the major components. During the Phase II of composting 50% of both xylan and cellulose were metabolized by microbial activity, while lignin structures were unaltered. During A. bisporus’ mycelium growth (Phase III) carbohydrates were only slightly consumed and xylan was found to be partially degraded. At the same time, lignin was metabolized for 45% based on pyrolysis GC/MS. Remaining lignin was found to be modified by an increase in the ratio of syringyl (S) to guaiacyl (G) units from 0.5 to 0.7 during mycelium growth, while fewer decorations on the phenolic skeleton of both S and G units remained. PMID:26436656

3. Photograph of a photograph in possession of Rock Island ...

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

3. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. NORTH ELEVATION IN UNALTERED CONDITION. DATED NOVEMBER 21, 1944. - Rock Island Arsenal, Building No. 103, Rodman Avenue & First Street, Rock Island, Rock Island County, IL

3. Photograph of a photograph in possession of Rock Island ...

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

3. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH ELEVATION IN UNALTERED CONDITION. DATED MARCH 19, 1945. - Rock Island Arsenal, Building No. 61, Rodman Avenue & First Street, Rock Island, Rock Island County, IL

4. Photograph of a photograph in possession of Rock Island ...

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

4. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. NORTH ELEVATION IN UNALTERED CONDITION. DATED NOVEMBER 21, 1944. - Rock Island Arsenal, Building No. 109, Rodman Avenue & Fourth Street, Rock Island, Rock Island County, IL

40 CFR 300.400 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... unaltered form, or altered solely through naturally occurring processes or phenomena, from a location where... federal agency, and a state or political subdivision operating pursuant to a contract or cooperative... or political subdivision operating pursuant to a contract or cooperative agreement under CERCLA...

8. Photograph of a photograph in possession of Rock Island ...

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

8. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH ELEVATON IN UNALTERED CONDITION. ORIGINALLY PUBLISHED 1898. - Rock Island Arsenal, Building No. 68, Rodman Avenue between Fourth Street & East Avenue, Rock Island, Rock Island County, IL

10. Photograph of a photograph in possession of Rock Island ...

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

10. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH AND WEST ELEVATIONS IN UNALTERED CONDITION. DATED APRIL 18, 1941. - Rock Island Arsenal, Building No. 56, North Avenue & East Avenue, Rock Island, Rock Island County, IL

SPAWNING SUCCESS OF FATHEAD MINNOWS ON SELECTED ARTIFICIAL SUBSTRATES

EPA Science Inventory

Spawning success of fathead minnows (Pimephales promelas) on six different substrates was tested and evaluated. Egg adhesiveness was equally good on cement-asbestos tile and sand-coated stainless steel substrates, but was poor on unaltered stainless steel, shot-peened stainless s...

A New Modal Analysis Method to put Constraints on the Aqueous Alteration of CR Chondrites and Estimate the Unaltered CR Composition

NASA Technical Reports Server (NTRS)

Perronnet, M.; Zolensky, M. E.; Gounelle, M.; Schwandt, C. S.

2007-01-01

CR carbonaceous chondrites are of the major interest since they contain one of the most primitive organic matters. However, aqueous alteration has more or less overprinted their original features in a way that needed to be assessed. That was done in the present study by comparing the mineralogy of the most altered CR1 chondrite, GRO 95577, to a less altered CR2, Renazzo. Their modal analyses were achieved thanks to a new method, based on X-ray elemental maps acquired on electron microprobe, and on IDL image treatment. It allowed the collection of new data on the composition of Renazzo and confirmed the classification of GRO 95577 as a CR1. New alteration products for CRs, vermiculite and clinochlore, were observed. The homogeneity of the Fe-poor clays in the CR1 and the distinctive matrix composition in the two chondrites suggest a wide-range of aqueous alteration on CRs. The preservation of the outlines of the chondrules in GRO 95577 and the elemental transfers of Al, Fe and Ca throughout the chondrule and of Fe and S from the matrix to the chondrule favor the idea of an asteroidal location of the aqueous alteration. From their mineralogical descriptions and modal abundances, the element repartitions in Renazzo and GRO 95577 were computed. It indicates a possible relationship between these two chondrites via an isochemical alteration process. Knowing the chemical reactions that occurred during the alteration, it was thus possible to decipher the mineralogical modal abundances in the unaltered CR body.

A New Modal Analysis Method to put Constraints on the Aqueous Alteration of CR Chondrites and Estimate the Unaltered CR Composition

NASA Technical Reports Server (NTRS)

Perronnet, M.; Zolensky, M. E.; Gounelle, M.; Schwandt, C. S.

2007-01-01

carbonaceous chondrites are of the major interest since they contain one of the most primitive organic matters. However, aqueous alteration has more or less overprinted their original features in a way that needed to be assessed. That was done in the present study by comparing the mineralogy of the most altered CR1 chondrite, GRO 95577, to a less altered CR2, Renazzo. Their modal analyses were achieved thanks to a new method, based on X-ray elemental maps acquired on electron microprobe, and on IDL image treatment. It allowed the collection of new data on the composition of Renazzo and confirmed the classification of GRO 95577 as a CR1. New alteration products for CRs, vermiculite and clinochlore, were observed. The homogeneity of the Fe-poor clays in the CR1 and the distinctive matrix composition in the two chondrites suggest a wide-range of aqueous alteration on CRs. The preservation of the outlines of the chondrules in GRO 95577 and the elemental transfers of Al, Fe and Ca throughout the chondrule and of Fe and S from the matrix to the chondrule favor the idea of an asteroidal location of the aqueous alteration. From their mineralogical descriptions and modal abundances, the element repartitions in Renazzo and GRO 95577 were computed. It indicates a possible relationship between these two chondrites via an isochemical alteration process. Knowing the chemical reactions that occurred during the alteration, it was thus possible to decipher the mineralogical modal abundances in the unaltered CR body.

Auto-inhibition and phosphorylation-induced activation of PLC-γ isozymes

PubMed Central

Hajicek, Nicole; Charpentier, Thomas H.; Rush, Jeremy R.; Harden, T. Kendall; Sondek, John

2013-01-01

Multiple extracellular stimuli, such as growth factors and antigens, initiate signaling cascades through tyrosine phosphorylation and activation of phospholipase C (PLC)-γ isozymes. Like most other PLCs, PLC-γ1 is basally auto-inhibited by its X-Y linker, which separates the X-and Y-boxes of the catalytic core. The C-terminal SH2 (cSH2) domain within the X-Y linker is the critical determinant for auto-inhibition of phospholipase activity. Release of auto-inhibition requires an intramolecular interaction between the cSH2 domain and a phosphorylated tyrosine, Tyr783, also located within the X-Y linker. The molecular mechanisms that mediate auto-inhibition and phosphorylation-induced activation have not been defined. Here, we describe structures of the cSH2 domain both alone and bound to a PLC-γ1 peptide encompassing phosphorylated Tyr783. The cSH2 domain remains largely unaltered by peptide engagement. Point mutations in the cSH2 domain located at the interface with the peptide were sufficient to constitutively activate PLC-γ1 suggesting that peptide engagement directly interferes with the capacity of the cSH2 domain to block the lipase active site. This idea is supported by mutations in a complimentary surface of the catalytic core that also enhanced phospholipase activity. PMID:23777354

Circulating Irisin Levels Are Not Regulated by Nutritional Status, Obesity, or Leptin Levels in Rodents.

PubMed

Quiñones, Mar; Folgueira, Cintia; Sánchez-Rebordelo, Estrella; Al-Massadi, Omar

2015-01-01

Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5) that is mainly released by skeletal muscle and was proposed to mediate the beneficial effects of exercise on metabolism. In the present study we aim to investigate the regulation of the circulating levels of irisin in obese animal models (diet-induced obese (DIO) rats and leptin-deficient (ob/ob) mice), as well as the influence of nutritional status and leptin. Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and Radioimmunoassay (RIA). Serum irisin levels remained unaltered in DIO rats and ob/ob mice. Moreover, its circulating levels were also unaffected by fasting, leptin deficiency, and exogenous leptin administration in rodents. In spite of these negative results we find a negative correlation between irisin and insulin in DIO animals and a positive correlation between irisin and glucose under short-term changes in nutritional status. Our findings indicate that serum irisin levels are not modulated by different physiological settings associated to alterations in energy homeostasis. These results suggest that in rodents circulating levels of irisin are not involved in the pathophysiology of obesity and could be unrelated to metabolic status; however, further studies should clarify its precise role in states of glucose homeostasis imbalance.

Food deprivation modulates gamma-aminobutyric acid receptors and peripheral benzodiazepine binding sites in rats.

PubMed

Weizman, A; Bidder, M; Fares, F; Gavish, M

1990-12-03

The effect of 5 days of food deprivation followed by 5 days of refeeding on gamma-aminobutyric acid (GABA) receptors, central benzodiazepine receptors (CBR), and peripheral benzodiazepine binding sites (PBzS) was studied in female Sprague-Dawley rats. Starvation induced a decrease in the density of PBzS in peripheral organs: adrenal (35%; P less than 0.001), kidney (33%; P less than 0.01), and heart (34%; P less than 0.001). Restoration of [3H]PK 11195 binding to normal values was observed in all three organs after 5 days of refeeding. The density of PBzS in the ovary, pituitary, and hypothalamus was not affected by starvation. Food deprivation resulted in a 35% decrease in cerebellar GABA receptors (P less than 0.01), while CBR in the hypothalamus and cerebral cortex remained unaltered. The changes in PBzS observed in the heart and kidney may be related to the long-term metabolic stress associated with starvation and to the functional changes occurring in these organs. The down-regulation of the adrenal PBzS is attributable to the suppressive effect of hypercortisolemia on pituitary ACTH release. The reduction in cerebellar GABA receptors may be an adaptive response to food deprivation stress and may be relevant to the proaggressive effect of hunger.

Differential expression of ryanodine receptor isoforms after spinal cord injury.

PubMed

Pelisch, Nicolas; Gomes, Cynthia; Nally, Jacqueline M; Petruska, Jeffrey C; Stirling, David P

2017-11-01

Ryanodine receptors (RyRs) are highly conductive intracellular Ca 2+ release channels and are widely expressed in many tissues, including the central nervous system. RyRs have been implicated in intracellular Ca 2+ overload which can drive secondary damage following traumatic injury to the spinal cord (SCI), but the spatiotemporal expression of the three isoforms of RyRs (RyR1-3) after SCI remains unknown. Here, we analyzed the gene and protein expression of RyR isoforms in the murine lumbar dorsal root ganglion (DRG) and the spinal cord lesion site at 1, 2 and 7 d after a mild contusion SCI. Quantitative RT PCR analysis revealed that RyR3 was significantly increased in lumbar DRGs and at the lesion site at 1 and 2 d post contusion compared to sham (laminectomy only) controls. Additionally, RyR2 expression was increased at 1 d post injury within the lesion site. RyR2 and -3 protein expression was localized to lumbar DRG neurons and their spinal projections within the lesion site acutely after SCI. In contrast, RyR1 expression within the DRG and lesion site remained unaltered following trauma. Our study shows that SCI initiates acute differential expression of RyR isoforms in DRG and spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

Human immunodeficiency virus infection of helper T cell clones. Early proliferative defects despite intact antigen-specific recognition and interleukin 4 secretion.

PubMed Central

Laurence, J; Friedman, S M; Chartash, E K; Crow, M K; Posnett, D N

1989-01-01

HIV selectively inhibited the proliferative response of clonal CD4+ T lymphocytes to alloantigen while other alloantigen-dependent responses were unperturbed. Specifically, impaired blastogenesis could be dissociated from alloantigen-specific induction of the B cell activation molecule CD23, IL-4 release, and inositol lipid hydrolysis. In addition, membrane expression of pertinent T cell receptor molecules, including CD2, CD3, and T cell antigen receptor (Ti), remained intact. Using two MHC class II-specific human CD4+ helper T cell clones, the proliferative defect was shown to be an early consequence of HIV infection, occurring within 4 d of viral inoculation and preceding increases in mature virion production. It was generalizable to three distinct methods of T cell activation, all independent of antigen-presenting cells: anti-CD3 mediated cross-linking of the CD3/Ti complex; anti-CD2 and phorbol 12-myristic 13-acetate (PMA); and anti-CD28 plus PMA. These abnormalities were not mitigated by addition of exogenous IL-2, even though expression of the IL-2 receptor (CD25) was unaltered. These studies define a selective blockade in T cell function early after HIV exposure that could serve as a model for certain in vivo manifestations of AIDS. PMID:2470786

Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble [(3,5,5-trimethylhexanoyl)ferrocene].

PubMed

Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan; Skovgaard, Lene Theil; Moos, Torben

2007-01-01

Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month-old rats following supplementation with the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of alpha- and gamma-tocopherols and glutathione (GSH) were also higher. In contrast, the brain displayed unaltered levels of the tocopherols and GSH. Malondialdehyde (MDA) level was also higher in the cerebrospinal fluid (CSF) and the liver but not in the brain. In old rats, the absence of an increase in iron concentration in the brain was reflected by unaltered concentrations of GSH, tocopherols, and MDA as compared to that in untreated rats. In the aging liver, concentrations of GSH and MDA increased with TMHF treatment. Morphological studies revealed unaltered levels of iron, ferritin, heme oxygenase-1 (HO-1), nitrotyrosine (NT), or MDA in the brains of both young and old rats treated with TMHF. In contrast, TMHF treatment increased the level of HO-1 in Kupffer cells, NT in hepatic endothelial cells, and MDA and ferritin in hepatocytes. Although these results demonstrated an increase in the biochemical markers of oxidative stress and damage in response to increasing concentrations of iron in the liver, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.

Paclitaxel-induced painful neuropathy is associated with changes in mitochondrial bioenergetics, glycolysis, and an energy deficit in dorsal root ganglia neurons

PubMed Central

Duggett, Natalie A.; Griffiths, Lisa A.; Flatters, Sarah J.L.

2017-01-01

Abstract Painful neuropathy is the major dose-limiting side effect of paclitaxel chemotherapy. Mitochondrial dysfunction and adenosine triphosphate (ATP) deficit have previously been shown in peripheral nerves of paclitaxel-treated rats, but the effects of paclitaxel in the dorsal root ganglia (DRGs) have not been explored. The aim of this study was to determine the bioenergetic status of DRG neurons following paclitaxel exposure in vitro and in vivo. Utilising isolated DRG neurons, we measured respiratory function under basal conditions and at maximal capacity, glycolytic function, and Adenosine diphosphate (ADP)/ATP levels at 3 key behavioural timepoints; prior to pain onset (day 7), peak pain severity and pain resolution. At day 7, maximal respiration and spare reserve capacity were significantly decreased in DRG neurons from paclitaxel-treated rats. This was accompanied by decreased basal ATP levels and unaltered ADP levels. At peak pain severity, respiratory function was unaltered, yet glycolytic function was significantly increased. Reduced ATP and unaltered ADP levels were also observed at the peak pain timepoint. All these effects in DRG neurons had dissipated by the pain resolution timepoint. None of these paclitaxel-evoked changes could be replicated from in vitro paclitaxel exposure to naive DRG neurons, demonstrating the impact of in vivo exposure and the importance of in vivo models. These data demonstrate the nature of mitochondrial dysfunction evoked by in vivo paclitaxel in the DRG for the first time. Furthermore, we have identified paclitaxel-evoked changes in the bioenergetics of DRG neurons, which result in a persistent energy deficit that is causal to the development and maintenance of paclitaxel-induced pain. PMID:28541258

Biological Invasion Influences the Outcome of Plant-Soil Feedback in the Invasive Plant Species from the Brazilian Semi-arid.

PubMed

de Souza, Tancredo Augusto Feitosa; de Andrade, Leonaldo Alves; Freitas, Helena; da Silva Sandim, Aline

2017-05-30

Plant-soil feedback is recognized as the mutual interaction between plants and soil microorganisms, but its role on the biological invasion of the Brazilian tropical seasonal dry forest by invasive plants still remains unclear. Here, we analyzed and compared the arbuscular mycorrhizal fungi (AMF) communities and soil characteristics from the root zone of invasive and native plants, and tested how these AMF communities affect the development of four invasive plant species (Cryptostegia madagascariensis, Parkinsonia aculeata, Prosopis juliflora, and Sesbania virgata). Our field sampling revealed that AMF diversity and frequency of the Order Diversisporales were positively correlated with the root zone of the native plants, whereas AMF dominance and frequency of the Order Glomerales were positively correlated with the root zone of invasive plants. We grew the invasive plants in soil inoculated with AMF species from the root zone of invasive (I changed ) and native (I unaltered ) plant species. We also performed a third treatment with sterilized soil inoculum (control). We examined the effects of these three AMF inoculums on plant dry biomass, root colonization, plant phosphorous concentration, and plant responsiveness to mycorrhizas. We found that I unaltered and I changed promoted the growth of all invasive plants and led to a higher plant dry biomass, mycorrhizal colonization, and P uptake than control, but I changed showed better results on these variables than I unaltered . For plant responsiveness to mycorrhizas and fungal inoculum effect on plant P concentration, we found positive feedback between changed-AMF community (I changed ) and three of the studied invasive plants: C. madagascariensis, P. aculeata, and S. virgata.

Soil Communities Promote Temporal Stability and Species Asynchrony in Experimental Grassland Communities

PubMed Central

Pellkofer, Sarah; van der Heijden, Marcel G. A.; Schmid, Bernhard; Wagg, Cameron

2016-01-01

Background Over the past two decades many studies have demonstrated that plant species diversity promotes primary productivity and stability in grassland ecosystems. Additionally, soil community characteristics have also been shown to influence the productivity and composition of plant communities, yet little is known about whether soil communities also play a role in stabilizing the productivity of an ecosystem. Methodology/Principal Findings Here we use microcosms to assess the effects of the presence of soil communities on plant community dynamics and stability over a one-year time span. Microcosms were filled with sterilized soil and inoculated with either unaltered field soil or field soil sterilized to eliminate the naturally occurring soil biota. Eliminating the naturally occurring soil biota not only resulted in lower plant productivity, and reduced plant species diversity, and evenness, but also destabilized the net aboveground productivity of the plant communities over time, which was largely driven by changes in abundance of the dominant grass Lolium perenne. In contrast, the grass and legumes contributed more to net aboveground productivity of the plant communities in microcosms where soil biota had been inoculated. Additionally, the forbs exhibited compensatory dynamics with grasses and legumes, thus lowering temporal variation in productivity in microcosms that received the unaltered soil inocula. Overall, asynchrony among plant species was higher in microcosms where an unaltered soil community had been inoculated, which lead to higher temporal stability in community productivity. Conclusions/Significance Our results suggest that soil communities increase plant species asynchrony and stabilize plant community productivity by equalizing the performance among competing plant species through potential antagonistic and facilitative effects on individual plant species. PMID:26829481

Application of sodium carbonate prevents sulphur poisoning of catalysts in automated total mercury analysis

NASA Astrophysics Data System (ADS)

McLagan, David S.; Huang, Haiyong; Lei, Ying D.; Wania, Frank; Mitchell, Carl P. J.

2017-07-01

Analysis of high sulphur-containing samples for total mercury content using automated thermal decomposition, amalgamation, and atomic absorption spectroscopy instruments (USEPA Method 7473) leads to rapid and costly SO2 poisoning of catalysts. In an effort to overcome this issue, we tested whether the addition of powdered sodium carbonate (Na2CO3) to the catalyst and/or directly on top of sample material increases throughput of sulphur-impregnated (8-15 wt%) activated carbon samples per catalyst tube. Adding 5 g of Na2CO3 to the catalyst alone only marginally increases the functional lifetime of the catalyst (31 ± 4 g of activated carbon analyzed per catalyst tube) in relation to unaltered catalyst of the AMA254 total mercury analyzer (17 ± 4 g of activated carbon). Adding ≈ 0.2 g of Na2CO3 to samples substantially increases (81 ± 17 g of activated carbon) catalyst life over the unaltered catalyst. The greatest improvement is achieved by adding Na2CO3 to both catalyst and samples (200 ± 70 g of activated carbon), which significantly increases catalyst performance over all other treatments and enables an order of magnitude greater sample throughput than the unaltered samples and catalyst. It is likely that Na2CO3 efficiently sequesters SO2, even at high furnace temperatures to produce Na2SO4 and CO2, largely negating the poisonous impact of SO2 on the catalyst material. Increased corrosion of nickel sampling boats resulting from this methodological variation is easily resolved by substituting quartz boats. Overall, this variation enables an efficient and significantly more affordable means of employing automated atomic absorption spectrometry instruments for total mercury analysis of high-sulphur matrices.

Acute effect on ambulatory blood pressure from aerobic exercise: a randomised cross-over study among female cleaners.

PubMed

Lund Rasmussen, Charlotte; Nielsen, Line; Linander Henriksen, Marie; Søgaard, Karen; Krustrup, Peter; Holtermann, Andreas; Korshøj, Mette

2018-02-01

High occupational physical activity (OPA) is shown to increase the risk for elevated blood pressure, cardiovascular diseases and mortality. Conversely, aerobic exercise acutely lowers the blood pressure up to 25 h post exercise. However, it is unknown if this beneficial effect also apply for workers exposed to high levels of OPA. Cleaners constitute a relevant occupational group for this investigation because of a high prevalence of OPA and cardiovascular disease. Accordingly, the objective was to investigate the acute effects on ambulatory blood pressure from a single aerobic exercise session among female cleaners. Twenty-two female cleaners were randomised to a cross-over study with a reference and an aerobic exercise session. Differences in 24-h, work hours, leisure time, and sleep ambulatory blood pressure (ABP) were evaluated using repeated measure 2 × 2 mixed-models. After the aerobic exercise session, the 24-h systolic ambulatory blood pressure was significantly lowered by 2.4 mmHg (p < 0.01) compared to the reference session. The 24-h diastolic ABP was unaltered. During work hours, a lowered systolic ABP of 2.2 mmHg (p = 0.02) and a higher diastolic ABP of 1.5 mmHg (p = 0.03) were found after the aerobic exercise session. During leisure time, the systolic ABP was lowered by 1.7 mmHg (p = 0.04) and the diastolic ABP was unaltered. During sleep, the systolic and diastolic ABP was unaltered. A single aerobic exercise session lowered 24-h systolic ABP of 2.4 mmHg. Thus, an aerobic exercise session seems to be beneficial for lowering the risk of hypertension among cleaners.

7. Photograph of a photograph in possession of Rock Island ...

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

7. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. WEST AND SOUTH ELEVATIONS, IN UNALTERED CONDITION. PROBABLY TAKEN ABOUT 1910. - Rock Island Arsenal, Building No. 60, Rodman Avenue between Gillespie Avenue & First Street, Rock Island, Rock Island County, IL

Valuing ecosystem services of an impacted waterway in the Southwestern US

EPA Science Inventory

While many studies of ecosystem services focus on unaltered areas such as wilderness, management insight is also needed for those more impacted. This case study values ecosystem services of the Santa Cruz River, an effluent-dominated waterway in southern Arizona. Wastewater treat...

10 CFR 960.4-2-2 - Geochemistry.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REPOSITORY Postclosure Guidelines § 960.4-2-2 Geochemistry. (a) Qualifying condition. The present and... future, not affect or would favorably affect the ability of the geologic repository to isolate the waste... subjected to expected repository conditions, would remain unaltered or would alter to mineral assemblages...

Soil-plant-microbial relations in hydrothermally altered soils of Northern California

USDA-ARS?s Scientific Manuscript database

Soils developed on relict hydrothermally altered soils throughout the Western United States present unique opportunities to study the role of geology on above and belowground biotic activity and composition. Soil and vegetation samples were taken at three unaltered andesite and three hydrothermally ...

Moon Illusion: An Observation.

PubMed

Goldstein, G

1962-12-21

Size comparisons of the moon are made from different locations by direct viewing (as opposed to comparisons by instrumental techniques). Under the proper conditions, the illusion is seen while the moon's position remains essentially unaltered. By this means, evidence is adduced in favor of Ptolemy's apparent-distance hypothesis.

Reducing the negative effects of media exposure on body image: Testing the effectiveness of subvertising and disclaimer labels.

PubMed

Frederick, David A; Sandhu, Gaganjyot; Scott, Terri; Akbari, Yasmin

2016-06-01

Body image activists have proposed adding disclaimer labels to digitally altered media as a way to promote positive body image. Another approach advocated by activists is to alter advertisements through subvertising (adding social commentary to the image to undermine the message of the advertisement). We examined if body image could be enhanced by attaching Photoshop disclaimers or subvertising to thin-ideal media images of swimsuit models. In Study 1 (N=1268), adult women exposed to disclaimers or subvertising did not report higher body state satisfaction or lower drive for thinness than women exposed to unaltered images. In Study 2 (N=820), adult women who were exposed to disclaimers or subvertising did not report higher state body satisfaction or lower state social appearance comparisons than women exposed to unaltered images or to no images. These results raise questions about the effectiveness of disclaimers and subvertising for promoting body satisfaction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Iron oxide magnetic nanoparticles with versatile surface functions based on dopamine anchors

NASA Astrophysics Data System (ADS)

Mazur, Mykola; Barras, Alexandre; Kuncser, Victor; Galatanu, Andrei; Zaitzev, Vladimir; Turcheniuk, Kostiantyn V.; Woisel, Patrice; Lyskawa, Joel; Laure, William; Siriwardena, Aloysius; Boukherroub, Rabah; Szunerits, Sabine

2013-03-01

The synthesis of multifunctional magnetic nanoparticles (MF-MPs) is one of the most active research areas in advanced materials as their multifunctional surfaces allow conjugation of biological and chemical molecules, thus making it possible to achieve target-specific diagnostic in parallel to therapeutics. We report here a simple strategy to integrate in a one-step reaction several reactive sites onto the particles. The preparation of MF-MPs is based on their simultaneous modification with differently functionalized dopamine derivatives using simple solution chemistry. The formed MF-MPs show comparable magnetic properties to those of naked nanoparticles with almost unaltered particle size of around 25 nm. The different termini, amine, azide and maleimide functions, enable further functionalization of MF-MPs by the grafting-on approach. Michael addition, Cu(i) catalyzed « click » chemistry and amidation reactions are performed on the MF-MPs integrating subsequently 6-(ferrocenyl)-hexanethiol, horseradish peroxidase (HRP) and mannose.

Selection of a seventh spectral band for the LANDSAT-D thematic mapper

NASA Technical Reports Server (NTRS)

Holmes, Q. A. (Principal Investigator); Nuesch, D. R.

1978-01-01

The author has identified the following significant results. Each of the candidate bands were examined in terms of the feasibility of gathering high quality imagery from space while taking into account solar illumination, atmospheric attenuation, and the signal/noise ratio achievable within the TM sensor constraints. For the 2.2 micron region and the thermal IR region, inband signal values were calculated from representative spectral reflectance/emittance curves and a linear discriminant analysis was employed to predict classification accuracies. Based upon the substantial improvement (from 78 t0 92%) in discriminating zones of hydrothermally altered rocks from unaltered zones, over a broad range of observation conditions, a 2.08-2.35 micron spectral band having a ground resolution of 30 meters was recommended.

Breakdown of the balanced lethals in Rhoeo: the structure of the Alethal Renner complex of the homozygotic stock of Rhoeo.

PubMed

Golczyk, H

2011-01-01

Fluorescence in situ hybridization, base-specific fluorescence, C-banding and silver-staining were performed to reveal the cyto-molecular constitution of the karyotype in the bivalent-forming Rhoeo spathacea concolor. It was shown that the genome of this form is almost identical to the β-complex of the ring-forming rhoeos. In spite of some modifications in the arrangement of a few distal rDNA sites and in the amount of pericentromeric AT-rich heterochromatin, the alethal genome of the bivalent-forming Rhoeo seems segmentally unaltered. Thus, the breakdown of balanced lethals in Rhoeo is most likely uncoupled from creating new chromosome arm combinations. Copyright © 2011 S. Karger AG, Basel.

Context-Conditioned Generalization in Adaptation to Distorted Speech

ERIC Educational Resources Information Center

Dahan, Delphine; Mead, Rebecca L.

2010-01-01

People were trained to decode noise-vocoded speech by hearing monosyllabic stimuli in distorted and unaltered forms. When later presented with different stimuli, listeners were able to successfully generalize their experience. However, generalization was modulated by the degree to which testing stimuli resembled training stimuli: Testing stimuli's…

Habitat selection is unaltered after severe insect infestation: Concerns for forest-dependent species

Treesearch

Claire A. Zugmeyer; John L. Koprowski

2009-01-01

Severe disturbance may alter or eliminate important habitat structure that helps preserve food caches of foodhoarding species. Recent recolonization of an insect-damaged forest by the endangered Mt. Graham red squirrel (Tamiasciurus hudsonicus grahamensis) provided an opportunity to examine habitat selection for midden (cache) sites following...

USE OF FLUORESCENT POLYCYLIC AROMATIC HYDROCARBON PROBES IN STUDYING THE IMPACT OF COLLOIDS ON POLLUTANT TRANSPORT IN GROUNDWATER

EPA Science Inventory

A fluorescence-quenching method was developed to assess the hydrophobic organic pollutant binding potential of organic colloids (OC) in unaltered natural waters. This method allows (1) direct assessment of the importance of OC-enhanced pollutant transport for environmental sam- p...

Recent temporal trends in sleep duration, domain-specific sedentary behaviour and physical activity. A survey among 25-79-year-old Danish adults.

PubMed

Aadahl, Mette; Andreasen, Anne Helms; Hammer-Helmich, Lene; Buhelt, Lone; Jørgensen, Torben; Glümer, Charlotte

2013-11-01

Prevalence of sedentary behaviour is high in many countries, but little is known about temporal trends in sitting time. To examine temporal changes in sleep and domain-specific sedentary behaviour and moderate to vigorous leisure time physical activity (MVPA). Two cross-sectional population-based surveys of 25-79-year-old inhabitants were conducted in The Capital Region of Denmark in 2007 (N = 69.800, response rate 52.3%) and 2010 (N = 77.517, response rate 54.8%). Information on sedentary behaviour and physical activity was obtained from self-report questionnaire and sociodemographic information from central registers. Data were weighted for survey design and for non-response and were analysed by multiple regression analyses. In 2007, the entire survey population reported a mean daily sleeping duration of 7.4 hours, leisure time sitting of 3.4 hours per day, occupational sitting of 4.4 hours per day, MVPA of 0.87 hours per day and a total 24-hour energy expenditure of 40.12 METs per day. In 2010, duration of sleep was unaltered (p = 0.1), sedentary leisure time and sedentary work time had increased by 12.6 minutes (p < 0.0001) and 13.2 minutes (p < 0.0001) per day, respectively. Time spent on MVPA had increased by 2.9 minutes per day (p < 0.0001). The 24-hour energy expenditure had decreased by 0.41 METs (p < 0.0001). Adult Danish men and women spend an increased amount of time sitting down at work and during leisure time, but also on leisure time MVPA. As duration of sleep is unaltered findings suggest that low intensity physical activity may be displaced in everyday life.

Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice.

PubMed

Hänninen, Arno; Toivonen, Raine; Pöysti, Sakari; Belzer, Clara; Plovier, Hubert; Ouwerkerk, Janneke P; Emani, Rohini; Cani, Patrice D; De Vos, Willem M

2017-12-21

Intestinal microbiota is implicated in the pathogenesis of autoimmune type 1 diabetes in humans and in non-obese diabetic (NOD) mice, but evidence on its causality and on the role of individual microbiota members is limited. We investigated if different diabetes incidence in two NOD colonies was due to microbiota differences and aimed to identify individual microbiota members with potential significance. We profiled intestinal microbiota between two NOD mouse colonies showing high or low diabetes incidence by 16S ribosomal RNA gene sequencing and colonised the high-incidence colony with the microbiota of the low-incidence colony. Based on unaltered incidence, we identified a few taxa which were not effectively transferred and thereafter, transferred experimentally one of these to test its potential significance. Although the high-incidence colony adopted most microbial taxa present in the low-incidence colony, diabetes incidence remained unaltered. Among the few taxa which were not transferred, Akkermansia muciniphila was identified. As A. muciniphila abundancy is inversely correlated to the risk of developing type 1 diabetes-related autoantibodies, we transferred A. muciniphila experimentally to the high-incidence colony. A. muciniphila transfer promoted mucus production and increased expression of antimicrobial peptide Reg3γ , outcompeted Ruminococcus torques from the microbiota, lowered serum endotoxin levels and islet toll-like receptor expression, promoted regulatory immunity and delayed diabetes development. Transfer of the whole microbiota may not reduce diabetes incidence despite a major change in gut microbiota, but single symbionts such as A. muciniphila with beneficial metabolic and immune signalling effects may reduce diabetes incidence when administered as a probiotic. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Inducing self-selected human engagement in robotic locomotion training.

PubMed

Collins, Steven H; Jackson, Rachel W

2013-06-01

Stroke leads to severe mobility impairments for millions of individuals each year. Functional outcomes can be improved through manual treadmill therapy, but high costs limit patient exposure and, thereby, outcomes. Robotic gait training could increase the viable duration and frequency of training sessions, but robotic approaches employed thus far have been less effective than manual therapy. These shortcomings may relate to subconscious energy-minimizing drives, which might cause patients to engage less actively in therapy when provided with corrective robotic assistance. We have devised a new method for gait rehabilitation that harnesses, rather than fights, least-effort tendencies. Therapeutic goals, such as increased use of the paretic limb, are made easier than the patient's nominal gait through selective assistance from a robotic platform. We performed a pilot test on a healthy subject (N = 1) in which altered self-selected stride length was induced using a tethered robotic ankle-foot orthosis. The subject first walked on a treadmill while wearing the orthosis with and without assistance at unaltered and voluntarily altered stride length. Voluntarily increasing stride length by 5% increased metabolic energy cost by 4%. Robotic assistance decreased energy cost at both unaltered and voluntarily increased stride lengths, by 6% and 8% respectively. We then performed a test in which the robotic system continually monitored stride length and provided more assistance if the subject's stride length approached a target increase. This adaptive assistance protocol caused the subject to slowly adjust their gait patterns towards the target, leading to a 4% increase in stride length. Metabolic energy consumption was simultaneously reduced by 5%. These results suggest that selective-assistance protocols based on targets relevant to rehabilitation might lead patients to self-select desirable gait patterns during robotic gait training sessions, possibly facilitating better adherence and outcomes.

Influence of enriched environment on viral encephalitis outcomes: behavioral and neuropathological changes in albino Swiss mice.

PubMed

de Sousa, Aline Andrade; Reis, Renata; Bento-Torres, João; Trévia, Nonata; Lins, Nara Alves de Almeida; Passos, Aline; Santos, Zaire; Diniz, José Antonio Picanço; Vasconcelos, Pedro Fernando da Costa; Cunningham, Colm; Perry, Victor Hugh; Diniz, Cristovam Wanderley Picanço

2011-01-11

An enriched environment has previously been described as enhancing natural killer cell activity of recognizing and killing virally infected cells. However, the effects of environmental enrichment on behavioral changes in relation to virus clearance and the neuropathology of encephalitis have not been studied in detail. We tested the hypothesis that environmental enrichment leads to less CNS neuroinvasion and/or more rapid viral clearance in association with T cells without neuronal damage. Stereology-based estimates of activated microglia perineuronal nets and neurons in CA3 were correlated with behavioral changes in the Piry rhabdovirus model of encephalitis in the albino Swiss mouse. Two-month-old female mice maintained in impoverished (IE) or enriched environments (EE) for 3 months were behaviorally tested. After the tests, an equal volume of Piry virus (IEPy, EEPy)-infected or normal brain homogenates were nasally instilled. Eight days post-instillation (dpi), when behavioral changes became apparent, brains were fixed and processed to detect viral antigens, activated microglia, perineuronal nets, and T lymphocytes by immuno- or histochemical reactions. At 20 or 40 dpi, the remaining animals were behaviorally tested and processed for the same markers. In IEPy mice, burrowing activity decreased and recovered earlier (8-10 dpi) than open field (20-40 dpi) but remained unaltered in the EEPy group. EEPy mice presented higher T-cell infiltration, less CNS cell infection by the virus and/or faster virus clearance, less microgliosis, and less damage to the extracellular matrix than IEPy. In both EEPy and IEPy animals, CA3 neuronal number remained unaltered. The results suggest that an enriched environment promotes a more effective immune response to clear CNS virus and not at the cost of CNS damage.

19 CFR 142.50 - Line Release data base corrections or changes.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Line Release data base corrections or changes. 142...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.50 Line Release data base corrections... numbers or bond information on a Line Release Data Loading Sheet as soon as possible. Notification shall...

19 CFR 142.50 - Line Release data base corrections or changes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Line Release data base corrections or changes. 142...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.50 Line Release data base corrections... numbers or bond information on a Line Release Data Loading Sheet as soon as possible. Notification shall...

19 CFR 142.50 - Line Release data base corrections or changes.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Line Release data base corrections or changes. 142...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.50 Line Release data base corrections... numbers or bond information on a Line Release Data Loading Sheet as soon as possible. Notification shall...

19 CFR 142.50 - Line Release data base corrections or changes.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Line Release data base corrections or changes. 142...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.50 Line Release data base corrections... numbers or bond information on a Line Release Data Loading Sheet as soon as possible. Notification shall...

19 CFR 142.50 - Line Release data base corrections or changes.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Line Release data base corrections or changes. 142...; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.50 Line Release data base corrections... numbers or bond information on a Line Release Data Loading Sheet as soon as possible. Notification shall...

21 CFR 137.190 - Cracked wheat.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Cracked wheat. 137.190 Section 137.190 Food and... Related Products § 137.190 Cracked wheat. Cracked wheat is the food prepared by so cracking or cutting... such wheat, other than moisture, remain unaltered. Cracked wheat contains not more than 15 percent of...

EXTERIOR PERSPECTIVE OF GRANARY WITH DRIVE, LOOKING SOUTH. (In compliance ...

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

EXTERIOR PERSPECTIVE OF GRANARY WITH DRIVE, LOOKING SOUTH. (In compliance with the Secretary of the Interior’s Standards, the main façade of the granary was left unaltered in 1998, when the Smith family converted the granary into a family home.) - Smith Farm, Granary, 399 Ebey Road, Coupeville, Island County, WA

3 CFR 8409 - Proclamation 8409 of September 3, 2009. National Wilderness Month, 2009

Code of Federal Regulations, 2010 CFR

2010-01-01

... American people of present and future generations the benefits of an enduring resource of wilderness.” The... A Proclamation The American wilderness has inspired wonder and imagination for centuries and is an... far were struck by its splendor and purity. The unaltered American landscape stood apart from any...

Post-disturbance sediment recovery: Implications for watershed resilience

Treesearch

Sara L. Rathburn; Scott M. Shahverdian; Sandra E. Ryan

2017-01-01

Sediment recovery following disturbances is a measure of the time required to attain pre-disturbance sediment fluxes. Insight into the controls on recovery processes and pathways builds understanding of geomorphic resilience.We assess post-disturbance sediment recovery in three small (1.5-100 km2), largely unaltered watersheds within the northern Colorado...

Osborne. A Teacher's Handbook.

ERIC Educational Resources Information Center

Cooper, Rosemary; Fordham, Jennie

Osborne, located on the Isle of Wight, is almost entirely Victorian. It was designed, built, and furnished to the royal family's specifications (as a holiday home), and remains largely unaltered since Queen Victoria died in 1901. It offers unique resources for those studying not only the Victorian royal family but other aspects of 19th-century…

Auditory-motor Mapping for Pitch Control in Singers and Nonsingers

PubMed Central

Jones, Jeffery A.; Keough, Dwayne

2009-01-01

Little is known about the basic processes underlying the behavior of singing. This experiment was designed to examine differences in the representation of the mapping between fundamental frequency (F0) feedback and the vocal production system in singers and nonsingers. Auditory feedback regarding F0 was shifted down in frequency while participants sang the consonant-vowel /ta/. During the initial frequency-altered trials, singers compensated to a lesser degree than nonsingers, but this difference was reduced with continued exposure to frequency-altered feedback. After brief exposure to frequency altered auditory feedback, both singers and nonsingers suddenly heard their F0 unaltered. When participants received this unaltered feedback, only singers' F0 values were found to be significantly higher than their F0 values produced during baseline and control trials. These aftereffects in singers were replicated when participants sang a different note than the note they produced while hearing altered feedback. Together, these results suggest that singers rely more on internal models than nonsingers to regulate vocal productions rather than real time auditory feedback. PMID:18592224

TRICAINE METHANESULFONATE (MS-222) SEDATION AND ANESTHESIA IN THE PURPLE-SPINED SEA URCHIN (ARBACIA PUNCTULATA).

PubMed

Applegate, Jeffrey R; Dombrowski, Daniel S; Christian, Larry Shane; Bayer, Meredith P; Harms, Craig A; Lewbart, Gregory A

2016-12-01

The purple-spined sea urchin ( Arbacia punctulata ) is commonly found in shallow waters of the western Atlantic Ocean from the New England area of the United States to the Caribbean. Sea urchins play a major role in ocean ecology, echinoculture, and biomedical research. Additionally, sea urchins are commonly displayed in public aquaria. Baseline parameters were developed in unanesthetized urchins for righting reflex (time to regain oral recumbency) and spine response time to tactile stimulus. Tricaine methanesulfonate (MS-222) was used to sedate and anesthetize purple-spined sea urchins and assess sedation and anesthetic parameters, including adhesion to and release from a vertical surface, times to loss of response to tactile stimulus and recovery of righting reflex, and qualitative observations of induction of spawning and position of spines and pseudopodia. Sedation and anesthetic parameters were evaluated in 11 individuals in three circumstances: unaltered aquarium water for baseline behaviors, 0.4 g/L MS-222, and 0.8 g/L MS-222. Induction was defined as the release from a vertical surface with the loss of righting reflex, sedation as loss of righting reflex with retained tactile spine response, anesthesia as loss of righting reflex and loss of tactile spine response, and recovery as voluntary return to oral recumbency. MS-222 proved to be an effective sedative and anesthetic for the purple-spined sea urchin at 0.4 and 0.8 g/L, respectively. Sodium bicarbonate used to buffer MS-222 had no measurable sedative effects when used alone. Anesthesia was quickly reversed with transfer of each individual to anesthesia-free seawater, and no anesthetic-related mortality occurred. The parameters assessed in this study provide a baseline for sea urchin anesthesia and may provide helpful comparisons to similar species and populations that are in need of anesthesia for surgical procedures or research.

Pharmacological analysis of the inhibition produced by moxonidine and agmatine on the vasodepressor sensory CGRPergic outflow in pithed rats.

PubMed

Rubio-Beltrán, Eloísa; Labastida-Ramírez, Alejandro; Hernández-Abreu, Oswaldo; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

2017-10-05

Calcitonin gene-related peptide (CGRP) plays a role in several (patho)physiological functions, and modulation of its release is considered a therapeutic target. In this respect, electrical spinal (T 9 --T 12 ) stimulation of the perivascular sensory outflow in pithed rats produces vasodepressor responses mediated by CGRP release. This study investigated the role of imidazoline I 1 and I 2 receptors in the inhibition by moxonidine and agmatine of these vasodepressor responses. Male Wistar pithed rats (pretreated i.v. with 25mg/kg gallamine and 2mg/kg⋅min hexamethonium) received i.v. continuous infusions of methoxamine (20μg/kg⋅min) followed by physiological saline (0.02ml/min), moxonidine (1, 3, 10 or 30μg/kg⋅min) or agmatine (1000 or 3000μg/kg⋅min). Under these conditions, electrical stimulation (0.56-5.6Hz; 50V; 2ms) of the spinal cord (T 9 -T 12 ) produced frequency-dependent vasodepressor responses which were: (i) unchanged during saline infusion; and (ii) inhibited during the above infusions of moxonidine or agmatine. Moreover, using i.v. administrations, the inhibition by 3μg/kg⋅min moxonidine or 3000μg/kg⋅min agmatine (which failed to inhibit the vasodepressor responses by α-CGRP; 0.1-1µg/kg) was: (i) unaltered after saline (1ml/kg), rauwolscine (300μg/kg; α 2 -adrenoceptor antagonist) or BU224 (300μg/kg; imidazoline I 2 receptor antagonist); and (ii) reversed after AGN 192403 (3000μg/kg; imidazoline I 1 receptor antagonist). This reversion was relatively more pronounced after AGN 192403 plus rauwolscine. These blocking doses of antagonists lacked any effects on the electrically-induced vasodepressor responses. Therefore, the inhibition of the vasodepressor sensory CGRPergic outflow by moxonidine and agmatine is mainly mediated by prejunctional imidazoline I 1 receptors on perivascular sensory nerves. Copyright © 2017 Elsevier B.V. All rights reserved.

The adenosine A2A receptor — Myocardial protectant and coronary target in endotoxemia

PubMed Central

Reichelt, Melissa E.; Ashton, Kevin J.; Tan, Xing Lin; Mustafa, S. Jamal; Ledent, Catherine; Delbridge, Lea M.D.; Hofmann, Polly A.; Headrick, John P.; Morrison, R. Ray

2013-01-01

Background Cardiac injury and dysfunction are contributors to disease progression and mortality in sepsis. This study evaluated the cardiovascular role of intrinsic A2A adenosine receptor (A2AAR) activity during lipopolysaccharide (LPS)-induced inflammation. Methods We assessed the impact of 24 h of LPS challenge (20 mg/kg, IP) on cardiac injury, coronary function and inflammatory mediator levels in Wild-Type (WT) mice and mice lacking functional A2AARs (A2AAR KO). Results Cardiac injury was evident in LPS-treated WTs, with ∼7-fold elevation in serum cardiac troponin I (cTnI), and significant ventricular and coronary dysfunction. Absence of A2AARs increased LPS-provoked cTnI release at 24 h by 3-fold without additional demise of contraction function. Importantly, A2AAR deletion per se emulated detrimental effects of LPS on coronary function, and LPS was without effect in coronary vessels lacking A2AARs. Effects of A2AAR KO were independent of major shifts in circulating C-reactive protein (CRP) and haptoglobin. Cytokine responses were largely insensitive to A2AAR deletion; substantial LPS-induced elevations (up to 100-fold) in IFN-γ and IL-10 were unaltered in A2AAR KO mice, as were levels of IL-4 and TNF-α. However, late elevations in IL-2 and IL-5 were differentially modulated by A2AAR KO (IL-2 reduced, IL-5 increased). Data demonstrate that in the context of LPS-triggered cardiac and coronary injury, A2AAR activity protects myocardial viability without modifying contractile dysfunction, and selectively modulates cytokine (IL-2, IL-5) release. A2AARs also appear to be targeted by LPS in the coronary vasculature. Conclusions These experimental data suggest that preservation of A2AAR functionality might provide therapeutic benefit in human sepsis. PMID:22192288

Synaptic Activity and Muscle Contraction Increases PDK1 and PKCβI Phosphorylation in the Presynaptic Membrane of the Neuromuscular Junction.

PubMed

Hurtado, Erica; Cilleros, Víctor; Just, Laia; Simó, Anna; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A; Tomàs, Josep

2017-01-01

Conventional protein kinase C βI (cPKCβI) is a conventional protein kinase C (PKC) isoform directly involved in the regulation of neurotransmitter release in the neuromuscular junction (NMJ). It is located exclusively at the nerve terminal and both synaptic activity and muscle contraction modulate its protein levels and phosphorylation. cPKCβI molecular maturation includes a series of phosphorylation steps, the first of which is mediated by phosphoinositide-dependent kinase 1 (PDK1). Here, we sought to localize PDK1 in the NMJ and investigate the hypothesis that synaptic activity and muscle contraction regulate in parallel PDK1 and cPKCβI phosphorylation in the membrane fraction. To differentiate the presynaptic and postsynaptic activities, we abolished muscle contraction with μ-conotoxin GIIIB (μ-CgTx-GIIIB) in some experiments before stimulation of the phrenic nerve (1 Hz, 30 min). Then, we analyzed total and membrane/cytosol fractions of skeletal muscle by Western blotting. Results showed that PDK1 is located exclusively in the nerve terminal of the NMJ. After nerve stimulation with and without coincident muscle contraction, total PDK1 and phosphorylated PDK1 (pPDK1) protein levels remained unaltered. However, synaptic activity specifically enhanced phosphorylation of PDK1 in the membrane, an important subcellular location for PDK1 function. This increase in pPDK1 coincides with a significant increase in the phosphorylation of its substrate cPKCβI also in the membrane fraction. Moreover, muscle contraction maintains PDK1 and pPDK1 but increases cPKCβI protein levels and its phosphorylation. Thus, even though PDK1 activity is maintained, pcPKCβI levels increase in concordance with total cPKCβI. Together, these results indicate that neuromuscular activity could induce the membrane targeting of pPDK1 in the nerve terminal of the NMJ to promote the phosphorylation of the cPKCβI, which is involved in ACh release.

Synaptic Activity and Muscle Contraction Increases PDK1 and PKCβI Phosphorylation in the Presynaptic Membrane of the Neuromuscular Junction

PubMed Central

Hurtado, Erica; Cilleros, Víctor; Just, Laia; Simó, Anna; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A.; Tomàs, Josep

2017-01-01

Conventional protein kinase C βI (cPKCβI) is a conventional protein kinase C (PKC) isoform directly involved in the regulation of neurotransmitter release in the neuromuscular junction (NMJ). It is located exclusively at the nerve terminal and both synaptic activity and muscle contraction modulate its protein levels and phosphorylation. cPKCβI molecular maturation includes a series of phosphorylation steps, the first of which is mediated by phosphoinositide-dependent kinase 1 (PDK1). Here, we sought to localize PDK1 in the NMJ and investigate the hypothesis that synaptic activity and muscle contraction regulate in parallel PDK1 and cPKCβI phosphorylation in the membrane fraction. To differentiate the presynaptic and postsynaptic activities, we abolished muscle contraction with μ-conotoxin GIIIB (μ-CgTx-GIIIB) in some experiments before stimulation of the phrenic nerve (1 Hz, 30 min). Then, we analyzed total and membrane/cytosol fractions of skeletal muscle by Western blotting. Results showed that PDK1 is located exclusively in the nerve terminal of the NMJ. After nerve stimulation with and without coincident muscle contraction, total PDK1 and phosphorylated PDK1 (pPDK1) protein levels remained unaltered. However, synaptic activity specifically enhanced phosphorylation of PDK1 in the membrane, an important subcellular location for PDK1 function. This increase in pPDK1 coincides with a significant increase in the phosphorylation of its substrate cPKCβI also in the membrane fraction. Moreover, muscle contraction maintains PDK1 and pPDK1 but increases cPKCβI protein levels and its phosphorylation. Thus, even though PDK1 activity is maintained, pcPKCβI levels increase in concordance with total cPKCβI. Together, these results indicate that neuromuscular activity could induce the membrane targeting of pPDK1 in the nerve terminal of the NMJ to promote the phosphorylation of the cPKCβI, which is involved in ACh release. PMID:28890686

Trigeminal ganglion neuron subtype-specific alterations of CaV2.1 calcium current and excitability in a Cacna1a mouse model of migraine

PubMed Central

Fioretti, B; Catacuzzeno, L; Sforna, L; Gerke-Duncan, M B; van den Maagdenberg, A M J M; Franciolini, F; Connor, M; Pietrobon, D

2011-01-01

Abstract Familial hemiplegic migraine type-1 (FHM1), a monogenic subtype of migraine with aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium channels. The consequences of FHM1 mutations on the trigeminovascular pathway that generates migraine headache remain largely unexplored. Here we studied the calcium currents and excitability properties of two subpopulations of small-diameter trigeminal ganglion (TG) neurons from adult wild-type (WT) and R192Q FHM1 knockin (KI) mice: capsaicin-sensitive neurons without T-type calcium currents (CS) and capsaicin-insensitive neurons characterized by the expression of T-type calcium currents (CI-T). Small TG neurons retrogradely labelled from the dura are mostly CS neurons, while CI-T neurons were not present in the labelled population. CS and CI-T neurons express CaV2.1 channels with different activation properties, and the CaV2.1 channels are differently affected by the FHM1 mutation in the two TG neuron subtypes. In CI-T neurons from FHM1 KI mice there was a larger P/Q-type current density following mild depolarizations, a larger action potential (AP)-evoked calcium current and a longer AP duration when compared to CI-T neurons from WT mice. In striking contrast, the P/Q-type current density, voltage dependence and kinetics were not altered by the FHM1 mutation in CS neurons. The excitability properties of mutant CS neurons were also unaltered. Congruently, the FHM1 mutation did not alter depolarization-evoked CGRP release from the dura mater, while CGRP release from the trigeminal ganglion was larger in KI compared to WT mice. Our findings suggest that the facilitation of peripheral mechanisms of CGRP action, such as dural vasodilatation and nociceptor sensitization at the meninges, does not contribute to the generation of headache in FHM1. PMID:22005682

CALHM1 Deletion in Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, and Life Span

PubMed Central

Schmolling, Jared; Marambaud, Philippe; Rose-Hellekant, Teresa A.

2015-01-01

Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body weight, and life span. KO mice have no NG response to sweet and a suppressed response to bitter compared with control (wild-type [WT]) mice. KO mice showed some NG response to umami, suggesting that umami taste involves both CALHM1- and non-CALHM1-modulated signals. NG responses to sour and salty were not significantly different between KO and WT mice. Behavioral data conformed in general with the NG data. Adult KO mice consumed less food, weighed significantly less, and lived almost a year longer than WT mice. Taken together, these data demonstrate that sweet taste majorly influences food intake, body weight, and life span. PMID:25855639

Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.

PubMed

Marquèze-Pouey, Béatrice; Mailfert, Sébastien; Rouger, Vincent; Goaillard, Jean-Marc; Marguet, Didier

2014-01-01

Signaling mediated by the epidermal growth factor (EGF) is crucial in tissue development, homeostasis and tumorigenesis. EGF is mitogenic at picomolar concentrations and is known to bind its receptor on high affinity binding sites depending of the oligomerization state of the receptor (monomer or dimer). In spite of these observations, the cellular response induced by EGF has been mainly characterized for nanomolar concentrations of the growth factor, and a clear definition of the cellular response to circulating (picomolar) concentrations is still lacking. We investigated Ca2+ signaling, an early event in EGF responses, in response to picomolar doses in COS-7 cells where the monomer/dimer equilibrium is unaltered by the synthesis of exogenous EGFR. Using the fluo5F Ca2+ indicator, we found that picomolar concentrations of EGF induced in 50% of the cells a robust oscillatory Ca2+ signal quantitatively similar to the Ca2+ signal induced by nanomolar concentrations. However, responses to nanomolar and picomolar concentrations differed in their underlying mechanisms as the picomolar EGF response involved essentially plasma membrane Ca2+ channels that are not activated by internal Ca2+ store depletion, while the nanomolar EGF response involved internal Ca2+ release. Moreover, while the picomolar EGF response was modulated by charybdotoxin-sensitive K+ channels, the nanomolar response was insensitive to the blockade of these ion channels.

Class II glass ionomer/silver cermet restorations and their effect on interproximal growth of mutans streptococci.

PubMed

Berg, J H; Farrell, J E; Brown, L R

1990-02-01

The release of fluoride from glass ionomer materials is one of the most important features of this newly implemented material, and the remineralization effects of this phenomenon have been documented (Hicks and Silverstone 1986). This paper examines the effects of glass ionomer/silver cermet restorations on the plaque levels of interproximal mutans streptococci. Fifteen patients with Class II lesions in primary molars were selected for study. Interproximal plaque samples were obtained from each of the lesion sites and from one caries-free site approximal to a primary molar. One lesion was restored with composite resin to serve as a treated control to the glass ionomer/silver cermet (Ketac Silver, ESPE/Premier Sales Corp., Norristown, Pennsylvania) test site. A sound (unaltered) interproximal site served as the untreated control site. Plaque samples were collected before and at one week, one month, and three months post-treatment. Samples were serially diluted to enable colony counts of mutans streptococci. One week post-treatment counts showed that the glass ionomer/silver cermet restorations significantly reduced (P less than 0.05) the approximal plaque levels of mutans streptococci. Conversely, the untreated and treated control sites did not exhibit reductions in approximal plaque levels of mutans streptococci. These results indicate that glass ionomer restorations may be inhibitory to the growth of mutans streptococci in dental plaque approximal to this restorative material in the primary dentition.

Proteome and radioimmunoassay analyses of pituitary hormones and proteins in response to feed restriction of dairy cows.

PubMed

Kuhla, Björn; Albrecht, Dirk; Bruckmaier, Rupert; Viergutz, Torsten; Nürnberg, Gerd; Metges, Cornelia C

2010-12-01

The hypothalamic-pituitary system controls homeostasis during feed energy reduction. In order to examine which pituitary proteins and hormone variants are potentially associated with metabolic adaptation, pituitary glands from ad libitum and energy restrictively fed dairy cows were characterized using RIA and 2-DE followed by MALDI-TOF-MS. We found 64 different spots of regulatory hormones: growth hormone (44), preprolactin (16), luteinizing hormone (LH) (1), thyrotropin (1), proopiomelanocortin (1) and its cleavage product lipotropin (1), but none of these did significantly differ between feeding groups. Quantification of total pituitary LH and prolactin concentrations by RIA confirmed the results obtained by proteome analysis. Also, feed energy restriction provoked increasing non-esterified fatty acid, decreasing prolactin, but unaltered glucose, LH and growth hormone plasma concentrations. Energy restriction decreased the expression of glial fibrillary acidic protein, triosephosphate isomerase, purine-rich element-binding protein A and elongation factor Tu, whereas it increased expression of proline synthetase co-transcribed homolog, peroxiredoxin III, β-tubulin and annexin A5 which is involved in the hormone secretion process. Our results indicate that in response to feed energy restriction the pituitary reservoir of all posttranslationally modified hormone forms remains constant. Changing plasma hormone concentrations are likely attributed to a regulated releasing process from the gland into the blood. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC).

PubMed

Pathare, Ganesh; Anderegg, Manuel; Albano, Giuseppe; Lang, Florian; Fuster, Daniel G

2018-02-26

Fibroblast growth factor 23 (FGF23) participates in the orchestration of mineral metabolism by inducing phosphaturia and decreasing the production of 1,25(OH) 2 D 3 . It is known that FGF23 release is stimulated by aldosterone and extracellular volume depletion. To characterize this effect further in a model of mild hypovolemia, we studied mice lacking the thiazide sensitive NaCl cotransporter (NCC). Our data indicate that NCC knockout mice (KO) have significantly higher FGF23, PTH and aldosterone concentrations than corresponding wild type (WT) mice. However, 1,25(OH) 2 D 3 , fractional phosphate excretion and renal brush border expression of the sodium/phosphate co-transporter 2a were not different between the two genotypes. In addition, renal expression of FGF23 receptor FGFR1 and the co-receptor Klotho were unaltered in NCC KO mice. FGF23 transcript was increased in the bone of NCC KO mice compared to WT mice, but treatment of primary murine osteoblasts with the NCC inhibitor hydrochlorothiazide did not elicit an increase of FGF23 transcription. In contrast, the mineralocorticoid receptor blocker eplerenone reversed excess FGF23 levels in KO mice but not in WT mice, indicating that FGF23 upregulation in NCC KO mice is primarily aldosterone-mediated. Together, our data reveal that lack of renal NCC causes an aldosterone-mediated upregulation of circulating FGF23.

Review: Tau in biofluids - relation to pathology, imaging and clinical features.

PubMed

Zetterberg, H

2017-04-01

Tau is a microtubule-binding protein that is important for the stability of neuronal axons. It is normally expressed within neurons and is also secreted into the brain interstitial fluid that communicates freely with cerebrospinal fluid (CSF) and, in a more restricted manner, blood via the glymphatic clearance system of the brain. In Alzheimer's disease (AD), neuroaxonal degeneration results in increased release of tau from neurons. Furthermore, tau is truncated and phosphorylated, which leads to aggregation of tau in neurofibrillary tangles of the proximal axoplasm. Neuroaxonal degeneration and tangle formation are reflected by increased concentrations of total tau (T-tau, measured using assays that detect most forms of tau) and phospho-tau (P-tau, measured using assays with antibodies specific to phosphorylated forms of tau). In AD CSF, both T-tau and P-tau concentrations are increased. In stroke and other CNS disorders with neuroaxonal injury but without tangles, T-tau is selectively increased, whereas P-tau concentration often stays normal. In tauopathies (diseases with both neurodegeneration and neurofibrillary tangles) other than AD, CSF T-tau and P-tau concentrations are typically unaltered, which is a puzzling result that warrants further investigation. In the current review, I discuss the association of T-tau and P-tau concentrations in body fluids with neuropathological changes, imaging findings and clinical features in AD and other CNS diseases. © 2017 British Neuropathological Society.

Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees

PubMed Central

1994-01-01

The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase- alpha 1-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment F1+2 and thrombin- antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-alpha 2- antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin- induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees. PMID:8145042

Evaluation of frictional melting on the basis of trace element analyses of fault rocks

NASA Astrophysics Data System (ADS)

Ishikawa, T.; Ujiie, K.

2016-12-01

Pseudotachylytes (solidified frictional melts produced during seismic slip) found in exhumed accretionary complexes are considered to have formed originally at seismogenic depths, and help our understanding of the dynamics of earthquake faulting in subduction zones. The frictional melting should affect rock chemistry. Actually, major element compositions of unaltered pseudotachylyte matrix in the Shimanto accretionary complex are reported to be similar to that of illite, implying disequilibrium melting in the slip zone (Ujiie et al., 2007). Bulk-rock trace element analyses of the pseudotachylyte-bearing fault rocks also revealed their shift to the clay-mineral-like compositions (Honda et al., 2011). Toward better understanding of the frictional melting using chemical means, we carried out detailed major and trace element analyses for pseudotachylyte-bearing dark veins and surrounding host rocks from the Mugi area of the Shimanto accretionary complex (Ujiie et al., 2007). About one milligram each of samples was collected from a rock chip along the microstructure by using the PC-controlled micro-drilling apparatus, and then analyzed by ICP-MS. Host rocks showed a series of compositional trends controlled by mixing of detrital sedimentary components. Unaltered part of the pseudotachylyte vein, on the other hand, showed striking enrichment of fluid-immobile trace elements, consistent with selective melting of fine-grained, clay-rich matrix of the fault rock. Importantly, completely altered parts of the dark veins exhibit essentially the same characteristics as the unaltered part, indicating that the trace element composition of the pseudotachylyte is well preserved even after considerable alteration in the later stages. These results demonstrate that trace element and structural analyses are useful to detect preexistence of pseudotachylytes resulting from selective frictional melting of clay minerals. It has been controversial that pseudotachylytes are rarely formed or rarely preserved. Trace element analyses on clay-rich localized slipping zones shed light on this topic. References: Ujiie et al. (2007) J. Struct. Geol. 29, 599-613; Honda et al. (2011) GRL 38, L06310.

Moessbauer Mineralogy of Rock, Soil, and Dust at Gusev Crater, Mars: Spirit's Journey through Weakly Altered Olivine Basalt on the Plains and Pervasively Altered Basalt in the Columbia Hills

NASA Technical Reports Server (NTRS)

Morris, R. V.; Klingelhoefer, G.; Schroeder, C.; Rodionov, D. S.; Yen, A.; Ming, D. W.; deSouza, P. A., Jr.; Fleischer, I.; Wdowiak, T.; Gellert, R.;

Reconfigurable modified surface layers using plasma capillaries around the neutral inclusion regime

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

Varault, S.; Universite Paul Sabatier—CNRS-Laplace 118, Route de Narbonne, F-31062 Toulouse Cedex 9; Gabard, B.

We show both theoretically and experimentally reconfigurable properties achieved by plasma inclusions placed in modified surface layers generally used to tailor the transmission and beaming properties of electromagnetic bandgap based waveguiding structures. A proper parametrization of the plasma capillaries allows to reach the neutral inclusion regime, where the inclusions appear to be electromagnetically transparent, letting the surface mode characteristics unaltered. Varying the electron density of the plasma inclusions provoques small perturbations around this peculiar regime, and we observe significant modifications of the transmission/beaming properties. This offers a way to dynamically select the enhanced transmission frequency or to modify the radiationmore » pattern of the structure, depending on whether the modified surface layer is placed at the entrance/exit of the waveguide.« less

Hsp90 and environmental stress transform the adaptive value of natural genetic variation.

PubMed

Jarosz, Daniel F; Lindquist, Susan

2010-12-24

How can species remain unaltered for long periods yet also undergo rapid diversification? By linking genetic variation to phenotypic variation via environmental stress, the Hsp90 protein-folding reservoir might promote both stasis and change. However, the nature and adaptive value of Hsp90-contingent traits remain uncertain. In ecologically and genetically diverse yeasts, we find such traits to be both common and frequently adaptive. Most are based on preexisting variation, with causative polymorphisms occurring in coding and regulatory sequences alike. A common temperature stress alters phenotypes similarly. Both selective inhibition of Hsp90 and temperature stress increase correlations between genotype and phenotype. This system broadly determines the adaptive value of standing genetic variation and, in so doing, has influenced the evolution of current genomes.

A Note on the Wave Action Density of a Viscous Instability Mode on a Laminar Free-shear Flow

NASA Technical Reports Server (NTRS)

Balsa, Thomas F.

1994-01-01

Using the assumptions of an incompressible and viscous flow at large Reynolds number, we derive the evolution equation for the wave action density of an instability wave traveling on top of a laminar free-shear flow. The instability is considered to be viscous; the purpose of the present work is to include the cumulative effect of the (locally) small viscous correction to the wave, over length and time scales on which the underlying base flow appears inhomogeneous owing to its viscous diffusion. As such, we generalize our previous work for inviscid waves. This generalization appears as an additional (but usually non-negligible) term in the equation for the wave action. The basic structure of the equation remains unaltered.

Chemical composition of the continental crust: Insights from a quantitative interpretation of the Vp/Vs ratio

NASA Astrophysics Data System (ADS)

Guerri, M.; Youssof, M.; Fullea, J.

2017-12-01

The processes driving continental crust formation are not yet fully understood. One of the fundamental keys necessary to investigate the enigma is represented by crustal composition. The Vp/Vs ratio from seismic receiver functions or tomography studies is a powerful tool to constrain the crustal composition. However, to date only qualitative relationships between Vp/Vs and composition have been proposed. We present a quantitative interpretation of the Vp/Vs in terms of major oxide components, based on thermo-elastic constrained modelling of rock phase equilibria and physical properties. The geophysical-petrological approach is implemented in the new release of the software package LitMod, which now allows for integrated and self-consistent modeling of the entire lithosphere (crust + lithospheric mantle) and upper mantle. Forward modelling of the Vp/Vs, based on petrology and thermodynamics, reveals that, as expected, mafic compositions have higher Vp/Vs than felsic ones. However, in high temperature settings (surface heat flow > 75 mW/m2), the quartz alpha / quartz beta transition strongly increases Vp, leaving Vs almost unaltered, leading to SiO2-rich compositions displaying Vp/Vs values higher than those associated with mafic compositions. Additionally, we highlight the importance of H2O, the presence of which stabilizes amphibole (in place of pyroxene), characterized by a relatively low Vp/Vs. If H2O is present, mafic compositions show Vp/Vs ratios that are comparable to those produced by anhydrous SiO2-rich compositions. The destabilization of amphibole (in favour of pyroxene) generates a sharp seismic discontinuity, potentially detectable by, for example, seismic refraction and receiver function investigations. We invert the Vp/Vs ratio for composition and hydrous state of the crust in the Southern African cratons. Our results show that the Kaapvaal craton, Archean in age, has an intermediate (SiO2 60 wt%) composition. The finding has implications on our understanding of the mechanisms responsible for crustal formation as an intermediate bulk composition is potentially generated by subduction-related processes. We conclude that, already before the Meso-Archean (3.2 Ga), subduction related crust-forming processes were active in the area and potentially also in other cratons.

Species-specific Seedling Responses to Hurricane Disturbance in a Puerto Rican Rain Forest.

Treesearch

Lawrence R. Walker; D. Jean Lodge; Sandra M. Guzman-Grajales; Ned \\t Fetcher

2003-01-01

Seedling dynamics were followed in a Puerto Rican forest for 20 months following a severe hurricane to study the interactive effects of hurricane debris, nutrients, and light on seedling diversity, density, growth, and mortality. Three treatments (debris removal, an unaltered control with hurricane debris, and chemical fertilization added to hurricane debris) altered...

ROLE OF THE EGG JELLY COAT IN PROTECTING HYLA REGILLA AND BUFO CANORUS EMBRYOS FROM ULTRAVIOLET B RADIATION DURING DEVELOPMENT

EPA Science Inventory

Previous studies have suggested that Ultraviolet B (UVB) radiation may play a role in amphibian population declines. Some of these studies also indicate that egg hatching success is unaltered in some species of anurans as a result of UVB exposure. It has been proposed that the eg...

The Way We Educate: Twenty Million Miles for Some, a Twenty-Minute Walk for Others

ERIC Educational Resources Information Center

Smith, Grinell

2012-01-01

This article is about storytelling. In an effort to open opportunities similar to what we experienced while we were in school, many among the education professorate seem to have adopted well-used and familiar "academic" models of seminar instruction virtually unaltered from their experiences as graduate students. One suspects, however,…

Ring structure modifications of phenylalanine 19 increase fibrillation kinetics and reduce toxicity of amyloid β (1-40).

PubMed

Korn, Alexander; Surendran, Dayana; Krueger, Martin; Maiti, Sudipta; Huster, Daniel

2018-05-24

We investigated the influence of the chemical structure of the phenylalanine side chain in position 19 of the 40 residue amyloid β peptide. Side chain modifications in this position yielded fibrils of essentially unaltered morphology, structure, and dynamics, but significantly increased fibrillation kinetics and diminished the toxicity of the peptides.

Monitoring of Streambank Stabilization and River Restoration Structures on Ice-Affected Rivers in Northern Vermont

DTIC Science & Technology

2009-08-01

Site Characteristics River Site Drainage Area ( mi2 ) Valley Bottom Slope Bank- full Width (ft) Bank- full Depth (ft) Bankfull...relatively unaltered by human activities. Drainage areas range from 990 ERDC/CRREL TR-09-14 17 mi2 on the lower Winooski to 44 mi2 on the upper Trout

Kinetics of drug release from ointments: Role of transient-boundary layer.

PubMed

Xu, Xiaoming; Al-Ghabeish, Manar; Krishnaiah, Yellela S R; Rahman, Ziyaur; Khan, Mansoor A

2015-10-15

In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time. Published by Elsevier B.V.

Biocompatible and biodegradable dual-drug release system based on silk hydrogel containing silk nanoparticles.

PubMed

Numata, Keiji; Yamazaki, Shoya; Naga, Naofumi

2012-05-14

We developed a facile and quick ethanol-based method for preparing silk nanoparticles and then fabricated a biodegradable and biocompatible dual-drug release system based on silk nanoparticles and the molecular networks of silk hydrogels. Model drugs incorporated in the silk nanoparticles and silk hydrogels showed fast and constant release, respectively, indicating successful dual-drug release from silk hydrogel containing silk nanoparticles. The release behaviors achieved by this dual-drug release system suggest to be regulated by physical properties (e.g., β-sheet contents and size of the silk nanoparticles and network size of the silk hydrogels), which is an important advantage for biomedical applications. The present silk-based system for dual-drug release also demonstrated no significant cytotoxicity against human mesenchymal stem cells (hMSCs), and thus, this silk-based dual-drug release system has potential as a versatile and useful new platform of polymeric materials for various types of dual delivery of bioactive molecules.

Effects of water-supply reservoirs on streamflow in Massachusetts

USGS Publications Warehouse

Levin, Sara B.

2016-10-06

State and local water-resource managers need modeling tools to help them manage and protect water-supply resources for both human consumption and ecological needs. The U.S. Geological Survey, in cooperation with the Massachusetts Department of Environmental Protection, has developed a decision-support tool to estimate the effects of reservoirs on natural streamflow. The Massachusetts Reservoir Simulation Tool is a model that simulates the daily water balance of a reservoir. The reservoir simulation tool provides estimates of daily outflows from reservoirs and compares the frequency, duration, and magnitude of the volume of outflows from reservoirs with estimates of the unaltered streamflow that would occur if no dam were present. This tool will help environmental managers understand the complex interactions and tradeoffs between water withdrawals, reservoir operational practices, and reservoir outflows needed for aquatic habitats.A sensitivity analysis of the daily water balance equation was performed to identify physical and operational features of reservoirs that could have the greatest effect on reservoir outflows. For the purpose of this report, uncontrolled releases of water (spills or spillage) over the reservoir spillway were considered to be a proxy for reservoir outflows directly below the dam. The ratio of average withdrawals to the average inflows had the largest effect on spillage patterns, with the highest withdrawals leading to the lowest spillage. The size of the surface area relative to the drainage area of the reservoir also had an effect on spillage; reservoirs with large surface areas have high evaporation rates during the summer, which can contribute to frequent and long periods without spillage, even in the absence of water withdrawals. Other reservoir characteristics, such as variability of inflows, groundwater interactions, and seasonal demand patterns, had low to moderate effects on the frequency, duration, and magnitude of spillage. The reservoir simulation tool was used to simulate 35 single- and multiple-reservoir systems in Massachusetts over a 44-year period (water years 1961 to 2004) under two water-use scenarios. The no-pumping scenario assumes no water withdrawal pumping, and the pumping scenario incorporates average annual pumping rates from 2000 to 2004. By comparing the results of the two scenarios, the total streamflow alteration can be parsed into the portion of streamflow alteration caused by the presence of a reservoir and the additional streamflow alteration caused by the level of water use of the system.For each reservoir system, the following metrics were computed to characterize the frequency, duration, and magnitude of reservoir outflow volumes compared with unaltered streamflow conditions: (1) the median number of days per year in which the reservoir did not spill, (2) the median duration of the longest consecutive period of no-spill days per year, and (3) the lowest annual flow duration exceedance probability at which the outflows are significantly different from estimated unaltered streamflow at the 95-percent confidence level. Most reservoirs in the study do not spill during the summer months even under no-pumping conditions. The median number of days during which there was no spillage was less than 365 for all reservoirs in the study, indicating that, even under reported pumping conditions, the reservoirs refill to full volume and spill at least once during nondrought years, typically in the spring.Thirteen multiple-reservoir systems consisting of two or three hydrologically connected reservoirs were included in the study. Because operating rules used to manage multiple-reservoir systems are not available, these systems were simulated under two pumping scenarios, one in which water transfers between reservoirs are minimal and one in which reservoirs continually transferred water to intermediate or terminal reservoirs. These two scenarios provided upper and lower estimates of spillage under average pumping conditions from 2000 to 2004.For sites with insufficient data to simulate daily water balances, a proxy method to estimate the three spillage metrics was developed. A series of 4,000 Monte Carlo simulations of the reservoir water balance were run. In each simulation, streamflow, physical reservoir characteristics, and daily climate inputs were randomly varied. Tobit regression equations that quantify the relation between streamflow alteration and physical and operational characteristics of reservoirs were developed from the results of the Monte Carlo simulations and can be used to estimate each of the three spillage metrics using only the withdrawal ratio and the ratio of the surface area to the drainage area, which are available statewide for all reservoirs.A graphical user-interface for the Massachusetts Reservoir Simulation Tool was developed in a Microsoft Access environment. The simulation tool contains information for 70 reservoirs in Massachusetts and allows for simulation of additional scenarios than the ones considered in this report, including controlled releases, dam seepage and leakage, demand management plans, and alternative water withdrawal and transfer rules.

A Relationship between Reduced Nucleus Accumbens Shell and Enhanced Lateral Hypothalamic Orexin Neuronal Activation in Long-Term Fructose Bingeing Behavior

PubMed Central

Rorabaugh, Jacki M.; Stratford, Jennifer M.; Zahniser, Nancy R.

2014-01-01

Fructose accounts for 10% of daily calories in the American diet. Fructose, but not glucose, given intracerebroventricularly stimulates homeostatic feeding mechanisms within the hypothalamus; however, little is known about how fructose affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of fructose and glucose, increases neuronal activity in hedonic centers, the nucleus accumbens (NAc) shell and core, but not the hypothalamus. Rats given glucose in the intermittent access model (IAM) display signatures of hedonic feeding including bingeing and altered DA receptor (R) numbers within the NAc. Here we examined whether substituting fructose for glucose in this IAM produces bingeing behavior, alters DA Rs and activates hedonic and homeostatic feeding centers. Following long-term (21-day) exposure to the IAM, rats given 8–12% fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR). This activation was negatively correlated with orexin (Orx) neuron activation in the lateral hypothalamus/perifornical area (LH/PeF), a brain region linking homeostatic to hedonic feeding centers. Following short-term (2-day) access to the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term fructose bingeing increases Orx release. In long-term fructose bingeing rats, pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p.) equally reduced fructose bingeing and chow intake, resulting in a 50% reduction in calories. Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus, in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than palatability. Overall, our results, in combination with the literature, suggest individual monosaccharides activate distinct neuronal circuits to promote feeding behavior. Specifically, long-term fructose bingeing activates a hyperphagic circuit composed in part of NAc shell and LH/PeF Orx neurons. PMID:24736531

Elucidation of release characteristics of highly soluble drug trimetazidine hydrochloride from chitosan-carrageenan matrix tablets.

PubMed

Li, Liang; Wang, Linlin; Shao, Yang; Tian, Ye; Li, Conghao; Li, Ying; Mao, Shirui

2013-08-01

The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans [kappa (κ)-CG, iota (ι)-CG, and lambda (λ)-CG]. Highly soluble trimetazidine hydrochloride (TH) was used as a model drug. First, characteristics of drug release from different formulations were investigated, and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. Erosion and swelling of matrix were also characterized to better understand the drug-release mechanisms. Effects of pH and ionic strength on drug release were also studied. It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction, CS-ι-CG- and CS-λ-CG-based polyelectrolyte film could further modify the controlled-release behavior, but not CS-κ-CG. High pH and high ionic strength resulted in faster drug release from CS-κ-CG- and CS-ι-CG-based matrix, but drug release from CS-λ-CG-based matrix was less sensitive to pH and ionic strength. In conclusion, CS-λ-CG-based matrix tablets are quite promising as controlled-release drug carrier based on multiple mechanisms. Copyright © 2013 Wiley Periodicals, Inc.

Formulation development and release studies of indomethacin suppositories.

PubMed

Sah, M L; Saini, T R

2008-01-01

Indomethacin suppositories were prepared by using water-soluble and oil soluble suppository bases, and evaluated for in vitro release by USP I and modified continuous flow through bead bed apparatus. Effect of the Tween 80 (1% and 5%) was further studied on in vitro release of the medicament. Release rate was good in water-soluble suppositories bases in comparison to oil soluble suppositories bases. Release was found to be greater in modified continuous flow through bead bed apparatus. When surfactant was used in low concentration then release rate was much greater, as compared to high concentration. When stability studies were performed on the prepared indomethacin suppositories it was found that suppositories made by water-soluble base had no significant changes while suppositories prepared by oil soluble bases, had some signs of instability.

Water Vapor Adsorption on Biomass Based Carbons under Post-Combustion CO2 Capture Conditions: Effect of Post-Treatment

PubMed Central

Querejeta, Nausika; Plaza, Marta G.; Rubiera, Fernando; Pevida, Covadonga

2016-01-01

The effect of post-treatment upon the H2O adsorption performance of biomass-based carbons was studied under post-combustion CO2 capture conditions. Oxygen surface functionalities were partially replaced through heat treatment, acid washing, and wet impregnation with amines. The surface chemistry of the final carbon is strongly affected by the type of post-treatment: acid treatment introduces a greater amount of oxygen whereas it is substantially reduced after thermal treatment. The porous texture of the carbons is also influenced by post-treatment: the wider pore volume is somewhat reduced, while narrow microporosity remains unaltered only after acid treatment. Despite heat treatment leading to a reduction in the number of oxygen surface groups, water vapor adsorption was enhanced in the higher pressure range. On the other hand acid treatment and wet impregnation with amines reduce the total water vapor uptake thus being more suitable for post-combustion CO2 capture applications. PMID:28773488

Determination of wind tunnel constraint effects by a unified pressure signature method. Part 2: Application to jet-in-crossflow

NASA Technical Reports Server (NTRS)

Hackett, J. E.; Sampath, S.; Phillips, C. G.

1981-01-01

The development of an improved jet-in-crossflow model for estimating wind tunnel blockage and angle-of-attack interference is described. Experiments showed that the simpler existing models fall seriously short of representing far-field flows properly. A new, vortex-source-doublet (VSD) model was therefore developed which employs curved trajectories and experimentally-based singularity strengths. The new model is consistent with existing and new experimental data and it predicts tunnel wall (i.e. far-field) pressures properly. It is implemented as a preprocessor to the wall-pressure-signature-based tunnel interference predictor. The supporting experiments and theoretical studies revealed some new results. Comparative flow field measurements with 1-inch "free-air" and 3-inch impinging jets showed that vortex penetration into the flow, in diameters, was almost unaltered until 'hard' impingement occurred. In modeling impinging cases, a 'plume redirection' term was introduced which is apparently absent in previous models. The effects of this term were found to be very significant.

MIMO H∞ control of three-axis ship-mounted mobile antenna systems

NASA Astrophysics Data System (ADS)

Kuseyri, İ. Sina

2018-02-01

The need for on-line information in any environment has led to the development of mobile satellite communication terminals. These high data-rate terminals require inertial antenna pointing error tolerance within fractions of a degree. However, the base motion of the antenna platform in mobile applications complicates this pointing problem and must be accounted for. Gimbaled motorised pedestals are used to eliminate the effect of disturbance and maintain uninterrupted communication. In this paper, a three-axis ship-mounted antenna on a pedestal gimbal system is studied. Based on the derived dynamic model of the antenna pedestal multi input-multi output PID and H∞ linear controllers are designed to stabilise the antenna to keep its orientation unaltered towards the satellite while the sea waves disturb the antenna. Simulation results are presented to show the stabilisation performance of the system with the synthesised controllers. It is shown through performance comparison and analysis that the proposed H∞ control structure is preferable over PID controlled system in terms of system stability and the disturbance rejection.

Evaluations of Silica Aerogel-Based Flexible Blanket as Passive Thermal Control Element for Spacecraft Applications

NASA Astrophysics Data System (ADS)

Hasan, Mohammed Adnan; Rashmi, S.; Esther, A. Carmel Mary; Bhavanisankar, Prudhivi Yashwantkumar; Sherikar, Baburao N.; Sridhara, N.; Dey, Arjun

2018-03-01

The feasibility of utilizing commercially available silica aerogel-based flexible composite blankets as passive thermal control element in applications such as extraterrestrial environments is investigated. Differential scanning calorimetry showed that aerogel blanket was thermally stable over - 150 to 126 °C. The outgassing behavior, e.g., total mass loss, collected volatile condensable materials, water vapor regained and recovered mass loss, was within acceptable range recommended for the space applications. ASTM tension and tear tests confirmed the material's mechanical integrity. The thermo-optical properties remained nearly unaltered in simulated space environmental tests such as relative humidity, thermal cycling and thermo-vacuum tests and confirmed the space worthiness of the aerogel. Aluminized Kapton stitched or anchored to the blanket could be used to control the optical transparency of the aerogel. These outcomes highlight the potential of commercial aerogel composite blankets as passive thermal control element in spacecraft. Structural and chemical characterization of the material was also done using scanning electron microscopy, Fourier transform infrared spectroscopy and x-ray photoelectron spectroscopy.

On the Influence of Nb/Ti Ratio on Environmentally-Assisted Crack Growth in High-Strength Nickel-Based Superalloys

NASA Astrophysics Data System (ADS)

Németh, A. A. N.; Crudden, D. J.; Collins, D. M.; Kuksenko, V.; Liebscher, C. H.; Armstrong, D. E. J.; Wilkinson, A. J.; Reed, R. C.

2018-05-01

The effect of Nb/Ti ratio on environmentally-assisted crack growth of three prototype Ni-based superalloys is studied. For these alloys, the yield strength is unaltered with increasing Nb/Ti ratio due to an increase in grain size. This situation has allowed the rationalization of the factors influencing damage tolerance at 700 °C. Primary intergranular cracks have been investigated using energy-dispersive X-ray spectroscopy in a scanning transmission electron microscope and the analysis of electron back-scatter diffraction patterns. Any possible detrimental effect of Nb on the observed crack tip damage due to Nb-rich oxide formation is not observed. Instead, evidence is presented to indicate that the tertiary γ'-precipitates are dissolving ahead of the crack consistent with the formation of oxides such as alumina and rutile. Our results have implications for alloy design efforts; at any given strength level, both more and less damage-tolerant variants of these alloys can be designed.

Layered Nano-TiO2 Based Treatments for the Maintenance of Natural Stones in Historical Architecture.

PubMed

Gherardi, Francesca; Goidanich, Sara; Dal Santo, Vladimiro; Toniolo, Lucia

2018-06-18

Layered treatments of natural stones based on dispersions of experimental nano-TiO 2 and commercial TEOS showing photocatalytic and self-cleaning properties were set up and tested. To enhance nano-TiO 2 efficacy, a surface pre-treatment with tetraethyl orthosilicate was proposed to avoid the penetration of NPs into the crystalline porous substrates and to improve their adhesion to the stone. Two treatment applications (wet-on-wet and wet-on-dry) were compared, showing different results. A strong interaction Si-O-Ti was the key factor for the successful treatment, leaving the band gap and relevant properties of nano-TiO 2 unaltered. The layered treatments were tested on a porous calcarenite (Noto stone) and a very compact marble (Carrara marble). The combined SiO 2 -nano-TiO 2 treatments can find application in suitable cases where a surface consolidation is needed, ensuring a depolluting and self-cleaning durable activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multifunctional Magnetic and Upconverting Nanobeads as Dual Modal Imaging Tools.

PubMed

Materia, Maria Elena; Pernia Leal, Manuel; Scotto, Marco; Balakrishnan, Preethi Bala; Kumar Avugadda, Sahitya; García-Martín, María L; Cohen, Bruce E; Chan, Emory M; Pellegrino, Teresa

2017-11-15

We report the fabrication of aqueous multimodal imaging nanocomposites based on superparamagnetic nanoparticles (MNPs) and two different sizes of photoluminescent upconverting nanoparticles (UCNPs). The controlled and simultaneous incorporation of both types of nanoparticles (NPs) was obtained by controlling the solvent composition and the addition rate of the destabilizing solvent. The magnetic properties of the MNPs remained unaltered after their encapsulation into the polymeric beads as shown by the T2 relaxivity measurements. The UCNPs maintain photoluminescent properties even when embedded with the MNPs into the polymer bead. Moreover, the light emitted by the magnetic and upconverting nanobeads (MUCNBs) under NIR excitation (λ exc = 980 nm) was clearly observed through different thicknesses of agarose gel or through a mouse skin layer. The comparison with magnetic and luminescent nanobeads based on red-emitting quantum dots (QDs) demonstrated that while the QD-based beads show significant autofluorescence background from the skin, the signal obtained by the MUCNBs allows a decrease in this background. In summary, these results indicate that MUCNBs are good magnetic and optical probes for in vivo multimodal imaging sensors.

Building Development Monitoring in Multitemporal Remotely Sensed Image Pairs with Stochastic Birth-Death Dynamics.

PubMed

Benedek, C; Descombes, X; Zerubia, J

2012-01-01

In this paper, we introduce a new probabilistic method which integrates building extraction with change detection in remotely sensed image pairs. A global optimization process attempts to find the optimal configuration of buildings, considering the observed data, prior knowledge, and interactions between the neighboring building parts. We present methodological contributions in three key issues: 1) We implement a novel object-change modeling approach based on Multitemporal Marked Point Processes, which simultaneously exploits low-level change information between the time layers and object-level building description to recognize and separate changed and unaltered buildings. 2) To answer the challenges of data heterogeneity in aerial and satellite image repositories, we construct a flexible hierarchical framework which can create various building appearance models from different elementary feature-based modules. 3) To simultaneously ensure the convergence, optimality, and computation complexity constraints raised by the increased data quantity, we adopt the quick Multiple Birth and Death optimization technique for change detection purposes, and propose a novel nonuniform stochastic object birth process which generates relevant objects with higher probability based on low-level image features.

Spatiotemporal Programing for the On-Demand Release of Bupivacaine Based on an Injectable Composite Hydrogel.

PubMed

Dinh, Van Vuong; Suh, Yun-Suhk; Yang, Han-Kwang; Lim, Yong Taik

2016-12-01

We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-release platform (90% release after 24 h), bupivacaine hydrochloride was incorporated into collagen/poly(γ-glutamic acid) hydrogel, which exhibited gel formation at body temperature. PLGA microparticles (diameter 1-3 μm) containing bupivacaine base showed a very slow release of bupivacaine (95% after 240 h), whereas PLGA nanoparticles (124 ± 30 nm) containing bupivacaine base demonstrated an intermediate release rate (95% after 160 h). By changing the relative composition ratio between the 3 components in these injectable composite hydrogels, the release of bupivacaine could be easily controlled from very rapid (within 1 day) to very delayed (up to 9 days). The experimental results on the release data (cumulative release, time point release, average release rate) were coincident with the release profile generated by computer simulation. These injectable composite hydrogels with systematically tunable mixing ratios are expected to serve as a promising technology for the on-demand release of bupivacaine in pain management. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Theoretical analysis and modeling of a photonic integrated circuit for frequency 8-tupled and 24-tupled millimeter wave signal generation: erratum.

PubMed

Hasan, Mehedi; Guemri, Rabiaa; Maldonado-Basilio, Ramón; Lucarz, Frédéric; de Bougrenet de la Tocnaye, Jean-Louis; Hall, Trevor

2015-12-15

A novel photonic circuit design for implementing frequency 8-tupling and 24-tupling was presented [Opt. Lett.39, 6950 (2014)10.1364/OL.39.006950OPLEDP0146-9592], and although its key message remains unaltered, there were typographical errors in the equations that are corrected in this erratum.

Effects of restoration techniques on breeding birds in a thermally-impacted bottomland hardwood forest

Treesearch

J. Matthew Buffington; John C. Kilgo; Robert A. Sargent; Karl V. Miller; Brian R. Chapman

2000-01-01

We evaluated the effects of revegetation techniques on breeding bird communities in a bottomland hardwood forest impacted by thermal effluent. In 1993, sections of the Pen Branch bottomland on the Savannah River Site, South Carolina, were herbicide-treated (glyphosate), burned, and planted; other sections were planted only while others were unaltered and served as...

Drug Evaluation in the Plasmodium Falciparum - Aotus Model

DTIC Science & Technology

1994-03-15

falciparum infections. Althogh erythromycin is inactive against chloroquine -resistant falciparum infections, an analogue , azithromycin, is effective in vitro...response to chloroquine , and then expand the evaluation of WR 238605, a primaquine analogue against infections. Each cyopreserved sample was thawed rapidly...confirmedo.4 chloroquine -sensitive p. via -strai-n[as not Infective for unaltered Panamanian Aotus. 14. SUBJECT TERMS 15. NUMBER OF PAGES Malaria

Leaf litter decomposition and microbial activity in nutrient-enriched and unaltered reaches of a headwater stream

Treesearch

Vladislav Gulis; Keller Suberkropp

2003-01-01

1. Decomposition of red maple (Acer rubrum) and rhododendron (Rhododendron maximum) leaves and activity of associated microorganisms were compared in two reaches of a headwater stream in Coweeta Hydrologic Laboratory, NC, U.S.A. The downstream reach was enriched with ammonium, nitrate, and phosphate whereas the upstream reach was not altered.2. Decomposition...

Developmental Changes in the Perception of Adult Facial Age

ERIC Educational Resources Information Center

Gross, Thomas F.

2007-01-01

The author studied children's (aged 5-16 years) and young adults' (aged 18-22 years) perception and use of facial features to discriminate the age of mature adult faces. In Experiment 1, participants rated the age of unaltered and transformed (eyes, nose, eyes and nose, and whole face blurred) adult faces (aged 20-80 years). In Experiment 2,…

Toward an Understanding of the Use of Academic Theories in Public Relations Practice.

ERIC Educational Resources Information Center

Cornelissen, Joep P.

2000-01-01

Discusses a focal issue in the public relations field: the way that practitioners use academic theories. Offers an exploration of the possible modes of use of academic or scientific theory in public relations practice. Notes that the premise of this model is that scientific knowledge is seldom used in an unaltered form in practice. Closes by…

Unequal Cell Frequencies in Analysis of Variance: A Review and Extension of Methodology for Multiple Missing Observations.

ERIC Educational Resources Information Center

Proger, Barton B.; And Others

Many researchers assume that unequal cell frequencies in analysis of variance (ANOVA) designs result from poor planning. However, there are several valid reasons why one might have to analyze an unequal-n data matrix. The present study reviewed four categories of methods for treating unequal-n matrices by ANOVA: (a) unaltered data (least-squares…

40 CFR 436.32 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Construction Sand and Gravel Subcategory § 436.32 Effluent limitations guidelines representing the degree of... unaltered by man's activities, is or would be less than 6.0 and water quality criteria in water quality... adjusted downward to the pH water quality criterion for the receiving waters. In no case shall a pH...

Gender Significance of Dress in the Organizational Setting.

ERIC Educational Resources Information Center

Patton, Eleanor Nyquist; Patton, Bobby R.

Which, when, and how elements of a fashion are adopted by a particular person or group are indicators of how that person or group is viewed by others within their society. For men who have worked in business and commerce, the clothing has changed little since the rise of the commercial middle class. The business suit remains unaltered because its…

Antisense Inhibition of the 2-Oxoglutarate Dehydrogenase Complex in Tomato Demonstrates Its Importance for Plant Respiration and during Leaf Senescence and Fruit Maturation[W][OA

PubMed Central

Araújo, Wagner L.; Tohge, Takayuki; Osorio, Sonia; Lohse, Marc; Balbo, Ilse; Krahnert, Ina; Sienkiewicz-Porzucek, Agata; Usadel, Björn; Nunes-Nesi, Adriano; Fernie, Alisdair R.

2012-01-01

Transgenic tomato (Solanum lycopersicum) plants expressing a fragment of the gene encoding the E1 subunit of the 2-oxoglutarate dehydrogenase complex in the antisense orientation and exhibiting substantial reductions in the activity of this enzyme exhibit a considerably reduced rate of respiration. They were, however, characterized by largely unaltered photosynthetic rates and fruit yields but restricted leaf, stem, and root growth. These lines displayed markedly altered metabolic profiles, including changes in tricarboxylic acid cycle intermediates and in the majority of the amino acids but unaltered pyridine nucleotide content both in leaves and during the progression of fruit ripening. Moreover, they displayed a generally accelerated development exhibiting early flowering, accelerated fruit ripening, and a markedly earlier onset of leaf senescence. In addition, transcript and selective hormone profiling of gibberellins and abscisic acid revealed changes only in the former coupled to changes in transcripts encoding enzymes of gibberellin biosynthesis. The data obtained are discussed in the context of the importance of this enzyme in both photosynthetic and respiratory metabolism as well as in programs of plant development connected to carbon–nitrogen interactions. PMID:22751214

Perinatal hypothyroidism modulates antioxidant defence status in the developing rat liver and heart.

PubMed

Zhang, Hongmei; Dong, Yan; Su, Qing

2017-02-01

In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.

Hydrogeological behaviour of the Fuente-de-Piedra playa lake and tectonic origin of its basin (Malaga, southern Spain)

NASA Astrophysics Data System (ADS)

Rodriguez-Rodriguez, Miguel; Martos-Rosillo, Sergio; Pedrera, Antonio

2016-12-01

Changes in the quantity of groundwater input due to water extraction for irrigation and urban supply has modified the water balance in the Fuente de Piedra playa lake. We have analysed the hydrogeology of the playa-lake system and developed a water-level model by means of a simple long-term water balance and piezometric analysis. In addition, a tectonic model is proposed to explain the endorheic basin development that led to the formation of the playa. Upright folds developed since the late Miocene and density-driven subsidence favoured the setting-up of and endorheic system located between the Atlantic and the Mediterranean basins in the Quaternary. The underlying low permeability rocks beneath the playa form a very stable aquitard with highly saline groundwater that prevents groundwater recharge of the lake into the aquitard. The hydrological modelling allowed us to simulate the evolution of the wáter level under a scenario of unaltered conditions during a 13-year period, showing that the percentage of days with dry conditions varies from 24.8% of the time under altered conditions to 14.9% as far as an unaltered scenario is concerned.

Unaltered cosmic spherules in a 1.4-Gyr-old sandstone from Finland.

PubMed

Deutsch, A; Greshake, A; Pesonen, L J; Pihlaja, P

1998-09-10

Micrometeorites-submillimetre-sized particles derived from asteroids and comets-occur in significant quantities in deep sea sediments, and the ice sheets of Greenland and Antarctica. The most abundant micrometeorites are cosmic spherules, which contain nickel-rich spinels that were crystallized and oxidized during atmospheric entry, therefore recording the oxygen content in the uppermost atmosphere. But the use of micrometeorites for detecting past changes in the flux of incoming extraterrestrial matter, and as probes of the evolution of the atmosphere, has been hampered by the fact that most objects with depositional ages higher than 0.5 Myr show severe chemical alteration. Here we report the discovery of unaltered cosmic spherules in a 1.4-Gyr-old sandstone (red bed) from Finland. From this we infer that red beds, a common lithology in the Earth's history, may contain substantial unbiased populations of fossil micrometeorites. The study of such populations would allow systematic research on variations in the micrometeorite flux from the early Proterozoic era to recent times (a time span of about 2.5 Gyr), and could help to better constrain the time when the atmospheric oxygen content was raised to its present level.

Preliminary evaluation of the landsat-4 thematic mapper data for mineral exploration

USGS Publications Warehouse

Podwysocki, M.H.; Power, M.S.; Jones, O.D.

1985-01-01

Landsat-4 Thematic Mapper (TM) data recorded over an arid terrain were analyzed to determine the applicability of using of TM data for identifying and mapping hydrothermally altered, potentially mineralized rocks. Clays, micas, and other minerals bearing the OH anion in specific crystal lattice positions have absorption bands in the 2.2-??m region (TM channel 7, TM7) and commonly lack features in the 1.6-??m region (TM5). Channel ratios TM5/TM7, TM5/TM4, and TM3/TM1 were combined into a color-ratio-composite (CRC) image and used to distinguish hydrothermally altered rocks, unaltered rocks, and vegetation. These distinctions are made possible by using the TM5 and TM7, channels which are not available in the Landsat multispectral scanner (MSS). Digital masking was used to eliminate ambiguities due to water and shadows. However, some ambiguities in identification resulted between altered volcanic rocks and unaltered sedimentary deposits that contained clays, carbonates, and gypsum, and between altered volcanic rocks and volcanic tuffs diagenetically altered to zeolites. However, compared to MSS data, TM data should greatly improve the ability to map hydrothermally altered rocks in arid terrains. ?? 1985.

Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

PubMed

Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

2017-06-01

Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

Signal velocity and group velocity for an optical pulse propagating through a GaAs cavity.

PubMed

Centini, Marco; Bloemer, Mark; Myneni, Krishna; Scalora, Michael; Sibilia, Concita; Bertolotti, Mario; D'Aguanno, Giuseppe

2003-07-01

We present measurements of the signal and group velocities for chirped optical pulses propagating through a GaAs cavity. The signal velocity is based on a specified signal-to-noise ratio at the detector. Under our experimental conditions, the chirp substantially modifies the group velocity of the pulse, but leaves the signal velocity unaltered. At unity transmittance, the velocities are equal. In general, when the transmittance is less than unity, the group velocity is faster than the signal velocity. While the group velocity can be negative, the signal velocity is always less than c/n, where c is the speed of light in vacuum and n is the refractive index of GaAs. To our knowledge, this is the first measurement of both the group velocity and the signal velocity in any system.

Recycled-tire pyrolytic carbon made functional: A high-arsenite [As(III)] uptake material PyrC350®.

PubMed

Mouzourakis, E; Georgiou, Y; Louloudi, M; Konstantinou, I; Deligiannakis, Y

2017-03-15

A novel material, PyrC 350 ® , has been developed from pyrolytic-tire char (PyrC), as an efficient low-cost Arsenite [As(III)] adsorbent from water. PyrC 350 ® achieves 31mgg -1 As(III) uptake, that remains unaltered at pH=4-8.5. A theoretical Surface Complexation Model has been developed that explains the adsorption mechanism, showing that in situ formed Fe 3 C, ZnS particles act cooperatively with the carbon matrix for As(III) adsorption. Addressing the key-issue of cost-effectiveness, we provide a comparison of As(III)-uptake effectiveness in conjunction with a cost analysis, showing that PyrC 350 ® stands in the top of [effectiveness/cost] vs. existing carbon-based, low-cost materials. Copyright © 2016 Elsevier B.V. All rights reserved.

AGR-5/6/7 Irradiation Test Predictions using PARFUME

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

Skerjanc, William F.

PARFUME, (PARticle FUel ModEl) a fuel performance modeling code used for high temperature gas-cooled reactors (HTGRs), was used to model the Advanced Gas Reactor (AGR)-5/6/7 irradiation test using predicted physics and thermal hydraulics data. The AGR-5/6/7 test consists of the combined fifth, sixth, and seventh planned irradiations of the AGR Fuel Development and Qualification Program. The AGR-5/6/7 test train is a multi-capsule, instrumented experiment that is designed for irradiation in the 133.4-mm diameter north east flux trap (NEFT) position of Advanced Test Reactor (ATR). Each capsule contains compacts filled with uranium oxycarbide (UCO) unaltered fuel particles. This report documents themore » calculations performed to predict the failure probability of tristructural isotropic (TRISO)-coated fuel particles during the AGR-5/6/7 experiment. In addition, this report documents the calculated source term from the driver fuel. The calculations include modeling of the AGR-5/6/7 irradiation that is scheduled to occur from October 2017 to April 2021 over a total of 13 ATR cycles, including nine normal cycles and four Power Axial Locator Mechanism (PALM) cycle for a total between 500 – 550 effective full power days (EFPD). The irradiation conditions and material properties of the AGR-5/6/7 test predicted zero fuel particle failures in Capsules 1, 2, and 4. Fuel particle failures were predicted in Capsule 3 due to internal particle pressure. These failures were predicted in the highest temperature compacts. Capsule 5 fuel particle failures were due to inner pyrolytic carbon (IPyC) cracking causing localized stresses concentrations in the SiC layer. This capsule predicted the highest particle failures due to the lower irradiation temperature. In addition, shrinkage of the buffer and IPyC layer during irradiation resulted in formation of a buffer-IPyC gap. The two capsules at the two ends of the test train, Capsules 1 and 5 experienced the smallest buffer-IPyC gap formation due to the lower irradiation fluences and temperatures. Capsule 3 experienced the largest buffer-IPyC gap formation of just under 24 µm. The release fraction of fission products Ag, Cs, and Sr silver (Ag), cesium (Cs), and strontium (Sr) vary depending on capsule location and irradiation temperature. The maximum release fraction of Ag occurs in Capsule 3, reaching up to 84.8% for the TRISO fuel particles. The release fraction of the other two fission products, Cs and Sr are much smaller and, in most cases, less than 1%. The notable exception is again in Capsule 3, where the release fraction for Cs and Sr reach up to 9.7% and 19.1%, respectively.« less

Detection and mapping of hydrothermally altered rocks in the vicinity of the Comstock Lode, Virginia Range, Nevada, using enhanced Landsat images

USGS Publications Warehouse

Ashley, Roger P.; Goetz, A.F.H.; Rowan, L.C.; Abrams, M.J.

1979-01-01

The Virginia Range, immediately southeast of Reno, Nev., consists mainly of flows, breccias, and turfs of Miocene age. Most of these volcanic rocks are of intermediate composition; rhyodacite is the most common rock type. Basalt, rhyolite and rhyolite tuff, and tuffaceous sedimentary rocks of Miocene and Pliocene age also cover substantial areas in the range. Pre-Tertiary metasedimentary, metavolcanic, and granitic rocks are exposed in scattered inliers, mostly along the southern and eastern margins of the range. Several large areas and many small areas within the volcanic pile were subjected to hydrothermal alteration during and after the period of intermediate volcanic activity. Economic precious metal mineralization is spatially and temporally associated with the hydrothermal alteration in several areas. The most important deposit is the Comstock Lode, which produced 192 million troy ounces of silver and 8.3 million troy ounces of gold from epithermal veins (Bonham, 1969). The hydrothermally altered rocks include silicified, advanced argillic, montmorillonite-bearing argillic, and propylitic types. The first three types typically contain pyrite, and some propylitic rocks contain pyrite as well. Supergene oxidation of these pyritic rocks produces limonitic bleached rocks. The term 'limonite,' as used here, refers to any combination of the minerals hematite, goethite, and Jarosite. Where vegetation cover is sparse to moderate, these limonitic rocks are readily identified on Landsat images enhanced by the color-ratio composite technique developed by Rowan and others (1974), so the altered areas can be mapped. About 30 percent tree cover (here mainly pinyon pine) is sufficient to change the spectral signature of individual picture elements (pixels) enough so that limonitic materials can no longer be uniquely identified. As in all other areas where this technique has been applied, limonitic unaltered rocks with intermediate to high albedos have the same appearance on the color-ratio composite as limonitic altered rocks. This problem represents the most important limitation to the use of enhanced Landsat images for detection and mapping of hydrothermally altered rocks. Reflectance spectra of altered and unaltered rocks taken in the field in the Virginia Range show that most altered rocks have a conspicuous absorption band near 2.2 ?m produced by clay minerals or alunite, whereas unaltered rocks have no features in this spectral region. Thus spectral information for selected bands in the 1.1-2.5 ?m region may allow discrimination between limonitic altered and limonitic unaltered rocks (Rowan and others, 1977; Abrams and others, 1977; Rowan and Abrams, 1978). Another potential limitation is loss of spectral information on slopes with low effective sun angle. Although a minor problem in the Virginia Range, loss of information sufficient to preclude identification of limonitic altered rocks occurs with effective sun angle lower than 20-25 degrees. Thus, even at moderate latitudes substantial parts of areas with high topographic relief may be lost to observation.

CALHM1 Deletion in Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, and Life Span.

PubMed

Hellekant, Göran; Schmolling, Jared; Marambaud, Philippe; Rose-Hellekant, Teresa A

2015-07-01

Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body weight, and life span. KO mice have no NG response to sweet and a suppressed response to bitter compared with control (wild-type [WT]) mice. KO mice showed some NG response to umami, suggesting that umami taste involves both CALHM1- and non-CALHM1-modulated signals. NG responses to sour and salty were not significantly different between KO and WT mice. Behavioral data conformed in general with the NG data. Adult KO mice consumed less food, weighed significantly less, and lived almost a year longer than WT mice. Taken together, these data demonstrate that sweet taste majorly influences food intake, body weight, and life span. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary α2δ4 subunit

PubMed Central

Caputo, Antonella; Piano, Ilaria; Demontis, Gian Carlo; Bacchi, Niccolò; Casarosa, Simona; Santina, Luca Della; Gargini, Claudia

2015-01-01

Photoreceptors rely upon highly specialized synapses to efficiently transmit signals to multiple postsynaptic targets. Calcium influx in the presynaptic terminal is mediated by voltage-gated calcium channels (VGCC). This event triggers neurotransmitter release, but also gates calcium-activated chloride channels (TMEM), which in turn regulate VGCC activity. In order to investigate the relationship between VGCC and TMEM channels, we analyzed the retina of wild type (WT) and Cacna2d4 mutant mice, in which the VGCC auxiliary α2δ4 subunit carries a nonsense mutation, disrupting the normal channel function. Synaptic terminals of mutant photoreceptors are disarranged and synaptic proteins as well as TMEM16A channels lose their characteristic localization. In parallel, calcium-activated chloride currents are impaired in rods, despite unaltered TMEM16A protein levels. Co-immunoprecipitation revealed the interaction between VGCC and TMEM16A channels in the retina. Heterologous expression of these channels in tsA-201 cells showed that TMEM16A associates with the CaV1.4 subunit, and the association persists upon expression of the mutant α2δ4 subunit. Collectively, our experiments show association between TMEM16A and the α1 subunit of VGCC. Close proximity of these channels allows optimal function of the photoreceptor synaptic terminal under physiological conditions, but also makes TMEM16A channels susceptible to changes occurring to calcium channels. PMID:26557056

Enhanced reactivity of nZVI embedded into supermacroporous cryogels for highly efficient Cr(VI) and total Cr removal from aqueous solution.

PubMed

Jia, Zhenzhen; Shu, Yuehong; Huang, Renlong; Liu, Junguang; Liu, Lingling

2018-05-01

Novel supermacroporous PSA-nZVI composites with nanoscale zero-valent iron particles (nZVI) embedded into poly (sodium acrylate) (PSA) cryogels were synthesized through ion exchange followed by in-situ reduction. The magnetic composites were evaluated for material characterizations and their efficiency for Cr(VI) and total Cr removal from aqueous medium in batch experiments. PSA-nZVI composites with high nZVI loading capacity up to 128.70 mg Fe/g PSA were obtained, and the interconnected macroporous structure of PSA cryogel remained unaltered with nZVI uniformly distributed on PSA cryogel as determined by TGA, SEM, TEM, XRD and XPS analyses. PSA-nZVI composites showed faster reaction rate than free nZVI both for Cr(VI) and total Cr removal, suggesting no mass transfer resistance and the enhanced reactivity of nZVI in PSA carrier. PSA-nZVI composites exhibited much more remarkable performance for Cr(VI) and total Cr removal than free nZVI particles in high removal capacity and broad pH application range (pH 4-10). The reaction mechanisms were also elucidated with XPS analyses before and after Cr(VI) reduction reactions. These results demonstrate that PSA cryogel acts as an excellent carrier and shows multiple functions in nZVI particle dispersion, pH buffering and oxidation resistance in addition to immobilizing nZVI particles from release. Copyright © 2018 Elsevier Ltd. All rights reserved.

Oxygen plasma surface modification augments poly(L-lactide-co-glycolide) cytocompatibility toward osteoblasts and minimizes immune activation of macrophages.

PubMed

Scislowska-Czarnecka, Anna; Szmigiel, Dariusz; Genet, Michel; Dupont-Gillain, Christine; Pamula, Elzbieta; Kolaczkowska, Elzbieta

2015-12-01

Here, we report on modification of one of the model biomedical polymers, poly L-lactide-co-glycolide (PLGA; 85:15), by reactive ion etching (RIE) oxygen plasma treatment. PLGA's major disadvantage is high hydrophobicity which restrains binding of cell-adhesive proteins and host cells. In the current approach, we aimed to answer two questions: (1) will only short (10 s) and moderate (20-200 mTorr, 45-90 W) RIE oxygen plasma treatment, leading to decrease of water contact angle by only up to 10°, sufficiently improve PLGA adherence to cells, and (2) how will this affect osteoblasts and activation of the immune system? All obtained modified PLGAs had improved hydrophilicity but unaltered roughness (as revealed by water contact angle measurements, X-ray photoelectron spectroscopy, and atomic force microscopy) resulting in significantly improved adhesion of osteoblasts (MG-63) and their low activation. Importantly, macrophages (RAW 264.7), one of the key cells initiating inflammation and bone resorption, responded significantly less vigorously to the modified polymers, expressing/releasing lower amounts of nitric oxide, matrix metalloproteinases (MMP-9), and pro-inflammatory cytokines (TNF-α, IL-6, IL-12p70, IFN-γ, IL-10). We conclude that already slight RIE oxygen plasma modification of PLGA is sufficient to improve its surface properties, and enhance cytocompatibility. Most importantly, this type of modification prevents excessive immune response. © 2015 Wiley Periodicals, Inc.

Regulation of dendritic cell function by insulin/IGF-1/PI3K/Akt signaling through klotho expression.

PubMed

Xuan, Nguyen Thi; Hoang, Nguyen Huy; Nhung, Vu Phuong; Duong, Nguyen Thuy; Ha, Nguyen Hai; Hai, Nong Van

2017-06-01

Insulin or insulin-like growth factor 1 (IGF-1) promotes the activation of phosphoinositide 3 kinase (PI3K)/Akt signaling in immune cells including dendritic cells (DCs), the most potent professional antigen-presenting cells for naive T cells. Klotho, an anti-aging protein, participates in the regulation of the PI3K/Akt signaling, thus the Ca 2+ -dependent migration is reduced in klotho-deficient DCs. The present study explored the effects of insulin/IGF-1 on DC function through klotho expression. To this end, the mouse bone marrow cells were isolated and cultured with GM-CSF to attain bone marrow-derived DCs (BMDCs). Cells were treated with insulin or IGF-1 and followed by stimulating with lipopolysaccharides (LPS). Tumor necrosis factor (TNF)-α formation was examined by enzyme-linked immunosorbent assay (ELISA). Phagocytosis was analyzed by FITC-dextran uptake assay. The expression of klotho was determined by quantitative PCR, immunoprecipitation and western blotting. As a result, treatment of the cells with insulin/IGF-1 resulted in reducing the klotho expression as well as LPS-stimulated TNF-α release and increasing the FITC-dextran uptake but unaltering reactive oxygen species (ROS) production in BMDCs. The effects were abolished by using pharmacological inhibition of PI3K/Akt with LY294002 and paralleled by transfecting DCs with klotho siRNA. In conclusion, the regulation of klotho sensitive DC function by IGF-1 or insulin is mediated through PI3K/Akt signaling pathway in BMDCs.

Pavlovian autoshaping procedures increase plasma corticosterone and levels of norepinephrine and serotonin in prefrontal cortex in rats.

PubMed

Tomie, Arthur; Tirado, Aidaluz D; Yu, Lung; Pohorecky, Larissa A

2004-08-12

Pavlovian autoshaping procedures provide for pairings of a small object conditioned stimulus (CS) with a rewarding substance unconditioned stimulus (US), resulting in the acquisition of complex sequences of CS-directed skeletal-motor responses or autoshaping conditioned responses (CRs). Autoshaping procedures induce higher post-session levels of corticosterone than in controls receiving CS and US randomly, and the enhanced post-session corticosterone levels have been attributed to the appetitive or arousal-inducing effects of autoshaping procedures. Enhanced corticosterone release can be induced by aversive stimulation or stressful situations, where it is often accompanied by higher levels of norepinephrine (NE) and serotonin (5-HT) in prefrontal cortex (PFC) but not in striatum (ST). Effects of autoshaping procedures on post-session corticosterone levels, NE contents in PFC, and 5-HT contents in PFC and ST were investigated in male Long-Evans rats. Post-session blood samples revealed higher corticosterone levels in the CS-US Paired group (n = 46) than in the CS-US Random control group (n = 21), and brain samples revealed higher levels of PFC NE and 5-HT in CS-US Paired group. Striatal 5-HT levels were unaltered by the autoshaping procedures. Autoshaping procedures provide for appetitive stimulation and induce an arousal-like state, as well as simultaneous stress-like changes in plasma corticosterone and monoamine levels in PFC. Autoshaping, therefore, may be useful for the study of endocrine and central processes associated with appetitive conditions.

Mechanisms of Drug Toxicity and Antagonism.

DTIC Science & Technology

1984-01-29

nvestigation of various vaesogenle compounds Including the a-blocking adrenergic agents as cyanide antagonists. The a-adrenerwlc blocker...that the antidotal effect of phenoxybonsamine can be reversed with the a-monist. hethoxamine. Of all the other autonomie agents and vasodilators...unaltered In the OOS treated rats when compared with the levels in the corn oil treated group. Treatment with other agents prior to the OOS administratlon

Proceedings of the Meeting of the Study Committee of International Federation for Documentation "Research on the Theoretical Basis of Information" (Moscow, 24-26 February 1970).

ERIC Educational Resources Information Center

All-Union Inst. for Scientific and Technical Information, Moscow (USSR).

Reports given before the Committee on "Research on the Theoretical Basis of Information" of the International Federation for Documentation (FID/RI) are presented unaltered and unabridged in English or in Russian -- the language of their presentation. Each report is accompanied by an English or Russian resume. Generally, only original…

Evaluation of the use of scientific information in developing the 1997 Forest plan for the Tongass National Forest.

Treesearch

Fred H. Everest; Douglas N. Swanston; Charles G. Shaw; Winston P. Smith; Kent R. Julin; Stewart D. Allen

1997-01-01

The Tongass National Forest is the largest remaining relatively unaltered coastal temperate rain forest in the world. The Forest consists of 16.9 million acres of land distributed across more that 22,000 islands and a narrow strip of mainland in southeast Alaska. The Forest contains abundant timber, wildlife, fisheries, mineral, and scenic resources. The authors...

Comparisons of Stuttering Frequency during and after Speech Initiation in Unaltered Feedback, Altered Auditory Feedback and Choral Speech Conditions

ERIC Educational Resources Information Center

Saltuklaroglu, Tim; Kalinowski, Joseph; Robbins, Mary; Crawcour, Stephen; Bowers, Andrew

2009-01-01

Background: Stuttering is prone to strike during speech initiation more so than at any other point in an utterance. The use of auditory feedback (AAF) has been found to produce robust decreases in the stuttering frequency by creating an electronic rendition of choral speech (i.e., speaking in unison). However, AAF requires users to self-initiate…

Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets.

PubMed

Karkossa, Frank; Klein, Sandra

2017-10-01

The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength. Drug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied. Results from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible. © 2017 Royal Pharmaceutical Society.

Modulation of drug release kinetics of shellac-based matrix tablets by in-situ polymerization through annealing process.

PubMed

Limmatvapirat, Sontaya; Limmatvapirat, Chutima; Puttipipatkhachorn, Satit; Nunthanid, Jurairat; Luangtana-anan, Manee; Sriamornsak, Pornsak

2008-08-01

A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased.

Preparation and evaluation of fenoterol hydrobromide suppositories.

PubMed

Ghorab, D; Refai, H; Tag, R

2011-12-01

Fenoterol HBr is a bronchodilator known to be subject to first pass effect after oral administration. The aim of this study was to prepare and evaluate fenoterol HBr suppositories. Suppositories were prepared by a fusion method using different fatty bases, viz. Witepsol H15, Witepsol E75, Suppocire AP, and Suppocire BM, as well as different hydrophilic bases, viz. polyethylene glycol and poloxamer bases. In vitro release studies revealed a greater release of the drug from hydrophilic bases than from fatty bases. The effect of incorporating different types and concentrations of non-ionic surfactants (Tween 60 and Span 20) on the release rate of the drug from Witepsol H15, as a model fatty base, was investigated. Results showed an enhanced release at low surfactant concentrations. A very fast 100% drug release was achieved when the drug was incorporated as an aqueous solution in Witepsol H15 (F17). This formula was selected to test the effect of fenoterol HBr suppositories on histamine-induced bronchospasms in Guinea pigs. No dyspnea of the animals was recorded for up to 30 min. In addition, thermogel liquid suppositories of different poloxamer 188 and poloxamer 407 proportions in the presence of sodium alginate as a mucoadhesive polymer were prepared. The different formulations behaved similarly concerning sustainment of drug release, however, only the formula containing 15% poloxamer 188 and 25% poloxamer 407 (F20) showed optimal gelation at body temperature. In conclusion, among the studied suppository bases there are bases suitable for fast release of the drug like F17 and hydrophilic bases especially polyethylene glycol, as well as other bases for sustained release applications of fenoterol HBr like fatty and thermogel bases.

Assessment of skeletal changes after post-mortem exposure to fire as an indicator of decomposition stage.

PubMed

Keough, N; L'Abbé, E N; Steyn, M; Pretorius, S

2015-01-01

Forensic anthropologists are tasked with interpreting the sequence of events from death to the discovery of a body. Burned bone often evokes questions as to the timing of burning events. The purpose of this study was to assess the progression of thermal damage on bones with advancement in decomposition. Twenty-five pigs in various stages of decomposition (fresh, early, advanced, early and late skeletonisation) were exposed to fire for 30 min. The scored heat-related features on bone included colour change (unaltered, charred, calcined), brown and heat borders, heat lines, delineation, greasy bone, joint shielding, predictable and minimal cracking, delamination and heat-induced fractures. Colour changes were scored according to a ranked percentage scale (0-3) and the remaining traits as absent or present (0/1). Kappa statistics was used to evaluate intra- and inter-observer error. Transition analysis was used to formulate probability mass functions [P(X=j|i)] to predict decomposition stage from the scored features of thermal destruction. Nine traits displayed potential to predict decomposition stage from burned remains. An increase in calcined and charred bone occurred synchronously with advancement of decomposition with subsequent decrease in unaltered surfaces. Greasy bone appeared more often in the early/fresh stages (fleshed bone). Heat borders, heat lines, delineation, joint shielding, predictable and minimal cracking are associated with advanced decomposition, when bone remains wet but lacks extensive soft tissue protection. Brown burn/borders, delamination and other heat-induced fractures are associated with early and late skeletonisation, showing that organic composition of bone and percentage of flesh present affect the manner in which it burns. No statistically significant difference was noted among observers for the majority of the traits, indicating that they can be scored reliably. Based on the data analysis, the pattern of heat-induced changes may assist in estimating decomposition stage from unknown, burned remains. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Intervertebral anticollision constraints improve out-of-plane translation accuracy of a single-plane fluoroscopy-to-CT registration method for measuring spinal motion

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

Lin, Cheng-Chung; Tsai, Tsung-Yuan; Hsu, Shih-Jung

2013-03-15

Purpose: The study aimed to propose a new single-plane fluoroscopy-to-CT registration method integrated with intervertebral anticollision constraints for measuring three-dimensional (3D) intervertebral kinematics of the spine; and to evaluate the performance of the method without anticollision and with three variations of the anticollision constraints via an in vitro experiment. Methods: The proposed fluoroscopy-to-CT registration approach, called the weighted edge-matching with anticollision (WEMAC) method, was based on the integration of geometrical anticollision constraints for adjacent vertebrae and the weighted edge-matching score (WEMS) method that matched the digitally reconstructed radiographs of the CT models of the vertebrae and the measured single-plane fluoroscopymore » images. Three variations of the anticollision constraints, namely, T-DOF, R-DOF, and A-DOF methods, were proposed. An in vitro experiment using four porcine cervical spines in different postures was performed to evaluate the performance of the WEMS and the WEMAC methods. Results: The WEMS method gave high precision and small bias in all components for both vertebral pose and intervertebral pose measurements, except for relatively large errors for the out-of-plane translation component. The WEMAC method successfully reduced the out-of-plane translation errors for intervertebral kinematic measurements while keeping the measurement accuracies for the other five degrees of freedom (DOF) more or less unaltered. The means (standard deviations) of the out-of-plane translational errors were less than -0.5 (0.6) and -0.3 (0.8) mm for the T-DOF method and the R-DOF method, respectively. Conclusions: The proposed single-plane fluoroscopy-to-CT registration method reduced the out-of-plane translation errors for intervertebral kinematic measurements while keeping the measurement accuracies for the other five DOF more or less unaltered. With the submillimeter and subdegree accuracy, the WEMAC method was considered accurate for measuring 3D intervertebral kinematics during various functional activities for research and clinical applications.« less

Use of natural and biobased materials for controlled-release of urea in water: Environmental applications

USDA-ARS?s Scientific Manuscript database

Urea pearls were encapsulated in cloisite-based matrices using different natural materials (lignin, beeswax and latex) to control the release of urea over time. It was found that all cloisite-based fertilizer tablets showed better release profiles than neat urea tablets. The best release profile was...

Kinetics and mechanism of release from glyceryl monostearate-based implants: evaluation of release in a gel simulating in vivo implantation.

PubMed

Allababidi, S; Shah, J C

1998-06-01

The overall objective of the study was to design an implantable delivery system based on glyceryl monostearate (GMS) for the site-specific delivery of antibiotics for the prevention of surgical wound infection. To design the implant, a release method had to be developed that simulate the in vivo implantation conditions to be able to predict the release characteristics from the implants when they are actually used in vivo. Also, identifying the release kinetics and mechanism and evaluating the factors that influence the release of drugs from the GMS-based matrix were necessary to allow further design of implants that could yield a desired release rate. The release of cefazolin was monitored from GMS matrixes implanted into agar gel, simulating subcutaneous tissues with respect to viscosity and water content. The gel method resulted in observation of spatial and temporal concentration profiles in the immediate vicinity of the implants, indicating the benefits of local drug delivery; however, there was no significant difference between the cumulative release profiles by the gel method or the vial release method. The release of cefazolin from the GMS-based matrix with the vial method followed Higuchi's square root of time kinetics. The release rate was found to be directly proportional to cefazolin load (A) and the surface area (SA) of the matrix as expressed by the following equation: = 0.24ASA. On the basis of this equation, one can design a variety of GMS matrixes that would result in a desired release rate or release duration. This also indicated that cefazolin release followed the release kinetics of a freely soluble drug from an insoluble matrix and hence it is a diffusion-controlled process. The effect of drug solubility on the release kinetics was determined by comparing the release kinetics of the poorly water soluble ciprofloxacin (0.16 mg/mL) to that of the highly water soluble cefazolin (325 mg/mL). The release duration of ciprofloxacin (80 h) was longer than that of cefazolin (25 h) from identical GMS matrixes. Although ciprofloxacin release was initially controlled by the matrix, agitation accelerated disintegration of the matrix and release due to its poor solubility, and ciprofloxacin release appeared to be a dissolution-controlled process following zero-order release kinetics.

Disentangling the drivers of soil organic matter decay as temperature changes by integrating reductionist systems with soil data

NASA Astrophysics Data System (ADS)

Billings, Sharon; Ballantyne, Ford, IV; Min, Kyungjin; Lehmeier, Christoph; Ziegler, Susan

2014-05-01

Accurately predicting decomposition rates of soil organic matter (SOM) as temperature increases is critical for projecting future atmospheric [CO2]. SOM decay is catalyzed by exo-enzymes (EEs) produced by microorganisms and secreted into the soil. Microbes take up liberated resources for metabolic processes and release diverse compounds, including CO2. Historically, investigations of the influence of temperature on heterotrophic CO2 release have focused on CO2 response, including its isotopic composition; recent studies also assess EE activity and microbial community composition. However, it is difficult to generalize from such studies how temperature will influence SOM decay and CO2 release because the responses of EEs, microbial resource demand, biomass production rates, and respiration rates are not parsed. Quantifying the individual temperature responses of all of these processes in unaltered soil is not tractable. However, we can use experimentally simplified systems to quantify fundamental biochemical and physiological responses to temperature and compare these results to those from environmental samples. For example, we can quantify the degree to which EE kinetics in isolation induce changes in availability of microbially assimilable resources as temperature changes and calculate associated changes in relative availability of assimilable carbon and nitrogen (C:N flow ratio), in isolation from altered microbial resource demand or uptake. We also can assess EE activity and CO2 release at different temperatures in diverse soils, integrating temperature responses of EE kinetics and microbial communities. Discrepancies in the temperature responses between real soils and isolated enzyme-substrate reactions can reveal how adaptive responses of microbial communities influence the temperature responses of soil heterotrophic CO2 release. We have shown in purified reactions that C:N flow ratios increase with temperature at pH 4.5, but decline between pH 6.5 and 8.5. If soil microbes exhibited no change in resource demand or C allocation with altered C:N flow ratios and if relative C availability was tightly coupled to respiration, we would expect variation in C:N flow ratios predicted by purified solutions to be expressed in analogous, relative patterns of C mineralization. However, the positive response of heterotrophic CO2 release to similar temperature increases in five strongly acidic forest soils (three boreal, one cool temperate, and one warm temperate) was much smaller than in a neutral-pH grassland or an alkaline desert, the opposite of what we might predict if C:N flow ratio was the only driver of respiratory responses to temperature. We also observe distinct d13C of CO2 respired from pure cultures in which substrate composition and availability are strictly controlled as temperature changes, reflecting fundamental shifts in C flux through metabolic pathways. These changes in d13C-CO2 with warming are greater than those observed in soils. Combined, these CO2 and d13C-CO2 data suggest that soil microbial adaptation to temperature is a meaningful driver of heterotrophic respiratory responses to temperature. We highlight the utility of reductionist experimental systems for characterizing fundamental SOM decay rates and changes in microbial C metabolism at different temperatures, and integrating them with analogous data derived from soils to quantify the role of microbial adaptation as a driver of SOM decay.

An efficient removal of methyl orange dye from aqueous solution by adsorption onto chitosan/MgO composite: A novel reusable adsorbent

NASA Astrophysics Data System (ADS)

Haldorai, Yuvaraj; Shim, Jae-Jin

2014-02-01

We report a novel multi-functional magnesium oxide (MgO) immobilized chitosan (CS) composite was prepared by chemical precipitation method. The CS-MgO composite was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy and zeta potential. The composite was applied as a novel adsorbent for removal of methyl orange model dye and the effect of adsorbent dosage, pH and contact time were studied. The adsorption kinetics followed a pseudo second order reaction. The adsorbent efficiency was unaltered even after five cycles of reuse. In addition, the composite exhibited a superior antibacterial efficacy of 93% within 24 h against Escherichia coli as measured by colony forming units. Based on the data of present investigation the composite being a biocompatible, eco-friendly and low-cost adsorbent with antibacterial activity could find potential applications in variety of fields and in particular environmental applications.

Clay facial masks: physicochemical stability at different storage temperatures.

PubMed

Zague, Vivian; de Almeida Silva, Diego; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles

2007-01-01

Clay facial masks--formulations that contain a high percentage of solids dispersed in a liquid vehicle--have become of special interest due to specific properties presented by clays, such as particle size, cooling index, high adsorption capacity, and plasticity. Although most of the physicochemical properties of clay dispersions have been studied, specific aspects concerning the physicochemical stability of clay mask products remain unclear. This work aimed at investigating the accelerated physicochemical stability of clay mask formulations stored at different temperatures. Formulations were subjected to centrifuge testing and to thermal treatment for 15 days, during which temperature was varied from -5.0 degrees to 45.0 degrees C. The apparent viscosity and visual aspect (homogeneity) of all formulations were affected by temperature variation, whereas color, odor, and pH value remained unaltered. These results, besides the estimation of physicochemical stability under aging, can be useful in determining the best storage conditions for clay-based formulations.

An Ecoregion-Based Approach to Protecting Half the Terrestrial Realm.

PubMed

Dinerstein, Eric; Olson, David; Joshi, Anup; Vynne, Carly; Burgess, Neil D; Wikramanayake, Eric; Hahn, Nathan; Palminteri, Suzanne; Hedao, Prashant; Noss, Reed; Hansen, Matt; Locke, Harvey; Ellis, Erle C; Jones, Benjamin; Barber, Charles Victor; Hayes, Randy; Kormos, Cyril; Martin, Vance; Crist, Eileen; Sechrest, Wes; Price, Lori; Baillie, Jonathan E M; Weeden, Don; Suckling, Kierán; Davis, Crystal; Sizer, Nigel; Moore, Rebecca; Thau, David; Birch, Tanya; Potapov, Peter; Turubanova, Svetlana; Tyukavina, Alexandra; de Souza, Nadia; Pintea, Lilian; Brito, José C; Llewellyn, Othman A; Miller, Anthony G; Patzelt, Annette; Ghazanfar, Shahina A; Timberlake, Jonathan; Klöser, Heinz; Shennan-Farpón, Yara; Kindt, Roeland; Lillesø, Jens-Peter Barnekow; van Breugel, Paulo; Graudal, Lars; Voge, Maianna; Al-Shammari, Khalaf F; Saleem, Muhammad

2017-06-01

We assess progress toward the protection of 50% of the terrestrial biosphere to address the species-extinction crisis and conserve a global ecological heritage for future generations. Using a map of Earth's 846 terrestrial ecoregions, we show that 98 ecoregions (12%) exceed Half Protected; 313 ecoregions (37%) fall short of Half Protected but have sufficient unaltered habitat remaining to reach the target; and 207 ecoregions (24%) are in peril, where an average of only 4% of natural habitat remains. We propose a Global Deal for Nature-a companion to the Paris Climate Deal-to promote increased habitat protection and restoration, national- and ecoregion-scale conservation strategies, and the empowerment of indigenous peoples to protect their sovereign lands. The goal of such an accord would be to protect half the terrestrial realm by 2050 to halt the extinction crisis while sustaining human livelihoods.

An Ecoregion-Based Approach to Protecting Half the Terrestrial Realm

PubMed Central

Olson, David; Joshi, Anup; Burgess, Neil D.; Wikramanayake, Eric; Hahn, Nathan; Palminteri, Suzanne; Hedao, Prashant; Noss, Reed; Hansen, Matt; Locke, Harvey; Ellis, Erle C; Jones, Benjamin; Barber, Charles Victor; Hayes, Randy; Kormos, Cyril; Martin, Vance; Crist, Eileen; Sechrest, Wes; Price, Lori; Baillie, Jonathan E. M.; Weeden, Don; Suckling, Kierán; Davis, Crystal; Sizer, Nigel; Moore, Rebecca; Thau, David; Birch, Tanya; Potapov, Peter; Turubanova, Svetlana; Tyukavina, Alexandra; de Souza, Nadia; Pintea, Lilian; Brito, José C.; Llewellyn, Othman A.; Miller, Anthony G.; Patzelt, Annette; Ghazanfar, Shahina A.; Timberlake, Jonathan; Klöser, Heinz; Shennan-Farpón, Yara; Kindt, Roeland; Lillesø, Jens-Peter Barnekow; van Breugel, Paulo; Graudal, Lars; Voge, Maianna; Al-Shammari, Khalaf F.; Saleem, Muhammad

2017-01-01

Abstract We assess progress toward the protection of 50% of the terrestrial biosphere to address the species-extinction crisis and conserve a global ecological heritage for future generations. Using a map of Earth's 846 terrestrial ecoregions, we show that 98 ecoregions (12%) exceed Half Protected; 313 ecoregions (37%) fall short of Half Protected but have sufficient unaltered habitat remaining to reach the target; and 207 ecoregions (24%) are in peril, where an average of only 4% of natural habitat remains. We propose a Global Deal for Nature—a companion to the Paris Climate Deal—to promote increased habitat protection and restoration, national- and ecoregion-scale conservation strategies, and the empowerment of indigenous peoples to protect their sovereign lands. The goal of such an accord would be to protect half the terrestrial realm by 2050 to halt the extinction crisis while sustaining human livelihoods. PMID:28608869

Ethical reasons for narrowing the scope of biotech patents.

PubMed

Andreassen, Tom

2015-11-01

Patents on biotech products have a scope that goes well beyond what is covered by the most widely applied ethical justifications of intellectual property. Neither natural rights theory from Locke, nor public interest theory of IP rights justifies the wide scope of legal protection. The article takes human genes as an example, focusing on the component that is not invented but persists as unaltered gene information even in the synthetically produced complementary DNA, the cDNA. It is argued that patent on cDNA holds this information captive, or illegitimately appropriates it in limiting other researchers and inventors' opportunity to explore new functions and uses based on this non-invented information. A tighter connection between legal IP protection and the use description stated in the patent claim is suggested. By binding protection to the product's foreseeable functions and use, instead of the product itself and all future uses of it, legitimacy of biotech product patents is restored.

Effects of initial-state nucleon shadowing on the elliptic flow of thermal photons

NASA Astrophysics Data System (ADS)

Dasgupta, Pingal; Chatterjee, Rupa; Singh, Sushant K.; Alam, Jan-e.

2018-03-01

Recently the effect of nucleon shadowing on the Monte Carlo-Glauber initial condition was studied and its role on the centrality dependence of elliptic flow (v2) and fluctuations in initial eccentricity for different colliding nuclei were explored. It was found that the results with shadowing effects are closer to the QCD-based dynamical model as well as to the experimental data. Inspired by this outcome, in this work we study the transverse momentum (pT) spectra and elliptic flow of thermal photons for Au +Au collisions at the BNL Relativisitic Heavy Ion Collider and Pb +Pb collisions at the CERN Large Hadron Collider by incorporating the shadowing effects in deducing the initial energy density profile required to solve the relativistic hydrodynamical equations. We find that the thermal photon spectra remain almost unaltered; however, the elliptic flow of photons is found to be enhanced significantly due to shadowing effects.

Proteomic analysis in giant axonal neuropathy: new insights into disease mechanisms.

PubMed

Mussche, Silke; De Paepe, Boel; Smet, Joél; Devreese, Katrien; Lissens, Willy; Rasic, Vedrana Milic; Murnane, Matthew; Devreese, Bart; Van Coster, Rudy

2012-08-01

Giant axonal neuropathy (GAN) is a progressive hereditary disease that affects the peripheral and central nervous systems. It is characterized morphologically by aggregates of intermediate filaments in different tissues. Mutations have been reported in the gene that codes for gigaxonin. Nevertheless, the underlying molecular mechanism remains obscure. Cell lines from 4 GAN patients and 4 controls were analyzed by iTRAQ. Among the dysregulated proteins were ribosomal protein L29, ribosomal protein L37, galectin-1, glia-derived nexin, and aminopeptidase N. Also, nuclear proteins linked to formin-binding proteins were found to be dysregulated. Although the major role of gigaxonin is reported to be degradation of cytoskeleton-associated proteins, the amount of 76 structural cytoskeletal proteins was unaltered. Several of the dysregulated proteins play a role in cytoskeletal reorganization. Based on these findings, we speculate that disturbed cytoskeletal regulation is responsible for formation of aggregates of intermediate filaments. Copyright © 2012 Wiley Periodicals, Inc.

Drug disposition in obesity: toward evidence-based dosing.

PubMed

Knibbe, Catherijne A J; Brill, Margreke J E; van Rongen, Anne; Diepstraten, Jeroen; van der Graaf, Piet Hein; Danhof, Meindert

2015-01-01

Obesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion may be premature. Volume of distribution may vary largely, but the magnitude and direction of changes seem difficult to predict, with extrapolation on the basis of total body weight being the best approach to date. Changes in clearance may be smaller than in distribution, whereas there is growing evidence that the influence of obesity on clearance can be predicted on the basis of reported changes in the metabolic or elimination pathways involved. For obese children, we propose two methods to distinguish between developmental and obesity-related changes. Future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.

Precise Chemical Analyses of Planetary Surfaces

NASA Technical Reports Server (NTRS)

Kring, David; Schweitzer, Jeffrey; Meyer, Charles; Trombka, Jacob; Freund, Friedemann; Economou, Thanasis; Yen, Albert; Kim, Soon Sam; Treiman, Allan H.; Blake, David;

Non-explosive actuation for the ORBCOMM (TM) satellite

NASA Technical Reports Server (NTRS)

Robinson, Anthony; Courtney, Craig; Moran, Tom

1995-01-01

Spool-based non-explosive actuator (NEA) devices are used for three important holddown and release functions during the establishment of the ORBCOMM (TM) constellation. Non-explosive separation nuts are used to restrain and release the 26 individual satellites into low earth orbit. Cable release mechanisms based on the same technology are used to release the solar arrays and antenna boom.

Formulation and Evaluation of Tramadol hydrochloride Rectal Suppositories.

PubMed

Saleem, M A; Taher, M; Sanaullah, S; Najmuddin, M; Ali, Javed; Humaira, S; Roshan, S

2008-09-01

Rectal suppositories of tramadol hydrochloride were prepared using different bases and polymers like PEG, cocoa butter, agar and the effect of different additives on in vitro release of tramadol hydrochloride was studied. The agar-based suppositories were non-disintegrating/non-dissolving, whereas PEGs were disintegrating/dissolving and cocoa butter were melting suppositories. All the prepared suppositories were evaluated for various physical parameters like weight variation, drug content and hardness. The PEG and cocoa butter suppositories were evaluated for macromelting range, disintegration and liquefaction time. In vitro release study was performed by USP type I apparatus. The prepared suppositories were within the permissible range of all physical parameters. In vitro drug release was in the order of PEG>Agar>cocoa butter. Addition of PVP, HPMC in agar suppositories retards the release. The mechanism of drug release was diffusion controlled and follows first order kinetics. The results suggested that blends of PEG of low molecular weight (1000) with high molecular weight (4000 and 6000) in different percentage and agar in 10% w/w as base used to formulate rapid release suppositories. The sustained release suppositories can be prepared by addition of PVP, HPMC in agar-based suppositories and by use of cocoa butter as base.

Promoting International Energy Security. Volume 3: Sea-Lanes to Asia

DTIC Science & Technology

2012-01-01

commercial use only. Unauthorized posting of RAND electronic documents to a non-RAND website is prohibited. RAND electronic documents are protected under...copyright law. Permission is required from RAND to reproduce, or reuse in another form, any of our research documents for commercial use . For...trademark. © Copyright 2012 RAND Corporation Permission is given to duplicate this document for personal use only, as long as it is unaltered and

Response to comments on "Can we name Earth's species before they go extinct?".

PubMed

Costello, Mark J; May, Robert M; Stork, Nigel E

2013-07-19

Mora et al. disputed that most species will be discovered before they go extinct, but not our main recommendations to accelerate species' discoveries. We show that our conclusions would be unaltered by discoveries of more microscopic species and reinforce our estimates of species description and extinction rates, that taxonomic effort has never been greater, and that there are 2 to 8 million species on Earth.

Carrier-envelope phase control by a composite plate.

PubMed

Ell, Richard; Birge, Jonathan R; Araghchini, Mohammad; Kärtner, Franz X

2006-06-12

We demonstrate a new concept to vary the carrier-envelope phase of a mode-locked laser by a composite plate while keeping all other pulse parameters practically unaltered. The effect is verified externally in an interferometric autocorrelator, as well as inside the cavity of an octave-spanning femtosecond oscillator. The carrier-envelope frequency can be shifted by half the repetition rate with negligible impact on pulse spectrum and energy.

A New Formulation for the Removal and Remediation of Polychlorinated Biphenyls in Painted Structures

NASA Technical Reports Server (NTRS)

Quinn, Jacqueline; Brooks, Kathleen; Geiger, Cherie; Clausen, Christian

2009-01-01

This new technology report will describe the laboratory development of a new and innovative solution for the removal and destruction of PCBs found in painted structures or within the binding or caulking material on structures. The technology incorporates a Bimetallic Treatment System (BTS) that extracts and degrades only the PCBs found on the facilities, leaving in most cases the structure virtually unaltered.

Alteration of Airway Reactivity and Reduction of Ryanodine Receptor Expression by Cigarette Smoke in Mice.

PubMed

Donovan, Chantal; Seow, Huei Jiunn; Royce, Simon G; Bourke, Jane E; Vlahos, Ross

2015-10-01

Small airways are a major site of airflow limitation in chronic obstructive pulmonary disease (COPD). Despite the detrimental effects of long-term smoking in COPD, the effects of acute cigarette smoke (CS) exposure on small airway reactivity have not been fully elucidated. Balb/C mice were exposed to room air (sham) or CS for 4 days to cause airway inflammation. Changes in small airway lumen area in response to contractile agents were measured in lung slices in situ using phase-contrast microscopy. Separate slices were pharmacologically maintained at constant intracellular Ca(2+) using caffeine/ryanodine before contractile measurements. Gene and protein analysis of contractile signaling pathways were performed on separate lungs. Monophasic contraction to serotonin became biphasic after CS exposure, whereas contraction to methacholine was unaltered. This altered pattern of contraction was normalized by caffeine/ryanodine. Expression of contractile agonist-specific receptors was unaltered; however, all isoforms of the ryanodine receptor were down-regulated. This is the first study to show that acute CS exposure selectively alters small airway contraction to serotonin and down-regulates ryanodine receptors involved in maintaining Ca(2+) oscillations in airway smooth muscle. Understanding the contribution of ryanodine receptors to altered airway reactivity may inform the development of novel treatment strategies for COPD.

Elevated central venous pressure: a consequence of exercise training-induced hypervolemia?

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Mack, G. W.; Nadel, E. R.

1991-01-01

Resting blood volumes and arterial and central venous pressures (CVP) were measured in 14 men before and after exercise training to determine whether training-induced hypervolemia is accompanied by a change in total vascular capacitance. In addition, resting levels of plasma arginine vasopressin (AVP), atrial natriuretic peptide (ANP), aldosterone (Ald), and norepinephrine (NE) were measured. The same measurements were conducted in seven subjects who did not undergo exercise and acted as controls. Exercise training consisted of 10 wk of controlled cycle exercise for 30 min/day, 4 days/wk at 75-80% of maximal O2 uptake (VO2max). A training effect was verified by a 20% increase in VO2max, a resting bradycardia, and a 9% increase in blood volume. Mean arterial blood pressure was unaltered by exercise training, but resting CVP increased by 16% (P less than 0.05). The percent change in blood volume from before to after training was linearly related to the percent change in CVP (r = 0.903, P less than 0.05). As a consequence of elevations in both blood volume and CVP, the volume-to-pressure ratio was unchanged after exercise training. Plasma AVP, ANP, Ald, and NE were unaltered. Our results indicate that elevated CVP is a consequence of training-induced hypervolemia without alteration in total effective venous capacitance.

Earth's early atmosphere as seen from carbon and nitrogen isotopic analysis of Archean sediments

NASA Technical Reports Server (NTRS)

Gibson, E. K., Jr.; Carr, L. P.; Gilmour, I.; Pillinger, C. T.

1986-01-01

The origin and evolution of the Earth's early atmosphere has long been a topic of great interest but determination of actual compositions over geologic time is a difficult problem. However, recent systematic studies of stromatolite deposits (Precambrian Paleobiology Research Group) has extended our knowledge of Archean ecosystems. It has been shown that many stromatolite deposits have undergone negligible alteration since their time of formation. The discovery of primary fluid inclusions within unaltered 3.5 b.y. old Archiean sediments and the observation that the 3.3 b.y. old Barberton cherts have remained closed to argon loss and have not been subjected to thermal metamorphism suggests that an opportunity exists for the direct measurement of the volatile constituents present at their time of formation. Of primary interest to this study was the possibility that the stromatolites and other Archean sediments might retain a vestige of the atmosphere and thus afford an indication of the variations in carbon dioxide and nitrogen isotopic compositions with time. A suite of essentially unaltered Archean stromatolites and the cherts of different ages and geologic sites have been analyzed for their trapped carbon dioxide and nitrogen compositions by the stepped combustion extraction tech nique utilizing static mass spectrometers for the isotope measurements.

MYELIN IN THE CENTRAL NERVOUS SYSTEM AS OBSERVED IN EXPERIMENTALLY INDUCED EDEMA IN THE RAT

PubMed Central

Hirano, Asao; Zimmerman, H. M.; Levine, Seymour

1966-01-01

The compact arrangement of cells in the normal white matter of the brain makes an analysis of cellular architecture difficult. To overcome this difficulty, cerebral edema was induced in rats by means of the unilateral intracerebral implantation of silver nitrate. Within 48 hr, the brains were fixed by perfusion with glutaraldehyde followed by immersion in Dalton's chrome-osmium. Sections of the callosal radiations were studied in the electron microscope. The untreated hemisphere appeared entirely unaltered, whereas in the edematous hemisphere the edema fluid separated individual cell processes and small groups of them. The myelin sheaths and their relationships to the axons appeared essentially unaltered. In this material, analysis of cellular architecture was relatively easy, and the widely held theory of spiral wrapping could be confirmed. In addition, several other aspects of the myelin and myelin-forming cell relationships became apparent in the edematous tissue. Most of these were later confirmed by extensive and careful study of the nonedematous tissue. These included the presence of occasional isolated cytoplasmic areas in myelin and the presence of two complete sheaths around a single axon. Other observations, such as the appearance of mitochondria and dense bodies within the outer loop and the separation of myelin lamellae, are apparently limited to the edematous tissue. PMID:5971641

Lack of enzyme induction with oxcarbazepine (600 mg daily) in healthy subjects.

PubMed Central

Larkin, J G; McKee, P J; Forrest, G; Beastall, G H; Park, B K; Lowrie, J I; Lloyd, P; Brodie, M J

1991-01-01

1. Oxcarbazepine (OXC), the 10-keto analogue of carbamazepine (CBZ), has similar anticonvulsant efficacy and possibly improved patient tolerability. Unlike CBZ, it is metabolised by reduction and may not induce hepatic monooxygenase enzymes. 2. Serum concentrations of OXC and its active metabolite 10-OH-carbazepine (10-OH-CZ) were followed after a single 300 mg dose and during and after 300 mg OXC twice daily for 29 doses in eight healthy male volunteers. 3. Antipyrine metabolism, urinary 6-beta-hydroxycortisol excretion, sex hormone binding globulin (SHBG) levels and circulating androgens were measured as indices of hepatic enzyme induction before, during and after treatment with OXC. 4. Elimination half-lives (mean +/- s.e. mean) of 10-OH-CZ were unaltered by 2 weeks' therapy with OXC (before 11.3 +/- 1.1 h; after 13.9 +/- 3 h). Trough plasma concentrations of 10-OH-CZ at steady-state (31 +/- 2.2 mumol l-1) were higher than predicted (16.5 +/- 4 mumol l-1). 5. Antipyrine metabolism, urinary 6-beta-hydroxycortisol excretion, SHBG levels and circulating androgens were unaltered by treatment with OXC. 6. OXC (600 mg daily) does not induce hepatic monooxygenase enzymes and so is likely to have more predictable dose-concentration relationships and to produce fewer physiological and pharmacological interactions than CBZ. PMID:2015172

Hot-spring sinter deposits in the Alvord-Pueblo Valley, Harney County, Oregon

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

Cummings, M.L.; St. John, A.M.

1993-04-01

Silica sinter deposits occur at Borax Lake, Alvord Hot Springs, and Mickey Springs in the Alvord-Pueblo Valley. Although the sinter deposits occur in areas of active hot springs, sinter is not being deposited. Hot springs are localized along faults that have been active since the Pleistocene. The sinter deposits formed after the drying of glacial Lake Alvord, but before and during extensive wind deflation of glacial-lacustrine sediments. At Mickey Springs, sinter rests directly on unaltered, unconsolidated lithic-rich sand. At Borax Lake, sinter overlies unaltered diatomite, but some armoring, presumably by silica, of the 30 m vent has developed. Field relationsmore » suggest rapid dumping of silica from solution without alteration of the country rock at the vent. Discharge of thermal fluids and cold groundwater along the same structure may have produced colloidal silica carried in a solution stripped of dissolved silica. Sinter is composed of opal-a, traces of detrital feldspar and quartz, and evaporation-related boracite. The concentration of Sb is similar among the three sinter deposits (20 to 70 ppm); however, As, Cs, and Br are highest at Borax Lake (5 to 560 ppm; 26 to 118 ppm; 5 to 1,040 ppm) while Hg is highest at Mickey Springs (1.0 to 5.2 ppm).« less

Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

PubMed

Sandler, Roman A; Fetterhoff, Dustin; Hampson, Robert E; Deadwyler, Sam A; Marmarelis, Vasilis Z

2017-07-01

Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.

Influence of inclination angles on intra- and inter-limb load-sharing during uphill walking.

PubMed

Hong, Shih-Wun; Leu, Tsai-Hsueh; Li, Jia-Da; Wang, Ting-Ming; Ho, Wei-Ping; Lu, Tung-Wu

2014-01-01

Uphill walking is an inevitable part of daily living, placing more challenges on the locomotor system with greater risk of falls than level walking does. The current study aimed to investigate the effects of inclination angles on the inter-joint and inter-limb load-sharing during uphill walking in terms of total support moment and contributions of individual joint moments to the total support moment. Fifteen young adults walked up walkways with 0°, 5°, 10° and 15° of slope while kinematic and kinetic data were collected and analyzed. With increasing inclination angles, the first peak of the total support moment was increased with unaltered individual joint contributions, suggesting an unaltered inter-joint control pattern in the leading limb to meet the increased demands. The second peak of the total support moment remained unchanged with increasing inclination angles primarily through a compensatory redistribution of the hip and knee moments. During DLS, the leading limb shared the majority of the whole body support moments. The current results reveal basic intra- and inter-limb load-sharing patterns of uphill walking, which will be helpful for a better understanding of the control strategies adopted and for subsequent clinical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3

PubMed Central

Fetterhoff, Dustin; Hampson, Robert E.; Deadwyler, Sam A.; Marmarelis, Vasilis Z.

2017-01-01

Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs. PMID:28686594

Multimodality of Ca2+ signaling in rat atrial myocytes.

PubMed

Morad, Martin; Javaheri, Ashkan; Risius, Tim; Belmonte, Steve

2005-06-01

It has been suggested that the multiplicity of Ca(2+) signaling pathways in atrial myocytes may contribute to the variability of its function. This article reports on a novel Ca(2+) signaling cascade initiated by mechanical forces induced by "puffing" of solution onto the myocytes. Ca(i) transients were measured in fura-2 acetoxymethyl (AM) loaded cells using alternating 340- and 410-nm excitation waves at 1.2 kHz. Pressurized puffs of bathing solutions, applied by an electronically controlled micro-barrel system, activated slowly (approximately 300 ms) developing Ca(i) transients that lasted 1,693 +/- 68 ms at room temperature. Subsequent second and third puffs, applied at approximately 20 s intervals activated significantly smaller or no Ca(i) transients. Puff-triggered Ca(i) transients could be reactivated once again following caffeine (10 mM)-induced release of Ca(2+) from sarcoplasmic reticulum (SR). Puff-triggered Ca(i) transients were independent of [Ca(2+)](o), and activation of voltage-gated Ca(2+) or cationic stretch channels or influx of Ca(2+) on Na(+)/Ca(2+)exchanger, because puffing solution containing no Ca(2+), 10 microM diltiazem, 1 mM Cd(2+), 5 mM Ni(2+), or 100 microM Gd(3+) failed to suppress them. Puff-triggered Ca(i) transients were enhanced in paced compared to quiescent myocytes. Electrically activated Ca(i) transients triggered during the time course of puff-induced transients were unaltered, suggesting functionally separate Ca(2+) pools. Contribution of inositol 1,4,5-triphosphate (IP(3))-gated or mitochondrial Ca(2+) pools or modulation of SR stores by nitric oxide/nitric oxide synthase (NO/NOS) signaling were evaluated using 0.5 to 500 microM 2-aminoethoxydiphenyl borate (2-APB) and 0.1 to 1 microM carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and 1 mM Nomega-Nitro-L-arginine methyl ester (L-NAME) and 7-nitroindizole, respectively. Only FCCP appeared to significantly suppress the puff-triggered Ca(i) transients. It was concluded that neither Ca(2+) influx nor depolarization was required for activation of this signaling pathway. These studies suggest that pressurized puffs of solutions activate a mechanically sensitive receptor, which signals in turn the release of Ca(2+) from a limited Ca(2+) store of mitochondria. How mechanical forces are sensed and transmitted to mitochondria to induce Ca(2+) release and what role such a Ca(2+) signaling pathway plays in the physiology or pathophysiology of the heart remain to be worked out.

In vitro release of amoxycillin from lipophilic suppositories.

PubMed

Webster, J A; Dowse, R; Walker, R B

1998-04-01

The in vitro release characteristics of amoxycillin from different lipophilic suppository bases were investigated using the USP rotating basket method. Suppositories containing 250 mg amoxycillin were prepared in theobroma oil and in the semi-synthetic bases Witepsol W35, Suppocire A32, Novata BD, and Novata 299. Both freshly prepared and 1-month-old suppositories were tested. Analysis of amoxycillin was performed using a validated high-performance liquid chromatographic (HPLC) technique. Release profiles differed significantly between bases, with the greatest amount of amoxycillin being released from both newly made and 1-month-old Novata BD bases (87.57 +/- 8.18 and 99.66 +/- 6.63%, respectively), and the lowest amount released from the newly manufactured theobroma suppositories (8.82 +/- 0.75%) and the 1-month-old Suppocire A32 suppositories (7.78 +/- 0.27%).

Release time of residual oxygen after dental bleaching with 35% hydrogen peroxide: effect of a catalase-based neutralizing agent.

PubMed

Guasso, Bárbara; Salomone, Paloma; Nascimento, Paulo Cícero; Pozzobon, Roselaine Terezinha

2016-01-01

This article assessed the effect of a catalase-based agent on residual oxygen (O2) release from teeth exposed to 35% hydrogen peroxide (H2O2). The use of the catalase-based neutralizer agent for 2-3 minutes was able to release residual O2 5 days after exposure to a 35% H2O2-based bleaching gel.

A new compartmental method for the analysis of liver FDG kinetics in small animal models.

PubMed

Garbarino, Sara; Vivaldi, Valentina; Delbary, Fabrice; Caviglia, Giacomo; Piana, Michele; Marini, Cecilia; Capitanio, Selene; Calamia, Iolanda; Buschiazzo, Ambra; Sambuceti, Gianmario

2015-12-01

Compartmental analysis is a standard method to quantify metabolic processes using fluorodeoxyglucose-positron emission tomography (FDG-PET). For liver studies, this analysis is complex due to the hepatocyte capability to dephosphorylate and release glucose and FDG into the blood. Moreover, a tracer is supplied to the liver by both the hepatic artery and the portal vein, which is not visible in PET images. This study developed an innovative computational approach accounting for the reversible nature of FDG in the liver and directly computing the portal vein tracer concentration by means of gut radioactivity measurements. Twenty-one mice were subdivided into three groups: the control group 'CTR' (n = 7) received no treatment, the short-term starvation group 'STS' (n = 7) was submitted to food deprivation with free access to water within 48 h before imaging, and the metformin group 'MTF' (n = 7) was treated with metformin (750 mg/Kg per day) for 1 month. All mice underwent a dynamic micro-PET study for 50 min after an (18)F-FDG injection. The compartmental analysis considered two FDG pools (phosphorylated and free) in both the gut and liver. A tracer was carried into the liver by the hepatic artery and the portal vein, and tracer delivery from the gut was considered as the sole input for portal vein tracer concentration. Accordingly, both the liver and gut were characterized by two compartments and two exchange coefficients. Each one of the two two-compartment models was mathematically described by a system of differential equations, and data optimization was performed by applying a Newton algorithm to the inverse problems associated to these differential systems. All rate constants were stable in each group. The tracer coefficient from the free to the metabolized compartment in the liver was increased by STS, while it was unaltered by MTF. By contrast, the tracer coefficient from the metabolized to the free compartment was reduced by MTF and increased by STS. Data demonstrated that our method was able to analyze FDG kinetics under pharmacological or pathophysiological stimulation, quantifying the fraction of the tracer trapped in the liver or dephosphorylated and released into the bloodstream.

Mediation by 5-hydroxytryptamine of the femoral vasoconstriction induced by acid challenge of the rat gastric mucosa

PubMed Central

Wachter, Christof H; Heinemann, Ákos; Donnerer, Josef; Pabst, Maria A; Holzer, Peter

1998-01-01

Gastric mucosal barrier disruption in the presence of luminal acid causes femoral vasoconstriction via a pathway that appears to be stimulated by messengers generated in the injured gastric mucosa. This study was undertaken to analyse the gastric factors that are responsible for the femoral vasoconstrictor response. Gastric mucosal barrier disruption in the presence of luminal acid was induced by perfusing the stomach of urethane-anaesthetized rats with ethanol (15 %) in 0.01-0.15 M HCl. Blood flow in the left gastric and right femoral artery was estimated by the ultrasonic transit time shift technique. Gastric perfusion of ethanol in HCl caused loss of H+ ions from the gastric lumen, decreased the HCO3− concentration in hepatic portal vein blood, induced macroscopic histological damage to the gastric mucosa, dilated the left gastric artery and constricted the femoral artery. These responses were related to the HCl concentration in the ethanol-containing perfusion medium. The femoral vasoconstriction was also seen when, instead of ethanol, taurocholate (20 mM) was used to disrupt the gastric mucosal barrier in the presence of 0.15 M HCl. The femoral vasoconstriction evoked by gastric perfusion of ethanol in HCl was left unaltered by pharmacological blockade of gastrin and histamine receptors. In contrast, the 5-hydroxytryptamine 5-HT1/2 receptor antagonist methiothepin, but not the 5-HT2A receptor antagonist ketanserin or the 5-HT3 receptor antagonist granisetron, inhibited the ability of both 5-hydroxytryptamine and gastric acid back-diffusion to constrict the femoral artery. Gastric acid back-diffusion caused release of 5-hydroxytryptamine into the gastric lumen, which was related to the HCl concentration in the ethanol-containing perfusion medium. These data show that femoral vasoconstriction evoked by gastric mucosal barrier disruption depends on back-diffusion of acid into the mucosa. The acid-induced damage results in release of 5-hydroxytryptamine from the gastric mucosa, and the pathway leading to constriction of the femoral artery involves 5-hydroxytryptamine acting via 5-HT1/2 receptors as a messenger molecule. PMID:9575302

Diurnal secretion profiles of growth hormone, thyrotrophin and prolactin in Parkinson's disease.

PubMed

Aziz, N A; Pijl, H; Frölich, M; Roelfsema, F; Roos, R A C

2011-06-01

Recently, a massive loss of both hypocretin and melanin-concentrating hormone (MCH) neurones was found in the hypothalamus of Parkinson's disease (PD) patients. Because both hypocretin and MCH play a key role in the regulation of sleep, energy homeostasis and autonomic function, partly by modulation of the somatotrophic, thyrotrophic and lactotrophic axes, neuroendocrine dysregulation may contribute to some of the non-motor features of PD. In eight de novo, medication-free PD patients and eight age-, sex- and body mass index-matched controls, we measured serum levels of growth hormone (GH), thyroid-stimulating hormone (TSH) and prolactin every 10 min for 24 h. Auto-deconvolution, cosinor and approximate entropy analysis were applied to quantify GH, TSH and prolactin secretion rates, diurnal rhythmicity, as well as regularity of hormone release. Sleep was polygraphically-recorded throughout the night. Total 24-h secretion of GH (191 ± 31 versus 130 ± 39 mU/l/24 h), TSH (38 ± 9 versus 36 ± 2 mU/l/24 h) and prolactin (102 ± 14 versus 116 ± 17 μg/l/24 h), as well as their diurnal rhythmicity and regularity of release, were not significantly different between PD patients and controls (all P ≥ 0.12). Fasting levels of insulin-like growth factor-1 were also unaltered in PD patients. However, free thyroxine (T(4) ) levels were significantly higher in PD patients compared to controls (16.19 ± 0.80 versus 13.88 ± 0.40 pmol/l; P = 0.031). In PD patients, prolactin levels were related to disease duration (r = 0.76, P = 0.028), whereas both GH (r = -0.91, P = 0.002) and free T(4) (r = -0.71, P = 0.050) levels correlated inversely with body fat content. Apart from a mild increase in free T(4) levels, we found no indications for altered somatotrophic, thyrotrophic and lactotrophic axes activity in early-stage PD patients. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

Repaglinide acutely amplifies pulsatile insulin secretion by augmentation of burst mass with no effect on burst frequency.

PubMed

Juhl, C B; Pørksen, N; Hollingdal, M; Sturis, J; Pincus, S; Veldhuis, J D; Dejgaard, A; Schmitz, O

2000-05-01

Repaglinide is a new oral hypoglycemic agent that acts as a prandial glucose regulator proposed for the treatment of type 2 diabetes by stimulating insulin secretion. The aim of this study was to explore actions of repaglinide on the rapid pulsatile insulin release by high-frequency insulin sampling and analysis of insulin-concentration time series. We examined 8 healthy lean male subjects in a single-dose double-blind placebo-controlled crossover design. After the subjects underwent an overnight fast, blood sampling was initiated and continued every minute for 120 min. After 40 min, a single dose (0.5 mg) of repaglinide or placebo was given. Serum insulin-concentration time series were assessed by deconvolution analyses and the regularity statistic by approximate entropy (ApEn). Average insulin concentration was increased after repaglinide administration (basal vs. stimulated period, P values are placebo vs. repaglinide) (25.1 +/- 3.6 vs. 33.5 +/- 4.1 pmol/l, P < 0.001). Insulin secretory burst mass (15.8 +/- 2.2 vs. 19.6 +/- 2.8 pmol x l(-1) x pulse(-1), P = 0.02) and amplitude (6.1 +/- 0.9 vs. 7.7 +/- 1.2 pmol x l(-1) x min(-1), P = 0.008) were augmented after repaglinide administration. A concomitant trend toward an increase in basal insulin secretion was observed (2.5 +/- 0.3 vs. 3.2 +/- 0.4 pmol x l(-1) x min(-1), p = 0.06), while the interpulse interval was unaltered (6.8 +/- 1.0 vs. 5.4 +/- 0.4 min/pulse, P = 0.38). ApEn increased significantly after repaglinide administration (0.623 +/- 0.045 vs. 0.670 +/- 0.034, P = 0.04), suggesting less orderly oscillatory patterns of insulin release. In conclusion, a single dose of repaglinide amplifies insulin secretory burst mass (and basal secretion) with no change in burst frequency. The possible importance of these mechanisms in the treatment of type 2 diabetes characterized by disrupted pulsatile insulin secretion remains to be clarified.

Graphene Quantum Dot-Aerogel: From Nanoscopic to Macroscopic Fluorescent Materials. Sensing Polyaromatic Compounds in Water.

PubMed

Martín-Pacheco, Ana; Del Río Castillo, Antonio Esaú; Martín, Cristina; Herrero, María Antonia; Merino, Sonia; García Fierro, José Luis; Díez-Barra, Enrique; Vázquez, Ester

2018-05-30

Fluorescence based on quantum confinement is a property restricted to the nanoscopic range. The incorporation of nanoparticles in a three-dimensional polymeric network could afford macroscopic scaffolds that show nanoscopic properties. Moreover, if these scaffolds are based on strong bonds, the stability of the resulting materials can be preserved, thus enhancing their final applications. We report for the first time the preparation of a graphene quantum dot (GQD) composite based on a cationic covalent network. This new material has unusual features: (i) the final composite remains stable after several swelling-deswelling cycles, thus demonstrating strong interactions between GQDs and the polymeric material, and therefore it could be used as a portable system. (ii) Fluorescence emission in the composite and in solution is quasi-independent to the excitation wavelength. (iii) However, and in contrast to the behavior observed in GQD solutions, the fluorescence of the composite remains unaltered over a wide pH range and in the presence of different ions commonly found in tap water. (iv) Fluorescence quenching is only observed as a consequence of molecules that bear aromatic systems, and this could be applied to the preparation of in situ water sensors.

Economic evaluation of audio based resilience training for depression in primary care.

PubMed

Koeser, Leonardo; Dobbin, Alastair; Ross, Sheila; McCrone, Paul

2013-07-01

Although there is some evidence on the effectiveness and cost-effectiveness of computerised cognitive behavioural therapy (CCBT) for treating anxiety and depression in primary care, alternative low-cost psychosocial interventions have not been investigated. The cost-effectiveness of an audio based resilience training (Positive Mental Training, PosMT) was examined using a decision model. Patient level cost and effectiveness data from a trial comparing a CCBT treatment and usual care and effectiveness data from a study on PosMT were used to inform this. Net benefits of CCBT and PosMT were approximately equal in individuals with 'moderate' depression at baseline and markedly in favour of PosMT for the 'severe' depression subgroup. With only four observations in the 'mild' depression category for PosMT, the existing evidence base remains unaltered. Efficacy data for the PosMT arm was derived from a study using a partially randomised preference design and the model structure contains simplifications due to lack of data availability. PosMT may represent good value for money in treatment of depression for certain groups of patients. More research in this area may be warranted. Copyright © 2013 Elsevier B.V. All rights reserved.

What factors are related to success on conditional release/discharge? Findings from the New Orleans forensic aftercare clinic: 2002-2013.

PubMed

Manguno-Mire, Gina M; Coffman, Kelly L; DeLand, Sarah M; Thompson, John W; Myers, Leann

2014-09-01

The present study investigated the empirically based factors that predicted success on conditional release among a sample of individuals conditionally discharged in Louisiana. Not guilty by reason of insanity acquittees and individuals on conditional release/discharge for incompetency to stand trial were included in the study. Success on conditional release was defined as maintenance of conditional release during the study period. Recidivism (arrest on new charges) and incidents were empirically evaluated. Success on conditional release was maintained in over 70% of individuals. Recidivism was low, with only five arrests on new charges. Success on conditional release was predicted by financial resources, not having a personality disorder, and having fewer total incidents in the program. After controlling for the influence of other variables, having an incident on conditional release was predicted by a substance use diagnosis and being released from jail. Individuals conditionally released from jail showed fewer number of days to first incident (67 vs. 575 days) compared with individuals discharged from the hospital. These data provide support for the successful management of forensic patients in the community via conditional release, although they highlight specific factors that should be considered when developing community-based release programming. Conditional release programs should consider empirical factors in the development of risk assessment and risk management approaches to improve successful maintenance of community-based forensic treatment alternatives. Copyright © 2014 John Wiley & Sons, Ltd.

An in situ-forming phospholipid-based phase transition gel prolongs the duration of local anesthesia for ropivacaine with minimal toxicity.

PubMed

Li, Hanmei; Liu, Tao; Zhu, Yuxuan; Fu, Qiang; Wu, Wanxia; Deng, Jie; Lan, Li; Shi, Sanjun

2017-08-01

An injectable, phospholipid-based phase transition gel (PPTG) has been developed for prolonging the release of ropivacaine (RO) for local anesthesia. PPTG was prepared by mixing phospholipids, medium-chain triglyceride and ethanol. Prior to injection, the PPTG is in a sol state with low viscosity. After subcutaneous injection, the PPTG rapidly forms a gel in situ, which acts as a drug release depot as verified by in vitro release profiles and in vivo pharmacokinetics. Administering RO-PPTG to rats led to a significantly smaller initial burst release than administering RO solution or RO base suspension. Nerve blockade in guinea pigs lasted 3-fold longer after injection of RO-PPTG than after injection of RO solution. RO-PPTG showed good biocompatibility and excellent degradability in vivo. These results suggest that this PPTG-based depot system may be useful for sustained release of local anesthetics to prolong analgesia without causing systemic toxicity. The sustained release of local anesthetics at the surgical site after a single injection is the optimal method to control post-surgical pain. In situ forming implant is an attractive alternative for the sustained release of local anesthetics. However, its practical use is highly limited by certain drawbacks including high viscosity, involved toxic organic solvents and fast drug release. To date, phospholipids-based phase transition gel (PPTG) is emerging for clinical development because of the non-toxicity, biocompatibility and ready availability of phospholipids in body. Thus, we present a novel strategy for sustained release of local anesthetics to control post-surgical pain based on PPTG, which showed a prolonged duration of nerve blockade and excellent biocompatibility. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Magma-ice-sediment interactions and the origin of lava/hyaloclastite sequences in the Síða formation, South Iceland

USGS Publications Warehouse

Banik, Tenley J.; Wallace, Paul J.; Höskuldsson, Ármann; Miller, Calvin F.; Bacon, Charles R.; Furbish, David J.

2013-01-01

Products of subglacial volcanism can illuminate reconstructions of paleo-environmental conditions on both local and regional scales. Competing interpretations of Pleistocene conditions in south Iceland have been proposed based on an extensive sequence of repeating lava-and-hyaloclastite deposits in the Síða district. We propose here a new eruptive model and refine the glacial environment during eruption based on field research and analytical data for the Síða district lava/hyaloclastite units. Field observations from this and previous studies reveal a repeating sequence of cogenetic lava and hyaloclastite deposits extending many kilometers from their presumed eruptive source. Glasses from lava selvages and unaltered hyaloclastites have very low H2O, S, and CO2 concentrations, indicating significant degassing at or close to atmospheric pressure prior to quenching. We also present a scenario that demonstrates virtual co-emplacement of the two eruptive products. Our data and model results suggest repeated eruptions under thin ice or partially subaerial conditions, rather than eruption under a thick ice sheet or subglacial conditions as previously proposed.

Use of an ion mobility spectrometer for detecting uranium compounds

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

McLain, Derek R.; Steeb, Jennifer L.; Smith, Nicholas A.

The safeguards community currently lacks a method to rapidly determine the chemical form of radioactive and non-radioactive compounds in real time during inspection activities. Chemical speciation identification can provide important information on both the types of materials that are collected during environmental sampling and can inform inspectors as to where to focus efforts during inspections or complementary access visits. Ion Mobility Spectrometry (IMS) is an established field technique for the detection of explosives, narcotics, and other organic compounds. More recently, electrospray ionization (ESI) has been used to introduce inorganic compounds to IMS instruments for analysis. These techniques have shown themore » ability to supply chemical information about the compounds being analyzed. Although these laboratory based instruments use a liquid-based injection system, there is evidence in the literature of unaltered and intact pharmaceutical tablets being volatilized and ionized in open atmosphere using heat and a Ni-63 source. Lastly, this work determined that a commercial-off-the-shelf (COTS) IMS could be used for the identification of solid uranium compounds directly after sampling using a COTS sample swipe.« less

Evaluation of effectiveness of various devices for attenuation of trailing vortices based on model tests in a large towing basin

NASA Technical Reports Server (NTRS)

Kirkman, K. L.; Brown, C. E.; Goodman, A.

1973-01-01

The effectiveness of various candidate aircraft-wing devices for attenuation of trailing vortices generated by large aircraft is evaluated on basis of results of experiments conducted with a 0.03-scale model of a Boeing 747 transport aircraft using a technique developed at the HYDRONAUTICS Ship Model Basin. Emphasis is on the effects produced by these devices in the far-field (up to 8 kilometers downstream of full-scale generating aircraft) where the unaltered vortex-wakes could still be hazardous to small following aircraft. The evaluation is based primarily on quantitative measurements of the respective vortex velocity distributions made by means of hot-film probe traverses in a transverse plane at selected stations downstream. The effects of these altered wakes on rolling moment induced on a small following aircraft are also studied using a modified lifting-surface theory with a synthesized Gates Learjet as a typical example. Lift and drag measurements concurrently obtained in the model tests are used to appraise the effects of each device investigated on the performance characteristics of the generating aircraft.

Use of an ion mobility spectrometer for detecting uranium compounds

DOE PAGES

McLain, Derek R.; Steeb, Jennifer L.; Smith, Nicholas A.

2018-03-09

The safeguards community currently lacks a method to rapidly determine the chemical form of radioactive and non-radioactive compounds in real time during inspection activities. Chemical speciation identification can provide important information on both the types of materials that are collected during environmental sampling and can inform inspectors as to where to focus efforts during inspections or complementary access visits. Ion Mobility Spectrometry (IMS) is an established field technique for the detection of explosives, narcotics, and other organic compounds. More recently, electrospray ionization (ESI) has been used to introduce inorganic compounds to IMS instruments for analysis. These techniques have shown themore » ability to supply chemical information about the compounds being analyzed. Although these laboratory based instruments use a liquid-based injection system, there is evidence in the literature of unaltered and intact pharmaceutical tablets being volatilized and ionized in open atmosphere using heat and a Ni-63 source. Lastly, this work determined that a commercial-off-the-shelf (COTS) IMS could be used for the identification of solid uranium compounds directly after sampling using a COTS sample swipe.« less

Remote detection of fluid-related diagenetic mineralogical variations in the Wingate Sandstone at different spatial and spectral resolutions

NASA Astrophysics Data System (ADS)

Okyay, Unal; Khan, Shuhab D.

2016-02-01

Well-exposed eolian units of the Jurassic system on the Colorado Plateau including the Wingate Sandstone, show prominent color variations throughout southeastern Utah due to diagenetic changes that include precipitation and/or removal of iron oxide, clay, and carbonate cement. Spatially variable characteristic diagenetic changes suggest fluid-rock interactions through the sandstone. Distinctive spectral signatures of diagenetic minerals can be used to map diagenetic mineral variability and possibly fluid-flow pathways. The main objective of this work was to identify characteristic diagenetic minerals, and map their spatial variability from regional to outcrop scale in Wingate Sandstone exposures of Lisbon Valley, Utah. Laboratory reflectance spectroscopy analysis of the samples facilitated identification of diagnostic spectral characteristics of the common diagenetic minerals and their relative abundances between altered and unaltered Wingate Sandstone. Comparison of reflectance spectroscopy with satellite, airborne, and ground-based imaging spectroscopy data provided a method for mapping and evaluating spatial variations of diagenetic minerals. The Feature-oriented Principal Component Selection method was used on Advanced Spaceborne Thermal Emission and Reflection Radiometer data so as to map common mineral groups throughout the broader Wingate Sandstone exposure in the area. The Minimum Noise Fraction and Spectral Angle Mapper methods were applied on airborne HyMap and ground-based hyperspectral imaging data to identify and map mineralogical changes. The satellite and airborne data showed that out of 25.55 km2 total exposure of Wingate Sandstone in Lisbon Valley, unaltered sandstone cover 12.55 km2, and altered sandstone cover 8.90 km2 in the northwest flank and 5.09 km2 in the southern flank of the anticline. The ground-based hyperspectral data demonstrated the ability to identify and map mineral assemblages with two-dimensional lateral continuity on near-vertical rock faces. The results showed that 39.71% of the scanned outcrop is bleached and 20.60% is unbleached while 6.33% remain unclassified, and 33.36% is masked-out as vegetation. The bleached and unbleached areas are alternating throughout the vertical face of the outcrop. The relative hematite abundance observed in the unbleached areas are somewhat symmetrical. This indicates fairly similar reaction intensities along the upper and lower reaction fronts observed in the vertical section. The distribution geometry and relative abundances of diagenetic minerals not only suggest multiple paths of fluid-flow in Wingate Sandstone but also provides some insight about relative direction of past fluid-flow.

A long term study of fluoride release from metal-containing conventional and resin-modified glass-ionomer cements.

PubMed

Williams, J A; Billington, R W; Pearson, G J

2001-01-01

The objective of this study was to determine long term release of fluoride from a resin-modified glass-ionomer cement (RMGIC) (Fuji II LC (FLC)) compared with that from two conventional acid-base setting cements (HiDense (HD) and KetacSilver (KS)) marketed for similar restorative purposes. Fluoride release from discs of cement immersed in water or artificial saliva was measured for 2.7 years using an ion selective electrode technique. The RMGIC was affected by water if immersed immediately after setting. This is similar to conventional acid-base cements and the experimental method was designed to allow for this. Over the 2.7-year period, the RMGIC and HD released similar amounts of fluoride into both water and artificial saliva. In water, the RMGIC released the most fluoride, while in artificial saliva the highest release was from HD. KS released the least amount of fluoride in both immersing liquids. In artificial saliva, release was reduced to 17-25% of that found in water, with the RMGIC showing the greatest reduction. Both acid-base cured cements showed changes in colour over the 2.7-year span, while the colour of the RMGIC was stable. It was concluded that the RMGIC released equivalent or greater amounts of fluoride than the two acid-base cure glass-ionomers over a period of 2.7 years.

Controlled and extended drug release behavior of chitosan-based nanoparticle carrier.

PubMed

Yuan, Q; Shah, J; Hein, S; Misra, R D K

2010-03-01

Controlled drug release is presently gaining significant attention. In this regard, we describe here the synthesis (based on the understanding of chemical structure), structural morphology, swelling behavior and drug release response of chitosan intercalated in an expandable layered aluminosilicate. In contrast to pure chitosan, for which there is a continuous increase in drug release with time, the chitosan-aluminosilicate nanocomposite carrier was characterized by controlled and extended release. Drug release from the nanocomposite particle carrier occurred by degradation of the carrier to its individual components or nanostructures with a different composition. In both the layered aluminosilicate-based mineral and chitosan-aluminosilicate nanocomposite carriers the positively charged chemotherapeutic drug strongly bound to the negatively charged aluminosilicate and release of the drug was slow. Furthermore, the pattern of drug release from the chitosan-aluminosilicate nanocomposite carrier was affected by pH and the chitosan/aluminosilicate ratio. The study points to the potential application of this hybrid nanocomposite carrier in biomedical applications, including tissue engineering and controlled drug delivery. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Local Anesthetic Microcapsulation.

DTIC Science & Technology

1982-06-14

viscosities as disparate as R. S. V. 4.~O~6dl/g. ’ Microencapsulation of lidocaine (base) yielded 212-300 micron microcapsules with 50% in vitro drug...release in 6 hours; 150-212 micron microcapsules released 3-0% i7n-2 hours. Etidocaing and bupivacaine vo> 41’. were microencapsulated in a more...Etidocaine Microencapsulation 9 c. Bupivacaine Microencapsulation 12 3. In Vitro Drug Release from Microcapsules 15 a. Lidocaine (base) Release Studies

Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization.

PubMed

Moreno, Miguel; Pow, Poh Yih; Tabitha, Tan Su Teng; Nirmal, Sonali; Larsson, Andreas; Radhakrishnan, Krishna; Nirmal, Jayabalan; Quah, Soo Tng; Geifman Shochat, Susana; Agrawal, Rupesh; Venkatraman, Subbu

2017-08-01

This paper describes the synthesis of thiolated chitosan-based hydrogels with varying degrees of crosslinking that has been utilized to modulate release kinetics of two clinically relevant FDA-approved anti-VEGF protein drugs, ranibizumab and aflibercept. These hydrogels have been fabricated into disc shaped structures for potential use as patches on ocular surface. Protein conformational changes and aggregation after loading and release was evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, electrophoresis and size-exclusion chromatography (SEC). Finally, the capacity of both released proteins to bind to VEGF was tested by ELISA and surface plasmon resonance (SPR) technology. The study demonstrates the versatility of thiolated chitosan-based hydrogels for delivering proteins. The effect of various parameters of the hydrogel on protein release kinetics and mechanism of protein release was studied using the Korsmeyer-Peppas release model. Furthermore, we have studied the stability of released proteins in detail while comparing it with non-entrapped proteins under physiological conditions to understand the effect of formulation conditions on protein stability. The disc-shaped thiolated chitosan-based hydrogels provide a potentially useful platform to deliver ranibizumab and aflibercept for the treatments of ocular diseases such as wet AMD, DME and corneal neovascularization.

OrganoRelease - A framework for modeling the release of organic chemicals from the use and post-use of consumer products.

PubMed

Tao, Mengya; Li, Dingsheng; Song, Runsheng; Suh, Sangwon; Keller, Arturo A

2018-03-01

Chemicals in consumer products have become the focus of recent regulatory developments including California's Safer Consumer Products Act. However, quantifying the amount of chemicals released during the use and post-use phases of consumer products is challenging, limiting the ability to understand their impacts. Here we present a comprehensive framework, OrganoRelease, for estimating the release of organic chemicals from the use and post-use of consumer products given limited information. First, a novel Chemical Functional Use Classifier estimates functional uses based on chemical structure. Second, the quantity of chemicals entering different product streams is estimated based on market share data of the chemical functional uses. Third, chemical releases are estimated based on either chemical product categories or functional uses by using the Specific Environmental Release Categories and EU Technological Guidance Documents. OrganoRelease connects 19 unique functional uses and 14 product categories across 4 data sources and provides multiple pathways for chemical release estimation. Available user information can be incorporated in the framework at various stages. The Chemical Functional Use Classifier achieved an average accuracy above 84% for nine functional uses, which enables the OrganoRelease to provide release estimates for the chemical, mostly using only the molecular structure. The results can be can be used as input for methods estimating environmental fate and exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Additive manufactured serialization

DOEpatents

Bobbitt, III, John T.

2017-04-18

Methods for forming an identifying mark in a structure are described. The method is used in conjunction with an additive manufacturing method and includes the alteration of a process parameter during the manufacturing process. The method can form in a unique identifying mark within or on the surface of a structure that is virtually impossible to be replicated. Methods can provide a high level of confidence that the identifying mark will remain unaltered on the formed structure.

High-resolution mass spectrometry of nitrogenous compounds of the Colorado Green River formation oil shale.

NASA Technical Reports Server (NTRS)

Simoneit, B. R.; Schnoes, H. K.; Haug, P.; Burlingame, A. L.

1971-01-01

Basic nitrogenous compounds isolated from extracts of Green River Formation oil shale were analyzed. The major homologous constituents found were the compositional types - namely, quinolines, tetrahydrequinolines with minor amounts of pyridines and indoles series and traces of more aromatized nitrogen compounds. These results are correlated with nitrogen compounds isolated from Green River Formation retort oil and are a survey of the unaltered nitrogen compounds indigeneous to the shale.

Susceptibility Profiles of Amphotericin B and Posaconazole against Clinically Relevant Mucorales Species under Hypoxic Conditions

PubMed Central

Maurer, Elisabeth; Sparber, Manuela; Lackner, Michaela; Caramalho, Rita; Lass-Flörl, Cornelia

2014-01-01

The effect of hypoxic conditions on the in vitro efficacy of amphotericin B and posaconazole against Mucorales was evaluated by defining MICs with Etest and broth microdilution and identifying minimal fungicidal concentrations (MFCs). With Etest, oxygen-dependent changes were detected, while the MIC and the MFC determined with broth microdilution remained unaltered with reduced oxygen levels. The observed differences depended on the method used. PMID:25451049

Effect of Stress State on Fracture Features

NASA Astrophysics Data System (ADS)

Das, Arpan

2018-02-01

Present article comprehensively explores the influence of specimen thickness on the quantitative estimates of different ductile fractographic features in two dimensions, correlating tensile properties of a reactor pressure vessel steel tested under ambient temperature where the initial crystallographic texture, inclusion content, and their distribution are kept unaltered. It has been investigated that the changes in tensile fracture morphology of these steels are directly attributable to the resulting stress-state history under tension for given specimen dimensions.

In vivo monitoring of liposomal release in tumours following ultrasound stimulation.

PubMed

Evjen, Tove J; Hagtvet, Eirik; Moussatov, Alexei; Røgnvaldsson, Sibylla; Mestas, Jean-Louis; Fowler, R Andrew; Lafon, Cyril; Nilssen, Esben A

2013-08-01

Dioeleoylphosphatidylethanolamine (DOPE)-based liposomes were recently reported as a new class of liposomes for ultrasound (US)-mediated drug delivery. The liposomes showed both high stability and in vitro US-mediated drug release (sonosensitivity). In the current study, in vivo proof-of-principle of US triggered release in tumoured mice was demonstrated using optical imaging. Confocal non-thermal US was used to deliver cavitation to tumours in a well-controlled manner. To detect in vivo release, the near infrared fluorochrome Al (III) Phthalocyanine Chloride Tetrasulphonic acid (AlPcS₄) was encapsulated into both DOPE-based liposomes and control liposomes based on hydrogenated soy phosphatidylcholine (HSPC). Encapsulation causes concentration dependent quenching of fluorescence that is recovered upon AlPcS₄ release from the liposomes. Exposure of tumours to US resulted in a significant increase in fluorescence in mice administered with DOPE-based liposomes, but no change in the mice treated with HSPC-based liposomes. Thus, DOPE-based liposomes showed superior sonosensitivity compared to HSPC-based liposomes in vivo. Copyright © 2012 Elsevier B.V. All rights reserved.

Impact of opioid substitution therapy for Scotland's prisoners on drug‐related deaths soon after prisoner release

PubMed Central

Fischbacher, Colin M.; Graham, Lesley; Fraser, Andrew

2015-01-01

Abstract Aim To assess whether the introduction of a prison‐based opioid substitution therapy (OST) policy was associated with a reduction in drug‐related deaths (DRD) within 14 days after prison release. Design Linkage of Scotland's prisoner database with death registrations to compare periods before (1996–2002) and after (2003–07) prison‐based OST was introduced. Setting All Scottish prisons. Participants People released from prison between 1 January 1996 and 8 October 2007 following an imprisonment of at least 14 days and at least 14 weeks after the preceding qualifying release. Measurements Risk of DRD in the 12 weeks following release; percentage of these DRDs which occurred during the first 14 days. Findings Before prison‐based OST (1996–2002), 305 DRDs occurred in the 12 weeks after 80 200 qualifying releases, 3.8 per 1000 releases [95% confidence interval (CI) = 3.4–4.2]; of these, 175 (57%) occurred in the first 14 days. After the introduction of prison‐based OST (2003–07), 154 DRDs occurred in the 12 weeks after 70 317 qualifying releases, a significantly reduced rate of 2.2 per 1000 releases (95% CI = 1.8–2.5). However, there was no change in the proportion which occurred in the first 14 days, either for all DRDs (87: 56%) or for opioid‐related DRDs. Conclusions Following the introduction of a prison‐based opioid substitution therapy (OST) policy in Scotland, the rate of drug‐related deaths in the 12 weeks following release fell by two‐fifths. However, the proportion of deaths that occurred in the first 14 days did not change appreciably, suggesting that in‐prison OST does not reduce early deaths after release. PMID:25940815

Wax-based sustained release matrix pellets prepared by a novel freeze pelletization technique II. In vitro drug release studies and release mechanisms.

PubMed

Cheboyina, Sreekhar; Wyandt, Christy M

2008-07-09

A novel freeze pelletization technique was evaluated for the preparation of wax-based sustained release matrix pellets. Pellets containing water-soluble drugs were successfully prepared using a variety of waxes. The drug release significantly depended on the wax type used and the aqueous drug solubility. The drug release decreased as the hydrophobicity of wax increased and the drug release increased as the aqueous drug solubility increased. In glyceryl monostearate (GMS) pellets, drug release rate decreased as the loading of theophylline increased. On the contrary, the release rate increased as the drug loading of diltiazem HCl increased in Precirol pellets. Theophylline at low drug loads existed in a dissolved state in GMS pellets and the release followed desorption kinetics. At higher loads, theophylline existed in a crystalline state and the release followed dissolution-controlled constant release for all the waxes studied. However, with the addition of increasing amounts of Brij 76, theophylline release rate increased and the release mechanism shifted to diffusion-controlled square root time kinetics. But the release of diltiazem HCl from Precirol pellets at all drug loads, followed diffusion-controlled square root time kinetics. Therefore, pellets capable of providing a variety of release profiles for different drugs can be prepared using this freeze pelletization technique by suitably modifying the pellet forming matrix compositions.

Serum S100B Represents a New Biomarker for Mood Disorders

PubMed Central

Schroeter, Matthias L.; Sacher, Julia; Steiner, Johann; Schoenknecht, Peter; Mueller, Karsten

2013-01-01

Recently, mood disorders have been discussed to be characterized by glial pathology. The protein S100B, a growth and differentiation factor, is located in, and may actively be released by astro- and oligodendrocytes. This protein is easily assessed in human serum and provides a useful parameter for glial activation or injury. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Consistent with the glial hypothesis of mood disorders, serum S100B levels interact with age with higher levels in elderly depressed subjects. Successful antidepressive treatment has been associated with serum S100B reduction in major depression, whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered in mood disorders. Recently, serum S100B has been linked to specific imaging parameters in the human white matter suggesting a role for S100B as an oligodendrocytic marker protein. In sum, serum S100B can be regarded as a promising in vivo biomarker for mood disorders deepening the understanding of the pathogenesis and plasticity-changes in these disorders. Future longitudinal studies combining serum S100B with other cell-specific serum parameters and multimodal imaging are warranted to further explore this serum protein in the development, monitoring and treatment of mood disorders. PMID:23701298

Temperature response of soil respiration largely unaltered with experimental warming.

PubMed

Carey, Joanna C; Tang, Jianwu; Templer, Pamela H; Kroeger, Kevin D; Crowther, Thomas W; Burton, Andrew J; Dukes, Jeffrey S; Emmett, Bridget; Frey, Serita D; Heskel, Mary A; Jiang, Lifen; Machmuller, Megan B; Mohan, Jacqueline; Panetta, Anne Marie; Reich, Peter B; Reinsch, Sabine; Wang, Xin; Allison, Steven D; Bamminger, Chris; Bridgham, Scott; Collins, Scott L; de Dato, Giovanbattista; Eddy, William C; Enquist, Brian J; Estiarte, Marc; Harte, John; Henderson, Amanda; Johnson, Bart R; Larsen, Klaus Steenberg; Luo, Yiqi; Marhan, Sven; Melillo, Jerry M; Peñuelas, Josep; Pfeifer-Meister, Laurel; Poll, Christian; Rastetter, Edward; Reinmann, Andrew B; Reynolds, Lorien L; Schmidt, Inger K; Shaver, Gaius R; Strong, Aaron L; Suseela, Vidya; Tietema, Albert

2016-11-29

The respiratory release of carbon dioxide (CO 2 ) from soil is a major yet poorly understood flux in the global carbon cycle. Climatic warming is hypothesized to increase rates of soil respiration, potentially fueling further increases in global temperatures. However, despite considerable scientific attention in recent decades, the overall response of soil respiration to anticipated climatic warming remains unclear. We synthesize the largest global dataset to date of soil respiration, moisture, and temperature measurements, totaling >3,800 observations representing 27 temperature manipulation studies, spanning nine biomes and over 2 decades of warming. Our analysis reveals no significant differences in the temperature sensitivity of soil respiration between control and warmed plots in all biomes, with the exception of deserts and boreal forests. Thus, our data provide limited evidence of acclimation of soil respiration to experimental warming in several major biome types, contrary to the results from multiple single-site studies. Moreover, across all nondesert biomes, respiration rates with and without experimental warming follow a Gaussian response, increasing with soil temperature up to a threshold of ∼25 °C, above which respiration rates decrease with further increases in temperature. This consistent decrease in temperature sensitivity at higher temperatures demonstrates that rising global temperatures may result in regionally variable responses in soil respiration, with colder climates being considerably more responsive to increased ambient temperatures compared with warmer regions. Our analysis adds a unique cross-biome perspective on the temperature response of soil respiration, information critical to improving our mechanistic understanding of how soil carbon dynamics change with climatic warming.

Does thrombin stimulation of human platelets proceed via a simultaneous Na/sup +/-H/sup +/ exchange

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

Davies, T.A.; Katona, E.; Vasilescu, V.

1986-03-05

Thrombin stimulation of human platelets initiates a membrane depolarization attributable to a Na/sup +/ influx into, and an alkalinization of, the cytoplasm, both of which follow a similar rapid time scale and thrombin dose dependence. These responses precede secretion of the contents of dense granules (serotonin) and, after 1 min, of lysosomes (..beta..-glucuronidase). These markers have been used to determine whether the Na/sup +/ influx and H/sup +/ efflux are sequential or simultaneous. They have examined these parameters in D/sub 2/O-Hepes buffers. NMR evidence indicates that equilibration is rapid, and virtually complete within the 3 minute pre-stimulation platelets equilibration period.more » The rate of depolarization is 70-80% slower in D/sub 2/O than in H/sub 2/O. The time to reach maximal depolarization is 5-10 sec longer, the extent of depolarization 60% inhibited, and the (H/sup +/) change 85-100% inhibited. The serotonin secretion is unaltered, and the ..beta..-glucuronidase secretion is 130-180% enhanced. 10/sup -4/ M amiloride inhibits Na/sup +/ influx, i.e. depolarization, and the pH change completely. Adjustment to pH/sub i/ 7.3 with NH/sub 4/Cl led to a 30-80% enhanced ..beta..-glucuronidase release upon thrombin exposure. These results suggest that the Na/sup +/ and H/sup +/ fluxes across the platelet membrane occur sequentially, the Na/sup +/ occurring first. Furthermore, granule secretion, previously shown by us to be independent of the existent Na/sup +/ gradient, depends on the cytoplasmic K/sup +/ and H/sup +/ concentrations.« less

Oro-gustatory perception of dietary lipids and calcium signaling in taste bud cells are altered in nutritionally obesity-prone Psammomys obesus.

PubMed

Abdoul-Azize, Souleymane; Atek-Mebarki, Feriel; Bitam, Arezki; Sadou, Hassimi; Koceïr, Elhadj Ahmed; Khan, Naim Akhtar

2013-01-01

Since the increasing prevalence of obesity is one of the major health problems of the modern era, understanding the mechanisms of oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. We have conducted the present study on Psammomys obesus, the rodent desert gerbil which is a unique polygenic natural animal model of obesity. Our results show that obese animals exhibit a strong preference for lipid solutions in a two-bottle test. Interestingly, the expression of CD36, a lipido-receptor, in taste buds cells (TBC), isolated from circumvallate papillae, was decreased at mRNA level, but remained unaltered at protein level, in obese animals. We further studied the effects of linoleic acid (LA), a long-chain fatty acid, on the increases in free intracellular calcium (Ca(2+)) concentrations, [Ca(2+)]i, in the TBC of P. obesus. LA induced increases in [Ca(2+)]i, largely via CD36, from intracellular pool, followed by the opening of store-operated Ca(2+) (SOC) channels in the TBC of these animals. The action of this fatty acid on the increases in [Ca(2+)]i was higher in obese animals than that in controls. However, the release of Ca(2+) from intracellular stores, studied also by employing thapsigargin, was lower in TBC of obese animals than control rodents. In this study, we show, for the first time, that increased lipid intake and altered Ca(2+) signaling in TBC are associated with obesity in Psammomys obesus.

C-Terminal Protein Characterization by Mass Spectrometry: Isolation of C-Terminal Fragments from Cyanogen Bromide-Cleaved Protein

PubMed Central

Nika, Heinz; Hawke, David H.; Angeletti, Ruth Hogue

2014-01-01

A sample preparation method for protein C-terminal peptide isolation from cyanogen bromide (CNBr) digests has been developed. In this strategy, the analyte was reduced and carboxyamidomethylated, followed by CNBr cleavage in a one-pot reaction scheme. The digest was then adsorbed on ZipTipC18 pipette tips for conjugation of the homoserine lactone-terminated peptides with 2,2′-dithiobis (ethylamine) dihydrochloride, followed by reductive release of 2-aminoethanethiol from the derivatives. The thiol-functionalized internal and N-terminal peptides were scavenged on activated thiol sepharose, leaving the C-terminal peptide in the flow-through fraction. The use of reversed-phase supports as a venue for peptide derivatization enabled facile optimization of the individual reaction steps for throughput and completeness of reaction. Reagents were replaced directly on the support, allowing the reactions to proceed at minimal sample loss. By this sequence of solid-phase reactions, the C-terminal peptide could be recognized uniquely in mass spectra of unfractionated digests by its unaltered mass signature. The use of the sample preparation method was demonstrated with low-level amounts of a whole, intact model protein. The C-terminal fragments were retrieved selectively and efficiently from the affinity support. The use of covalent chromatography for C-terminal peptide purification enabled recovery of the depleted material for further chemical and/or enzymatic manipulation. The sample preparation method provides for robustness and simplicity of operation and is anticipated to be expanded to gel-separated proteins and in a scaled-up format to high-throughput protein profiling in complex biological mixtures. PMID:24688319

Neurotensin inversely modulates maternal aggression

PubMed Central

Gammie, Stephen C.; D’Anna, Kimberly L.; Gerstein, Hilary; Stevenson, Sharon A.

2008-01-01

Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia, and schizophrenia. Although NT is released from and acts upon brain regions involved in social behaviors, it has not been linked to a social behavior. We previously selected mice for high maternal aggression (maternal defense), an important social behavior that protects offspring, and found significantly lower NT expression in the CNS of highly protective females. Our current study directly tested NT’s role in maternal defense. Intracerebroventricular (icv) injections of NT significantly impaired defense in terms of time aggressive and number of attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 μg). Other maternal behaviors, including pup retrieval, were unaltered following NT injections (0.05 μg) relative to vehicle, suggesting specificity of NT action on defense. Further, icv injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30 μg), significantly elevated maternal aggression in terms of time aggressive and attack number. To understand where NT may regulate aggression, we examined Fos following injection of either 0.1 μg NT or vehicle. 13 of 26 brain regions examined exhibited significant Fos increases with NT, including regions expressing NT1 and previously implicated in maternal aggression, such as lateral septum, bed nucleus of stria terminalis, paraventricular nucleus, and central amygdala. Together, our results indicate that NT inversely regulates maternal aggression and provide the first direct evidence that lowering of NT signaling can be a mechanism for maternal aggression. To our knowledge, this is the first study to directly link NT to a social behavior. PMID:19118604

Phylogeny and expression analysis of C-reactive protein (CRP) and serum amyloid-P (SAP) like genes reveal two distinct groups in fish.

PubMed

Lee, P T; Bird, S; Zou, J; Martin, S A M

2017-06-01

The acute phase response (APR) is an early innate immune function that is initiated by inflammatory signals, leading to the release of acute phase proteins to the bloodstream to re-establish homeostasis following microbial infection. In this study we analysed the Atlantic salmon (Salmo salar) whole-genome database and identified five C-reactive protein (CRP)/serum amyloid P component (SAP) like molecules namely CRP/SAP-1a, CRP/SAP-1b, CRP/SAP-1c, CRP/SAP-2 and CRP/SAP-3. These CRP/SAP genes formed two distinct sub-families, a universal group (group I) present in all vertebrates and a fish/amphibian specific group (group II). Salmon CRP/SAP-1a, CRP/SAP-1b and CRP/SAP-1c and CRP/SAP-2 belong to the group I family whilst salmon CRP/SAP-3 is a member of group II. Gene expression analysis showed that the salmon CRP/SAP-1a as well as serum amyloid A-5 (SAA-5), one of the major acute phase proteins, were significantly up-regulated by recombinant cytokines (rIL-1β and rIFNγ) in primary head kidney cells whilst the other four CRP/SAPs remained refractory. Furthermore, SAA-5 was produced as the main acute phase protein (APP) in Atlantic salmon challenged with Aeromonas salmonicida (aroA(-) strain) whilst salmon CRP/SAPs remained unaltered. Overall, these data illustrate the potential different functions of expanded salmon CRP/SAPs to their mammalian homologues. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Differential upregulation in DRG neurons of an α2δ-1 splice variant with a lower affinity for gabapentin after peripheral sensory nerve injury

PubMed Central

Lana, Beatrice; Schlick, Bettina; Martin, Stuart; Pratt, Wendy S.; Page, Karen M.; Goncalves, Leonor; Rahman, Wahida; Dickenson, Anthony H.; Bauer, Claudia S.; Dolphin, Annette C.

2014-01-01

The α2δ-1 protein is an auxiliary subunit of voltage-gated calcium channels, critical for neurotransmitter release. It is upregulated in dorsal root ganglion (DRG) neurons following sensory nerve injury, and is also the therapeutic target of the gabapentinoid drugs, which are efficacious in both experimental and human neuropathic pain conditions. α2δ-1 has 3 spliced regions: A, B, and C. A and C are cassette exons, whereas B is introduced via an alternative 3′ splice acceptor site. Here we have examined the presence of α2δ-1 splice variants in DRG neurons, and have found that although the main α2δ-1 splice variant in DRG is the same as that in brain (α2δ-1 ΔA+B+C), there is also another α2δ-1 splice variant (ΔA+BΔC), which is expressed in DRG neurons and is differentially upregulated compared to the main DRG splice variant α2δ-1 ΔA+B+C following spinal nerve ligation. Furthermore, this differential upregulation occurs preferentially in a small nonmyelinated DRG neuron fraction, obtained by density gradient separation. The α2δ-1 ΔA+BΔC splice variant supports CaV2 calcium currents with unaltered properties compared to α2δ-1 ΔA+B+C, but shows a significantly reduced affinity for gabapentin. This variant could therefore play a role in determining the efficacy of gabapentin in neuropathic pain. PMID:24315988

Temperature response of soil respiration largely unaltered with experimental warming

USGS Publications Warehouse

Carey, Joanna C.; Tang, Jianwu; Templer, Pamela H.; Kroeger, Kevin D.; Crowther, Thomas W.; Burton, Andrew J.; Dukes, Jeffrey S.; Emmett, Bridget; Frey, Serita D.; Heskel, Mary A.; Jiang, Lifen; Machmuller, Megan B.; Mohan, Jacqueline; Panetta, Anne Marie; Reich, Peter B.; Reinsch, Sabine; Wang, Xin; Allison, Steven D.; Bamminger, Chris; Bridgham, Scott; Collins, Scott L.; de Dato, Giovanbattista; Eddy, William C.; Enquist, Brian J.; Estiarte, Marc; Harte, John; Henderson, Amanda; Johnson, Bart R.; Steenberg Larsen, Klaus; Luo, Yiqi; Marhan, Sven; Melillo, Jerry M.; Penuelas, Josep; Pfeifer-Meister, Laurel; Poll, Christian; Rastetter, Edward B.; Reinmann, Andrew B.; Reynolds, Lorien L.; Schmidt, Inger K.; Shaver, Gaius R.; Strong, Aaron L.; Suseela, Vidya; Tietema, Albert

2016-01-01

The respiratory release of carbon dioxide (CO2) from soil is a major yet poorly understood flux in the global carbon cycle. Climatic warming is hypothesized to increase rates of soil respiration, potentially fueling further increases in global temperatures. However, despite considerable scientific attention in recent decades, the overall response of soil respiration to anticipated climatic warming remains unclear. We synthesize the largest global dataset to date of soil respiration, moisture, and temperature measurements, totaling >3,800 observations representing 27 temperature manipulation studies, spanning nine biomes and over 2 decades of warming. Our analysis reveals no significant differences in the temperature sensitivity of soil respiration between control and warmed plots in all biomes, with the exception of deserts and boreal forests. Thus, our data provide limited evidence of acclimation of soil respiration to experimental warming in several major biome types, contrary to the results from multiple single-site studies. Moreover, across all nondesert biomes, respiration rates with and without experimental warming follow a Gaussian response, increasing with soil temperature up to a threshold of ∼25 °C, above which respiration rates decrease with further increases in temperature. This consistent decrease in temperature sensitivity at higher temperatures demonstrates that rising global temperatures may result in regionally variable responses in soil respiration, with colder climates being considerably more responsive to increased ambient temperatures compared with warmer regions. Our analysis adds a unique cross-biome perspective on the temperature response of soil respiration, information critical to improving our mechanistic understanding of how soil carbon dynamics change with climatic warming.

Temperature response of soil respiration largely unaltered with experimental warming

PubMed Central

Carey, Joanna C.; Tang, Jianwu; Templer, Pamela H.; Kroeger, Kevin D.; Crowther, Thomas W.; Burton, Andrew J.; Dukes, Jeffrey S.; Emmett, Bridget; Frey, Serita D.; Heskel, Mary A.; Jiang, Lifen; Machmuller, Megan B.; Mohan, Jacqueline; Panetta, Anne Marie; Reich, Peter B.; Reinsch, Sabine; Wang, Xin; Allison, Steven D.; Bamminger, Chris; Bridgham, Scott; de Dato, Giovanbattista; Eddy, William C.; Enquist, Brian J.; Estiarte, Marc; Harte, John; Henderson, Amanda; Johnson, Bart R.; Luo, Yiqi; Marhan, Sven; Melillo, Jerry M.; Peñuelas, Josep; Pfeifer-Meister, Laurel; Poll, Christian; Rastetter, Edward; Reinmann, Andrew B.; Reynolds, Lorien L.; Schmidt, Inger K.; Shaver, Gaius R.; Strong, Aaron L.; Suseela, Vidya; Tietema, Albert

2016-01-01

The respiratory release of carbon dioxide (CO2) from soil is a major yet poorly understood flux in the global carbon cycle. Climatic warming is hypothesized to increase rates of soil respiration, potentially fueling further increases in global temperatures. However, despite considerable scientific attention in recent decades, the overall response of soil respiration to anticipated climatic warming remains unclear. We synthesize the largest global dataset to date of soil respiration, moisture, and temperature measurements, totaling >3,800 observations representing 27 temperature manipulation studies, spanning nine biomes and over 2 decades of warming. Our analysis reveals no significant differences in the temperature sensitivity of soil respiration between control and warmed plots in all biomes, with the exception of deserts and boreal forests. Thus, our data provide limited evidence of acclimation of soil respiration to experimental warming in several major biome types, contrary to the results from multiple single-site studies. Moreover, across all nondesert biomes, respiration rates with and without experimental warming follow a Gaussian response, increasing with soil temperature up to a threshold of ∼25 °C, above which respiration rates decrease with further increases in temperature. This consistent decrease in temperature sensitivity at higher temperatures demonstrates that rising global temperatures may result in regionally variable responses in soil respiration, with colder climates being considerably more responsive to increased ambient temperatures compared with warmer regions. Our analysis adds a unique cross-biome perspective on the temperature response of soil respiration, information critical to improving our mechanistic understanding of how soil carbon dynamics change with climatic warming. PMID:27849609

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats.

PubMed

Fuentes, Silvia; Carrasco, Javier; Armario, Antonio; Nadal, Roser

2014-08-01

Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23-28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors. Copyright © 2014 Elsevier Inc. All rights reserved.

Mechanisms of transport and exocytosis of dense-core granules containing tissue plasminogen activator in developing hippocampal neurons.

PubMed

Silverman, Michael A; Johnson, Scooter; Gurkins, Dmitri; Farmer, Meredith; Lochner, Janis E; Rosa, Patrizia; Scalettar, Bethe A

2005-03-23

Dense-core granules (DCGs) are organelles found in specialized secretory cells, including neuroendocrine cells and neurons. Neuronal DCGs facilitate many critical processes, including the transport and secretion of proteins involved in learning, and yet their transport and exocytosis are poorly understood. We have used wide-field and total internal reflection fluorescence microscopy, in conjunction with transport theory, to visualize the transport and exocytosis of DCGs containing a tissue plasminogen activator-green fluorescent protein hybrid in cell bodies, neurites, and growth cones of developing hippocampal neurons and to quantify the roles that diffusion, directed motion, and immobility play in these processes. Our results demonstrate that shorter-ranged transport of DCGs near sites of exocytosis in hippocampal neurons and neuroendocrine cells differs markedly. Specifically, the immobile fraction of DCGs within growth cones and near the plasma membrane of hippocampal neurons is small and relatively unaltered by actin disruption, unlike in neuroendocrine cells. Moreover, transport of DCGs in these domains of hippocampal neurons is unusually heterogeneous, being significantly rapid and directed as well as slow and diffusive. Our results also demonstrate that exocytosis is preceded by substantial movement and heterogeneous transport; this movement may facilitate delivery of DCG cargo in hippocampal neurons, given the relatively low abundance of neuronal DCGs. In addition, the extensive mobility of DCGs in hippocampal neurons argues strongly against the hypothesis that cortical actin is a major barrier to membrane-proximal DCGs in these cells. Instead, our results suggest that extended release of DCG cargo from hippocampal neurons arises from heterogeneity in DCG mobility.

Overexpression of inducible 70-kDa heat shock protein in mouse improves structural and functional recovery of skeletal muscles from atrophy.

PubMed

Miyabara, Elen H; Nascimento, Tabata L; Rodrigues, Débora C; Moriscot, Anselmo S; Davila, Wilmer F; AitMou, Younss; deTombe, Pieter P; Mestril, Ruben

2012-04-01

Heat shock proteins play a key regulatory role in cellular defense. To investigate the role of the inducible 70-kDa heat shock protein (HSP70) in skeletal muscle atrophy and subsequent recovery, soleus (SOL) and extensor digitorum longus (EDL) muscles from overexpressing HSP70 transgenic mice were immobilized for 7 days and subsequently released from immobilization and evaluated after 7 days. Histological analysis showed that there was a decrease in cross-sectional area of type II myofiber from EDL and types I and II myofiber from SOL muscles at 7-day immobilization in both wild-type and HSP70 mice. At 7-day recovery, EDL and SOL myofibers from HSP70 mice, but not from wild-type mice, recovered their size. Muscle tetanic contraction decreased only in SOL muscles from wild-type mice at both 7-day immobilization and 7-day recovery; however, it was unaltered in the respective groups from HSP70 mice. Although no effect in a fatigue protocol was observed among groups, we noticed a better contractile performance of EDL muscles from overexpressing HSP70 groups as compared to their matched wild-type groups. The number of NCAM positive-satellite cells reduced after immobilization and recovery in both EDL and SOL muscles from wild-type mice, but it was unchanged in the muscles from HSP70 mice. These results suggest that HSP70 improves structural and functional recovery of skeletal muscle after disuse atrophy, and this effect might be associated with preservation of satellite cell amount.

Effects of depth and chest volume on cardiac function during breath-hold diving.

PubMed

Marabotti, Claudio; Scalzini, Alessandro; Cialoni, Danilo; Passera, Mirko; Ripoli, Andrea; L'Abbate, Antonio; Bedini, Remo

2009-07-01

Cardiac response to breath-hold diving in human beings is primarily characterized by the reduction of both heart rate and stroke volume. By underwater Doppler-echocardiography we observed a "restrictive/constrictive" left ventricular filling pattern compatible with the idea of chest squeeze and heart compression during diving. We hypothesized that underwater re-expansion of the chest would release heart constriction and normalize cardiac function. To this aim, 10 healthy male subjects (age 34.2 +/- 10.4) were evaluated by Doppler-echocardiography during breath-hold immersion at a depth of 10 m, before and after a single maximal inspiration from a SCUBA device. During the same session, all subjects were also studied at surface (full-body immersion) and at 5-m depth in order to better characterize the relationship of echo-Doppler pattern with depth. In comparison to surface immersion, 5-m deep diving was sufficient to reduce cardiac output (P = 0.042) and increase transmitral E-peak velocity (P < 0.001). These changes remained unaltered at a 10-m depth. Chest expansion at 10 m decreased left ventricular end-systolic volume (P = 0.024) and increased left ventricular stroke volume (P = 0.024). In addition, it decreased transmitral E-peak velocity (P = 0.012) and increased deceleration time of E-peak (P = 0.021). In conclusion the diving response, already evident during shallow diving (5 m) did not progress during deeper dives (10 m). The rapid improvement in systolic and diastolic function observed after lung volume expansion is congruous with the idea of a constrictive effect on the heart exerted by chest squeeze.

[Molecular mechanisms of lung cancer development at its different stages in nuclear industry workers].

PubMed

Rusinova, G G; Vyazovskaya, N S; Azizova, T V; Revina, V S; Glazkova, I V; Generozov, E V; Zakharzhevskaya, N B; Guryanov, M Yu; Belosokhov, M V; Osovets, S V

2015-01-01

to assess mutational events in exons 5, 7, and 8 of the p53 gene and to reveal mutant p53 protein in verified cases of morphologically altered (proliferative and precancerous changes, lung cancer) and histologically unaltered, lung tissues in workers exposed to occupational radiation. The investigation used formalin-fixed paraffin-embedded unaltered and altered lung tissue blocks (FFPBs) obtained from the human radiobiological tissue repository. The shelf-life of FFPBs was 5-31 years. An immunohistochemical technique using mouse antibodies against p53 protein (, Denmark), stained with diaminobenzidine (DAB) chromogen, was employed to determine p53 protein. DNA was isolated from lung tissue FFPBs with QIAmp DNA FFPE Tissue Kit, (, USA). Polymerase chain reaction (PCR) was performed to amplify the p53 gene exons 5, 7, and 8 selected for examination, by applying the sequences of genes and primers, the specificity of which was checked using the online resource (http://www.ncbi.nlm.nih.gov/blast). PCR products were detected by temporal temperature gradient gel-electrophoresis and the Sanger sequencing method. The obtained DNA fragments were analyzed on a sequencer ABI Prism 3100 Genetic Analizer (, USA). Computer-aided DNA analysis was made using the BLAST program. A package of applied Statistica 6.0 programs was employed for statistical data processing. Results. Immunohistochemical analysis showed that mutant p53 protein was absent in the cells of unaltered lung tissue and the number of cells with mutant p53 protein increased in all the patients with proliferative and precancerous changes and lung cancer, suggesting p53 protein dysfunction. The total number of p53 gene mutations in exons 5, 7, and 8, if there were proliferative and precancerous lung tissue changes and lung cancer, were 25, 20, and 40%, respectively. All the found mutations were transversions (the substitution of purine for pyrimidine or, conversely), indicating the action of exogenous mutagens. The results of this investigation have confirmed other investigators' data showing that p53 gene mutations in lung cancer are observed in 40-70% of cases. The differences in the number of cases of altered lung tissue with mutations in the p53 gene (not more than 40%) and in those of p53 protein expression were found in 100%, suggesting the regulation of p53 gene function in the cell at multiple levels.

Design of tablets for the delayed and complete release of poorly water-soluble weak base drugs using SBE7M-β-CD as a solubilizing agent.

PubMed

Rao, Venkatramana M; Zannou, Erika A; Stella, Valentino J

2011-04-01

The challenge of designing a delayed-release oral dosage form is significantly increased when the drug substance is poorly water soluble. This manuscript describes the design and characterization of a novel controlled-release film-coated tablet for the pH-triggered delayed and complete release of poorly water-soluble weak base drugs. Delivery of weak bases is specifically highlighted with the use of dipyridamole and prazosin as model compounds. Tailored delayed release is achieved with a combination of an insoluble but semipermeable polymer and an enteric polymer, such as cellulose acetate and hydroxypropyl cellulose phthalate, respectively, as coatings. The extent of the time lag prior to complete release depends on the film-coating composition and thickness. Complete release is achieved by the addition of a cyclodextrin, namely SBE7M-β-CD with or without a pH modifier added to the tablet core to ensure complete solubilization and release of the drug substance. The film-coating properties allow the complex formation/solubilization to occur in situ. Additionally, the drug release rate can be modulated on the basis of the cyclodextrin to drug molar ratio. This approach offers a platform technology for delayed release of potent but poorly soluble drugs and the release can be modulated by adjusting the film-coating composition and thickness and/or the cyclodextrin and pH modifier, if necessary. Copyright © 2010 Wiley-Liss, Inc.

Isoniazid release from suppositories compounded with selected bases.

PubMed

Hudson, Kristofer C; Asbill, C Scott; Webster, Andrew A

2007-01-01

There is an increasing need for an alternative route of isoniazid adminstration for prophylaxis and treatment of tuberculosis in children. The purpose of this study is to evaluate the in vitro release of isoniazid from extemporaneously compounded isoniazid suppositories with a goal of optimizing the suppository dosage form for this indication. Suppositories were compounded using three different base formulations (cocoa butter, Witepsol H15 Base F, and a combination of polyethylene glycols 3350, 1000, and 400). The release profiles of six compounded suppositories with isoniazid (100 mg) were tested with a United States Pharmacopeial Convention-approved dissolution apparatus. Isoniazid concentrations at predetermined time points were determined using high-performance liquid chromatographic analysis. The results show that drug release from the water-solutble base (mixed polyethylene glycols) was significantly greater than that from the lipophilic bases (cocoa butter and Witepsol H15). The percentage of isoniazid release form the polyethylene glycol suppository formulation (70 +/- 1.4 mg/mL) was greater than that from the cocoa butter (55 +/- 1.1 mg/mL) and Witepsol H15 Base F (18 +/- 0.36 mg/mL) suppository formulations.

Evaluation of the resistance of a geopolymer-based drug delivery system to tampering.

PubMed

Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne

2014-04-25

Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users. Copyright © 2014 Elsevier B.V. All rights reserved.

78 FR 30800 - Reopening of Comment Periods for Certain Proposed Rulemaking Releases and Policy Statements...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-23

..., among other things: (1) The registration and comprehensive oversight of security-based swap dealers and... SECURITIES AND EXCHANGE COMMISSION 17 CFR Parts 240, 242, and 249 [Release No. 34-69491; File Nos... Releases and Policy Statements Applicable to Security-Based Swaps AGENCY: Securities and Exchange...

Non-invasive continuous imaging of drug release from soy-based skin equivalent using wide-field interferometry

NASA Astrophysics Data System (ADS)

Gabai, Haniel; Baranes-Zeevi, Maya; Zilberman, Meital; Shaked, Natan T.

2013-04-01

We propose an off-axis interferometric imaging system as a simple and unique modality for continuous, non-contact and non-invasive wide-field imaging and characterization of drug release from its polymeric device used in biomedicine. In contrast to the current gold-standard methods in this field, usually based on chromatographic and spectroscopic techniques, our method requires no user intervention during the experiment, and only one test-tube is prepared. We experimentally demonstrate imaging and characterization of drug release from soy-based protein matrix, used as skin equivalent for wound dressing with controlled anesthetic, Bupivacaine drug release. Our preliminary results demonstrate the high potential of our method as a simple and low-cost modality for wide-field imaging and characterization of drug release from drug delivery devices.

Mangala Valles, Mars: A reassessment of formation processes based on a new geomorphological and stratigraphic analysis of the geological units

NASA Astrophysics Data System (ADS)

Leone, Giovanni

2017-05-01

Mangala Valles has always been viewed as the typical outflow channel formed by catastrophic floods of water. A new analysis has shown that the geomorphological traces of fluvial or lacustrine processes within Mangala Valles can be better explained by fluid lava flooding the channels and filling pre-existing impact craters. As for the circum-Chryse outflow channels, where no clear source of water or mechanism able to replenish water at its hydraulic head is observed, there is no geologic trace of a sudden removal of a volume of water (ice) necessary to carve Mangala Valles. Neither maars nor rootless cones, typical volcanic features indicative of interaction between lava and ground ice, were found. Past works suggested that the formation of Mangala Valles occurred in late Amazonian age when the climate of Mars was similar to that seen today, that is absolutely not liquid water friendly. The present work shows how the origin of Mangala Valles may go back to Noachian or even Pre-Noachian when other studies have concluded that the climate was not liquid water friendly. Even assuming limited periods of obliquity favourable to liquid water in the history of Mars, which is at odds with the widespread presence of unaltered olivine and jarosite, it is very difficult to find plausible mechanisms of aquifer recharge or signs of catastrophic water release at the Notch of Mangala Valles that could feed the multiple episodes, or even a single episode, of fluvial flooding suggested in the literature. This evidence and other analysis will show that the presence of water and, eventually, ground ice is not incontrovertible in the equatorial regions and should not be given for granted as commonly done so far in the literature. The geomorphological analysis of the Mars Reconnaissance Orbiter (MRO) images provided in this paper, combined with THEMIS and MOLA data, show how Mangala Fossa, from which Mangala Valles originated as a breakout, is an erosional channel formed by the flow of lava in a original tube coming from Daedalia Planum rather than a tectonic graben or the sign of a dike rupturing to the surface.

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

PubMed

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

Stream ecosystems change with urban development

USGS Publications Warehouse

Bell, Amanda H.; James, F. Coles; McMahon, Gerard

2012-01-01

The healthy condition of the physical living space in a natural stream—defined by unaltered hydrology (streamflow), high diversity of habitat features, and natural water chemistry—supports diverse biological communities with aquatic species that are sensitive to disturbances. In a highly degraded urban stream, the poor condition of the physical living space—streambank and tree root damage from altered hydrology, low diversity of habitat, and inputs of chemical contaminants—contributes to biological communities with low diversity and high tolerance to disturbance.

Orbital elements of Charon from speckle interferometry

NASA Technical Reports Server (NTRS)

Beletic, J. W.; Goody, R. M.; Tholen, D. J.

1989-01-01

The semimajor axis and the inclination are the two most important quantities presently determined from 56 well-calibrated speckle-interferometric observations of the position of Charon, which are presented in conjunction with an orbit solution that incorporates them. Both values in the best solution obtained are noted to significantly differ from earlier determinations. The new value for the semimajor axis represents a 2.7 percent increase over the previously accepted value; the mean density of the system, however, remains unaltered.

Neurotoxins and Neurodegenerative Disorders in Japanese-American Men Living in Hawaii

DTIC Science & Technology

2007-04-01

incidental Lewy bodies rose significantly to 31.6% (6/19) in men with 5 signs ( p =0.004). Associations were unaltered after adjustments for age at death...Petrovitch H, Fujikami G, Makski KH, Fong K, White LR, Blanchette P , Ross W. Depressive symptoms and Parkinson’s disease: The Honolulu-Asia Aging ...striatal dopamine levels ). Our ability to measure levels of DAMD17-98-1-8621 Final Addendum 10 organochlorine compounds in the brains of deceased

Devils Hole, Nevada—A photographic story of a restricted subaqueous environment

USGS Publications Warehouse

Hoffman, Ray J.

2017-07-24

This report presents selected photographic images taken by the author during U.S. Geological Survey (USGS) research into paleoclimatology and geochemistry in Devils Hole cavern during 1984 to 1993 in cooperation with the National Park Service. The unaltered suite of photographs was prepared by the USGS dive team as an aid to assist nondiving scientists with a visual perspective of the environment where earth-science samples were collected and subsequently analyzed for chemical and isotopic composition.

DSN system performance test Doppler noise models; noncoherent configuration

NASA Technical Reports Server (NTRS)

Bunce, R.

1977-01-01

The newer model for variance, the Allan technique, now adopted for testing, is analyzed in the subject mode. A model is generated (including considerable contribution from the station secondary frequency standard), and rationalized with existing data. The variance model is definitely sound; the Allan technique mates theory and measure. The mean-frequency model is an estimate; this problem is yet to be rigorously resolved. The unaltered defining expressions are noncovergent, and the observed mean is quite erratic.

Sodium lauryl sulphate alters the mRNA expression of lipid-metabolizing enzymes and PPAR signalling in normal human skin in vivo.

PubMed

Törmä, Hans; Berne, Berit

2009-12-01

Detergents irritate skin and affect skin barrier homeostasis. In this study, healthy skin was exposed to 1% sodium lauryl sulphate (SLS) in water for 24 h. Biopsies were taken 6 h to 8 days post exposure. Lipid patterns were stained in situ and real-time polymerase chain reaction (PCR) was used to examine mRNA expression of enzymes synthesizing barrier lipids, peroxisome proliferator-activated receptors (PPAR) and lipoxygenases. The lipid pattern was disorganized from 6 h to 3 days after SLS exposure. Concomitant changes in mRNA expression included: (i) reduction, followed by induction, of ceramide-generating beta-glucocerebrosidase, (ii) increase on day 1 of two other enzymes for ceramide biosynthesis and (iii) persistent reduction of acetyl-CoA carboxylase-B, a key enzyme in fatty acid synthesis. Surprisingly, the rate-limiting enzyme in cholesterol synthesis, HMG-CoA reductase, was unaltered. Among putative regulators of barrier lipids synthesis, PPARalpha and PPARgamma exhibited reduced mRNA expression, while PPARbeta/delta and LXRbeta were unaltered. Epidermal lipoxygenase-3, which may generate PPARalpha agonists, exhibited reduced expression. In conclusion, SLS induces reorganization of lipids in the stratum corneum, which play a role in detergents' destruction of the barrier. The changes in mRNA expression of enzymes involved in synthesizing barrier lipids are probably important for the restoration of the barrier.

Cerebral pressure–flow relationship in lowlanders and natives at high altitude

PubMed Central

Smirl, Jonathan D; Lucas, Samuel J E; Lewis, Nia C S; duManior, Gregory R; Smith, Kurt J; Bakker, Akke; Basnyat, Aperna S; Ainslie, Philip N

2014-01-01

We investigated if dynamic cerebral pressure–flow relationships in lowlanders are altered at high altitude (HA), differ in HA natives and after return to sea level (SL). Lowlanders were tested at SL (n=16), arrival to 5,050 m, after 2-week acclimatization (with and without end-tidal PO2 normalization), and upon SL return. High-altitude natives (n=16) were tested at 5,050 m. Testing sessions involved resting spontaneous and driven (squat–stand maneuvers at very low (VLF, 0.05 Hz) and low (LF, 0.10 Hz) frequencies) measures to maximize blood pressure (BP) variability and improve assessment of the pressure–flow relationship using transfer function analysis (TFA). Blood flow velocity was assessed in the middle (MCAv) and posterior (PCAv) cerebral arteries. Spontaneous VLF and LF phases were reduced and coherence was elevated with acclimatization to HA (P<0.05), indicating impaired pressure–flow coupling. However, when BP was driven, both the frequency- and time-domain metrics were unaltered and comparable with HA natives. Acute mountain sickness was unrelated to TFA metrics. In conclusion, the driven cerebral pressure–flow relationship (in both frequency and time domains) is unaltered at 5,050 m in lowlanders and HA natives. Our findings indicate that spontaneous changes in TFA metrics do not necessarily reflect physiologically important alterations in the capacity of the brain to regulate BP. PMID:24169852

Activation of Multiple Antibiotic Resistance in Uropathogenic Escherichia coli Strains by Aryloxoalcanoic Acid Compounds

PubMed Central

Balagué, Claudia; Véscovi, Eleonora García

2001-01-01

Clofibric and ethacrynic acids are prototypical pharmacological agents administered in the treatment of hypertrigliceridemia and as a diuretic agent, respectively. They share with 2,4-dichlorophenoxyacetic acid (the widely used herbicide known as 2,4-D) a chlorinated phenoxy structural moiety. These aryloxoalcanoic agents (AOAs) are mainly excreted by the renal route as unaltered or conjugated active compounds. The relatedness of these agents at the structural level and their potential effect on therapeutically treated or occupationally exposed individuals who are simultaneously undergoing a bacterial urinary tract infection led us to analyze their action on uropathogenic, clinically isolated Escherichia coli strains. We found that exposure to these compounds increases the bacterial resistance to an ample variety of antibiotics in clinical isolates of both uropathogenic and nonpathogenic E. coli strains. We demonstrate that the AOAs induce an alteration of the bacterial outer membrane permeability properties by the repression of the major porin OmpF in a micF-dependent process. Furthermore, we establish that the antibiotic resistance phenotype is primarily due to the induction of the MarRAB regulatory system by the AOAs, while other regulatory pathways that also converge into micF modulation (OmpR/EnvZ, SoxRS, and Lrp) remained unaltered. The fact that AOAs give rise to uropathogenic strains with a diminished susceptibility to antimicrobials highlights the impact of frequently underestimated or ignored collateral effects of chemical agents. PMID:11353631

Identification of specific gravity sensitive signal transduction pathways in human A431 carcinoma cells

NASA Astrophysics Data System (ADS)

Rijken, P. J.; de Groot, R. P.; Kruijer, W.; de Laat, S. W.; Verkleij, A. J.; Boonstra, J.

Epidermal growth factor (EGF) activates a well characterized signal transduction cascade in human A431 epidermoid carcinoma cells. The influence of gravity on EGF-induced EGF-receptor clustering and early gene expression as well as on actin polymerization and actin organization have been investigated. Different signalling pathways induced by the agents TPA, forskolin and A23187 that activate gene expression were tested for sensitivity to gravity. EGF-induced c-fos and c-jun expression were decreased in microgravity. However, constitutive β-2 microglobulin expression remained unaltered. Under simulated weightlessness conditions EGF- and TPA-induced c-fos expression was decreased, while forskolin- and A23187-induced c-fos expression was independent of the gravity conditions. These results suggest that gravity affects specific signalling pathways. Preliminary results indicate that EGF-induced EGF-receptor clustering remained unaltered irrespective of the gravity conditions. Furthermore, the relative filamentous actin content of steady state A431 cells was enhanced under microgravity conditions and actin filament organization was altered. Under simulated weightlessness actin filament organization in steady state cells as well as in EGF-treated cells was altered as compared to the 1 G reference experiment. Interestingly the microtubule and keratin organization in untreated cells showed no difference with the normal gravity samples. This indicates that gravity may affect specific components of the signal transduction circuitry.

Chemical compositions of primitive solar system particles

NASA Technical Reports Server (NTRS)

Sutton, Steve R.; Bajt, S.

1994-01-01

Chemical studies of micrometeorites are of fundamental importance primarily because atmospheric entry selection effects (such as destruction of friable objects) are less significant than those for conventional meteorites. As a result, particles that have experienced very little postaccretional processing have a significant chance of surviving the Earth encounter and subsequent collection. Thus, chemical analyses of these relatively unaltered micrometeorites may lead to a better understanding of the compositions of the most primitive materials in the solar system and thereby constrain the conditions (physical and chemical) that existed in the early solar nebula. Micrometeorites have been collected from the stratosphere, polar ices, and ocean sediments, but the stratospheric collection is the best source for the most unaltered material because they are small and are not heated to their melting points. Despite the fact that the stratospheric micrometeorites have masses in the nanogram range, a variety of microanalytical techniques have been applied to bulk chemical analyses with part-per-million sensitivity. In some cases, multi-disciplinary studies (e.g., chemistry and mineralogy) have been performed on individual particles. The first-order conclusion is that the chondrite-like particles are chemically similar to carbonaceous chondrites but in detail are distinct from members of the conventional meteorite collection. The purpose of this paper is to provide an overview of the results to date and identify important areas for further study.

Long-term alterations in neuroimmune responses after neonatal exposure to lipopolysaccharide.

PubMed

Boissé, Lysa; Mouihate, Abdeslam; Ellis, Shaun; Pittman, Quentin J

2004-05-26

Fever is an integral part of the host's defense to infection that is orchestrated by the brain. A reduced febrile response is associated with reduced survival. Consequently, we have asked if early life immune exposure will alter febrile and neurochemical responses to immune stress in adulthood. Fourteen-day-old neonatal male rats were given Escherichia coli lipopolysaccharide (LPS) that caused either fever or hypothermia depending on ambient temperature. Control rats were given pyrogen-free saline. Regardless of the presence of neonatal fever, adult animals that had been neonatally exposed to LPS displayed attenuated fevers in response to intraperitoneal LPS but unaltered responses to intraperitoneal interleukin 1beta or intracerebroventricular prostaglandin E(2). The characteristic reduction in activity that accompanies fever was unaltered, however, as a function of neonatal LPS exposure. Treatment of neonates with an antigenically dissimilar LPS (Salmonella enteritidis) was equally effective in reducing adult responses to E. coli LPS, indicating an alteration in the innate immune response. In adults treated as neonates with LPS, basal levels of hypothalamic cyclooxygenase 2 (COX-2), determined by semiquantitative Western blot analysis, were significantly elevated compared with controls. In addition, whereas adult controls responded to LPS with the expected induction of COX-2, adults pretreated neonatally with LPS responded to LPS with a reduction in COX-2. Thus, neonatal LPS can alter CNS-mediated inflammatory responses in adult rats.

Yellow and the Novel Aposematic Signal, Red, Protect Delias Butterflies from Predators

PubMed Central

Wee, Jocelyn Liang Qi

2017-01-01

Butterflies of the South Asian and Australian genus Delias possess striking colours on the ventral wings that are presumed to serve as warning signals to predators. However, this has not been shown empirically. Here we experimentally tested whether the colours of one member of this diverse genus, Delias hyparete, function as aposematic signals. We constructed artificial paper models with either a faithful colour representation of D. hyparete, or with all of its colours converted to grey scale. We also produced models where single colours were left intact, while others were converted to grey-scale or removed entirely. We placed all model types simultaneously in the field, attached to a live mealworm, and measured relative attack rates at three separate field sites. Faithful models of D. hyparete, suffered the least amount of attacks, followed by grey-scale models with unaltered red patches, and by grey-scale models with unaltered yellow patches. We conclude that red and yellow colours function as warning signals. By mapping dorsal and ventral colouration onto a phylogeny of Delias, we observed that yellow and red colours appear almost exclusively on the ventral wing surfaces, and that basal lineages have mostly yellow, white, and black wings, whereas derived lineages contain red colour in addition to the other colours. Red appears to be, thus, a novel adaptive trait in this lineage of butterflies. PMID:28060944

Elevated circulating IL-1beta and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome.

PubMed

Vitoratos, Nicolaos; Papadias, Constantinos; Economou, Emmanuel; Makrakis, Evangelos; Panoulis, Constantinos; Creatsas, George

2006-01-01

The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1) and discharge (group B2) and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C) who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1beta and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1beta, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome.

Elevated Circulating IL-1β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome

PubMed Central

Vitoratos, Nicolaos; Papadias, Constantinos; Economou, Emmanuel; Makrakis, Evangelos; Panoulis, Constantinos; Creatsas, George

2006-01-01

The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1) and discharge (group B2) and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C) who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1β and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1β, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome. PMID:17047289

Yellow and the Novel Aposematic Signal, Red, Protect Delias Butterflies from Predators.

PubMed

Wee, Jocelyn Liang Qi; Monteiro, Antónia

2017-01-01

Butterflies of the South Asian and Australian genus Delias possess striking colours on the ventral wings that are presumed to serve as warning signals to predators. However, this has not been shown empirically. Here we experimentally tested whether the colours of one member of this diverse genus, Delias hyparete, function as aposematic signals. We constructed artificial paper models with either a faithful colour representation of D. hyparete, or with all of its colours converted to grey scale. We also produced models where single colours were left intact, while others were converted to grey-scale or removed entirely. We placed all model types simultaneously in the field, attached to a live mealworm, and measured relative attack rates at three separate field sites. Faithful models of D. hyparete, suffered the least amount of attacks, followed by grey-scale models with unaltered red patches, and by grey-scale models with unaltered yellow patches. We conclude that red and yellow colours function as warning signals. By mapping dorsal and ventral colouration onto a phylogeny of Delias, we observed that yellow and red colours appear almost exclusively on the ventral wing surfaces, and that basal lineages have mostly yellow, white, and black wings, whereas derived lineages contain red colour in addition to the other colours. Red appears to be, thus, a novel adaptive trait in this lineage of butterflies.

Capillary Trapping of CO2 in Oil Reservoirs: Observations in a Mixed-Wet Carbonate Rock.

PubMed

Al-Menhali, Ali S; Krevor, Samuel

2016-03-01

Early deployment of carbon dioxide storage is likely to focus on injection into mature oil reservoirs, most of which occur in carbonate rock units. Observations and modeling have shown how capillary trapping leads to the immobilization of CO2 in saline aquifers, enhancing the security and capacity of storage. There are, however, no observations of trapping in rocks with a mixed-wet-state characteristic of hydrocarbon-bearing carbonate reservoirs. Here, we found that residual trapping of supercritical CO2 in a limestone altered to a mixed-wet state with oil was significantly less than trapping in the unaltered rock. In unaltered samples, the trapping of CO2 and N2 were indistinguishable, with a maximum residual saturation of 24%. After the alteration of the wetting state, the trapping of N2 was reduced, with a maximum residual saturation of 19%. The trapping of CO2 was reduced even further, with a maximum residual saturation of 15%. Best-fit Land-model constants shifted from C = 1.73 in the water-wet rock to C = 2.82 for N2 and C = 4.11 for the CO2 in the mixed-wet rock. The results indicate that plume migration will be less constrained by capillary trapping for CO2 storage projects using oil fields compared with those for saline aquifers.

Cerebral pressure-flow relationship in lowlanders and natives at high altitude.

PubMed

Smirl, Jonathan D; Lucas, Samuel J E; Lewis, Nia C S; duManoir, Gregory R; Dumanior, Gregory R; Smith, Kurt J; Bakker, Akke; Basnyat, Aperna S; Ainslie, Philip N

2014-02-01

We investigated if dynamic cerebral pressure-flow relationships in lowlanders are altered at high altitude (HA), differ in HA natives and after return to sea level (SL). Lowlanders were tested at SL (n=16), arrival to 5,050 m, after 2-week acclimatization (with and without end-tidal PO2 normalization), and upon SL return. High-altitude natives (n=16) were tested at 5,050 m. Testing sessions involved resting spontaneous and driven (squat-stand maneuvers at very low (VLF, 0.05 Hz) and low (LF, 0.10 Hz) frequencies) measures to maximize blood pressure (BP) variability and improve assessment of the pressure-flow relationship using transfer function analysis (TFA). Blood flow velocity was assessed in the middle (MCAv) and posterior (PCAv) cerebral arteries. Spontaneous VLF and LF phases were reduced and coherence was elevated with acclimatization to HA (P<0.05), indicating impaired pressure-flow coupling. However, when BP was driven, both the frequency- and time-domain metrics were unaltered and comparable with HA natives. Acute mountain sickness was unrelated to TFA metrics. In conclusion, the driven cerebral pressure-flow relationship (in both frequency and time domains) is unaltered at 5,050 m in lowlanders and HA natives. Our findings indicate that spontaneous changes in TFA metrics do not necessarily reflect physiologically important alterations in the capacity of the brain to regulate BP.

Encapsulation of Volatile Citronella Essential Oil by Coacervation: Efficiency and Release Study

NASA Astrophysics Data System (ADS)

Manaf, M. A.; Subuki, I.; Jai, J.; Raslan, R.; Mustapa, A. N.

2018-05-01

The volatile citronella essential oil was encapsulated by simple coacervation and complex coacervation using Arabic gum and gelatin as wall material. Glutaraldehyde was used in the methodology as crosslinking agent. The citronella standard calibration graph obtained with R2 of 0.9523 was used for the accurate determination of encapsulation efficiency and release study. The release kinetic was analysed based on Fick"s law of diffusion for polymeric system and linear graph of Log fraction release over Log time was constructed to determine the release rate constant, k and diffusion coefficient, n. Both coacervation methods in the present study produce encapsulation efficiency around 94%. The produced capsules for both coacervation processes were discussed based on the capsules morphology and release kinetic mechanisms.

In silico and in vitro methods to optimize the performance of experimental gastroretentive floating mini-tablets.

PubMed

Eberle, Veronika A; Häring, Armella; Schoelkopf, Joachim; Gane, Patrick A C; Huwyler, Jörg; Puchkov, Maxim

2016-01-01

Development of floating drug delivery systems (FDDS) is challenging. To facilitate this task, an evaluation method was proposed, which allows for a combined investigation of drug release and flotation. It was the aim of the study to use functionalized calcium carbonate (FCC)-based lipophilic mini-tablet formulations as a model system to design FDDS with a floating behavior characterized by no floating lag time, prolonged flotation and loss of floating capability after complete drug release. Release of the model drug caffeine from the mini-tablets was assessed in vitro by a custom-built stomach model. A cellular automata-based model was used to simulate tablet dissolution. Based on the in silico data, floating forces were calculated and analyzed as a function of caffeine release. Two floating behaviors were identified for mini-tablets: linear decrease of the floating force and maintaining of the floating capability until complete caffeine release. An optimal mini-tablet formulation with desired drug release time and floating behavior was developed and tested. A classification system for a range of varied floating behavior of FDDS was proposed. The FCC-based mini-tablets had an ideal floating behavior: duration of flotation is defined and floating capability decreases after completion of drug release.

Modulation of the release of ( sup 3 H)norepinephrine from the base and body of the rat urinary bladder by endogenous adrenergic and cholinergic mechanisms

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

Somogyi, G.T.; de Groat, W.C.

Modulation of (3H)NE release was studied in rat urinary bladder strips prelabeled with (3H)NE. (3H)NE uptake occurred in strips from the bladder base and body, but was very prominent in the base where the noradrenergic innervation is most dense. Electrical field stimulation markedly increased (3H)NE outflow from the superfused tissue. The quantity of (3H)NE release was approximately equal during three consecutive periods of stimulation. Activation of presynaptic muscarinic receptors by 1.0 microM oxotremorine reduced (3H)NE release to 46% of the control. Atropine (1 microM) blocked the effect of oxotremorine and increased the release to 147% of predrug control levels. Activationmore » of presynaptic alpha-2 adrenoceptors by 1 microM clonidine reduced (3H)NE release to 55% of control. Yohimbine blocked the action of clonidine and increased the release to 148% of control. The release of (3H)NE from the bladder base and body was increased by both 1 microM atropine (to 167% and 174% of control, respectively) and 1 microM yohimbine (to 286% and 425% of control, respectively). Atropine and yohimbine administered in combination had similar facilitatory effects as when administered alone. We conclude that the release of (3H)NE from adrenergic nerve endings in electrically stimulated bladder strips is modulated via endogenous transmitters acting on both muscarinic and alpha-2 adrenergic presynaptic receptors and that the latter provide the most prominent control.« less

A Voltage-Responsive Free-Blockage Controlled-Release System Based on Hydrophobicity Switching.

PubMed

Jiao, Xiangyu; Sun, Ruijuan; Cheng, Yaya; Li, Fengyu; Du, Xin; Wen, Yongqiang; Song, Yanlin; Zhang, Xueji

2017-05-19

Controlled-release systems based on mesoporous silica nanomaterials (MSNs) have drawn great attention owing to their potential biomedical applications. Various switches have been designed to control the release of cargoes through the construction of physical blocking units on the surface of MSNs. However, such physical blockages are limited by poor sealing ability and low biocompatibility, and most of them lack closure ability. Herein, a voltage-responsive controlled-release system was constructed by functionalizing the nanopore of MSNs with ferrocene. The system realized free-blockage controlled release and achieved pulsatile release. The nanopores of the ferrocene-functionalized MSNs were hydrophobic enough to prevent invasion of the solution. Once a suitable voltage was applied, the nanopores became hydrophilic, which was followed by invasion of the solution and the release of the cargos. Moreover, pulsatile release was realized, which avoided unexpected release after the stimulus disappeared. Thus, we believe that our studies provide new insight into highly effective blockage for MSNs. Furthermore, the voltage-responsive release system is expected to find use in electrical stimulation combination therapy and bioelectricity-responsive release. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental Studies on Dehydration Embrittlement of Serpentinized Peridotite and Effect of Pressure on Creep of Olivine

NASA Astrophysics Data System (ADS)

Xia, Gang

The origin of intermediate depth earthquakes has been debated for 90 years yet is still under active discussion. These earthquakes are localized in double seismic zones in descending lithosphere; both zones originate very close to oceanic trenches. A leading proposed initiation mechanism for these earthquakes since 1968 has been dehydration embrittlement of serpentine under stress. Despite the considerable evidence favoring this mechanism, a major argument against it has been that the lower seismic zone initiates at ˜40 km depth almost immediately below trenches and there does not appear to be a vehicle to carry water sufficiently deep to hydrate otherwise dry lithosphere. To directly address this problem, an experimental study has been carried out to investigate the minimum amount of serpentine that is required to trigger the dehydration embrittlement instability in serpentinized peridotite at high pressure (1-3 GPa) and temperature (720-750˚C). The results show that embrittlement occurs during dehydration of antigorite (the phase of serpentine stable at elevated pressure) in a wide range of compositions but both nearly dry peridotite and extensively altered peridotite are ductile. Fresh, unaltered, synthetic harzburgite and harzburgite with 4 vol% distributed antigorite are ductile, as are specimens with greater than 65% antigorite. Only compositions between 8 vol% and 65 vol% antigorite develop the instability. We suggest that very small degrees of serpentinization do not release sufficient H 2O to trigger the instability and that extensive serpentinization avoids the instability because soft, ductile, antigorite becomes the interconnected matrix with olivine and pyroxene existing only as isolated crystals. In that case, dehydration simply facilitates flow. These systematics suggest that small amounts of H2O transported down deep normal (bending) faults at trenches are sufficient to enable the instability in the lower seismic zones, thus providing additional support for dehydration embrittlement as the mechanism of intermediate-depth earthquakes. At the other end of the spectrum of serpentinization, these results are consistent with previous suggestions that extensive dehydration of altered subducting crust and mantle release copious amounts of H2O that rise to the surface of the descending slab and react with the cool mantle of the overlying plate to lead to extensive serpentinization, thereby explaining serpentine diapers in the forearc and lack of seismicity along the plate interface deeper than about 35 km. Another long-lived controversy in mantle geophysics involves the pressure dependence of creep in olivine, the most abundant and softest phase in unaltered mantle rocks. The pressure dependence of any thermodynamically-controlled phenomenon is commonly expressed as the activation volume, DeltaV*. Previous experimental investigations on the effect of pressure on creep in olivine have produced bimodal results. DeltaV* obtained from solid-medium (Griggs) and gas-medium (Paterson) deformation apparatus at relatively lower pressures is ˜15 cm3/mol or higher. In contrast, higher-pressure studies using multianvil apparatus at sites of synchrotron X-radiation (D-DIA apparatus) report a DeltaV* near zero. To decipher this enigma and to provide a much-needed calibration of stress in the D-DIA apparatus, I have conducted systematic experiments on a synthetic, iron-free, forsterite at 1200 ˚C and pressure between 1 and 2.5 GPa using the UCR 5 GPa modified Griggs apparatus, the only apparatus capable of performing these experiments. Our results show a robust DeltaV* value of 12 +/- 2 cm3/mol, indicating a fairly significant pressure dependence of creep in olivine to pressures of ˜3 GPa (approximately 100 km). In collaboration with other experimentalists, we plan to measure the DeltaV* for creep of this material over a pressure range of 2-8 GPa in the D-DIA apparatus to both calibrate stress measurement in the D-DIA and resolve the question of change in DeltaV* at higher pressures.

Bioavailability of ambroxol sustained release preparations. Part II: Single and multiple oral dose studies in man.

PubMed

Janssen, T J; Guelen, P J; Vree, T B; Botterblom, M H; Valducci, R

1988-01-01

The bioavailability of a new ambroxol sustained release preparation (75 mg) based on a dialyzing membrane for controlled release was studied in healthy volunteers after single and multiple oral dose in comparison with a standard sustained release formulation in a cross-over study under carefully controlled conditions. Plasma concentrations of ambroxol were measured by means of a HPLC method. Based on AUC data both preparations are found to be bioequivalent, but show different plasma concentration profiles. The test preparation showed a more pronounced sustained release profile than the reference preparation (single dose) resulting in significantly higher steady state plasma levels.

Xylan-Modified-Based Hydrogels with Temperature/pH Dual Sensitivity and Controllable Drug Delivery Behavior

PubMed Central

Kong, Wei-Qing; Gao, Cun-Dian; Hu, Shu-Feng; Ren, Jun-Li; Zhao, Li-Hong; Sun, Run-Cang

2017-01-01

Among the natural macromolecules potentially used as the scaffold material in hydrogels, xylan has aroused great interest in many fields because of its biocompatibility, low toxicity, and biodegradability. In this work, new pH and thermoresponsive hydrogels were prepared by the cross-linking polymerization of maleic anhydride-modified xylan (MAHX) with N-isopropylacrylamide (NIPAm) and acrylic acid (AA) under UV irradiation to form MAHX-g-P(NIPAm-co-AA) hydrogels. The pore volume, the mechanical properties, and the release rate for drugs of hydrogels could be controlled by the degree of substitution of MAHX. These hydrogels were characterized by swelling ability, lower critical solution temperature (LCST), Fourier-transform infrared (FTIR), and SEM. Furthermore, the cumulative release rate was investigated for acetylsalicylic acid and theophylline, as well as the cytocompatibility MAHX-based hydrogels. Results showed that MAHX-based hydrogels exhibited excellent swelling–deswelling properties, uniform porous structure, and the temperature/pH dual sensitivity. In vitro, the cumulative release rate of acetylsalicylic acid for MAHX-based hydrogels was higher than that for theophylline, and in the gastrointestinal sustained drug release study, the acetylsalicylic acid release rate was extremely slow during the initial 3 h in the gastric fluid (24.26%), and then the cumulative release rate reached to 90.5% after sustained release for 5 h in simulated intestinal fluid. The cytotoxicity experiment demonstrated that MAHX-based hydrogels could promote cell proliferation and had satisfactory biocompatibility with NIH3T3 cells. These results indicated that MAHX-based hydrogels, as new drug carriers, had favorable behavior for intestinal-targeted drug delivery. PMID:28772664

Near-infrared remotely triggered drug-release strategies for cancer treatment

NASA Astrophysics Data System (ADS)

Goodman, Amanda M.; Neumann, Oara; Nørregaard, Kamilla; Henderson, Luke; Choi, Mi-Ran; Clare, Susan E.; Halas, Naomi J.

2017-11-01

Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO2 core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects.

Active food packaging based on molecularly imprinted polymers: study of the release kinetics of ferulic acid.

PubMed

Otero-Pazos, Pablo; Rodríguez-Bernaldo de Quirós, Ana; Sendón, Raquel; Benito-Peña, Elena; González-Vallejo, Victoria; Moreno-Bondi, M Cruz; Angulo, Immaculada; Paseiro-Losada, Perfecto

2014-11-19

A novel active packaging based on molecularly imprinted polymer (MIP) was developed for the controlled release of ferulic acid. The release kinetics of ferulic acid from the active system to food simulants (10, 20, and 50% ethanol (v/v), 3% acetic acid (w/v), and vegetable oil), substitutes (95% ethanol (v/v) and isooctane), and real food samples at different temperatures were studied. The key parameters of the diffusion process were calculated by using a mathematical modeling based on Fick's second law. The ferulic acid release was affected by the temperature as well as the percentage of ethanol of the simulant. The fastest release occurred in 95% ethanol (v/v) at 20 °C. The diffusion coefficients (D) obtained ranged between 1.8 × 10(-11) and 4.2 × 10(-9) cm(2)/s. A very good correlation between experimental and estimated data was obtained, and consequently the model could be used to predict the release of ferulic acid into food simulants and real food samples.

Ion release from dental casting alloys as assessed by a continuous flow system: Nutritional and toxicological implications.

PubMed

López-Alías, José F; Martinez-Gomis, Jordi; Anglada, Josep M; Peraire, Maria

2006-09-01

The aims of this study were to quantify the metallic ions released by various dental alloys subjected to a continuous flow of saliva and to estimate the nutritional and toxicological implications of such a release. Four pieces of three nickel-based, one noble, one high-noble and two copper-aluminum alloys were cast and then immersed in a continuous flow of artificial saliva for 15 days. To simulate three meals a day, casts were subjected to thrice-daily episodes, lasting 30 min each and consisting of pH decreases and salinity increases. After 15 days, the metallic ions in the artificial saliva were analyzed. Data were expressed as averaged release rate: microg/cm2/day of ion released for each alloy. The highest value of 95% Cl of each ion was adapted to a hypothetical worst scenario of a subject with 100 cm2 of exposed metal surface. The results were compared with the tolerable upper daily intake level of each ion. The copper-aluminum alloys released copper, aluminum, nickel, manganese and iron. The nickel-based alloys essentially released nickel and chromium, while the beryllium-containing alloy released beryllium and significantly more nickel. The noble and high-noble alloys were very resistant to corrosion. The amount of ions released remained far below the upper tolerable intake level, with the exception of nickel, released by beryllium-containing nickel-based alloy, whose levels approach 50% of this threshold. The daily amount of ions released seems to be far below the tolerable upper intake levels for each ion.

Chemical release module facility

NASA Technical Reports Server (NTRS)

Reasoner, D. L.

1980-01-01

The chemical release module provides the capability to conduct: (1) thermite based metal vapor releases; (2) pressurized gas releases; (3) dispersed liquid releases; (4) shaped charge releases from ejected submodules; and (5) diagnostic measurements with pi supplied instruments. It also provides a basic R-F and electrical system for: (1) receiving and executing commands; (2) telemetering housekeeping data; (3) tracking; (4) monitoring housekeeping and control units; and (5) ultrasafe disarming and control monitoring.

Experimental and modeling studies showing the effect of lipid type and level on flavor release from milk-based liquid emulsions.

PubMed

Roberts, Deborah D; Pollien, Philippe; Watzke, Brigitte

2003-01-01

The purpose of this work was to study two key parameters of the lipid phase that influence flavor release-lipid level and lipid type-and to relate the results to a mass balance partition coefficient-based mathematical model. Release of 10 volatile compounds from milk-based emulsions at 10, 25, and 50 degrees C was monitored by 1-min headspace sampling with a solid-phase microextraction fiber, followed by GC-MS analysis. As compared to the observations for milk fat, changing to a lipophilic lipid (medium-chain triglycerides, MCT) and adding a monoglyceride-based surfactant did not influence the volatiles release. However, increasing the solid fat content was found to increase the release. At 25 degrees C, and even more so at 10 degrees C, concurrent with an increase in their solid fat content, hydrogenated palm fat emulsions showed increased flavor release over that observed for emulsions made with coconut oil, coconut oil with surfactant, milk fat, and MCT. However, at 50 degrees C, when hydrogenated palm fat emulsions had zero solid fat content, there was no difference in flavor release from that observed for milk fat emulsions. Varying milk fat at nine levels between 0 and 4.5% showed a systematic dependence of the release on the lipid level, dependent on compound lipophilicity. Close correlations were found between the experimental and model predictions with lipid level and percent liquid lipid as variables.

In vitro BMP-2 peptide release from thiolated chitosan based hydrogel.

PubMed

Liu, Xujie; Yu, Bo; Huang, Qianli; Liu, Rui; Feng, Qingling; Cai, Qiang; Mi, Shengli

2016-12-01

Thiolated chitosan based thermo-sensitive hydrogel is a water soluble system and the existing thiol groups are beneficial for the delivery of cysteine-rich peptides. In the present study, a kind of thiolated chitosan, i.e. chitosan-4-thio-butylamidine (CS-TBA) conjugate was characterized and used to prepare CS-TBA/hydroxyapatite (HA)/beta-glycerophosphate disodium (β-GP) thermo-sensitive hydrogel. The cysteine terminated peptide 24 (P24) containing residues 73-92 of the knuckle epitope of BMP-2 (N→C: KIPKASSVPTELSAISTLYLSGGC) was synthesized and characterized. The release behavior of P24 from CS-TBA based hydrogel was investigated in vitro. The thiol groups in CS-TBA may react with thiol groups in P24, thus decreases the P24 release rate and maintains the peptide release for a longer time compared with unmodified chitosan based hydrogel. Moreover, the bioactivity of P24 is preserved during release process. These results indicate that P24 loaded CS-TBA based thermosensitive hydrogel is a potential material for minimally invasive surgery of bone repair. Copyright © 2016 Elsevier B.V. All rights reserved.

Spent fuel radionuclide source-term model for assessing spent fuel performance in geological disposal. Part I: Assessment of the instant release fraction

NASA Astrophysics Data System (ADS)

Johnson, Lawrence; Ferry, Cécile; Poinssot, Christophe; Lovera, Patrick

2005-11-01

A source-term model for the short-term release of radionuclides from spent nuclear fuel (SNF) has been developed. It provides quantitative estimates of the fraction of various radionuclides that are expected to be released rapidly (the instant release fraction, or IRF) when water contacts the UO 2 or MOX fuel after container breaching in a geological repository. The estimates are based on correlation of leaching data for radionuclides with fuel burnup and fission gas release. Extrapolation of the data to higher fuel burnup values is based on examination of data on fuel restructuring, such as rim development, and on fission gas release data, which permits bounding IRF values to be estimated assuming that radionuclide releases will be less than fission gas release. The consideration of long-term solid-state changes influencing the IRF prior to canister breaching is addressed by evaluating alpha self-irradiation enhanced diffusion, which may gradually increase the accumulation of fission products at grain boundaries.

Swelling, erosion and drug release characteristics of salbutamol sulfate from hydroxypropyl methylcellulose-based matrix tablets.

PubMed

Chaibva, Faith A; Khamanga, Sandile M M; Walker, Roderick B

2010-12-01

Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.

Long-Term Effect of Fault-Controlled CO2 Alteration on the Weakening and Strengthening of Reservoir and Seal Lithologies at Crystal Geyser, Green River, Utah

NASA Astrophysics Data System (ADS)

Major, J. R.; Eichhubl, P.; Dewers, T. A.

2014-12-01

An understanding of the coupled chemical and mechanical properties and behavior of reservoir and seal rocks is critical for assessing both the short and long term security of sequestered CO2. A combined structural diagenesis approach using observations from natural analogs has great advantages for understanding these properties over longer time scales than is possible using laboratory or numerical experiments. Current numerical models evaluating failure of reservoirs and seals during and after CO2 injection in the subsurface are just beginning to account for such coupled processes. Well-characterized field studies of natural analogs such as Crystal Geyser, Utah, are essential for providing realistic input parameters, calibration, and testing of numerical models across a range of spatial and temporal scales. Fracture mechanics testing was performed on a suite of naturally altered and unaltered reservoir and seal rocks exposed at the Crystal Geyser field site. These samples represent end-products of CO2-related alteration over geologic (>103 yr) time scales. Both the double torsion and short rod test methods yield comparable results on the same samples. Tests demonstrate that CO2-related alteration has weakened one reservoir sandstone lithology by approximately 50%, but the subcritical index is not significantly affected. An altered siltstone sample also shows a reduction in fracture toughness values and lowered subcritical index in comparison to unaltered siltstone. In contrast, elevated calcite content in shales due to CO2 alteration has increased fracture toughness. Similarly, fracture toughness was increased in what is otherwise a weak, poorly cemented sandstone unit due to increased calcite cement. Combined, these results demonstrate that CO2-related alteration generally weakens rock to fracturing (i.e. lowers fracture toughness), except in cases where calcite cementation is significantly increased. The natural system at Crystal Geyser demonstrates that water-CO2-rock interaction driven by changes in the geochemical environment have measurably altered rock geomechanical properties and that some rock units may become more prone to failure, ultimately leading to fracturing and leakage of subsurface reservoirs. These results also have application for CO2-based enhanced oil recovery.

Accumulation of lipids and oxidatively damaged DNA in hepatocytes exposed to particles

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

Vesterdal, Lise K.; Danielsen, Pernille H.; Folkmann, Janne K.

Exposure to particles has been suggested to generate hepatosteatosis by oxidative stress mechanisms. We investigated lipid accumulation in cultured human hepatocytes (HepG2) and rat liver after exposure to four different carbon-based particles. HepG2 cells were exposed to particles for 3 h and subsequently incubated for another 18 h to manifest lipid accumulation. In an animal model of metabolic syndrome we investigated the association between intake of carbon black (CB, 14 nm) particles and hepatic lipid accumulation, inflammation and gene expression of Srebp-1, Fasn and Scd-1 involved in lipid synthesis. There was a concentration-dependent increase in intracellular lipid content after exposuremore » to CB in HepG2 cells, which was only observed after co-exposure to oleic/palmitic acid. Similar results were observed in HepG2 cells after exposure to diesel exhaust particles, fullerenes C{sub 60} or pristine single-walled carbon nanotubes. All four types of particles also generated oxidatively damaged DNA, assessed as formamidopyrimidine DNA glycosylase (FPG) sensitive sites, in HepG2 cells after 3 h exposure. The animal model of metabolic syndrome showed increased lipid load in the liver after one oral exposure to 6.4 mg/kg of CB in lean Zucker rats. This was not associated with increased iNOS staining in the liver, indicating that the oral CB exposure was associated with hepatic steatosis rather than steatohepatitis. The lipid accumulation did not seem to be related to increased lipogenesis because there were unaltered gene expression levels in both the HepG2 cells and rat livers. Collectively, exposure to particles is associated with oxidative stress and steatosis in hepatocytes. - Highlights: • Oral exposure to nanosized carbon black was associated with hepatosteatosis in rats. • In vitro studies included carbon black, C{sub 60}, diesel exhaust particles and SWCNTs. • Exposure to particles and free fatty acids increased lipid load in HepG2 cells. • Unaltered expression of lipogenesis genes despite oxidative stress in hepatocytes • Particles evoke hepatosteatosis by increased uptake rather than synthesis of lipids.« less

DNA strand breaks and TDP-43 mislocation are absent in the murine hSOD1G93A model of amyotrophic lateral sclerosis in vivo and in vitro

PubMed Central

Witte, Otto W.; Grosskreutz, Julian

2017-01-01

Mutations in the human Cu/Zn superoxide dismutase type-1 (hSOD1) gene are common in familial amyotrophic lateral sclerosis (fALS). The pathophysiology has been linked to, e.g., organelle dysfunction, RNA metabolism and oxidative DNA damage conferred by SOD1 malfunction. However, apart from metabolically evoked DNA oxidation, it is unclear whether severe genotoxicity including DNA single-strand breaks (SSBs) and double-strand breaks (DSBs), originates from loss of function of nuclear SOD1 enzyme. Factors that endogenously interfere with DNA integrity and repair complexes in hSOD1-mediated fALS remain similarly unexplored. In this regard, uncontrolled activation of transposable elements (TEs) might contribute to DNA disintegration and neurodegeneration. The aim of this study was to elucidate the role of the fALS-causing hSOD1G93A mutation in the generation of severe DNA damage beyond well-characterized DNA base oxidation. Therefore, DNA damage was assessed in spinal tissue of hSOD1G93A-overexpressing mice and in corresponding motor neuron-enriched cell cultures in vitro. Overexpression of the hSOD1G93A locus did not change the threshold for severe DNA damage per se. We found that levels of SSBs and DSBs were unaltered between hSOD1G93A and control conditions, as demonstrated in post-mitotic motor neurons and in astrocytes susceptible to replication-dependent DNA breakage. Analogously, parameters indicative of DNA damage response processes were not activated in vivo or in vitro. Evidence for a mutation-related elevation in TE activation was not detected, in accordance with the absence of TAR DNA binding protein 43 (TDP-43) proteinopathy in terms of cytoplasmic mislocation or nuclear loss, as nuclear TDP-43 is supposed to silence TEs physiologically. Conclusively, the superoxide dismutase function of SOD1 might not be required to preserve DNA integrity in motor neurons, at least when the function of TDP-43 is unaltered. Our data establish a foundation for further investigations addressing functional TDP-43 interaction with ALS-relevant genetic mutations. PMID:28832631

ChemCam passive reflectance spectroscopy of the Lubango, Okoruso, and Oudam drill targets in Gale Crater, Mars

NASA Astrophysics Data System (ADS)

Johnson, J. R.; Cloutis, E.; Fraeman, A.; Wiens, R. C.; Maurice, S.; Blaney, D. L.; Gasnault, O.

2016-12-01

The ChemCam laser-induced breakdown spectroscopy instrument on the MSL rover Curiosity was used in passive mode (without the laser) to obtain relative reflectance spectra (400-840 nm) of drill tailings and sieved dump piles associated with the targets Lubango, Okoruso, and Oudam between mission sols 1324-1369 near the base of Mt. Sharp. The Lubango and Okoruso drill holes were studied to compare the light-toned zones in the Stimson sandstone (Lubango; 61 wt % SiO2 from ChemCam LIBS data) with nearby unaltered materials (Okoruso; 42 wt % SiO2). Passive spectra of the Lubango tailings (derived from 1-2 cm near the surface) were 50% brighter than the sieved samples (obtained from >2 cm depths). All samples exhibited flat spectra with a slight decrease in reflectance toward the near-infrared. The presence of a weak band near 433 nm (from trace ferric materials such as ferric sulfate) was likely enhanced by the relatively transparent, silica-rich matrix. Lubango was spectrally similar to Greenhorn, another high-silica alteration zone observed in the Stimson unit (Sol 1139). Okoruso passive spectra exhibited flat but increasing reflectance towards the near-infrared with a minor downturn past 800 nm likely related to minor pyroxene. The spectra were darker than the Lubango sieved samples, with no evidence for a 433 nm band. They were similar to the spectra of Big Sky (the unaltered Stimson companion observation to Greenhorn). The Oudam drill tailings pile was observed at two locations: along its outer edge and at a more inward location. Both areas exhibited broad bands near 535 nm and 670 nm and a near-infrared dropoff consistent with hematite. Peak reflectances were near 785 nm for the edge sample but closer to 765 nm for the inner surface (similar to the hematite-bearing Confidence Hills sample from Sol 762). The difference likely results from the presence of other ferric materials in addition to hematite along the edge. This may indicate minor variations in oxidation state with depth in the drilled sampled.

Smart drug release systems based on stimuli-responsive polymers.

PubMed

Qing, Guangyan; Li, Minmin; Deng, Lijing; Lv, Ziyu; Ding, Peng; Sun, Taolei

2013-07-01

Stimuli-responsive polymers could respond to external stimuli, such as temperature, pH, photo-irradiation, electric field, biomolecules in solution, etc., which further induce reversible transformations in the structures and conformations of polymers, providing an excellent platform for controllable drug release, while the accuracy of drug delivery could obtain obvious improvement in this system. In this review, recent progresses in the drug release systems based on stimuli-responsive polymers are summarized, in which drugs can be released in an intelligent mode with high accuracy and efficiency, while potential damages to normal cells and tissues can also be effectively prevented owing to the unique characteristics of materials. Moreover, we introduce some smart nanoparticles-polymers conjugates and drug release devices, which are especially suitable for the long-term sustained drug release.

Elucidating the Role of cAbl and the Abi-Family of cAbl Target Proteins in Cancer Development and Progression

DTIC Science & Technology

1999-07-01

patients with Ph’-positive leukemias also revealed loss of Abi proteins. We determined by RNase protection assay and reverse transcriptase polymerase...myelogenous leukemia . Abi protein levels also appeared unaltered by Western blot analysis of human lung, liver, colon, and breast carcinoma tissues as...generated in the presence of Bcr-Abl • Abi protein degradation was observed in Ph’+ leukemia -derived cells, but not in Ph1- leukemias or in human breast

Structural Characterization of Atomically Thin Hexagonal Boron Nitride via Raman Spectroscopy

DTIC Science & Technology

2014-03-27

thickness and the use of depth profiling to maximize spectral returns. Chapter 3 also outlines the experimental set-up and procedures related to...section. 46 Figure 4.8: Unaltered spectral return of both Site 1 (A) and Site 2 ( B ). As to be expected the relative intensity of the Raman...Dent, Modern Raman Spectroscopy : A Practical Approach. Wiley, 2006, p. 224. 59 25. A. B . Kaul, E. W . Wong, L. Epp, and B . D. Hunt, “Two

Industrial Preparedness in an Arms Control Environment: A Study of the Potential Impact of Sharp Increases in Military Procurement. Volume 2. Complete Report

DTIC Science & Technology

1974-12-01

military expenditures • Attitude toward increased taxation or reduction in federal budget expenditures • Willingness to experience governmental controls...if allocation, rationing, wane and price con- trols, and increased taxation arc not resorted to, as was case in the early of the Vietnam War...n incor; \\ into thv malysi . • Financing through taxation would allow g< non-defense spending to continue unaltered. 39 ACDA/MEA-24 6

Sparsening Filter Design for Iterative Soft-Input Soft-Output Detectors

DTIC Science & Technology

2012-02-29

filter/detector structure. Since the BP detector itself is unaltered from [1], it can accommodate a system employing channel codes such as LDPC encoding...considered in [1], or can readily be extended to the MIMO case with, for example, space-time coding as in [2,8]. Since our focus is on the design of...simplex method of [15], since it was already available in Matlab , via the “fminsearch” function. 6 Cost surfaces To visualize the cost surfaces, consider

Susceptibility profiles of amphotericin B and posaconazole against clinically relevant mucorales species under hypoxic conditions.

PubMed

Maurer, Elisabeth; Binder, Ulrike; Sparber, Manuela; Lackner, Michaela; Caramalho, Rita; Lass-Flörl, Cornelia

2015-02-01

The effect of hypoxic conditions on the in vitro efficacy of amphotericin B and posaconazole against Mucorales was evaluated by defining MICs with Etest and broth microdilution and identifying minimal fungicidal concentrations (MFCs). With Etest, oxygen-dependent changes were detected, while the MIC and the MFC determined with broth microdilution remained unaltered with reduced oxygen levels. The observed differences depended on the method used. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Erythrocyte volume in acidified venous blood from exercising limbs.

NASA Technical Reports Server (NTRS)

Van Beaumont, W.; Rochelle, R. H.

1973-01-01

Five male volunteers performed arm exercises in the sitting position by cranking the pedals of a bicycle ergometer at 50 revolutions per min. The initial mechanical work load of 0 kgm/min was increased every minute by 75 kgm/min until exhaustion occurred. The data obtained show a significant acidification of the venous blood from the working arms and a substantial increase in venous pCO2 during this type of muscular activity. However, the erythrocyte volume remained unaltered during the exercise.

A Critical Review of the State of Finite Plasticity

DTIC Science & Technology

1990-05-01

finite deformation of elastic-plastic materials, the development of which began with the work of Green and Naghdi (1965, 1966). A point of departure which...related results, see Naghdi (1972, p. 485) and Green and Naghdi (1979). The equations ot motion (3.2) or (3.3), as well as the fields which occur in...unaltered apart from onentation as defined by Green and Naghdi (1979). However. it should be emphasized that the use of the term objective hire differs from

Erratum: Evidence of b -jet quenching in PbPb collisions at s N N = 2.76 TeV [Phys. Rev. Lett. 113 , 132301 (2014)

DOE PAGES

Chatrchyan, S.

2015-07-10

In our Letter, there was a component of the statistical uncertainty from the simulated PbPb Monte Carlo samples. This uncertainty was not propagated to all of the results. Figures 3 and 4 have been updated to reflect this source of uncertainty. In this case, the statistical uncertainties remain smaller than the systematic uncertainties in all cases such that the conclusions of the Letter are unaltered.

Application of micro-X-ray fluorescence to chemical mapping of polar ice

NASA Astrophysics Data System (ADS)

Fourcade, M. C. Morel; Barnola, J. M.; Susini, J.; Baker, R.; Durand, G.; de Angelis, M.; Duval, P.

Synchrotron-based micro-X-ray fluorescence (μXRF) equipment has been used to analyze impurities in polar ice. A customized sample holder has been developed and the μXRF equipment has been adapted with a thermal control system to keep samples unaltered during analyses. Artificial ice samples prepared from ultra-pure water were analyzed to investigate possible contamination and/or experimental artefacts. Analyses of polar ice from Antarctica (Dome C and Vostok) confirm this μXRF technique is non-destructive and sensitive. Experiments can be reproduced to confirm or refine results by focusing on interesting spots such as crystal grain boundaries or specific inclusions. Integration times and resolution can be adjusted to optimize sensitivity. Investigation of unstable particles is possible due to the short analysis time. In addition to identification of elements in impurities, μXRF is able to determine their speciations. The accuracy and reliability of the results confirm the potential of this technique for research in glaciology.

Remote Sensing of Mars: Detection of Impact Craters on the Mars Global Surveyor DTM by Integrating Edge- and Region-Based Algorithms

NASA Astrophysics Data System (ADS)

Athanassas, C. D.; Vaiopoulos, A.; Kolokoussis, P.; Argialas, D.

2018-03-01

This study integrates two different computer vision approaches, namely the circular Hough transform (CHT) and the determinant of Hessian (DoH), to detect automatically the largest number possible of craters of any size on the digital terrain model (DTM) generated by the Mars Global Surveyor mission. Specifically, application of the standard version of CHT to the DTM captured a great number of craters with diameter smaller than 50 km only, failing to capture larger craters. On the other hand, DoH was successful in detecting craters that were undetected by CHT, but its performance was deterred by the irregularity of the topographic surface encompassed: strongly undulated and inclined (trended) topographies hindered crater detection. When run on a de-trended DTM (and keeping the topology unaltered) DoH scored higher. Current results, although not optimal, encourage combined use of CHT and DoH for routine crater detection undertakings.

Efficient transduction of equine adipose-derived mesenchymal stem cells by VSV-G pseudotyped lentiviral vectors.

PubMed

Petersen, Gayle F; Hilbert, Bryan; Trope, Gareth; Kalle, Wouter; Strappe, Padraig

2014-12-01

Equine adipose-derived mesenchymal stem cells (EADMSC) provide a unique cell-based approach for treatment of a variety of equine musculoskeletal injuries, via regeneration of diseased or damaged tissue, or the secretion of immunomodulatory molecules. These capabilities can be further enhanced by genetic modification using lentiviral vectors, which provide a safe and efficient method of gene delivery. We investigated the suitability of lentiviral vector technology for gene delivery into EADMSC, using GFP expressing lentiviral vectors pseudotyped with the G glycoprotein from the vesicular stomatitis virus (V-GFP) or, for the first time, the baculovirus gp64 envelope protein (G-GFP). In this study, we produced similarly high titre V-GFP and G-GFP lentiviral vectors. Flow cytometric analysis showed efficient transduction using V-GFP; however G-GFP exhibited a poor ability to transduce EADMSC. Transduction resulted in sustained GFP expression over four passages, with minimal effects on cell viability and doubling time, and an unaltered chondrogenic differentiation potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

Study of harsh environment operation of flexible ferroelectric memory integrated with PZT and silicon fabric

NASA Astrophysics Data System (ADS)

Ghoneim, M. T.; Hussain, M. M.

2015-08-01

Flexible memory can enable industrial, automobile, space, and smart grid centered harsh/extreme environment focused electronics application(s) for enhanced operation, safety, and monitoring where bent or complex shaped infrastructures are common and state-of-the-art rigid electronics cannot be deployed. Therefore, we report on the physical-mechanical-electrical characteristics of a flexible ferroelectric memory based on lead zirconium titanate as a key memory material and flexible version of bulk mono-crystalline silicon (100). The experimented devices show a bending radius down to 1.25 cm corresponding to 0.16% nominal strain (high pressure of ˜260 MPa), and full functionality up to 225 °C high temperature in ambient gas composition (21% oxygen and 55% relative humidity). The devices showed unaltered data retention and fatigue properties under harsh conditions, still the reduced memory window (20% difference between switching and non-switching currents at 225 °C) requires sensitive sense circuitry for proper functionality and is the limiting factor preventing operation at higher temperatures.

High-speed noise-free optical quantum memory

NASA Astrophysics Data System (ADS)

Kaczmarek, K. T.; Ledingham, P. M.; Brecht, B.; Thomas, S. E.; Thekkadath, G. S.; Lazo-Arjona, O.; Munns, J. H. D.; Poem, E.; Feizpour, A.; Saunders, D. J.; Nunn, J.; Walmsley, I. A.

2018-04-01

Optical quantum memories are devices that store and recall quantum light and are vital to the realization of future photonic quantum networks. To date, much effort has been put into improving storage times and efficiencies of such devices to enable long-distance communications. However, less attention has been devoted to building quantum memories which add zero noise to the output. Even small additional noise can render the memory classical by destroying the fragile quantum signatures of the stored light. Therefore, noise performance is a critical parameter for all quantum memories. Here we introduce an intrinsically noise-free quantum memory protocol based on two-photon off-resonant cascaded absorption (ORCA). We demonstrate successful storage of GHz-bandwidth heralded single photons in a warm atomic vapor with no added noise, confirmed by the unaltered photon-number statistics upon recall. Our ORCA memory meets the stringent noise requirements for quantum memories while combining high-speed and room-temperature operation with technical simplicity, and therefore is immediately applicable to low-latency quantum networks.

Recognition of Conformational Changes in β-Lactoglobulin by Molecularly Imprinted Thin Films

PubMed Central

Turner, Nicholas W.; Liu, Xiao; Piletsky, Sergey A.; Hlady, Vladimir; Britt, David W.

2008-01-01

Pathogenesis in protein conformational diseases is initiated by changes in protein secondary structure. This molecular restructuring presents an opportunity for novel shape-based detection approaches, as protein molecular weight and chemistry are otherwise unaltered. Here we apply molecular imprinting to discriminate between distinct conformations of the model protein β-lactoglobulin (BLG). Thermal- and fluoro-alcohol-induced BLG isoforms were imprinted in thin films of 3-aminophenylboronic acid on quartz crystal microbalance chips. Enhanced rebinding of the template isoform was observed in all cases when compared to the binding of nontemplate isoforms over the concentration range of 1–100 µg mL−1. Furthermore, it was observed that the greater the changes in the secondary structure of the template protein the lower the binding of native BLG challenges to the imprint, suggesting a strong steric influence in the recognition system. This feasibility study is a first demonstration of molecular imprints for recognition of distinct conformations of the same protein. PMID:17665947

Recognition of conformational changes in beta-lactoglobulin by molecularly imprinted thin films.

PubMed

Turner, Nicholas W; Liu, Xiao; Piletsky, Sergey A; Hlady, Vladimir; Britt, David W

2007-09-01

Pathogenesis in protein conformational diseases is initiated by changes in protein secondary structure. This molecular restructuring presents an opportunity for novel shape-based detection approaches, as protein molecular weight and chemistry are otherwise unaltered. Here we apply molecular imprinting to discriminate between distinct conformations of the model protein beta-lactoglobulin (BLG). Thermal- and fluoro-alcohol-induced BLG isoforms were imprinted in thin films of 3-aminophenylboronic acid on quartz crystal microbalance chips. Enhanced rebinding of the template isoform was observed in all cases when compared to the binding of nontemplate isoforms over the concentration range of 1-100 microg mL(-1). Furthermore, it was observed that the greater the changes in the secondary structure of the template protein the lower the binding of native BLG challenges to the imprint, suggesting a strong steric influence in the recognition system. This feasibility study is a first demonstration of molecular imprints for recognition of distinct conformations of the same protein.

A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells

PubMed Central

Ferraro, Francesco; Kriston-Vizi, Janos; Metcalf, Daniel J.; Martin-Martin, Belen; Freeman, Jamie; Burden, Jemima J.; Westmoreland, David; Dyer, Clare E.; Knight, Alex E.; Ketteler, Robin; Cutler, Daniel F.

2014-01-01

Summary Weibel-Palade bodies (WPBs), endothelial-specific secretory granules that are central to primary hemostasis and inflammation, occur in dimensions ranging between 0.5 and 5 μm. How their size is determined and whether it has a functional relevance are at present unknown. Here, we provide evidence for a dual role of the Golgi apparatus in controlling the size of these secretory carriers. At the ministack level, cisternae constrain the size of nanostructures (“quanta”) of von Willebrand factor (vWF), the main WPB cargo. The ribbon architecture of the Golgi then allows copackaging of a variable number of vWF quanta within the continuous lumen of the trans-Golgi network, thereby generating organelles of different sizes. Reducing the WPB size abates endothelial cell hemostatic function by drastically diminishing platelet recruitment, but, strikingly, the inflammatory response (the endothelial capacity to engage leukocytes) is unaltered. Size can thus confer functional plasticity to an organelle by differentially affecting its activities. PMID:24794632

Application of micro-Raman spectroscopy for fight against terrorism and smuggling

NASA Astrophysics Data System (ADS)

Almaviva, Salvatore; Botti, Sabina; Palucci, Antonio; Puiu, Adriana; Schnürer, Frank; Schweikert, Wenka; Romolo, Francesco Saverio

2014-04-01

We report the results of Raman measurements on some common military explosives and explosives precursors deposited on clothing fabrics, both synthetic and natural, in concentration comparable to those obtained from a single fingerprint or mixed with similar harmless substances to detect illegal compounds for smuggling activities. Raman spectra were obtained using an integrated portable Raman system equipped with an optical microscope and a 785-nm laser in an analysis of <1 min. The spectral features of each illicit substance have been identified and distinguished from those belonging to the substrate fabric or from the interfering compound. Our results show that the application of Raman spectroscopy (RS) with a microscope-based portable apparatus can provide interpretable Raman spectra for a fast, in-situ analysis, directly from explosive particles of some μ, despite the contribution of the substrate, leaving the sample completely unaltered for further, more specific, and propedeutic laboratory analysis. We also show how the RS is suitable for detecting illegal compounds mixed with harmless substances for smuggling purposes or for counterfeiting activities.

Can rodents conceive hyperbolic spaces?

PubMed Central

Urdapilleta, Eugenio; Troiani, Francesca; Stella, Federico; Treves, Alessandro

2015-01-01

The grid cells discovered in the rodent medial entorhinal cortex have been proposed to provide a metric for Euclidean space, possibly even hardwired in the embryo. Yet, one class of models describing the formation of grid unit selectivity is entirely based on developmental self-organization, and as such it predicts that the metric it expresses should reflect the environment to which the animal has adapted. We show that, according to self-organizing models, if raised in a non-Euclidean hyperbolic cage rats should be able to form hyperbolic grids. For a given range of grid spacing relative to the radius of negative curvature of the hyperbolic surface, such grids are predicted to appear as multi-peaked firing maps, in which each peak has seven neighbours instead of the Euclidean six, a prediction that can be tested in experiments. We thus demonstrate that a useful universal neuronal metric, in the sense of a multi-scale ruler and compass that remain unaltered when changing environments, can be extended to other than the standard Euclidean plane. PMID:25948611

Pinosylvin-Based Polymers: Biodegradable Poly(Anhydride-Esters) for Extended Release of Antibacterial Pinosylvin.

PubMed

Bien-Aime, Stephan; Yu, Weiling; Uhrich, Kathryn E

2016-07-01

Pinosylvin is a natural stilbenoid known to exhibit antibacterial bioactivity against foodborne bacteria. In this work, pinosylvin is chemically incorporated into a poly(anhydride-ester) (PAE) backbone via melt-condensation polymerization, and characterized with respect to its physicochemical and thermal properties. In vitro release studies demonstrate that pinosylvin-based PAEs hydrolytically degrade over 40 d to release pinosylvin. Pseudo-first order kinetic experiments on model compounds, butyric anhydride and 3-butylstilbene ester, indicate that the anhydride linkages hydrolyze first, followed by the ester bonds to ultimately release pinosylvin. An antibacterial assay shows that the released pinosylvin exhibit bioactivity, while in vitro cytocompatibility studies demonstrate that the polymer is noncytotoxic toward fibroblasts. These preliminary findings suggest that the pinosylvin-based PAEs can serve as food preservatives in food packaging materials by safely providing antibacterial bioactivity over extended time periods. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation and Characterization of Azadirachtin Alginate-Biosorbent Based Formulations: Water Release Kinetics and Photodegradation Study.

PubMed

Flores-Céspedes, Francisco; Martínez-Domínguez, Gerardo P; Villafranca-Sánchez, Matilde; Fernández-Pérez, Manuel

2015-09-30

The botanical insecticide azadirachtin was incorporated in alginate-based granules to obtain controlled release formulations (CRFs). The basic formulation [sodium alginate (1.47%) - azadirachtin (0.28%) - water] was modified by the addition of biosorbents, obtaining homogeneous hybrid hydrogels with high azadirachtin entrapment efficiency. The effect on azadirachtin release rate caused by the incorporation of biosorbents such as lignin, humic acid, and olive pomace in alginate formulation was studied by immersion of the granules in water under static conditions. The addition of the biosorbents to the basic alginate formulation reduces the rate of release because the lignin-based formulation produces a slower release. Photodegradation experiments showed the potential of the prepared formulations in protecting azadirachtin against simulated sunlight, thus improving its stability. The results showed that formulation prepared with lignin provided extended protection. Therefore, this study provides a new procedure to encapsulate the botanical insecticide azadirachtin, improving its delivery and photostability.

A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents.

PubMed

O'Neill, Hugh S; Herron, Caroline C; Hastings, Conn L; Deckers, Roel; Lopez Noriega, Adolfo; Kelly, Helena M; Hennink, Wim E; McDonnell, Ciarán O; O'Brien, Fergal J; Ruiz-Hernández, Eduardo; Duffy, Garry P

2017-01-15

Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome retention, thus providing a prolonged release in target tissues. Moreover, release can be controlled through the use of a minimally invasive external hyperthermic stimulus. Temporal control of release is particularly important for complex multi-step physiological processes, such as angiogenesis, in which different signals are required at different times in order to produce a robust vasculature. In the present work, we demonstrate the ability of Lipogel to provide a flexible, easily modifiable release platform. It is possible to tune the release kinetics of different drugs providing a passive release of one therapeutic agent loaded within the gel and activating the release of a second LTSL encapsulated agent via a hyperthermic stimulus. In addition, it was possible to modify the drug dosage within Lipogel by varying the duration of hyperthermia. This can allow for adaption of drug dosing in real time. As an in vitro proof of concept with this system, we investigated Lipogels ability to recruit stem cells and then elevate their production of vascular endothelial growth factor (VEGF) by controlling the release of a pro-angiogenic drug, desferroxamine (DFO) with an external hyperthermic stimulus. Initial cell recruitment was accomplished by the passive release of hepatocyte growth factor (HGF) from the hydrogel, inducing a migratory response in cells, followed by the delayed release of DFO from thermosensitive liposomes, resulting in a significant increase in VEGF expression. This delayed release could be controlled up to 14days. Moreover, by changing the duration of the hyperthermic pulse, a fine control over the amount of DFO released was achieved. The ability to trigger the release of therapeutic agents at a specific timepoint and control dosing level through changes in duration of hyperthermia enables sequential multi-dose profiles. This paper details the development of a heat responsive liposome loaded hydrogel for the controlled release of pro-angiogenic therapeutics. Lysolipid-based thermosensitive liposomes (LTSLs) embedded in a chitosan-based thermoresponsive hydrogel matrix represents a novel approach for the spatiotemporal release of therapeutic agents. This hydrogel platform demonstrates remarkable flexibility in terms of drug scheduling and sequencing, enabling the release of multiple agents and the ability to control drug dosing in a minimally invasive fashion. The possibility to tune the release kinetics of different drugs independently represents an innovative platform to utilise for a variety of treatments. This approach allows a significant degree of flexibility in achieving a desired release profile via a minimally invasive stimulus, enabling treatments to be tuned in response to changing symptoms and complications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment

PubMed Central

Rajan, Sujata Sundara; Turovskiy, Yevgeniy; Singh, Yashveer; Chikindas, Michael L.; Sinko, Patrick J.

2014-01-01

Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH 7.4) and acetate buffer (AB, pH 4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%–14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV. PMID:25223229

Hydrogen release reactions of Al-based complex hydrides enhanced by vibrational dynamics and valences of metal cations

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

Sato, T.; Ramirez-Cuesta, Anibal J.; Daemen, Luke L.

2016-08-31

Hydrogen release from Al-based complex hydrides composed of metal cation(s) and [AlH4] – was investigated using inelastic neutron scattering viewed from vibrational dynamics. Here, the hydrogen release followed the softening of translational and [AlH4] – librational modes, which was enhanced by vibrational dynamics and the valence(s) of the metal cation(s).

A Robust Open Framework Formed by Decavanadate Clusters and Copper(II) Complexes of Macrocyclic Polyamines: Permanent Microporosity and Catalytic Oxidation of Cycloalkanes.

PubMed

Martín-Caballero, Jagoba; San José Wéry, Ana; Reinoso, Santiago; Artetxe, Beñat; San Felices, Leire; El Bakkali, Bouchra; Trautwein, Guido; Alcañiz-Monge, Juan; Vilas, José Luis; Gutiérrez-Zorrilla, Juan M

2016-05-16

The first decavanadate-based microporous hybrid, namely, [Cu(cyclam)][{Cu(cyclam)}2(V10O28)]·10H2O (1, cyclam = 1,4,8,11-tetraazacyclotetradecane) was prepared by reaction of (VO3)(-) anions and {Cu(cyclam)}(2+) complexes in NaCl (aq) at pH 4.6-4.7 and characterized by elemental analyses, thermogravimetry, and X-ray diffraction (powder, single-crystal) techniques. Compound 1 exhibits a POMOF-like supramolecular open-framework built of covalent decavanadate/metalorganic layers with square-like voids, the stacking of which is aided by interlamellar cementing complexes and generates water-filled channels with approximate cross sections of 10.4 × 8.8 Å(2). The framework is robust enough to remain virtually unaltered upon thermal evacuation of all water molecules of hydration, as demonstrated through single-crystal X-ray diffraction studies on the anhydrous phase 1a. This permanent microporosity renders interesting functionality to 1, such as selective adsorption of CO2 over N2 and remarkable activity as heterogeneous catalyst toward the H2O2-based oxidation of the highly-stable, tricyclic alkane adamantane.

Accuracy-based proficiency testing for testosterone measurements with immunoassays and liquid chromatography-mass spectrometry.

PubMed

Cao, Zhimin Tim; Botelho, Julianne Cook; Rej, Robert; Vesper, Hubert

2017-06-01

Accurate testosterone measurements are needed to correctly diagnose and treat patients. Proficiency Testing (PT) programs using modified specimens for testing can be limited because of matrix effects and usage of non-reference measurement procedure (RMP)-defined targets for evaluation. Accuracy-based PT can overcome such limitations; however, there is a lack of information on accuracy-based PT and feasibility of its implementation in evaluation for testosterone measurements. Unaltered, single-donor human serum from 2 male and 2 female adult donors were analyzed for testosterone by 142 NYSDH-certified clinical laboratories using 16 immunoassays and LC-MS/MS methods. Testosterone target values were determined using an RMP. The testosterone target concentrations for the 4 specimens were 15.5, 30.0, 402 and 498ng/dl. The biases ranged from -17.8% to 73.1%, 3.1% to 21.3%, -24.8% to 8.6%, and -22.1% to 6.8% for the 4 specimens, respectively. Using a total error target of ±25.1%, which was calculated using the minimum allowable bias and imprecision, 73% of participating laboratories had ≥3 of the 4 results within these limits. The variability in total testosterone measurements can affect clinical decisions. Accuracy-based PT can significantly contribute to improving testosterone testing by providing reliable data on accuracy in patient care to laboratories, assay manufacturers, and standardization programs. Copyright © 2017. Published by Elsevier B.V.

Survival of a native toxigenic isolate of Listeria monocytogenes CFR 1302 during storage of milk-based foods can be a potential cause of health risk.

PubMed

Jayanth, Hampapura S; Varadaraj, Mandyam C

2017-07-01

The ability of a native toxigenic culture of Listeria monocytogenes CFR 1302 to survive and elaborate associated toxigenic trait in ice cream and mango pulp-based lactic fermented milk was studied. The culture of L. monocytogenes inoculated at two initial levels of 4.6 and 5.6 log 10  CFU/ml almost remained unaltered during storage of the food products. However, in both the milk-based products, a marginal increase in viable population was observed during 2-4 d of storage as against the initial inoculum levels. The toxigenic trait, listeriolysin "O" was detected by PCR based on species-specific hlyA primers in the two products without any step of enrichment. The positive amplification in PCR was evidenced with initial population levels of 6.3, 7.3, and 8.3 log 10  CFU/ml of the respective products. In culture broth, PCR detection was positive with the lowest level of 2.3 log 10  CFU/ml. The established pathogenic strain of L. monocytogenes Scott A used as a reference culture revealed almost the same behavior to that of native culture in the food products. The findings of present study bring into focus that, irrespective of low storage temperatures, there exists the potential health hazard associated with foods initially contaminated with risk population levels of L. monocytogenes.

Ferulic Acid-Based Polymers with Glycol Functionality as a Versatile Platform for Topical Applications.

PubMed

Ouimet, Michelle A; Faig, Jonathan J; Yu, Weiling; Uhrich, Kathryn E

2015-09-14

Ferulic acid-based polymers with aliphatic linkages have been previously synthesized via solution polymerization methods, yet they feature relatively slow ferulic acid release rates (∼11 months to 100% completion). To achieve a more rapid release rate as required in skin care formulations, ferulic acid-based polymers with ethylene glycol linkers were prepared to increase hydrophilicity and, in turn, increase ferulic acid release rates. The polymers were characterized using nuclear magnetic resonance and Fourier transform infrared spectroscopies to confirm chemical composition. The molecular weights, thermal properties (e.g., glass transition temperature), and contact angles were also obtained and the polymers compared. Polymer glass transition temperature was observed to decrease with increasing linker molecule length, whereas increasing oxygen content decreased polymer contact angle. The polymers' chemical structures and physical properties were shown to influence ferulic acid release rates and antioxidant activity. In all polymers, ferulic acid release was achieved with no bioactive decomposition. These polymers demonstrate the ability to strategically release ferulic acid at rates and concentrations relevant for topical applications such as skin care products.

Ablation of Perlecan Domain 1 Heparan Sulfate Reduces Progressive Cartilage Degradation, Synovitis, and Osteophyte Size in a Preclinical Model of Posttraumatic Osteoarthritis.

PubMed

Shu, Cindy C; Jackson, Miriam T; Smith, Margaret M; Smith, Susan M; Penm, Steven; Lord, Megan S; Whitelock, John M; Little, Christopher B; Melrose, James

2016-04-01

To investigate the role of the heparan sulfate (HS) proteoglycan perlecan (HSPG-2) in regulating fibroblast growth factor (FGF) activity, bone and joint growth, and the onset and progression of posttraumatic osteoarthritis (OA) in a mouse gene-knockout model. Maturational changes were evaluated histologically in the knees of 3-, 6-, and 12-week-old wild-type (WT) mice and Hspg2(Δ3-/Δ3-) mice (Hspg2 lacking domain 1 HS, generated by ablation of exon 3 of perlecan). Cartilage damage, subchondral bone sclerosis, osteophytosis, and synovial inflammation were scored at 4 and 8 weeks after surgical induction of OA in WT and Hspg2(Δ3-/Δ3-) mice. Changes in cartilage expression of FGF-2, FGF-18, HSPG-2, FGF receptor 1 (FGFR-1), and FGFR-3 were examined immunohistochemically. Femoral head cartilage from both mouse genotypes was cultured in the presence or absence of interleukin-1α (IL-1α), FGF-2, and FGF-18, and the content and release of glycosaminoglycan (GAG) and expression of messenger RNA (mRNA) for key matrix molecules, enzymes, and inhibitors were quantified. No effect of perlecan HS ablation on growth plate or joint development was detected. After induction of OA, Hspg2(Δ3-/Δ3-) mice had significantly reduced cartilage erosion, osteophytosis, and synovitis. OA-induced loss of chondrocyte expression of FGF-2, FGF-18, and HSPG-2 occurred in both genotypes. Expression of FGFR-1 after OA induction was maintained in WT mice, while FGFR-3 loss after OA induction was significantly reduced in Hspg2(Δ3-/Δ3-) mice. There were no genotypic differences in GAG content or release between unstimulated control cartilage and IL-1α-stimulated cartilage. However, IL-1α-induced cartilage expression of Mmp3 mRNA was significantly reduced in Hspg2(Δ3-/Δ3-) mice. Cartilage GAG release in either the presence or absence of IL-1α was unaltered by FGF-2 in both genotypes. In cartilage cultures with FGF-18, IL-1α-stimulated GAG loss was significantly reduced only in Hspg2(Δ3-/Δ3-) mice, and this was associated with maintained expression of Fgfr3 mRNA and reduced expression of Mmp2/Mmp3 mRNA. Perlecan HS has significant roles in directing the development of posttraumatic OA, potentially via the alteration of FGF/HS/FGFR signaling. These data suggest that the chondroprotection conferred by perlecan HS ablation could be attributed, at least in part, to the preservation of FGFR-3 and increased FGF signaling. © 2016, American College of Rheumatology.

Multi-scale characterization of nanostructured sodium aluminum hydride

NASA Astrophysics Data System (ADS)

NaraseGowda, Shathabish

Complex metal hydrides are the most promising candidate materials for onboard hydrogen storage. The practicality of this class of materials is counter-poised on three critical attributes: reversible hydrogen storage capacity, high hydrogen uptake/release kinetics, and favorable hydrogen uptake/release thermodynamics. While a majority of modern metallic hydrides that are being considered are those that meet the criteria of high theoretical storage capacity, the challenges lie in addressing poor kinetics, thermodynamics, and reversibility. One emerging strategy to resolve these issues is via nanostructuring or nano-confinement of complex hydrides. By down-sizing and scaffolding them to retain their nano-dimensions, these materials are expected to improve in performance and reversibility. This area of research has garnered immense interest lately and there is active research being pursued to address various aspects of nanostructured complex hydrides. The research effort documented here is focused on a detailed investigation of the effects of nano-confinement on aspects such as the long range atomic hydrogen diffusivities, localized hydrogen dynamics, microstructure, and dehydrogenation mechanism of sodium alanate. A wide variety of microporous and mesoporous materials (metal organic frameworks, porous silica and alumina) were investigated as scaffolds and the synthesis routes to achieve maximum pore-loading are discussed. Wet solution infiltration technique was adopted using tetrahydrofuran as the medium and the precursor concentrations were found to have a major role in achieving maximum pore loading. These concentrations were optimized for each scaffold with varying pore sizes and confinement was quantitatively characterized by measuring the loss in specific surface area. This work is also aimed at utilizing neutron and synchrotron x-ray characterization techniques to study and correlate multi-scale material properties and phenomena. Some of the most advanced instruments were utilized for this work and their data collection and analysis are reported. Quasielastic neutron scattering experiments were conducted at NIST Center for Neutron Research to characterize atomic hydrogen diffusion in bulk and nano-confined NaAlH4. It was observed that upon confinement of NaAlH4, a significantly higher fraction of hydrogen atoms were involved in diffusive motion on the pico-second to nano-second timescales. However, the confinement had no impact on the lattice diffusivities (jump/hopping rates) of atomic hydrogen, indicating that the improved hydrogen release rates were not due to any kinetic destabilization effects. Instead, the investigation strongly suggested thermodynamic destabilization as the major effect of nano-confinement. The local interaction of the metal sites in metal organic frameworks with the infiltrated hydride was studied using extended x-ray absorption spectroscopy technique. The experiments were conducted at Center for Advanced Microstructures and Devices at Louisiana State University. The metal sites were found to be chemically un-altered, hence ruling out any catalytic role in the dehydrogenation at room temperatures. The fractal morphology of NaAlH4 was characterized by ultra-small angle x-ray scattering experiments performed at Argonne National Lab. The studies quantitatively estimated the extent of densification in the course of one desorption cycle. The particle sizes were found to increase two-fold during heat treatment. Also, the nano-confinement procedure was shown to produce dense mass fractals as opposed to pristine NaAlH4, exhibiting a surface fractal morphology. Based on this finding, a new method to identify confined material from un-confined material in nano-composites was developed and is presented. Preliminary results of modeling and correlating multi-scale phenomena using a phase-field approach are also presented as the foundation for future work.

Beyond Static and Dynamic Risk Factors: The Incremental Validity of Release Planning for Predicting Sex Offender Recidivism

ERIC Educational Resources Information Center

Scoones, Carwyn D.; Willis, Gwenda M.; Grace, Randolph C.

2012-01-01

Both desistance research and strengths-based approaches to offender rehabilitation suggest that attempts to reduce sex offender recidivism should attend to an offender's release environment. Recent research has demonstrated that better quality release planning is associated with reduced recidivism; however, whether release planning contributes…

Bio-based Interpenetrating Network Polymer Composites from Locust Sawdust as Coating Material for Environmentally Friendly Controlled-Release Urea Fertilizers.

PubMed

Zhang, Shugang; Yang, Yuechao; Gao, Bin; Wan, Yongshan; Li, Yuncong C; Zhao, Chenhao

2016-07-20

A novel polymer-coated nitrogen (N) fertilizer was developed using bio-based polyurethane (PU) derived from liquefied locust sawdust as the coating material. The bio-based PU was successfully coated on the surface of the urea fertilizer prills to form polymer-coated urea (PCU) fertilizer for controlled N release. Epoxy resin (EP) was also used to further modify the bio-based PU to synthesize the interpenetrating network (IPN), enhancing the slow-release properties of the PCU. The N release characteristics of the EP-modified PCU (EMPCU) in water were determine at 25 °C and compared to that of PCU and EP-coated urea (ECU). The results showed that the EP modification reduced the N release rate and increased the longevity of the fertilizer coated with bio-based PU. A corn growth study was conducted to further evaluate the filed application of the EMPCU. In comparison to commercial PCU and conventional urea fertilizer, EMPCU was more effective and increased the yield and total dry matter accumulation of the corn. Findings from this work indicated that bio-based PU derived from sawdust can be used as coating materials for PCU, particularly after EP modification. The resulting EMPCU was more environmentally friendly and cost-effective than conventional urea fertilizers coated by EP.

Assembled modules technology for site-specific prolonged delivery of norfloxacin.

PubMed

Oliveira, Paulo Renato; Bernardi, Larissa Sakis; Strusi, Orazio Luca; Mercuri, Salvatore; Segatto Silva, Marcos A; Colombo, Paolo; Sonvico, Fabio

2011-02-28

The aim of this research was to design and study norfloxacin (NFX) release in floating conditions from compressed hydrophilic matrices of hydroxypropylmethylcellulose (HPMC) or poly(ethylene oxide) (PEO). Module assembling technology for drug delivery system manufacturing was used. Two differently cylindrical base curved matrix/modules, identified as female and male, were assembled in void configuration by friction interlocking their concave bases obtaining a floating release system. Drug release and floatation behavior of this assembly was investigated. Due to the higher surface area exposed to the release medium, faster release was observed for individual modules compared to their assembled configuration, independently on the polymer used and concentration. The release curves analyzed using the Korsmeyer exponential equation and Peppas & Sahlin binomial equation showed that the drug release was controlled both by drug diffusion and polymer relaxation or erosion mechanisms. However, convective transport was predominant with PEO and at low content of polymers. NFX release from PEO polymeric matrix was more erosion dependent than HPMC. The assembled systems were able to float in vitro for up to 240min, indicating that this drug delivery system of norfloxacin could provide gastro-retentive site-specific release for increasing norfloxacin bioavailability. Copyright © 2010. Published by Elsevier B.V.

Release behavior and stability of encapsulated D-limonene from emulsion-based edible films.

PubMed

Marcuzzo, Eva; Debeaufort, Frédéric; Sensidoni, Alessandro; Tat, Lara; Beney, Laurent; Hambleton, Alicia; Peressini, Donatella; Voilley, Andrée

2012-12-12

Edible films may act as carriers of active molecules, such as flavors. This possibility confers to them the status of active packaging. Two different film-forming biopolymers, gluten and ι-carrageenans, have been compared. D-Limonene was added to the two film formulations, and its release kinetics from emulsion-based edible films was assessed with HS-SPME. Results obtained for edible films were compared with D-limonene released from the fatty matrix called Grindsted Barrier System 2000 (GBS). Comparing ι-carrageenans with gluten-emulsified film, the latter showed more interesting encapsulating properties: in fact, D-limonene was retained by gluten film during the process needed for film preparation, and it was released gradually during analysis time. D-Limonene did not show great affinity to ι-carrageenans film, maybe due to high aroma compound hydrophobicity. Carvone release from the three different matrices was also measured to verify the effect of oxygen barrier performances of edible films to prevent D-limonene oxidation. Further investigations were carried out by FT-IR and liquid permeability measurements. Gluten film seemed to better protect D-limonene from oxidation. Gluten-based edible films represent an interesting opportunity as active packaging: they could retain and release aroma compounds gradually, showing different mechanical and nutritional properties from those of lipid-based ingredients.

Development and evaluation of a novel modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride as model drugs.

PubMed

Zeeshan, Farrukh; Bukhari, Nadeem Irfan

2010-06-01

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

Iron oxide nanoparticle-based magnetic resonance method to monitor release kinetics from polymeric particles with high resolution.

PubMed

Chan, Minnie; Schopf, Eric; Sankaranarayanan, Jagadis; Almutairi, Adah

2012-09-18

A new method to precisely monitor rapid release kinetics from polymeric particles using super paramagnetic iron oxide nanoparticles, specifically by measuring spin-spin relaxation time (T(2)), is reported. Previously, we have published the formulation of logic gate particles from an acid-sensitive poly-β-aminoester ketal-2 polymer. Here, a series of poly-β-aminoester ketal-2 polymers with varying hydrophobicities were synthesized and used to formulate particles. We attempted to measure fluorescence of released Nile red to determine whether the structural adjustments could finely tune the release kinetics in the range of minutes to hours; however, this standard technique did not differentiate each release rate of our series. Thus, a new method based on encapsulation of iron oxide nanoparticles was developed, which enabled us to resolve the release kinetics of our particles. Moreover, the kinetics matched the relative hydrophobicity order determined by octanol-water partition coefficients. To the best of our knowledge, this method provides the highest resolution of release kinetics to date.

Predicting red wolf release success in the southeastern United States

USGS Publications Warehouse

van Manen, Frank T.; Crawford, Barron A.; Clark, Joseph D.

2000-01-01

Although the red wolf (Canis rufus) was once found throughout the southeastern United States, indiscriminate killing and habitat destruction reduced its range to a small section of coastal Texas and Louisiana. Wolves trapped from 1973 to 1980 were taken to establish a captive breeding program that was used to repatriate 2 mainland and 3 island red wolf populations. We collected data from 320 red wolf releases in these areas and classified each as a success or failure based on survival and reproductive criteria, and whether recaptures were necessary to resolve conflicts with humans. We evaluated the relations between release success and conditions at the release sites, characteristics of released wolves, and release procedures. Although <44% of the variation in release success was explained, model performance based on jackknife tests indicated a 72-80% correct prediction rate for the 4 operational models we developed. The models indicated that success was associated with human influences on the landscape and the level of wolf habituation to humans prior to release. We applied the models to 31 prospective areas for wolf repatriation and calculated an index of release success for each area. Decision-makers can use these models to objectively rank prospective release areas and compare strengths and weaknesses of each.

Optimum Parameters for Freeze-Drying Decellularized Arterial Scaffolds

PubMed Central

Sheridan, William S.; Duffy, Garry P.

2013-01-01

Decellularized arterial scaffolds have achieved success in advancing toward clinical use as vascular grafts. However, concerns remain regarding long-term preservation and sterilization of these scaffolds. Freeze drying offers a means of overcoming these concerns. In this study, we investigated the effects of various freeze-drying protocols on decellularized porcine carotid arteries and consequently, determined the optimum parameters to fabricate a stable, preserved scaffold with unaltered mechanical properties. Freeze drying by constant slow cooling to two final temperatures ((Tf), −10°C and −40°C) versus instant freezing was investigated by histological examination and mechanical testing. Slow cooling to Tf= −10°C produced a stiffer and less distensible response than the non freeze-dried scaffolds and resulted in disruption to the collagen fibers. The mechanical response of Tf= −40°C scaffolds demonstrated disruption to the elastin network, which was confirmed with histology. Snap freezing scaffolds in liquid nitrogen and freeze drying to Tf= −40°C with a precooled shelf at −60°C produced scaffolds with unaltered mechanical properties and a histology resembling non-freeze-dried scaffolds. The results of this study demonstrate the importance of optimizing the nucleation and ice crystal growth/size to ensure homogenous drying, preventing extracellular matrix disruption and subsequent inferior mechanical properties. This new manufacturing protocol creates the means for the preservation and sterilization of decellularized arterial scaffolds while simultaneously maintaining the mechanical properties of the tissue. PMID:23614758

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

PubMed

Kaplan, Kara; Echert, Ashley E; Massat, Ben; Puissant, Madeleine M; Palygin, Oleg; Geurts, Aron M; Hodges, Matthew R

2016-05-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. Copyright © 2016 the American Physiological Society.

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats

PubMed Central

Kaplan, Kara; Echert, Ashley E.; Massat, Ben; Puissant, Madeleine M.; Palygin, Oleg; Geurts, Aron M.

2016-01-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DATph2−/−) rats. DATph2−/− rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DATph2−/− rats. Body temperature was also maintained in adult DATph2−/− rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DATph2−/− rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. PMID:26869713

A spectroscopic analysis of Martian crater central peaks: Formation of the ancient crust

NASA Astrophysics Data System (ADS)

Skok, J. R.; Mustard, J. F.; Tornabene, L. L.; Pan, C.; Rogers, D.; Murchie, S. L.

2012-11-01

The earliest formed crust on a single plate planet such as Mars should be preserved, deeply buried under subsequent surface materials. Mars' extensive cratering history would have fractured and disrupted the upper layers of this ancient crust. Large impacts occurring late in Martian geologic history would have excavated and exposed this deeply buried material. We report the compositional analysis of unaltered mafic Martian crater central peaks with high-resolution spectral data that was used to characterize the presence, distribution and composition of mafic mineralogy. Reflectance spectra of mafic outcrops are modeled with the Modified Gaussian Model (MGM) to determine cation composition of olivine and pyroxene mineral deposits. Observations show that central peaks with unaltered mafic units are only observed in four general regions of Mars. Each mafic unit exhibits spectrally unmixed outcrops of olivine or pyroxene, indicating dunite and pyroxenite dominated compositions instead of basaltic composition common throughout much of the planet. Compositional analysis shows a wide range of olivine Fo# ranging from Fo60 to Fo5. This variation is best explained by a high degree of fractionation in a slowly cooling, differentiating magma body. Pyroxene analysis shows that all the sites in the Southern Highlands are consistent with moderately Fe-rich, low-Ca pyroxene. Mineral segregation in the ancient crust could be caused by cumulate crystallization and settling in a large, potentially global, lava lake or near surface plutons driven by a hypothesized early Martian mantle overturn.

Elevated central venous pressure: A consequence of exercise training-induced hypervolemia

NASA Technical Reports Server (NTRS)

Convertino, Victor A.; Mack, Gary W.; Nadel, Ethan R.

1990-01-01

Resting plasma volumes, and arterial and central venous pressures (CVP) were measured in 16 men before and after exercise training to determine if training-induced hypervolemia could be explained by a change in total vascular capacitance. In addition, resting levels of plasma vasopressin (AVP), atrial natriuretic peptide (ANP), aldosterone (ALD), and norepinephrine (NE) were measured before and after training. The same measurements of vacular volume, pressures, and plasma hormones were measured in 8 subjects who did not undergo exercise and acted as controls. The exercise training program consisted of 10 weeks of controlled cycle exercise for 30 min/d, 4 d/wk at 75 to 80 percent of maximal oxygen uptake (VO2max). A training effect was verified by a 20 percent increase in VO2max, a resting bradycardia, and a 370 ml (9 percent) increase in blood volume. Mean arterial blood pressure was unaltered by exercise training, but resting CVP increased. The percent change in blood volume from before to after training was linearly related to the percent change in CVP. As a consequence of elevations in both blood volume and CVP, the volume-to-pressure ratio was essentially unchanged following exercise training. Plasma AVP, ANP, ALD, and NE were unaltered. Results indicate that elevated CVP is a consequence of training-induced hypervolemia without alteration in total effective venous capacitance. This may represent a resetting of the pressure-volume stimulus-response relation for regulation of blood volume.

Impact of the Ebola epidemic on general and HIV care in Macenta, Forest Guinea, 2014.

PubMed

Leuenberger, David; Hebelamou, Jean; Strahm, Stefan; De Rekeneire, Nathalie; Balestre, Eric; Wandeler, Gilles; Dabis, François

2015-09-10

The current Ebola epidemic massively affected the Macenta district in Forest Guinea. We aimed at investigating its impact on general and HIV care at the only HIV care facility in the district. Prospective observational single-facility study. Routinely collected data on use of general hospital services and HIV care were linked to Ebola surveillance data published by the Guinea Ministry of Health. In addition, we compared retention among HIV-infected patients enrolled into care in the first semesters of 2013 and 2014. Throughout 2014, service offer was continuous and unaltered at the facility. During the main epidemic period (August-December 2014), compared with the same period of 2013, there were important reductions in attendance at the primary care outpatient clinic (-40%), in HIV tests done (-46%), in new diagnoses of tuberculosis (-53%) and in patients enrolled into HIV care (-47%). There was a smaller reduction in attendance at the HIV follow-up clinic (-11%). Kaplan-Meier estimates of retention were similar among the patients enrolled into care in 2014 and 2013. In a multivariable Cox regression analysis, the year of enrolment was not associated with attrition (hazard ratio 1.02; 95% confidence interval: 0.72-1.43). The Ebola epidemic resulted in an important decrease in utilization of the facility despite unaltered service offer. Effects on care of HIV-positive patients enrolled prior to the epidemic were limited. HIV care in such circumstances is challenging, but not impossible.

Effect of high hydrostatic pressure on Aeromonas hydrophila AH 191 growth in milk.

PubMed

Durães-Carvalho, Ricardo; Souza, Ancelmo R; Martins, Luciano M; Sprogis, Adriane C S; Bispo, Jose A C; Bonafe, Carlos F S; Yano, Tomomasa

2012-08-01

Exposure to high pressure is an efficient method of bacterial inactivation that is particularly important for reducing the microbial load present in foods. In this study, we examined the high pressure inactivation of Aeromonas hydrophila AH 191, a virulent strain that produces aerolysin, a cytotoxic, enterotoxic, and hemolytic toxin. High pressure treatment (250 MPa for 30 min at 25 °C in 0.1 M PBS, pH 7.4) of A. hydrophila grown in milk reduced bacterial viability by at least 9 orders of magnitude. Under these conditions, the enterotoxic, hemolytic, and cytotoxic activities of A. hydrophila culture supernatants were unaltered. These results indicate the need for caution in the use of high pressure for food processing since although truly toxigenic bacteria may be inactivated, their toxins may not be, thus posing a risk to human health. At higher pressure (350 MPa) the inactivation of bacteria was much more effective. Scanning electron microscopy showed a significant decrease in the number of bacteria after higher pressurization (350 MPa for 1 h) and transmission electron microscopy showed irregular shaped bacteria, suggestive of important cell wall and membrane damage, and cytoplasm condensation. High pressure inactivates Aeromonas hydrophila efficiently but is enhanced when combined with moderate temperature (40 °C). The biological activities of toxins from this bacterium are unaltered under these conditions. Journal of Food Science © 2012 Institute of Food Technologists® No claim to original US government works.

Canonical Transient Receptor Channel 5 (TRPC5) and TRPC1/4 Contribute to Seizure and Excitotoxicity by Distinct Cellular Mechanisms

PubMed Central

Phelan, Kevin D.; Shwe, U Thaung; Abramowitz, Joel; Wu, Hong; Rhee, Sung W.; Howell, Matthew D.; Gottschall, Paul E.; Freichel, Marc; Flockerzi, Veit; Birnbaumer, Lutz

2013-01-01

Seizures are the manifestation of highly synchronized burst firing of a large population of cortical neurons. Epileptiform bursts with an underlying plateau potential in neurons are a cellular correlate of seizures. Emerging evidence suggests that the plateau potential is mediated by neuronal canonical transient receptor potential (TRPC) channels composed of members of the TRPC1/4/5 subgroup. We previously showed that TRPC1/4 double-knockout (DKO) mice lack epileptiform bursting in lateral septal neurons and exhibit reduced seizure-induced neuronal cell death, but surprisingly have unaltered pilocarpine-induced seizures. Here, we report that TRPC5 knockout (KO) mice exhibit both significantly reduced seizures and minimal seizure-induced neuronal cell death in the hippocampus. Interestingly, epileptiform bursting induced by agonists for metabotropic glutamate receptors in the hippocampal CA1 area is unaltered in TRPC5 KO mice, but is abolished in TRPC1 KO and TRPC1/4 DKO mice. In contrast, long-term potentiation is greatly reduced in TRPC5 KO mice, but is normal in TRPC1 KO and TRPC1/4 DKO mice. The distinct changes from these knockouts suggest that TRPC5 and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms. Furthermore, the reduced seizure and excitotoxicity and normal spatial learning exhibited in TRPC5 KO mice suggest that TRPC5 is a promising novel molecular target for new therapy. PMID:23188715

Canonical transient receptor channel 5 (TRPC5) and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms.

PubMed

Phelan, Kevin D; Shwe, U Thaung; Abramowitz, Joel; Wu, Hong; Rhee, Sung W; Howell, Matthew D; Gottschall, Paul E; Freichel, Marc; Flockerzi, Veit; Birnbaumer, Lutz; Zheng, Fang

2013-02-01

Seizures are the manifestation of highly synchronized burst firing of a large population of cortical neurons. Epileptiform bursts with an underlying plateau potential in neurons are a cellular correlate of seizures. Emerging evidence suggests that the plateau potential is mediated by neuronal canonical transient receptor potential (TRPC) channels composed of members of the TRPC1/4/5 subgroup. We previously showed that TRPC1/4 double-knockout (DKO) mice lack epileptiform bursting in lateral septal neurons and exhibit reduced seizure-induced neuronal cell death, but surprisingly have unaltered pilocarpine-induced seizures. Here, we report that TRPC5 knockout (KO) mice exhibit both significantly reduced seizures and minimal seizure-induced neuronal cell death in the hippocampus. Interestingly, epileptiform bursting induced by agonists for metabotropic glutamate receptors in the hippocampal CA1 area is unaltered in TRPC5 KO mice, but is abolished in TRPC1 KO and TRPC1/4 DKO mice. In contrast, long-term potentiation is greatly reduced in TRPC5 KO mice, but is normal in TRPC1 KO and TRPC1/4 DKO mice. The distinct changes from these knockouts suggest that TRPC5 and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms. Furthermore, the reduced seizure and excitotoxicity and normal spatial learning exhibited in TRPC5 KO mice suggest that TRPC5 is a promising novel molecular target for new therapy.

Intrinsic attenuation of post-irradiation calcium and ER stress imparts significant radioprotection to lepidopteran insect cells.

PubMed

Guleria, Ayushi; Thukral, Neha; Chandna, Sudhir

2018-04-15

Sf9 lepidopteran insect cells are 100-200 times more radioresistant than mammalian cells. This distinctive feature thus makes them suitable for studies exploring radioprotective molecular mechanisms. It has been established from previous studies of our group that downstream mitochondrial apoptotic signaling pathways in Sf9 cells are quite similar to mammalian cells, implicating the upstream signaling pathways in their extensive radioresistance. In the present study, intracellular and mitochondrial calcium levels remained unaltered in Sf9 cells in response to radiation, in sharp contrast to human (HEK293T) cells. The isolated mitochondria from Sf9 cells exhibited nearly 1.5 times greater calcium retention capacity than mammalian cells, highlighting their inherent stress resilience. Importantly, UPR/ER stress marker proteins (p-eIF2α, GRP4 and SERCA) remained unaltered by radiation and suggested highly attenuated ER and calcium stress. Lack of SERCA induction further corroborates the lack of radiation-induced calcium mobilization in these cells. The expression of CaMKII, an important effector molecule of calcium signaling, did not alter in response to radiation. Inhibiting CaMKII by KN-93 or suppressing CaM by siRNA failed to alter Sf9 cells response to radiation and suggests CaM-CaMKII independent radiation signaling. Therefore, this study suggests that attenuated calcium signaling/ER stress is an important determinant of lepidopteran cell radioresistance. Copyright © 2018 Elsevier Inc. All rights reserved.

Winter habitat use by cutthroat trout in the Snake River near Jackson, Wyoming

USGS Publications Warehouse

Harper, D.D.; Farag, A.M.

2004-01-01

Winter habitat use by Yellowstone cutthroat trout Oncorhynchus clarki bouvieri was monitored with radiotelemetry during November-March 1998-2001 in channelized and unaltered sections of the Snake River near Jackson, Wyoming. The use of run and off-channel pool habitat was significantly correlated to water temperature; run use was most frequent when mean water temperature exceeded 1.0°C, and off-channel pool use was greatest when mean water temperature was below 1.0°C. Available habitat was surveyed during winter 1999-2000 and was compared with actual habitat use. This comparison indicated that cutthroat trout avoided riffle habitat, selected deep runs, and strongly selected off-channel pool habitat. Large, deep, off-channel pools with groundwater influence were uncommon in the study area but were frequently selected as over-wintering habitat in the channelized section during all three study years. During 2000-2001, mainstem water temperatures were significantly colder than in 1998-1999 or 1999-2000, and anchor ice was observed more frequently in 2000-2001 than in 1998-1999 or 1999-2000 (on 18 d versus 5 d and 3 d, respectively). Mean water temperatures in off-channel pools were not significantly different among years. Depth and shelf ice were most frequently identified as cover elements in the channelized section. Run habitat was more common and used more frequently upstream of the channelized section. Large woody debris was more common and selected more frequently as cover in the unaltered section than in the channelized section.

Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.

PubMed

Yi, Tao; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

2008-08-07

The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.

Preparation and characterisation of a novel hydrogel based on Auricularia polytricha β-glucan and its bio-release property for vitamin B12 delivery.

PubMed

Zhu, Kai; Chen, Xiaoyuan; Yu, Da; He, Yue; Song, Guanglei

2018-05-01

This study investigates a novel hydrogel synthesis method and its bio-release property. This hydrogel, with a three-dimensional network structure based on Auricularia polytricha β-glucan, was characterised by means of Fourier transform infrared spectroscopy, 1 H NMR and scanning electron microscopy. Vitamin B 12 (VB 12 , cobalamin) as a hydrophilic functional food component was entrapped into these hydrogels. The in vitro release profile of VB 12 was established in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The results showed that the hydrogel had medium pore size from 30 to 300 µm, and the swelling ratio increased with the degree of substitution. The hydrogel demonstrated good stability in SGF and bio-release capability in SIF for VB 12 . The accumulated release rate is about 80% in SIF and below 20% in SGF, which indicated the significant different release property in stomach and intestine. The Auricularia polytricha β-glucan-based hydrogel has a good swelling ratio, pepsin stability and pancrelipase-catalysed biodegradation property. The bio-release rate is significantly different in SIF and SGF, which indicated that this hydrogel could be a good intestinal target carrier of VB 12 . © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Preparation and In vitro Evaluation of Naproxen Suppositories

PubMed Central

Hargoli, S.; Farid, J.; Azarmi, S. H.; Ghanbarzadeh, S.; Zakeri-Milani, P.

2013-01-01

The aim of this work was to develop the best formulations for naproxen suppositories. The effects of different bases and surfactants on the physicochemical characteristics of the suppositories were determined by several tests such as weight variation, melting point, assay, hardness, and release rate. All formulations met the standard criteria for tested physicochemical parameters; weight variation (97-112%), content uniformity (97-105%), melting point (4.66-8.7 min) and hardness tests (>5400 g). Based on release rate studies, hydrophilic, and lipophilic bases without surfactants were not suitable bases for naproxen suppository. Amongst the formulations containing surfactants only Witepsol H15 with 0.5% w/w of Tween 80 and Witepsol W35 with 0.5% of cetylpyridinium chloride were suitable and released nearly complete drug during 30 and 60 min, respectively. This study demonstrates the effects of incorporation of known agents on the in vitro release characteristics of naproxen suppository. PMID:24019561

Studies related to the development of the Viking 1975 labeled release experiment

NASA Technical Reports Server (NTRS)

Devincenzi, D. L.; Deal, P. H.

1976-01-01

The labeled release life detection experiment on the Viking 1975 Mars mission is based on the concept that microorganisms will metabolize radioactive organic substrates in a nutrient medium and release radioactive carbon dioxide. Several experiments, using laboratory equipment, were carried out to evaluate various aspects of the concept. Results indicate: (1) label is released by sterilization-treated soil, (2) substantial quantities of label are retained in solution under basic conditions, (3) the substrate used, as well as position of label in the molecule, affect release of label, (4) label release is depressed by radiolytic decomposition of substrates, and (5) About 100,000 organisms are required to produce a detectable response. These results, suggest additional areas for testing, add to the data base for interpretation of flight results, and have significance for broader application of this technique for assessing microbial activity.

Guidance for Evaluating the Safety of Experimental Releases of Mosquitoes, Emphasizing Mark-Release-Recapture Techniques.

PubMed

Benedict, Mark Q; Charlwood, J Derek; Harrington, Laura C; Lounibos, L Philip; Reisen, William K; Tabachnick, Walter J

2018-01-01

Experimental releases of mosquitoes are performed to understand characteristics of populations related to the biology, ability to transmit pathogens, and ultimately their control. In this article, we discuss considerations related to the safety of experimental releases of living mosquitoes, applying principles of good practice in vector biology that protect human health and comfort. We describe specific factors of experimental releases of mosquitoes that we believe are critical to inform institutional biosafety committees and similar review boards to which proposals to conduct mosquito release experiments have been submitted. In this study, "experimental releases" means those that do not significantly increase vector capacity or nuisance biting relative to the unperturbed natural baseline. This document specifically does not address releases of mosquitoes for ongoing control programs or trials of new control methods for which broader assessments of risk are required. It also does not address releases of transgenic or exotic (non-native) mosquito species, both of which require particular regulatory approval. Experimental releases may include females and males and evaluation must consider their effects based on the number released, their genotype and phenotype, the environment into which they are released, and postrelease collection activities. We consider whether increases of disease transmission and nuisance biting might result from proposed experimental releases against the backdrop of natural population size variation. We recommend that experimental releases be conducted in a manner that can be reasonably argued to have insignificant negative effects. Reviewers of proposals for experimental releases should expect applicants to provide such an argument based on evidence from similar studies and their planned activities. This document provides guidance for creating and evaluating such proposals.

Tabletted microspheres containing Cynara scolymus (var. Spinoso sardo) extract for the preparation of controlled release nutraceutical matrices.

PubMed

Gavini, E; Alamanni, M C; Cossu, M; Giunchedi, P

2005-08-01

Controlled release dosage forms based on tabletted microspheres containing fresh artichoke Cynara scolymus extract were performed for the oral administration of a nutritional supplement. Microspheres were prepared using a spray-drying technique; lactose or hypromellose have been chosen as excipients. Microspheres were characterized in terms of encapsulated extract content, size and morphology. Qualitative and quantitative composition of the extract before and after the spray process was determined. Compressed matrices (tablets) were prepared by direct compression of the spray-dried microspheres. In vitro release tests of microparticles and tablets prepared were carried out in both acidic and neutral media. Spray-drying is a good method to prepare microspheres containing the artichoke extract. The microspheres encapsulate an amount of extract close to the theoretical value. Particle size analyses indicate that the microparticles have dvs of approximately 6-7 microm. Electronic microscopy observations reveal that particles based on lactose have spherical shape and particles containing hypromellose are almost collapsed. The hydroalcoholic extract is stable to the microsphere production process: its polyphenolic composition (qualitative and quantitative) did not change after spraying. In vitro release studies show that microparticles characterized by a quick polyphenolic release both in acidic and neutral media due to the high water solubility of the carrier lactose. On the contrary, microspheres based hypromellose release only 20% of the loaded extract at pH 1.2 in 2 h and the total amount of polyphenols is released only after about further 6 h at pH 6.8. Matrices prepared tabletting lactose microspheres and hypromellose microparticles in the weight ratio 1:1 show a slow release rate, that lasts approximately 24 h. This one-a-day sustained release formulation containing Cynara scolymus extract could be proposed as a nutraceutical controlled release dosage form for oral administration.

Ketoprofen suppository dosage forms: in vitro release and in vivo absorption studies in rabbits.

PubMed

Babar, A; Bellete, T; Plakogiannis, F M

1999-02-01

In vitro release of ketoprofen from suppository bases and in vivo absorption in rabbits were studied. Suppositories containing 50 mg of ketoprofen were prepared using theobroma oil, esterified (c10-c18) fatty acids, and polyethylene glycol 1000 bases. The displacement values of the drug were determined and found to be of the order of theobroma oil > esterified (c10-c18) fatty acids and polyethylene glycol 1000 bases. The suppository hardness data revealed that the theobroma oil base produced relatively brittle suppositories. Using the USP dissolution method, the release of ketoprofen was observed to be greatest from polyethylene glycol 1000 suppositories. With the dialysis technique, the maximum release of drug was obtained from theobroma oil suppository containing polysorbate 40 at a 6% level. Selected suppository formulations were evaluated for rectal absorption studies in rabbits. The in vivo data showed that the optimum drug absorption took place from the polyethylene glycol 1000 base and theobroma oil formulation containing 6% polysorbate 40.

Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery.

PubMed

Niedermayer, Stefan; Weiss, Veronika; Herrmann, Annika; Schmidt, Alexandra; Datz, Stefan; Müller, Katharina; Wagner, Ernst; Bein, Thomas; Bräuchle, Christoph

2015-05-07

A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core-shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform offers (i) tuneable interactions and release kinetics with the cargo drug in the mesopores based on chemically orthogonal core-shell design, (ii) an extremely robust and reversible closure and release mechanism based on endosomal acidification of the covalently attached PVP polymer block, (iii) high colloidal stability due to a covalently coupled PEG shell, and (iv) the ability to covalently attach a wide variety of dyes, targeting ligands and other functionalities at the outer periphery of the PEG shell. The functionality of the system was demonstrated in several cell studies, showing pH-triggered release in the endosome, light-triggered endosomal escape with an on-board photosensitizer, and efficient folic acid-based cell targeting.

The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide

PubMed Central

Thompson, AJ; Mander, PK; Brown, GC

2009-01-01

Background and purpose: It has been previously shown that high levels of nitric oxide (NO), from NO donors, kill neurones, but the mechanisms are unclear. Experimental approach: The effects of NO donors on the electrical properties of rat cultured cerebellar granule cells (CGC neurones) were investigated using the whole-cell patch-clamp technique. Key results: The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate or NOC-18) caused a rapid, persistent, but fully reversible inward current that was associated with an increase in baseline noise and was concentration dependent (100 µM–10 mM). The response to 3 mM DETA-NONOate was completely inhibited by 1 mM gadolinium, but not by NO scavengers (1 mM haemoglobin or 1 mM PTIO) or glutamate receptor antagonists (10 µM MK-801 or 60 µM CNQX). Application of decomposed 3 mM DETA-NONOate or 3 mM nitrite had no effect. In contrast, the NO donor S-nitrosoglutathione (GSNO) caused a rapid, persistent, but fully reversible outward current that was also concentration dependent (1–10 mM). The 3 mM GSNO response was unaltered by NO scavengers, glutamate antagonists or gadolinium, but was mimicked by decomposed 3 mM GSNO and 3 mM oxidized glutathione. Conclusions and implications: These results suggest that DETA-NONOate directly activates cation-selective channels, causing an inward current in CGCs. In contrast, GSNO causes an outward current in these cells. Some of the effects of these NO donors are independent of NO, and thus caution is required in interpreting results when using high concentrations of these compounds. PMID:19785659

The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide.

PubMed

Thompson, A J; Mander, P K; Brown, G C

2009-11-01

It has been previously shown that high levels of nitric oxide (NO), from NO donors, kill neurones, but the mechanisms are unclear. The effects of NO donors on the electrical properties of rat cultured cerebellar granule cells (CGC neurones) were investigated using the whole-cell patch-clamp technique. The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate or NOC-18) caused a rapid, persistent, but fully reversible inward current that was associated with an increase in baseline noise and was concentration dependent (100 microM-10 mM). The response to 3 mM DETA-NONOate was completely inhibited by 1 mM gadolinium, but not by NO scavengers (1 mM haemoglobin or 1 mM PTIO) or glutamate receptor antagonists (10 microM MK-801 or 60 microM CNQX). Application of decomposed 3 mM DETA-NONOate or 3 mM nitrite had no effect. In contrast, the NO donor S-nitrosoglutathione (GSNO) caused a rapid, persistent, but fully reversible outward current that was also concentration dependent (1-10 mM). The 3 mM GSNO response was unaltered by NO scavengers, glutamate antagonists or gadolinium, but was mimicked by decomposed 3 mM GSNO and 3 mM oxidized glutathione. These results suggest that DETA-NONOate directly activates cation-selective channels, causing an inward current in CGCs. In contrast, GSNO causes an outward current in these cells. Some of the effects of these NO donors are independent of NO, and thus caution is required in interpreting results when using high concentrations of these compounds.

Delayed pubertal onset and prepubertal Kiss1 expression in female mice lacking central oestrogen receptor beta.

PubMed

Naulé, Lydie; Robert, Vincent; Parmentier, Caroline; Martini, Mariangela; Keller, Matthieu; Cohen-Solal, Martine; Hardin-Pouzet, Hélène; Grange-Messent, Valérie; Franceschini, Isabelle; Mhaouty-Kodja, Sakina

2015-12-20

Ovarian oestradiol is essential for pubertal maturation and adult physiology of the female reproductive axis. It acts at central and peripheral sites through two main oestrogen receptors (ER) α and β. Here we investigate the role of ERβ on central effects of oestradiol, by generating a mouse line specifically lacking the ERβ gene in neuronal and glial cells. Central ERβ deletion delays the age at vaginal opening and first oestrous and reduces uterine weight without affecting body growth. Analysis of factors necessary for pubertal progression shows reduced levels of Kiss1 transcripts at postnatal (P) day 25 in the preoptic area, but not in the mediobasal hypothalamus (MBH) of mutant females. In agreement with these data, the number of kisspeptin-immunoreactive neurons was decreased by 57-72% in the three subdivisions of the rostral periventricular area of the third ventricle (RP3V), whereas the density of kisspeptin-immunoreactive fibres was unchanged in the arcuate nucleus of mutant mice. These alterations do not involve changes in ERα mRNAs in the preoptic area and protein levels in the RP3V. The number and distribution of GnRH-immunoreactive cells were unaffected, but gonadotropin-releasing hormone (GnRH) transcript levels were higher in the P25 preoptic area of mutants. At adulthood, mutant females have normal oestrous cyclicity, kisspeptin system and exhibit unaltered sexual behaviour. They display, however, reduced ovary weight and increased anxiety-related behaviour during the follicular phase. This argues for the specific involvement of central ERβ in the regulation of pubertal onset in female reproduction, possibly through prepubertal induction of kisspeptin expression in the RP3V. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

CsPLDalpha1 and CsPLDgamma1 are differentially induced during leaf and fruit abscission and diurnally regulated in Citrus sinensis.

PubMed

Malladi, Anish; Burns, Jacqueline K

2008-01-01

Understanding leaf and fruit abscission is essential in order to develop strategies for controlling the process in fruit crops. Mechanisms involved in signalling leaf and fruit abscission upon induction by abscission agents were investigated in Citrus sinensis cv. 'Valencia'. Previous studies have suggested a role for phospholipid signalling; hence, two phospholipase D cDNA sequences, CsPLDalpha1 and CsPLDgamma1, were isolated and their role was examined. CsPLDalpha1 expression was reduced in leaves but unaltered in fruit peel tissue treated with an ethylene-releasing compound (ethephon), or a fruit-specific abscission agent, 5-chloro-3-methyl-4-nitro-1H-pyrazole (CMNP). By contrast, CsPLDgamma1 expression was up-regulated within 6 h (leaves) and 24 h (fruit peel) after treatment with ethephon or CMNP, respectively. CsPLDalpha1 expression was diurnally regulated in leaf blade but not fruit peel. CsPLDgamma1 exhibited strong diurnal oscillation in expression in leaves and fruit peel with peak expression around midday. While diurnal fluctuation in CsPLDalpha1 expression appeared to be light-entrained in leaves, CsPLDgamma1 expression was regulated by light and the circadian clock. The diurnal expression of both genes was modulated by ethylene-signalling. The ethephon-induced leaf abscission and the ethephon- and CMNP-induced decrease in fruit detachment force were enhanced by application during rising diurnal expression of CsPLDgamma1. The results indicate differential regulation of CsPLDalpha1 and CsPLDgamma1 in leaves and fruit, and suggest possible roles for PLD-dependent signalling in regulating abscission responses in citrus.

N1L is an ectromelia virus virulence factor and essential for in vivo spread upon respiratory infection.

PubMed

Gratz, Meike S; Suezer, Yasemin; Kremer, Melanie; Volz, Asisa; Majzoub, Monir; Hanschmann, Kay-Martin; Kalinke, Ulrich; Schwantes, Astrid; Sutter, Gerd

2011-04-01

The emergence of zoonotic orthopoxvirus infections and the threat of possible intentional release of pathogenic orthopoxviruses have stimulated renewed interest in understanding orthopoxvirus infections and the resulting diseases. Ectromelia virus (ECTV), the causative agent of mousepox, offers an excellent model system to study an orthopoxvirus infection in its natural host. Here, we investigated the role of the vaccinia virus ortholog N1L in ECTV infection. Respiratory infection of mice with an N1L deletion mutant virus (ECTVΔN1L) demonstrated profound attenuation of the mutant virus, confirming N1 as an orthopoxvirus virulence factor. Upon analysis of virus dissemination in vivo, we observed a striking deficiency of ECTVΔN1L spreading from the lungs to the livers or spleens of infected mice. Investigating the immunological mechanism controlling ECTVΔN1L infection, we found the attenuated phenotype to be unaltered in mice deficient in Toll-like receptor (TLR) or RIG-I-like RNA helicase (RLH) signaling as well as in those missing the type I interferon receptor or lacking B cells. However, in RAG-1(-/-) mice lacking mature B and T cells, ECTVΔN1L regained virulence, as shown by increasing morbidity and virus spread to the liver and spleen. Moreover, T cell depletion experiments revealed that ECTVΔN1L attenuation was reversed only by removing both CD4(+) and CD8(+) T cells, so the presence of either cell subset was still sufficient to control the infection. Thus, the orthopoxvirus virulence factor N1 may allow efficient ECTV infection in mice by interfering with host T cell function.

Effect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan and theophylline in patients with metastatic castration-resistant prostate cancer.

PubMed

Chi, K N; Tolcher, A; Lee, P; Rosen, P J; Kollmannsberger, C K; Papadopoulos, K P; Patnaik, A; Molina, A; Jiao, J; Pankras, C; Kaiser, B; Bernard, A; Tran, N; Acharya, M

2013-01-01

To assess the effect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan HBr (CYP2D6 substrate) and theophylline (CYP1A2 substrate) in patients with metastatic castration-resistant prostate cancer (mCRPC). Men with progressive metastatic mCRPC who failed gonadotropin-releasing hormone therapy and ≥1 lines of chemotherapy were enrolled. Patients received two doses of dextromethorphan HBr-30 mg (n = 18; group A) or theophylline-100 mg (n = 16; group B) under fasting conditions; one dose on cycle 1, day -8, and the other dose on cycle 1, day 8. Only patients with extensive CYP2D6 metabolizing status were assigned to group A. All patients received continuous daily oral abiraterone acetate (1,000 mg) plus prednisone (10 mg) starting on cycle 1, day 1. Coadministration of abiraterone acetate plus prednisone increased the systemic exposure of dextromethorphan by approximately 100%. Ratios of geometric means for maximum plasma concentration (C(max)) (275.36%) and area under plasma concentration-time curves from time 0 to 24 h (AUC(24h)) (268.14%) of dextromethorphan were outside the bioequivalence limit. The pharmacokinetics of theophylline was unaltered following coadministration of abiraterone acetate plus prednisone. Ratios of geometric means [C(max); 102.36% and AUC(24h); 108.03%] of theophylline exposure parameters were within the bioequivalence limit. The safety profile of abiraterone acetate was consistent with reported toxicities. Abiraterone acetate plus prednisone increased the exposure of dextromethorphan, suggesting a need for caution when coadministrating with known CYP2D6 substrates. The pharmacokinetics of theophylline was unaffected when coadministered with abiraterone acetate plus prednisone.

Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function

PubMed Central

Markwart, Robby; Condotta, Stephanie A.; Requardt, Robert P.; Borken, Farina; Schubert, Katja; Weigel, Cynthia; Bauer, Michael; Griffith, Thomas S.; Förster, Martin; Brunkhorst, Frank M.; Badovinac, Vladimir P.; Rubio, Ignacio

2014-01-01

Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4+/CD8+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells. PMID:25541945

The acute response of pericytes to muscle-damaging eccentric contraction and protein supplementation in human skeletal muscle.

PubMed

De Lisio, Michael; Farup, Jean; Sukiennik, Richard A; Clevenger, Nicole; Nallabelli, Julian; Nelson, Brett; Ryan, Kelly; Rahbek, Stine K; de Paoli, Frank; Vissing, Kristian; Boppart, Marni D

2015-10-15

Skeletal muscle pericytes increase in quantity following eccentric exercise (ECC) and contribute to myofiber repair and adaptation in mice. The purpose of the present investigation was to examine pericyte quantity in response to muscle-damaging ECC and protein supplementation in human skeletal muscle. Male subjects were divided into protein supplement (WHY; n = 12) or isocaloric placebo (CHO; n = 12) groups and completed ECC using an isokinetic dynamometer. Supplements were consumed 3 times/day throughout the experimental time course. Biopsies were collected prior to (PRE) and 3, 24, 48, and 168 h following ECC. Reflective of the damaging protocol, integrin subunits, including α7, β1A, and β1D, increased (3.8-fold, 3.6-fold and 3.9-fold, respectively, P < 0.01) 24 h post-ECC with no difference between supplements. Pericyte quantity did not change post-ECC. WHY resulted in a small, but significant, decrease in ALP(+) pericytes when expressed as a percentage of myonuclei (CHO 6.8 ± 0.3% vs. WHY 5.8 ± 0.3%, P < 0.05) or per myofiber (CHO 0.119 ± 0.01 vs. WHY 0.098 ± 0.01, P < 0.05). The quantity of myonuclei expressing serum response factor and the number of pericytes expressing serum response factor, did not differ as a function of time post-ECC or supplement. These data demonstrate that acute muscle-damaging ECC increases α7β1 integrin content in human muscle, yet pericyte quantity is largely unaltered. Future studies should focus on the capacity for ECC to influence pericyte function, specifically paracrine factor release as a mechanism toward pericyte contribution to repair and adaptation postexercise. Copyright © 2015 the American Physiological Society.

Late Cenozoic structure and stratigraphy of south-central Washington

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

Reidel, S.P.; Campbell, N.P.; Fecht, K.R.

1993-09-01

The structural framework of the Columbia Basin began developing before Columbia River Basalt Group (CRBG) volcanism. Prior to 17.5 Ma, the eastern part of the basin was a relatively stable area, with a basement of Paleozoic and older crystalline rock. The western part was an area of subsidence in which large volumes of sediment and volcanic rocks accumulated. Concurrent with eruption of the CRBG, anticlinal ridges of the Yakima Fold Belt (YFB) were growing under north-south compression. Topographic expression of these features was later masked by the large volume of CRBG basalt flowing west from fissures in the eastern Columbiamore » Basin. The folds continued to develop after cessation of volcanism, leading to as much as 1,000 m of structural relief in the past 10 million years. Post-CRBG evolution of the Columbia Basin is recorded principally in folding and faulting in the YFB and sediments deposited in the basins. The accompanying tectonism resulted in lateral migration of major depositional systems into subsiding structural lows. Although known late Cenozoic faults are on anticlinal ridges, earthquake focal mechanisms and contemporary strain measurements indicate most stress release is occurring in the synclinal areas under north-south compression. There is no obvious correlation between focal mechanisms for earthquakes whose foci are in the CRBG and the location of known faults. High in situ stress values help to explain the occurrence of microseismicity in the Columbia Basin but not the pattern. Microseismicity appears to occur in unaltered fresh basalt. Faulted basalt associated with the YFB is highly brecciated and commonly altered to clay. The high stress, abundance of ground water in confined aquifers of the CRBG, and altered basalt in fault zones suggest that the frontal faults on the anticlinal ridges probably have some aseismic deformation. 85 refs.« less

Differential upregulation in DRG neurons of an α2δ-1 splice variant with a lower affinity for gabapentin after peripheral sensory nerve injury.

PubMed

Lana, Beatrice; Schlick, Bettina; Martin, Stuart; Pratt, Wendy S; Page, Karen M; Goncalves, Leonor; Rahman, Wahida; Dickenson, Anthony H; Bauer, Claudia S; Dolphin, Annette C

2014-03-01

The α2δ-1 protein is an auxiliary subunit of voltage-gated calcium channels, critical for neurotransmitter release. It is upregulated in dorsal root ganglion (DRG) neurons following sensory nerve injury, and is also the therapeutic target of the gabapentinoid drugs, which are efficacious in both experimental and human neuropathic pain conditions. α2δ-1 has 3 spliced regions: A, B, and C. A and C are cassette exons, whereas B is introduced via an alternative 3' splice acceptor site. Here we have examined the presence of α2δ-1 splice variants in DRG neurons, and have found that although the main α2δ-1 splice variant in DRG is the same as that in brain (α2δ-1 ΔA+B+C), there is also another α2δ-1 splice variant (ΔA+BΔC), which is expressed in DRG neurons and is differentially upregulated compared to the main DRG splice variant α2δ-1 ΔA+B+C following spinal nerve ligation. Furthermore, this differential upregulation occurs preferentially in a small nonmyelinated DRG neuron fraction, obtained by density gradient separation. The α2δ-1 ΔA+BΔC splice variant supports CaV2 calcium currents with unaltered properties compared to α2δ-1 ΔA+B+C, but shows a significantly reduced affinity for gabapentin. This variant could therefore play a role in determining the efficacy of gabapentin in neuropathic pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Generation of Trichoderma atroviride mutants with constitutively activated G protein signaling by using geneticin resistance as selection marker.

PubMed

Gruber, Sabine; Omann, Markus; Rodrìguez, Carolina Escobar; Radebner, Theresa; Zeilinger, Susanne

2012-11-17

Species of the fungal genus Trichoderma are important industrial producers of cellulases and hemicellulases, but also widely used as biocontrol agents (BCAs) in agriculture. In the latter function Trichoderma species stimulate plant growth, induce plant defense and directly antagonize plant pathogenic fungi through their mycoparasitic capabilities. The recent release of the genome sequences of four mycoparasitic Trichoderma species now forms the basis for large-scale genetic manipulations of these important BCAs. Thus far, only a limited number of dominant selection markers, including Hygromycin B resistance (hph) and the acetamidase-encoding amdS gene, have been available for transformation of Trichoderma spp. For more extensive functional genomics studies the utilization of additional dominant markers will be essential. We established the Escherichia coli neomycin phosphotransferase II-encoding nptII gene as a novel selectable marker for the transformation of Trichoderma atroviride conferring geneticin resistance. The nptII marker cassette was stably integrated into the fungal genome and transformants exhibited unaltered phenotypes compared to the wild-type. Co-transformation of T. atroviride with nptII and a constitutively activated version of the Gα subunit-encoding tga3 gene (tga3Q207L) resulted in a high number of mitotically stable, geneticin-resistant transformants. Further analyses revealed a co-transformation frequency of 68% with 15 transformants having additionally integrated tga3Q207L into their genome. Constitutive activation of the Tga3-mediated signaling pathway resulted in increased vegetative growth and an enhanced ability to antagonize plant pathogenic host fungi. The neomycin phosphotransferase II-encoding nptII gene from Escherichia coli proved to be a valuable tool for conferring geneticin resistance to the filamentous fungus T. atroviride thereby contributing to an enhanced genetic tractability of these important BCAs.

Cyclooxygenase-dependent alterations in substance P-mediated contractility and tachykinin NK1 receptor expression in the colonic circular muscle of patients with slow transit constipation.

PubMed

Liu, Lu; Shang, Fei; Morgan, Matthew J; King, Denis W; Lubowski, David Z; Burcher, Elizabeth

2009-04-01

Tachykinins are important neurotransmitters regulating intestinal motility. Slow transit constipation (STC) represents an extreme colonic dysmotility with unknown etiology that predominantly affects women. We examined whether the tachykinin system is involved in the pathogenesis of STC. Isolated sigmoid colon circular muscle from female STC and control patients was studied using functional and quantitative reverse transcriptase-polymerase chain reaction methods. A possible alteration of neurotransmission was investigated by electrical field stimulation (EFS) and ganglionic stimulation by dimethylphenylpiperazinium (DMPP). Substance P (SP)-mediated contractions in circular muscle strips were significantly diminished in STC compared with age-matched control (P < 0.001). In contrast, contractile responses to neurokinin A, the selective tachykinin NK(2) receptor agonist, [Lys(5),MeLeu(9),Nle(10)]NKA(4-10), and acetylcholine were unaltered in STC. The reduced responses to SP in STC were fully restored by indomethacin, partially reversed by tetrodotoxin (TTX), but unaffected by atropine or hexamethonium. The restoration by indomethacin was blocked by the NK(1) receptor antagonist CP99994 [(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] and TTX. In STC colonic muscle, there was a significant increase of NK(1) receptor mRNA expression, but no difference in NK(2) mRNA level. DMPP generated biphasic responses, relaxation at lower and contraction at higher concentrations. Although the responses to DMPP were similar in STC and control, an altered contractile pattern in response to EFS was observed in STC circular muscle. In conclusion, we postulate that the diminished contractile response to SP in STC is due to an increased release of inhibitory prostaglandins through activation of up-regulated NK(1) receptors. Our results also indicate some malfunction of the enteric nervous system in STC.

Chemical and isotopic equilibrium between CO 2 and CH 4 in fumarolic gas discharges: Generation of CH 4 in arc magmatic-hydrothermal systems

NASA Astrophysics Data System (ADS)

Fiebig, Jens; Chiodini, Giovanni; Caliro, Stefano; Rizzo, Andrea; Spangenberg, Jorge; Hunziker, Johannes C.

2004-05-01

The chemical and isotopic composition of fumarolic gases emitted from Nisyros Volcano, Greece, and of a single gas sample from Vesuvio, Italy, was investigated in order to determine the origin of methane (CH 4) within two subduction-related magmatic-hydrothermal environments. Apparent temperatures derived from carbon isotope partitioning between CH 4 and CO 2 of around 340°C for Nisyros and 470°C for Vesuvio correlate well with aquifer temperatures as measured directly and/or inferred from compositional data using the H 2O-H 2-CO 2-CO-CH 4 geothermometer. Thermodynamic modeling reveals chemical equilibrium between CH 4, CO 2 and H 2O implying that carbon isotope partitioning between CO 2 and CH 4 in both systems is controlled by aquifer temperature. N 2/ 3He and CH 4/ 3He ratios of Nisyros fumarolic gases are unusually low for subduction zone gases and correspond to those of midoceanic ridge environments. Accordingly, CH 4 may have been primarily generated through the reduction of CO 2 by H 2 in the absence of any organic matter following a Fischer-Tropsch-type reaction. However, primary occurrence of minor amounts of thermogenic CH 4 and subsequent re-equilibration with co-existing CO 2 cannot be ruled out entirely. CO 2/ 3He ratios and δ 13C CO 2 values imply that the evolved CO 2 either derives from a metasomatized mantle or is a mixture between two components, one outgassing from an unaltered mantle and the other released by thermal breakdown of marine carbonates. The latter may contain traces of organic matter possibly decomposing to CH 4 during thermometamorphism.

In-vitro Cell Exposure Studies for the Assessment of Nanoparticle Toxicity in the Lung - A Dialogue between Aerosol Science and Biology

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

Hanns-Rudolf, Paur; Cassee, Flemming R.; Teeguarden, Justin G.

The rapid introduction of engineered nanostructured materials into numerous industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of consumer products. The dynamic development of new nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety. In this consensus document from a workshop on in-vitro cell systems for nanotoxicity testing an overview is given of the main issues concerningmore » inhalation exposure to nanoparticles, lung physiology, nanoparticle-related biological mechanisms, in-vitro cell exposure systems for nanoparticles and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanotoxicity. For the investigation of pulmonary nanotoxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.« less

The obesity-associated transcription factor ETV5 modulates circulating glucocorticoids

PubMed Central

Gutierrez-Aguilar, Ruth; Thompson, Abigail; Marchand, Nathalie; Dumont, Patrick; Woods, Stephen C.; de Launoit, Yvan; Seeley, Randy J.; Ulrich-Lai, Yvonne M.

2015-01-01

The transcription factor E-twenty-six version 5 (ETV5) has been linked with obesity in genome-wide association studies. Moreover, ETV5-deficient mice (knockout; KO) have reduced body weight, lower fat mass, and are resistant to diet-induced obesity, directly linking ETV5 to the regulation of energy balance and metabolism. ETV5 is expressed in hypothalamic brain regions that regulate both metabolism and HPA axis activity, suggesting that ETV5 may also modulate HPA axis function. In order to test this possibility, plasma corticosterone levels were measured in ETV5 KO and wildtype (WT) mice before (pre-stress) and after (post-stress) a mild stressor (intraperitoneal injection). ETV5 deficiency increased both pre- and post-stress plasma corticosterone, suggesting that loss of ETV5 elevated glucocorticoid tone. Consistent with this idea, ETV5 KO mice have reduced thymus weight, suggestive of increased glucocorticoid-induced thymic involution. ETV5 deficiency also decreased the mRNA expression of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and vasopressin receptor 1A in the hypothalamus, without altering vasopressin, corticotropin-releasing hormone, or oxytocin mRNA expression. In order to test whether reduced MR and GR expression affected glucocorticoid negative feedback, a dexamethasone suppression test was performed. Dexamethasone reduced plasma corticosterone in both ETV5 KO and WT mice, suggesting that glucocorticoid negative feedback was unaltered by ETV5 deficiency. In summary, these data suggest that the obesity-associated transcription factor ETV5 normally acts to diminish circulating glucocorticoids. This might occur directly via ETV5 actions on HPA-regulatory brain circuitry, and/or indirectly via ETV5-induced alterations in metabolic factors that then influence the HPA axis. PMID:25813907

Effect of settled diatom‐aggregates on benthic nitrogen cycling

PubMed Central

Thamdrup, Bo; Stief, Peter; Glud, Ronnie N.

2017-01-01

Abstract The marine sediment hosts a mosaic of microhabitats. Recently it has been demonstrated that the settlement of phycodetrital aggregates can induce local changes in the benthic O2 distribution due to confined enrichment of organic material and alteration of the diffusional transport. Here, we show how this microscale O2 shift substantially affects benthic nitrogen cycling. In sediment incubations, the settlement of diatom‐aggregates markedly enhanced benthic O2 and NO3− consumption and stimulated NO2− and NH4+ production. Oxygen microprofiles revealed the rapid development of anoxic niches within and underneath the aggregates. During 120 h following the settling of the aggregates, denitrification of NO3− from the overlying water increased from 13.5 μmol m−2 h−1 to 24.3 μmol m−2 h−1, as quantified by 15N enrichment experiment. Simultaneously, N2 production from coupled nitrification‐denitrification decreased from 33.4 μmol m−2 h−1 to 25.9 μmol m−2 h−1, probably due to temporary inhibition of the benthic nitrifying community. The two effects were of similar magnitude and left the total N2 production almost unaltered. At the aggregate surface, nitrification was, conversely, very efficient in oxidizing NH4+ liberated by mineralization of the aggregates. The produced NO3− was preferentially released into the overlying water and only a minor fraction contributed to denitrification activity. Overall, our data indicate that the abrupt change in O2 microdistribution caused by aggregates stimulates denitrification of NO3− from the overlying water, and loosens the coupling between benthic nitrification and denitrification both in time and space. The study contributes to expanding the conceptual and quantitative understanding of how nitrogen cycling is regulated in dynamic benthic environments. PMID:29456269

Activation of the sigma receptor 1 modulates AMPA receptor-mediated light-evoked excitatory postsynaptic currents in rat retinal ganglion cells.

PubMed

Liu, Lei-Lei; Deng, Qin-Qin; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

2016-09-22

Sigma receptor (σR), a unique receptor family, is classified into three subtypes: σR1, σR2 and σR3. It was previously shown that σR1 activation induced by 1μM SKF10047 (SKF) suppressed N-methyl-d-aspartate (NMDA) receptor-mediated responses of rat retinal ganglion cells (GCs) and the suppression was mediated by a distinct Ca(2+)-dependent phospholipase C (PLC)-protein kinase C (PKC) pathway. In the present work, using whole-cell patch-clamp techniques in rat retinal slice preparations, we further demonstrate that SKF of higher dosage (50μM) significantly suppressed AMPA receptor (AMPAR)-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) of retinal ON-type GCs (ON GCs), and the effect was reversed by the σR1 antagonist BD1047, suggesting the involvement of σR1. The SKF (50μM) effect was unlikely due to a change in glutamate release from bipolar cells, as suggested by the unaltered paired-pulse ratio (PPR) of AMPAR-mediated EPSCs of ON GCs. SKF (50μM) did not change L-EPSCs of ON GCs when the G protein inhibitor GDP-β-S or the protein kinase G (PKG) inhibitor KT5823 was intracellularly infused. Calcium imaging further revealed that SKF (50μM) did not change intracellular calcium concentration in GCs and persisted to suppress L-EPSCs when intracellular calcium was chelated by BAPTA. The SKF (50μM) effect was intact when protein kinase A (PKA) and phosphatidylinostiol (PI)-PLC signaling pathways were both blocked. We conclude that the SKF (50μM) effect is Ca(2+)-independent, PKG-dependent, but not involving PKA, PI-PLC pathways. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Carboxy-terminal glycosyl hydrolase 18 domain of a carbohydrate active protein of Chitinophaga pinensis is a non-processive exochitinase.

PubMed

Ramakrishna, Bellamkonda; Vaikuntapu, PapaRao; Mallakuntla, Mohan Krishna; Bhuvanachandra, Bhoopal; Sivaramakrishna, Dokku; Uikey, Sheetal; Podile, Appa Rao

2018-05-01

The recombinant C-terminal domain of chitinase C of Chitinophaga pinensis (CpChiC-GH18 C ) exhibits the highest activity at pH 6.0 and 35 °C, with a K m of 76.13 (mg -1  ml), a k cat of 10.16 (s -1 ), and a k cat /K m of 0.133 (mg -1  ml s -1 ) on colloidal chitin. Analysis of degradation of (GlcNAc) 3-6 oligomers shows that CpChiC-GH18 C releases (GlcNAc) 2 as the main product, indicating an exo-type cleavage pattern. CpChiC-GH18 C hydrolyzes the chitin polymers yielding GlcNAc, (GlcNAc) 2 , and (GlcNAc) 3 as end products with no sign of processivity. Circular dichroism spectra indicate that the secondary and tertiary structures of CpChiC-GH18 C are unaltered up to 45 °C and the protein denatures without an intermediate state. The urea-induced unfolding is a two-state process and the unfolding of native CpChiC-GH18 C occurs in a single step. Among the metal ions tested, Hg 2+ completely inhibits the enzyme activity. The chemical modulators, p-hydroxymercuribenzoic acid and N-bromosuccinimide considerably decrease the enzyme activity. Sequence analysis and homology modeling suggest that CpChiC-GH18 C lacks a tryptophan residue at the aglycon site. Further, the CpChiC-GH18 C has a shallow and open groove, suggesting that CpChiC-GH18 C is non-processive exo-type chitinase with properties suitable for the bioconversion of chitin waste. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of hyper- and hypothyroidism on acetylcholinesterase, (Na(+), K (+))- and Mg ( 2+ )-ATPase activities of adult rat hypothalamus and cerebellum.

PubMed

Carageorgiou, Haris; Pantos, Constantinos; Zarros, Apostolos; Stolakis, Vasileios; Mourouzis, Iordanis; Cokkinos, Dennis; Tsakiris, Stylianos

2007-03-01

Thyroid hormones (THs) are recognized as key metabolic hormones, and the metabolic rate increases in hyperthyroidism, while it decreases in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na(+), K(+))- and Mg(2+)-ATPase in the hypothalamus and the cerebellum of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, while hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. Neither hyper-, nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum, hyperthyroidism provoked a significant decrease in both the AChE (-23%, p < 0.001) and the Na(+), K(+)-ATPase activities (-26%, p < 0.001). Moreover, hypothyroidism had a similar effect on the examined enzyme activities: AChE (-17%, p < 0.001) and Na(+), K(+)-ATPase (-27%, p < 0.001). Mg(2+)-ATPase activity was found unaltered in both the hyper- and the hypothyroid brain regions. neither hyper-, nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum, hyperthyroidism provoked a significant decrease in both the AChE and the Na(+), K(+)-ATPase activities. The decreased (by the THs) Na(+), K(+)-ATPase activities may increase the synaptic acetylcholine release, and thus, could result in a decrease in the cerebellar AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems.

Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase constitutively expressed to high levels in Pichia pastoris.

PubMed

Hernández, Lázaro; Menéndez, Carmen; Pérez, Enrique R; Martínez, Duniesky; Alfonso, Dubiel; Trujillo, Luis E; Ramírez, Ricardo; Sobrino, Alina; Mazola, Yuliet; Musacchio, Alexis; Pimentel, Eulogio

2018-01-20

The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus). The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity. Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth. The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h) was 1422.2 U/l/h. Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C. The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities. Sa1-SSTrec converted sucrose (600 g/l) into 1-kestose (GF 2 ) and nystose (GF 3 ) in a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture. Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile. Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose. Copyright © 2017 Elsevier B.V. All rights reserved.

CsPLDα1 and CsPLDγ1 are differentially induced during leaf and fruit abscission and diurnally regulated in Citrus sinensis

PubMed Central

Malladi, Anish; Burns, Jacqueline K.

2008-01-01

Understanding leaf and fruit abscission is essential in order to develop strategies for controlling the process in fruit crops. Mechanisms involved in signalling leaf and fruit abscission upon induction by abscission agents were investigated in Citrus sinensis cv. ‘Valencia’. Previous studies have suggested a role for phospholipid signalling; hence, two phospholipase D cDNA sequences, CsPLDα1 and CsPLDγ1, were isolated and their role was examined. CsPLDα1 expression was reduced in leaves but unaltered in fruit peel tissue treated with an ethylene-releasing compound (ethephon), or a fruit-specific abscission agent, 5-chloro-3-methyl-4-nitro-1H-pyrazole (CMNP). By contrast, CsPLDγ1 expression was up-regulated within 6 h (leaves) and 24 h (fruit peel) after treatment with ethephon or CMNP, respectively. CsPLDα1 expression was diurnally regulated in leaf blade but not fruit peel. CsPLDγ1 exhibited strong diurnal oscillation in expression in leaves and fruit peel with peak expression around midday. While diurnal fluctuation in CsPLDα1 expression appeared to be light-entrained in leaves, CsPLDγ1 expression was regulated by light and the circadian clock. The diurnal expression of both genes was modulated by ethylene-signalling. The ethephon-induced leaf abscission and the ethephon- and CMNP-induced decrease in fruit detachment force were enhanced by application during rising diurnal expression of CsPLDγ1. The results indicate differential regulation of CsPLDα1 and CsPLDγ1 in leaves and fruit, and suggest possible roles for PLD-dependent signalling in regulating abscission responses in citrus. PMID:18799715

Striatal Synaptic Dysfunction and Hippocampal Plasticity Deficits in the Hu97/18 Mouse Model of Huntington Disease

PubMed Central

Kolodziejczyk, Karolina; Parsons, Matthew P.; Southwell, Amber L.; Hayden, Michael R.; Raymond, Lynn A.

2014-01-01

Huntington disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the gene (HTT) encoding the huntingtin protein (HTT). This mutation leads to multiple cellular and synaptic alterations that are mimicked in many current HD animal models. However, the most commonly used, well-characterized HD models do not accurately reproduce the genetics of human disease. Recently, a new ‘humanized’ mouse model, termed Hu97/18, has been developed that genetically recapitulates human HD, including two human HTT alleles, no mouse Hdh alleles and heterozygosity of the HD mutation. Previously, behavioral and neuropathological testing in Hu97/18 mice revealed many features of HD, yet no electrophysiological measures were employed to investigate possible synaptic alterations. Here, we describe electrophysiological changes in the striatum and hippocampus of the Hu97/18 mice. At 9 months of age, a stage when cognitive deficits are fully developed and motor dysfunction is also evident, Hu97/18 striatal spiny projection neurons (SPNs) exhibited small changes in membrane properties and lower amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs); however, release probability from presynaptic terminals was unaltered. Strikingly, these mice also exhibited a profound deficiency in long-term potentiation (LTP) at CA3-to-CA1 synapses. In contrast, at 6 months of age we found only subtle alterations in SPN synaptic transmission, while 3-month old animals did not display any electrophysiologically detectable changes in the striatum and CA1 LTP was intact. Together, these data reveal robust, progressive deficits in synaptic function and plasticity in Hu97/18 mice, consistent with previously reported behavioral abnormalities, and suggest an optimal age (9 months) for future electrophysiological assessment in preclinical studies of HD. PMID:24728353

Postjunctional inhibition of contractor responses in the mouse vas deferens by rat and human calcitonin gene-related peptides (CGRP).

PubMed Central

Al-Kazwini, S. J.; Craig, R. K.; Marshall, I.

1986-01-01

The effects of rat and human alpha-calcitonin gene-related peptide (CGRP) were compared in the mouse and rabbit isolated vas deferens preparation contracted by either field stimulation or acetylcholine. The peptides were about equipotent at inhibiting twitch responses of the mouse vas deferens to field stimulation at 0.2 Hz (IC50 12 +/- 4 nM and 15 +/- 3 nM, rat and human alpha-CGRP respectively). Rat alpha-CGRP was less potent at inhibiting responses to 10 Hz than to either 0.2 Hz or 1.0 Hz stimulation. The potency of rat alpha-CGRP at 1.0 Hz was unaltered by halving the calcium concentration of the Krebs solution. The inhibitory effect of human alpha-CGRP was not antagonized by either propranolol (300 nM) or idazoxan (300 nM), although in the same tissues these latter two drugs reduced responses to isoprenaline and clonidine respectively. Rat alpha-CGRP (100 nM) and human alpha-CGRP (1.0 microM) did not alter the uptake of [3H]-noradrenaline (30 nM) into mice isolated vasa deferentia. Rat alpha-CGRP (3-100 nM) did not alter the fractional release per pulse (1.0 Hz, 100 pulses) of tritium from vasa preloaded with [3H]-noradrenaline, although at the same time the peptide inhibited responses of the smooth muscle to field stimulation. Rat and human alpha-CGRP were equipotent at inhibiting contractions of the mouse vas deferens evoked by acetylcholine although the peptides were less potent than against twitch responses. In the rabbit vas deferens neither rat nor human alpha-CGRP (3 nM-1 microM) inhibited either twitch responses or acetylcholine contractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3486688

Characterization of an immunomodulatory Der p 2-FIP-fve fusion protein produced in transformed rice suspension cell culture.

PubMed

Su, Chin-Fen; Kuo, I-Chun; Chen, Peng-Wen; Huang, Chiung-Hui; Seow, See Voon; Chua, Kaw Yan; Yu, Su-May

2012-02-01

Der p 2, a major allergen of Dermatophagoides pteronyssinus mites, is one of the most clinically relevant allergens to allergic patients worldwide. FIP-fve protein (Fve) from the golden needle mushroom (Flammulina velutipes) is an immunomodulatory protein with potential Th1-skewed adjuvant properties. Here, we produced and immunologically evaluated a Der p 2-Fve fusion protein as a potential immunotherapeutic for allergic diseases. Using an inducible expression system in cultured rice suspension cells, the recombinant Der p 2-Fve fusion protein (designated as OsDp2Fve) was expressed in rice cells under the control of an α-amylase gene (αAmy8) promoter and secreted under sucrose starvation. OsDp2Fve was partially purified from the cultured medium. The conformation of Der p 2 in OsDp2Fve remains intact as reflected by its unaltered allergenicity, as assessed by human IgE ELISA and histamine release assays, compared to non-fusion Der p 2 protein. Furthermore, the Fve protein expressed in OsDp2Fve retains its in vitro lymphoproliferative activity but loses its hemagglutination and lymphoagglutination effects compared to the native protein. Notably, in vivo evaluation showed that mice administered with OsDp2Fve possessed an enhanced production of Der p 2-specific IgG antibodies without potentiating the production of Der p 2-specific IgE and Th2 effector cytokines in comparison with mice co-administered with native Fve and Der p 2 proteins. These results suggest that the recombinant Der p 2-Fve fusion protein produced in rice suspension cell cultures has a great potential for allergy immunotherapy.

γ-secretase binding sites in aged and Alzheimer's disease human cerebrum: the choroid plexus as a putative origin of CSF Aβ.

PubMed

Liu, Fei; Xue, Zhi-Qin; Deng, Si-Hao; Kun, Xiong; Luo, Xue-Gang; Patrylo, Peter R; Rose, Gregory M; Cai, Huaibin; Struble, Robert G; Cai, Yan; Yan, Xiao-Xin

2013-05-01

Deposition of β -amyloid (Aβ) peptides, cleavage products of β-amyloid precursor protein (APP) by β-secretase-1 (BACE1) and γ-secretase, is a neuropathological hallmark of Alzheimer's disease (AD). γ-Secretase inhibition is a therapeutical anti-Aβ approach, although changes in the enzyme's activity in AD brain are unclear. Cerebrospinal fluid (CSF) Aβ peptides are thought to derive from brain parenchyma and thus may serve as biomarkers for assessing cerebral amyloidosis and anti-Aβ efficacy. The present study compared active γ-secretase binding sites with Aβ deposition in aged and AD human cerebrum, and explored the possibility of Aβ production and secretion by the choroid plexus (CP). The specific binding density of [(3) H]-L-685,458, a radiolabeled high-affinity γ-secretase inhibitor, in the temporal neocortex and hippocampal formation was similar for AD and control cases with similar ages and post-mortem delays. The CP in post-mortem samples exhibited exceptionally high [(3) H]-L-685,458 binding density, with the estimated maximal binding sites (Bmax) reduced in the AD relative to control groups. Surgically resected human CP exhibited APP, BACE1 and presenilin-1 immunoreactivity, and β-site APP cleavage enzymatic activity. In primary culture, human CP cells also expressed these amyloidogenic proteins and released Aβ40 and Aβ42 into the medium. Overall, our results suggest that γ-secretase activity appears unaltered in the cerebrum in AD and is not correlated with regional amyloid plaque pathology. The CP appears to be a previously unrecognised non-neuronal contributor to CSF Aβ, probably at reduced levels in AD. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Diazeniumdiolate-doped poly(lactic-co-glycolic acid)-based nitric oxide releasing films as antibiofilm coatings.

PubMed

Cai, Wenyi; Wu, Jianfeng; Xi, Chuanwu; Meyerhoff, Mark E

2012-11-01

Nitric oxide (NO) releasing films with a bilayer configuration are fabricated by doping dibutyhexyldiamine diazeniumdiolate (DBHD/N2O2) in a poly(lactic-co-glycolic acid) (PLGA) layer and further encapsulating this base layer with a silicone rubber top coating. By incorporating pH sensitive dyes within the films, pH changes in the PLGA layer are visualized and correlated with the NO release profiles (flux vs. time). It is demonstrated that PLGA acts as both a promoter and controller of NO release from the coating by providing protons through its intrinsic acid residues (both end groups and monomeric acid impurities) and hydrolysis products (lactic acid and glycolic acid). Control of the pH changes within the PLGA layer can be achieved by adjusting the ratio of DBHD/N2O2 and utilizing PLGAs with different hydrolysis rates. Coatings with a variety of NO release profiles are prepared with lifetimes of up to 15 d at room temperature (23 °C) and 10 d at 37 °C. When incubated in a CDC flow bioreactor for a one week period at RT or 37 °C, all the NO releasing films exhibit considerable antibiofilm properties against gram-positive Staphylococcus aureus and gram-negative Escherichia coli. In particular, compared to the silicone rubber surface alone, an NO releasing film with a base layer of 30 wt% DBHD/N2O2 mixed with poly(lactic acid) exhibits an ∼98.4% reduction in biofilm biomass of S. aureus and ∼99.9% reduction for E. coli at 37 °C. The new diazeniumdiolate-doped PLGA-based NO releasing coatings are expected to be useful antibiofilm coatings for a variety of indwelling biomedical devices (e.g., catheters). Copyright © 2012 Elsevier Ltd. All rights reserved.

Polymeric nanotheranostics for real-time non-invasive optical imaging of breast cancer progression and drug release.

PubMed

Ferber, Shiran; Baabur-Cohen, Hemda; Blau, Rachel; Epshtein, Yana; Kisin-Finfer, Einat; Redy, Orit; Shabat, Doron; Satchi-Fainaro, Ronit

2014-09-28

Polymeric nanocarriers conjugated with low molecular weight drugs are designed in order to improve their efficacy and toxicity profile. This approach is particularly beneficial for anticancer drugs, where the polymer-drug conjugates selectively accumulate at the tumor site, due to the enhanced permeability and retention (EPR) effect. The conjugated drug is typically inactive, and upon its pH- or enzymatically-triggered release from the carrier, it regains its therapeutic activity. These settings lack information regarding drug-release time, kinetics and location. Thereby, real-time non-invasive intravital monitoring of drug release is required for theranostics (therapy and diagnostics). We present here the design, synthesis and characterization of a theranostic nanomedicine, based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer, owing its fluorescence-based monitoring of site-specific drug release to a self-quenched near-infrared fluorescence (NIRF) probe. We designed two HPMA copolymer-based systems that complement to a theranostic nanomedicine. The diagnostic system consists of self-quenched Cy5 (SQ-Cy5) as a reporter probe and the therapeutic system is based on the anticancer agent paclitaxel (PTX). HPMA copolymer-PTX/SQ-Cy5 systems enable site-specific release upon enzymatic degradation in cathepsin B-overexpressing breast cancer cells. The release of the drug occurs concomitantly with the activation of the fluorophore to its Turn-ON state. HPMA copolymer-SQ-Cy5 exhibits preferable body distribution and drug release compared with the free drug and probe when administered to cathepsin B-overexpressing 4T1 murine mammary adenocarcinoma-bearing mice. This approach of co-delivery of two complementary systems serves as a proof-of-concept for real-time deep tissue intravital orthotopic monitoring and may have the potential use in clinical utility as a theranostic nanomedicine. Copyright © 2014. Published by Elsevier Ireland Ltd.

Suicide after release from prison - a population-based cohort study from Sweden

PubMed Central

Haglund, Axel; Tidemalm, Dag; Jokinen, Jussi; Långström, Niklas; Liechtenstein, Paul; Fazel, Seena; Runeson, Bo

2015-01-01

Objective Released prisoners have high suicide rates compared with the general population, but little is known about risk factors and possible causal pathways. We conducted a population-based cohort study to investigate rates and risk factors for suicide in people previously imprisoned. Methods We identified individuals released from prison in Sweden between January 1, 2005 and December 31, 2009 through linkage of national population-based registers. Released prisoners were followed from the day of release until death, emigration, new incarceration, or December 31, 2009. Survival analyses were conducted to compare incidence rates and psychiatric morbidity with non-convicted population controls matched on gender and year of birth. Results We identified 38,995 releases among 26,953 prisoners (7.6% females) during 2005-2009. Overall, 127 suicides occurred, accounting for 14% of all deaths after release (n=920). The mean suicide rate was 204 per 100,000 person years yielding an incidence rate ratio of 18.2 (95% CI 13.9-23.8) compared with general population controls. Previous substance use disorder (Hazard Ratio [HR]=2.1, 1.4-3.2), suicide attempt (HR=2.5, 1.7-3.7), and being born in Sweden vs. abroad (HR=2.1, 1.2-3.6) were independent risk factors for suicide after release. Conclusions Released prisoners are at high suicide risk and with a slightly different pattern of psychiatric risk factors for suicide compared with the general population. Results suggest appropriate allocation of resources to facilitate transition to life outside prison and increased attention to prisoners with both a previous suicide attempt and substance use disorder. PMID:25373114

Mapping of hydrothermally altered rocks using airborne multispectral scanner data, Marysvale, Utah, mining district

USGS Publications Warehouse

Podwysocki, M.H.; Segal, D.B.; Jones, O.D.

1983-01-01

Multispectral data covering an area near Marysvale, Utah, collected with the airborne National Aeronautics and Space Administration (NASA) 24-channel Bendix multispectral scanner, were analyzed to detect areas of hydrothermally altered, potentially mineralized rocks. Spectral bands were selected for analysis that approximate those of the Landsat 4 Thematic Mapper and which are diagnostic of the presence of hydrothermally derived products. Hydrothermally altered rocks, particularly volcanic rocks affected by solutions rich in sulfuric acid, are commonly characterized by concentrations of argillic minerals such as alunite and kaolinite. These minerals are important for identifying hydrothermally altered rocks in multispectral images because they have intense absorption bands centered near a wavelength of 2.2 ??m. Unaltered volcanic rocks commonly do not contain these minerals and hence do not have the absorption bands. A color-composite image was constructed using the following spectral band ratios: 1.6??m/2.2??m, 1.6??m/0.48??m, and 0.67??m/1.0??m. The particular bands were chosen to emphasize the spectral contrasts that exist for argillic versus non-argillic rocks, limonitic versus nonlimonitic rocks, and rocks versus vegetation, respectively. The color-ratio composite successfully distinguished most types of altered rocks from unaltered rocks. Some previously unrecognized areas of hydrothermal alteration were mapped. The altered rocks included those having high alunite and/or kaolinite content, siliceous rocks containing some kaolinite, and ash-fall tuffs containing zeolitic minerals. The color-ratio-composite image allowed further division of these rocks into limonitic and nonlimonitic phases. The image did not allow separation of highly siliceous or hematitically altered rocks containing no clays or alunite from unaltered rocks. A color-coded density slice image of the 1.6??m/2.2??m band ratio allowed further discrimination among the altered units. Areas containing zeolites and some ash-fall tuffs containing montmorillonite were readily recognized on the color-coded density slice as having less intense 2.2-??m absorption than areas of highly altered rocks. The areas of most intense absorption, as depicted in the color-coded density slice, are dominated by highly altered rocks containing large amounts of alunite and kaolinite. These areas form an annulus, approximately 10 km in diameter, which surrounds a quartz monzonite intrusive body of Miocene age. The patterns of most intense alteration are interpreted as the remnants of paleohydrothermal convective cells set into motion during the emplacement of the central intrusive body. ?? 1983.

Tetrapeptide-coumarin conjugate 3D networks based on hydrogen-bonded charge transfer complexes: gel formation and dye release.

PubMed

Guo, Zongxia; Gong, Ruiying; Jiang, Yi; Wan, Xiaobo

2015-08-14

Oligopeptide-based derivatives are important synthons for bio-based functional materials. In this article, a Gly-(L-Val)-Gly-(L-Val)-coumarin (GVGV-Cou) conjugate was synthesized, which forms 3D networks in ethanol. The gel nanostructures were characterized by UV-vis spectroscopy, FT-IR spectroscopy, X-ray diffraction (XRD), SEM and TEM. It is suggested that the formation of charge transfer (CT) complexes between the coumarin moieties is the main driving force for the gel formation. The capability of the gel to encapsulate and release dyes was explored. Both Congo Red (CR) and Methylene Blue (MB) can be trapped in the CT gel matrix and released over time. The present gel might be used as a functional soft material for guest encapsulation and release.

Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation

PubMed Central

Cacciapaglia, Fabio; Wightman, R. Mark; Carelli, Regina M.

2015-01-01

Mesolimbic dopamine (DA) is phasically released during appetitive behaviors, though there is substantive disagreement about the specific purpose of these DA signals. For example, prediction error (PE) models suggest a role of learning, while incentive salience (IS) models argue that the DA signal imbues stimuli with value and thereby stimulates motivated behavior. However, within the nucleus accumbens (NAc) patterns of DA release can strikingly differ between subregions, and as such, it is possible that these patterns differentially contribute to aspects of PE and IS. To assess this, we measured DA release in subregions of the NAc during a behavioral task that spatiotemporally separated sequential goal-directed stimuli. Electrochemical methods were used to measure subsecond NAc dopamine release in the core and shell during a well learned instrumental chain schedule in which rats were trained to press one lever (seeking; SL) to gain access to a second lever (taking; TL) linked with food delivery, and again during extinction. In the core, phasic DA release was greatest following initial SL presentation, but minimal for the subsequent TL and reward events. In contrast, phasic shell DA showed robust release at all task events. Signaling decreased between the beginning and end of sessions in the shell, but not core. During extinction, peak DA release in the core showed a graded decrease for the SL and pauses in release during omitted expected rewards, whereas shell DA release decreased predominantly during the TL. These release dynamics suggest parallel DA signals capable of supporting distinct theories of appetitive behavior. SIGNIFICANCE STATEMENT Dopamine signaling in the brain is important for a variety of cognitive functions, such as learning and motivation. Typically, it is assumed that a single dopamine signal is sufficient to support these cognitive functions, though competing theories disagree on how dopamine contributes to reward-based behaviors. Here, we have found that real-time dopamine release within the nucleus accumbens (a primary target of midbrain dopamine neurons) strikingly varies between core and shell subregions. In the core, dopamine dynamics are consistent with learning-based theories (such as reward prediction error) whereas in the shell, dopamine is consistent with motivation-based theories (e.g., incentive salience). These findings demonstrate that dopamine plays multiple and complementary roles based on discrete circuits that help animals optimize rewarding behaviors. PMID:26290234

Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors.

PubMed

Chen, Shilan; Liu, Mingzhu; Jin, Shuping; Wang, Bin

2008-02-12

Drug-loaded chitosan (CS) beads were prepared under simple and mild condition using trisodium citrate as ionic crosslinker. The beads were further coated with poly(methacrylic acid) (PMAA) by dipping the beads in PMAA aqueous solution. The surface and cross-section morphology of these beads were observed by scanning electron microscopy and the observation showed that the coating beads had core-shell structure. In vitro release of model drug from these beads obtained under different reaction conditions was investigated in buffer medium (pH 1.8). The results showed that the rapid drug release was restrained by PMAA coating and the optimum conditions for preparing CS-based drug-loaded beads were decided through the effect of reaction conditions on the drug release behaviors. In addition, the drug release mechanism of CS-based drug-loaded beads was analyzed by Peppa's potential equation. According to this study, the ionic-crosslinked CS beads coated by PMAA could serve as suitable candidate for drug site-specific carrier in stomach.

Physical parameters of chlorphenamine maleate suppositories and its release as a function of particle size, concentration and nature of the base.

PubMed

el-Din, E N; Mursi, N M; Elbary, A A; Foda, N

1977-01-01

Suppositories of chlorphenamine maleate were formulated. The influence of particle size and percentage concentration of chlorphenamine maleate on the physical standards of its suppositories as well as the release of the drug from oily base (cacao butter), water-soluble base (carbowax) and emulsifying base (Witepsol) has been investigated.

LARC-1: a Los Alamos release calculation program for fission product transport in HTGRs during the LOFC accident

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

Carruthers, L.M.; Lee, C.E.

1976-10-01

The theoretical and numerical data base development of the LARC-1 code is described. Four analytical models of fission product release from an HTGR core during the loss of forced circulation accident are developed. Effects of diffusion, adsorption and evaporation of the metallics and precursors are neglected in this first LARC model. Comparison of the analytic models indicates that the constant release-renormalized model is adequate to describe the processes involved. The numerical data base for release constants, temperature modeling, fission product release rates, coated fuel particle failure fraction and aged coated fuel particle failure fractions is discussed. Analytic fits and graphicmore » displays for these data are given for the Ft. St. Vrain and GASSAR models.« less

Guidance for Evaluating the Safety of Experimental Releases of Mosquitoes, Emphasizing Mark-Release-Recapture Techniques

PubMed Central

Charlwood, J. Derek; Harrington, Laura C.; Lounibos, L. Philip; Reisen, William K.; Tabachnick, Walter J.

2018-01-01

Abstract Experimental releases of mosquitoes are performed to understand characteristics of populations related to the biology, ability to transmit pathogens, and ultimately their control. In this article, we discuss considerations related to the safety of experimental releases of living mosquitoes, applying principles of good practice in vector biology that protect human health and comfort. We describe specific factors of experimental releases of mosquitoes that we believe are critical to inform institutional biosafety committees and similar review boards to which proposals to conduct mosquito release experiments have been submitted. In this study, “experimental releases” means those that do not significantly increase vector capacity or nuisance biting relative to the unperturbed natural baseline. This document specifically does not address releases of mosquitoes for ongoing control programs or trials of new control methods for which broader assessments of risk are required. It also does not address releases of transgenic or exotic (non-native) mosquito species, both of which require particular regulatory approval. Experimental releases may include females and males and evaluation must consider their effects based on the number released, their genotype and phenotype, the environment into which they are released, and postrelease collection activities. We consider whether increases of disease transmission and nuisance biting might result from proposed experimental releases against the backdrop of natural population size variation. We recommend that experimental releases be conducted in a manner that can be reasonably argued to have insignificant negative effects. Reviewers of proposals for experimental releases should expect applicants to provide such an argument based on evidence from similar studies and their planned activities. This document provides guidance for creating and evaluating such proposals. PMID:29337660

Effect of degree of esterification of pectin and calcium amount on drug release from pectin-based matrix tablets.

PubMed

Sungthongjeen, Srisagul; Sriamornsak, Pornsak; Pitaksuteepong, Tasana; Somsiri, Atawit; Puttipipatkhachorn, Satit

2004-02-12

The aim of this work was to assess the effect of 2 formulation variables, the pectin type (with different degrees of esterification [DEs]) and the amount of calcium, on drug release from pectin-based matrix tablets. Pectin matrix tablets were prepared by blending indomethacin (a model drug), pectin powder, and various amounts of calcium acetate and then tableting by automatic hydraulic press machine. Differential scanning calorimetry, powder x-ray diffraction, and Fourier transformed-infrared spectroscopy studies of the compressed tablets revealed no drug-polymer interaction and the existence of drug with low crystallinity. The in-vitro release studies in phosphate buffer (United States Pharmacopeia) and tris buffer indicated that the lower the DE, the greater the time for 50% of drug release (T50). This finding is probably because of the increased binding capacity of pectin to calcium. However, when the calcium was excluded, the pectins with different DEs showed similar release pattern with insignificant difference of T50. When the amount of calcium acetate was increased from 0 to 12 mg/tablet, the drug release was significantly slower. However, a large amount of added calcium (ie, 24 mg/tablet) produced greater drug release because of the partial disintegration of tablets. The results were more pronounced in phosphate buffer, where the phosphate ions induced the precipitation of calcium phosphate. In conclusion, both pectin type and added calcium affect the drug release from the pectin-based matrix tablets.

ENVIRONMENTALLY-BENIGN POLYTETRAFLUOROETHYLENE (PTFE) COATINGS FOR MOLD RELEASE - PHASE II

EPA Science Inventory

GVD proposes to develop high performance, volatile organic compound (VOC)-free and perfluorooctanoic acid (PFOA)-free, non-stick mold release coatings based on its novel polytetrafluoroethylene (PTFE) fluoropolymer technology. Most commercial mold release agents make use of...

Controlled release from aspirin based linear biodegradable poly(anhydride esters) for anti-inflammatory activity.

PubMed

Dasgupta, Queeny; Movva, Sahitya; Chatterjee, Kaushik; Madras, Giridhar

2017-08-07

This work reports the synthesis of a novel, aspirin-loaded, linear poly (anhydride ester) and provides mechanistic insights into the release of aspirin from this polymer for anti-inflammatory activity. As compared to conventional drug delivery systems that rely on diffusion based release, incorporation of bioactives in the polymer backbone is challenging and high loading is difficult to achieve. In the present study, we exploit the pentafunctional sugar alcohol (xylitol) to provide sites for drug (aspirin) attachment at its non-terminal OH groups. The terminal OH groups are polymerized with a diacid anhydride. The hydrolysis of the anhydride and ester bonds under physiological conditions release aspirin from the matrix. The resulting poly(anhydride ester) has high drug loading (53%) and displays controlled release kinetics of aspirin. The polymer releases 8.5 % and 20%, of the loaded drug in one and four weeks, respectively and has a release rate constant of 0.0035h -0.61 . The release rate is suitable for its use as an anti-inflammatory agent without being cytotoxic. The polymer exhibits good cytocompatibility and anti-inflammatory properties and may find applications as injectable or as an implantable bioactive material. The physical insights into the release mechanism can provide development of other drug loaded polymers. Copyright © 2017 Elsevier B.V. All rights reserved.

Release behavior and bioefficacy of imazethapyr formulations based on biopolymeric hydrogels.

PubMed

Kumar, Vikas; Singh, Anupama; Das, T K; Sarkar, Dhruba Jyoti; Singh, Shashi Bala; Dhaka, Rashmi; Kumar, Anil

2017-06-03

Controlled release formulations of imazethapyr herbicide have been developed employing guar gum-g-cl-polyacrylate/bentonite clay hydrogel composite (GG-HG) and guar gum-g-cl-PNIPAm nano hydrogel (GG-NHG) as carriers, to assess the suitability of biopolymeric hydrogels as controlled herbicide release devices. The kinetics of imazethapyr release from the developed formulations was studied in water and it revealed that the developed formulations of imazethapyr behaved as slow release formulations as compared to commercial formulation. The calculated diffusion exponent (n) values showed that Fickian diffusion was the predominant mechanism of imazethapyr release from the developed formulations. Time for release of half of the loaded imazethapyr (t 1/2 ) ranged between 0.06 and 4.8 days in case of GG-NHG and 4.4 and 12.6 days for the GG-HG formulations. Weed control index (WCI) of GG-HG and GG-NHG formulations was similar to that of the commercial formulation and the herbicidal effect was observed for relatively longer period. Guar gum-based biopolymeric hydrogels in both macro and nano particle size range can serve as potential carriers in developing slow release herbicide formulations.

How controlled release technology can aid gene delivery.

PubMed

Jo, Jun-Ichiro; Tabata, Yasuhiko

2015-01-01

Many types of gene delivery systems have been developed to enhance the level of gene expression. Controlled release technology is a feasible gene delivery system which enables genes to extend the expression duration by maintaining and releasing them at the injection site in a controlled manner. This technology can reduce the adverse effects by the bolus dose administration and avoid the repeated administration. Biodegradable biomaterials are useful as materials for the controlled release-based gene delivery technology and various biodegradable biomaterials have been developed. Controlled release-based gene delivery plays a critical role in a conventional gene therapy and genetic engineering. In the gene therapy, the therapeutic gene is released from biodegradable biomaterial matrices around the tissue to be treated. On the other hand, the intracellular controlled release of gene from the sub-micro-sized matrices is required for genetic engineering. Genetic engineering is feasible for cell transplantation as well as research of stem cells biology and medicine. DNA hydrogel containing a sequence of therapeutic gene and the exosome including the individual specific nucleic acids may become candidates for controlled release carriers. Technologies to deliver genes to cell aggregates will play an important role in the promotion of regenerative research and therapy.

A novel tri-layered buccal mucoadhesive patch for drug delivery: assessment of nicotine delivery.

PubMed

Rao, Shasha; Song, Yunmei; Peddie, Frank; Evans, Allan M

2011-06-01

The aim of this study was to assess the potential of a novel delivery device for administering drugs that suffer from a high degree of first-pass metabolism. A tri-layered buccal mucoadhesive patch, comprising a medicated dry tablet adhered to a mucoadhesive film, was prepared and characterized by its physicochemical properties and mucoadhesive strength. Nicotine was used as a model drug for the characterization of drug release and drug permeation. The influence of different adsorbents on the release of nicotine base from the patches was evaluated in vitro. Different molecular forms of nicotine (base and complex salt) were evaluated for their effect on release performance and permeation in vitro. Results demonstrated acceptable physicochemical and mucoadhesive properties for the tri-layered patch. Rapid release of nicotine was observed when nicotine base was incorporated with calcium sulfate dihydrate as the adsorbent. Patches incorporating nicotine base showed distinct advantages over those containing nicotine polacrilex, in terms of drug release (complete drug release achieved at 30 vs 60 min) and transmucosal permeation (37.28 ± 4.25 vs 2.87 ± 0.26% of the dose permeating through mucosa within 120 min). The novel tri-layered patch can effectively adhere to, and deliver an active ingredient through the buccal mucosa, confirming its potential for buccal mucoadhesive drug delivery. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Drug loading optimization and extended drug delivery of corticoids from pHEMA based soft contact lenses hydrogels via chemical and microstructural modifications.

PubMed

García-Millán, Eva; Koprivnik, Sandra; Otero-Espinar, Francisco Javier

2015-06-20

This paper proposes an approach to improve drug loading capacity and release properties of poly(2-hydroxyethyl methacrylate) (p(HEMA)) soft contact lenses based on the optimization of the hydrogel composition and microstructural modifications using water during the polymerization process. P(HEMA) based soft contact lenses were prepared by thermal or photopolymerization of 2-hydroxyethyl methacrylate (HEMA) solutions containing ethylene glycol di-methacrylate as crosslinker and different proportions of N-vinyl-2-pyrrolidone (NVP) or methacrylic acid (MA) as co-monomers. Transmittance, water uptake, swelling, microstructure, drug absorption isotherms and in vitro release were characterized using triamcinolone acetonide (TA) as model drug. Best drug loading ratios were obtained with lenses containing the highest amount (200 mM) of MA. Incorporation of 40% V/V of water during the polymerization increases the hydrogel porosity giving a better drug loading capacity. In vitro TA release kinetics shows that MA hydrogels released the drug significantly faster than NVP-hydrogels. Drug release was found to be diffusion controlled and kinetics was shown to be reproducible after consecutive drug loading/release processes. Results of p(HEMA) based soft contact lenses copolymerized with ethylene glycol dimethacrylate (EGDMA) and different co-monomers could be a good alternative to optimize the loading and ocular drug delivery of this corticosteroid drug. Copyright © 2015. Published by Elsevier B.V.

Evaluating conditional release in not guilty by reason of insanity acquittees: a prospective follow-up study in Virginia.

PubMed

Vitacco, Michael J; Vauter, Rebecca; Erickson, Steven K; Ragatz, Laurie

2014-08-01

Detailed research on treatment and risk management approaches with not guilty by reason of insanity acquittees (NGRI) during their conditional release is needed as states increasingly use community-based services for these individuals. Grounded in case law, and supported by follow-up studies demonstrating low recidivism rates, states have been encouraged in their efforts to conditionally release NGRI acquittees. The authors evaluated a state-wide sample of 127 NGRI acquittees released into the community after spending a mean of 61.63 months (SD = 76.54) in the hospital. One hundred individuals were committed to the hospital for lengthier treatment (M hospital time = 77.23 months, SD = 79.84), but 27 individuals were released to the community after a relatively short hospital stay (M hospital time = 5.60 months, SD = 3.01). Regarding release, 96 individuals (75.6%) maintained their conditional release. After evaluating a host of demographic and standardized risk data, the following variables predicted revocation on conditional release: previous failure on conditional release, nonadherence with hospital treatment, dangerousness to others, and previous violent charges. A multivariate survival analysis determined criminal behavior and previous failure on conditional release predicted time to revocation. The results of this study demonstrate the importance of considering standardized risk variables in the community-based management of forensic patients. In addition, the data are supportive of continued attempts at moving insanity acquittees from the hospital to the community via conditional release.

Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent.

PubMed

Qin, Lingzhen; Mei, Liling; Shan, Ziyun; Huang, Ying; Pan, Xin; Li, Ge; Gu, Yukun; Wu, Chuanbin

2016-01-01

Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol-solvent-water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48 h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.

Assessment of the suitability of GOCE-based geoid models for the unification of the North American vertical datums

NASA Astrophysics Data System (ADS)

Amjadiparvar, Babak; Sideris, Michael

2015-04-01

Precise gravimetric geoid heights are required when the unification of vertical datums is performed using the Geodetic Boundary Value Problem (GBVP) approach. Five generations of Global Geopotential Models (GGMs) derived from Gravity field and steady-state Ocean Circulation Explorer (GOCE) observations have been computed and released so far (available via IAG's International Centre for Global Earth Models, ICGEM, http://icgem.gfz-potsdam.de/ICGEM/). The performance of many of these models with respect to geoid determination has been studied in order to select the best performing model to be used in height datum unification in North America. More specifically, Release-3, 4 and 5 of the GOCE-based global geopotential models have been evaluated using GNSS-levelling data as independent control values. Comparisons against EGM2008 show that each successive release improves upon the previous one, with Release-5 models showing an improvement over EGM2008 in Canada and CONUS between spherical harmonic degrees 100 and 210. In Alaska and Mexico, a considerable improvement over EGM2008 was brought by the Release-5 models when used up to spherical harmonic degrees of 250 and 280, respectively. The positive impact of the Release-5 models was also felt when a gravimetric geoid was computed using the GOCE-based GGMs together with gravity and topography data in Canada. This geoid model, with appropriately modified Stokes kernel between spherical harmonic degrees 190 and 260, performed better than the official Canadian gravimetric geoid model CGG2013, thus illustrating the advantages of using the latest release GOCE-based models for vertical datum unification in North America.

Extended effective field theory of inflation

NASA Astrophysics Data System (ADS)

Ashoorioon, Amjad; Casadio, Roberto; Cicoli, Michele; Geshnizjani, Ghazal; Kim, Hyung J.

2018-02-01

We present a general framework where the effective field theory of single field inflation is extended by the inclusion of operators with mass dimension 3 and 4 in the unitary gauge. These higher dimensional operators introduce quartic and sextic corrections to the dispersion relation. We study the regime of validity of this extended effective field theory of inflation and the effect of these higher dimensional operators on CMB observables associated with scalar perturbations, such as the speed of sound, the amplitude of the power spectrum and the tensor-to-scalar ratio. Tensor perturbations remain instead, unaltered.

Two-phase flow in short horizontal rectangular microchannels with a height of 300 μm

NASA Astrophysics Data System (ADS)

Chinnov, E. A.; Ron'shin, F. V.; Kabov, O. A.

2015-09-01

The two-phase flow in a narrow short horizontal channel with a rectangular cross section is studied experimentally. The channel has a width of 10, 20, or 30 mm and a height of 300 μm. The specifics of formation of such two-phase flows are investigated. It is demonstrated that the regions of bubble and churn flow regimes grow and constrain the region of jet flow as the channel gets wider. The boundaries of the regions of annular and stratified flow regimes remain almost unaltered.

Bedrock North of Terby Crater

NASA Image and Video Library

2016-06-29

This image samples the excellent bedrock exposures north of Terby Crater, which lies on the northern rim of the giant Hellas basin. An enhanced-color cutout shows a sample of this bedrock, which has a variety of colors and textures. The warm-colored bedrock probably contains hydrated minerals such as clays, whereas the blue-green bedrock is dominated by unaltered mafic minerals. These may be some of the oldest rocks exposed at the Martian surface. Such ancient rocks are extremely rare on Earth. http://photojournal.jpl.nasa.gov/catalog/PIA20737

Photodegradation of selected organics on Mars

NASA Astrophysics Data System (ADS)

ten Kate, I. L.; Boosman, A.; Fornaro, T.; King, H. E.; Kopacz, K. A.; Wolthers, M.

2017-09-01

At least as much as 2.4 million kg of unaltered organic material is estimated to be delivered to the Martian surface each year. However, intense UV irradiation and the highly oxidizing and acidic nature of Martian soil cause degradation of organic compounds. Here we present first results obtained with the recently developed PALLAS facility at Utrecht University. This facility is specifically designed to simulate planetary and asteroid surface conditions to study the photocatalytic properties of relevant planetary minerals. Our results tentatively show degradation of several compounds and preservation of others.

The Future of the Army’s Civilian Workforce: Comparing Projected Inventory with Anticipated Requirements and Estimating Cost Under Different Personnel Policies

DTIC Science & Technology

2014-01-01

person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number...CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT Same as Report (SAR) 18. NUMBER OF PAGES 96 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b...protected under copyright law. Permission is given to duplicate this document for personal use only, as long as it is unaltered and complete. Permission is

Anabolic steroid abuse and tooth size-arch dimensions in the rat.

PubMed

Barrett, R L; Harris, E F; Tolley, E A; Nutting, D F

1993-01-01

Anabolic steroids are misused by adolescents and adults to increase muscle mass and improve appearance and athletic performance. Since anabolics strongly enhance protein synthesis, it was speculated that alterations in tooth size and arch length could occur. This study quantified the effects of the anabolic steroid nandrolone phenpropionate on these parameters in a rat model. The steroid significantly increased mandibular arch length. No difference in mesiodistal dimensions of the molars occurred. In consequence, the increased arch dimensions combined with unaltered tooth size may result in dental spacing and/or other malocclusions.

Tuning the electronic structure of graphene through alkali metal and halogen atom intercalation

NASA Astrophysics Data System (ADS)

Ahmad, Sohail; Miró, Pere; Audiffred, Martha; Heine, Thomas

2018-04-01

The deposition, intercalation and co-intercalation of heavy alkali metals and light halogens atoms in graphene mono- and bilayers have been studied using first principles density-functional calculations. Both the deposition and the intercalation of alkali metals gives rise to n-type doping due to the formation of M+-C- pairs. The co-intercalation of a 1:1 ratio of alkali metals and halogens derives into the formation of ionic pairs among the intercalated species, unaltering the electronic structure of the layered material.

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

PubMed

Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

2016-01-01

Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients' compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box-Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box-Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box-Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms.

A Comparative Study on the Lot Release Systems for Vaccines as of 2016.

PubMed

Fujita, Kentaro; Naito, Seishiro; Ochiai, Masaki; Konda, Toshifumi; Kato, Atsushi

2017-09-25

Many countries have already established their own vaccine lot release system that is designed for each country's situation: while the World Health Organization promotes for the convergence of these regulatory systems so that vaccines of assured quality are provided globally. We conducted a questionnaire-based investigation of the lot release systems for vaccines in 7 countries and 2 regions. We found that a review of the summary protocol by the National Regulatory Authorities was commonly applied for the independent lot release of vaccines, however, we also noted some diversity between countries, especially in regard to the testing policy. Some countries and regions, including Japan, regularly tested every lot of vaccines, whereas the frequency of these tests was reduced in other countries and regions as determined based on the risk assessment of these products. Test items selected for the lot release varied among the countries or regions investigated, although there was a tendency to prioritize the potency tests. An understanding of the lot release policy may contribute to improving and harmonizing the lot release system globally in the future.

Press releases: translating research into news.

PubMed

Woloshin, Steven; Schwartz, Lisa M

2002-06-05

While medical journals strive to ensure accuracy and the acknowledgment of limitations in articles, press releases may not reflect these efforts. Telephone interviews conducted in January 2001 with press officers at 9 prominent medical journals and analysis of press releases (n = 127) about research articles for the 6 issues of each journal preceding the interviews. Seven of the 9 journals routinely issue releases; in each case, the editor with the press office selects articles based on perceived newsworthiness and releases are written by press officers trained in communications. Journals have general guidelines (eg, length) but no standards for acknowledging limitations or for data presentation. Editorial input varies from none to intense. Of the 127 releases analyzed, 29 (23%) noted study limitations and 83 (65%) reported main effects using numbers; 58 reported differences between study groups and of these, 26 (55%) provided the corresponding base rate, the format least prone to exaggeration. Industry funding was noted in only 22% of 23 studies receiving such funding. Press releases do not routinely highlight study limitations or the role of industry funding. Data are often presented using formats that may exaggerate the perceived importance of findings.

Development of an osmotic pump system for controlled delivery of diclofenac sodium.

PubMed

Emara, L H; Taha, N F; Badr, R M; Mursi, N M

2012-10-01

Based on an elementary osmotic pump, controlled release systems of diclofenac sodium (DS) were designed to deliver the drug in a zero-order release pattern. Osmotic pump tablets containing 100 mg DS were prepared and coated with either semipermeable (SPM) or microporous (PM) membranes. The tablet coats were composed of hydrophobic triacetin (TA) or hydrophilic polyethylene glycol 400 (PEG 400) incorporated in cellulose acetate (CA) solution, for SPM and PM, respectively. Variable tablet core compositions such as swelling polymers (PEO and HPMC) and osmotic agents (lactose, NaCl, and KCl) were studied. An optimized, sensitive and well controlled in vitro release design, based on the flow-through cell (FTC), was utilized to discriminate between preparations. The results revealed that the presence of PEG 400 in the coating membrane accelerated the drug release rate, while TA suppressed the release rate of DS. In the case of SPM, the amount of DS released was inversely proportional to the membrane thickness, where 5% (w/w) weight gain gave a higher DS release rate than 10% (w/w). Results of different tablet core compositions revealed that the release rate of DS decreased as PEO molecular weight increased. HPMC K15M showed the lowest DS release rate. The presence of lactose, KCl, or NaCl pronouncedly affected DS release rate depending on polymer type in the core. Scanning electron microscopy (SEM) confirmed formation of pores in the membrane that accounts for faster DS release rate. These results revealed that DS could be formulated as an osmotic pump system with a prolonged, zero-order release pattern.

Synthesis and Characterization of Chlorpyrifos/Copper(II) Schiff Base Mesoporous Silica with pH Sensitivity for Pesticide Sustained Release.

PubMed

Chen, Huayao; Lin, Yueshun; Zhou, Hongjun; Zhou, Xinhua; Gong, Sheng; Xu, Hua

2016-11-02

The salicylaldehyde-modified mesoporous silica (SA-MCM-41) was prepared through a co-condensation method. Through the bridge effect from the copper ion, which also acts as the nutrition of the plant, the model drug chlorpyrifos (CH) was supported on the copper(II) Schiff base mesoporous silica (Cu-MCM-41) to form a highly efficient sustained-release system (CH-Cu-MCM-41) for pesticide delivery. The experimental results showed that the larger the concentration of the copper ion, the more adsorption capacity (AC) of Cu-MCM-41 for chlorpyrifos and the smaller its release rate. The results confirmed the existence of a coordination bond between SA-MCM-41 and copper ions as well as a coordination bond between Cu-MCM-41 and chlorpyrifos. The AC of SA-MCM-41 is 106 mg/g, while that of Cu-MCM-41 is 295 mg/g. The as-synthesized system showed significant pH sensitivity. Under the condition of pH ≤ 7, the release rate of chlorpyrifos decreased with increasing pH, whereas its release rate in weak base conditions was slightly larger than that in weak acid conditions. Meanwhile, the drug release rate of the as-synthesized system was also affected by the temperature. Their sustained-release curves can be described by the Korsmeyer-Peppas equation.

Potential applications for halloysite nanotubes based drug delivery systems

NASA Astrophysics Data System (ADS)

Sun, Lin

Drug delivery refers to approaches, formulations, technologies, and systems for transporting a drug in the body. The purpose is to enhance the drug efficacy and to reduce side reactions, which can significantly improve treatment outcomes. Halloysite is a naturally occurred alumino-silicate clay with a tubular structure. It is a biocompatible material with a big surface area which can be used for attachment of targeted molecules. Besides, loaded molecules can present a sustained release manner in solution. These properties make halloysite nanotubes (HNTs) a good option for drug delivery. In this study, a drug delivery system was built based on halloysite via three different fabrication methods: physical adsorption, vacuum loading and layer-by-layer coating. Methotrexate was used as the model drug. Factors that may affect performance in both drug loading and release were tested. Results showed that methotrexate could be incorporated within the HNTs system and released in a sustained manner. Layer-by-layer coating showed a better potential than the other two methods in both MTX loading and release. Besides, lower pH could greatly improve MTX loading and release while the increased number of polyelectrolytes bilayers had a limited impact. Osteosarcoma is the most common primary bone malignancy in children and adolescents. Postoperative recurrence and metastasis has become one of the leading causes for patient death after surgical remove of the tumor mass. A strategy could be a sustained release of chemotherapeutics directly at the primary tumor sites where recurrence would mostly occur. Then, this HNTs based system was tested with osteosarcoma cells in vitro to show the potential of delivering chemotherapeutics in the treatment of osteosarcoma. Methotrexate was incorporated within HNTs with a layer-bylayer coating technique, and drug coated HNTs were filled into nylon-6 which is a common material for surgical sutures in industry. Results showed that (1) methotrexate could be released in a sustained manner; (2) cytotoxicity test confirmed the biocompatibility of HNTs and methotrexate coated HNTs; (3) proliferation test confirmed the growth inhibition of released methotrexate on osteosarcoma cells; and (4) nylon-6 could prolong the sustained release of methotrexate from polyelectrolytes coated HNTs. Another application comes from the prevention of surgical site infection. It is a common complication in surgery, which may prolong hospital stay, increase mortality rate, and cause additional financial burden for patients. By directly releasing antibiotics at the surgical site, it is supposed to enhance the drug efficacy and improve the treatment outcome. Therefore, the same HNTs based system was tested with E. coli in vitro to show the potential of delivering antibiotics to enhance the prevention of surgical site infection. Nitrofurantoin was incorporated within HNTs using the layer-by-layer coating technique, and the drug coated HNTs were filled into nylon-6 again. Results showed that (1) nitrofurantoin could be incorporated with this HNTs based drug delivery system, and released in a sustained manner; (2) nylon-6 could prolong the sustained release of nitrofurantoin from polyelectrolytes coated HNTs; and (3) released nitrofurantoin could severely inhibit E. coil growth. Therefore, a tunable drug delivery system based on HNTs was developed, and a great potential of medical application in drug delivery was shown.

Nickel Ion Release from Three Types of Nickel-titanium-based Orthodontic Archwires in the As-received State and After Oral Simulation

PubMed Central

Ramazanzadeh, Barat Ali; Ahrari, Farzaneh; Sabzevari, Berahman; Habibi, Samaneh

2014-01-01

Background and aims. This study aimed to investigate release of nickel ion from three types of nickel-titanium-based wires in the as-received state and after immersion in a simulated oral environment. Materials and methods. Forty specimens from each of the single-strand NiTi (Rematitan "Lite"), multi-strand NiTi (SPEED Supercable) and Copper NiTi (Damon Copper NiTi) were selected. Twenty specimens from each type were used in the as-received state and the others were kept in deflected state at 37ºC for 2 months followed by autoclave sterilization. The as-received and recycled wire specimens were immersed in glass bottles containing 1.8 mL of artificial saliva for 28 days and the amount of nickel ion released into the electrolyte was determined using atomic absorption spectrophotometry. Results. The single-strand NiTi released the highest quantity of nickel ion in the as-received state and the multi-strand NiTi showed the highest ion release after oral simulation. The quantity of nickelion released from Damon Copper NiTi was the lowest in both conditions. Oral simulation followed by sterilization did not have a significant influence on nickel ion release from multi-strand NiTi and Damon Copper NiTi wires, but single-strand NiTi released statistically lower quantities of nickel ion after oral simulation. Conclusion. The multi-strand nature of Supercable did not enhance the potential of corrosion after immersion in the simulated oral environment. In vitro use of nickel-titanium-based archwires followed by sterilization did not significantly increase the amount of nickel ion released from these wires. PMID:25093049

A model-based method for estimating Ca2+ release fluxes from linescan images in Xenopus oocytes.

PubMed

Baran, Irina; Popescu, Anca

2009-09-01

We propose a model-based method of interpreting linescan images observed in Xenopus oocytes with the use of Oregon Green-1 as a fluorescent dye. We use a detailed modeling formalism based on numerical simulations that incorporate physical barriers for local diffusion, and, by assuming a Gaussian distribution of release durations, we derive the distributions of release Ca(2+) amounts and currents, fluorescence amplitudes, and puff widths. We analyze a wide set of available data collected from 857 and 281 events observed in the animal and the vegetal hemispheres of the oocyte, respectively. A relatively small fraction of events appear to involve coupling of two or three adjacent clusters of Ca(2+) releasing channels. In the animal hemisphere, the distribution of release currents with a mean of 1.4 pA presents a maximum at 1.0 pA and a rather long tail extending up to 5 pA. The overall distribution of liberated Ca(2+) amounts exhibits a dominant peak at 120 fC, a smaller peak at 375 fC, and an average of 166 fC. Ca(2+) amounts and release fluxes in the vegetal hemisphere appear to be 3.6 and 1.6 times smaller than in the animal hemisphere, respectively. Predicted diameters of elemental release sites are approximately 1.0 microm in the animal and approximately 0.5 microm in the vegetal hemisphere, but the side-to-side separation between adjacent sites appears to be identical (approximately 0.4 microm). By fitting the model to individual puffs we can estimate the quantity of liberated calcium, the release current, the orientation of the scan line, and the dimension of the corresponding release site.

Development of theophylline sustained release dosage form based on Kollidon SR.

PubMed

Reza, Md Selim; Quadir, Mohiuddin Abdul; Haider, Syed Shabbir

2002-01-01

Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Four matrix tablet formulations were prepared by dry blending and direct compression of Kollidon SR and HPMC-15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage of theophylline. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release with an initial burst effect. Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug with subsequent minimization of burst effect as confirmed by mean dissolution time, T50 and Higuchi release rate data. Among the batches containing HPMC-15 cps, a direct relationship was obtained between release rate and the percentage of HPMC used. A suitable controlled release profile was obtained with the matrix tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed close resemblance to commercial products and compliance with USP specification. The results were explored and explained by the difference of physico-chemical property and hydration characteristics of the polymers. In addition to this result, the exponential model was applied to characterize the drug release behaviour from polymeric systems. It was found that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an important role in the release of drug from HPMC containing tablets with a trend towards zero-order or case II release. In vitro release profile of two commercial brands were also undertaken for comparison and modulation of the experimental batches.

Reducing the Use of Agrochemicals: A Simple Experiment

ERIC Educational Resources Information Center

Vidal, M. M.; Filipe, Olga M. S.; Costa, M. C. Cruz

2006-01-01

An experiment was performed on polymeric-based controlled-release agrochemicals that minimize leaching into groundwater while maintaining an adequate quantity for the desired agrochemical benefits. Gelatin gel containing inorganic Phosphorous provides controlled-release of an agrochemical where release curves show a linear relationship between…

Semi-Passive Oxidation-Based Approaches for Control of Large, Dilute Groundwater Plumes of Chlorinated Ethylenes

DTIC Science & Technology

2014-04-01

Permanganate gel (PG) for groundwater remediation: Compatibility, gelation, and release characteristics...26 4.4. Development and characterization of slow-release permanganate gel (SRP-G) for groundwater remediation...34 4.6. Geopolymers as slow-release materials for potassium permanganate

Preparation and in vitro evaluation of xanthan gum facilitated superabsorbent polymeric microspheres.

PubMed

Bhattacharya, Shiv Sankar; Mazahir, Farhan; Banerjee, Subham; Verma, Anurag; Ghosh, Amitava

2013-10-15

Interpenetrating polymer network (IPN) hydrogel microspheres of xanthan gum (XG) based superabsorbent polymer (SAP) and poly(vinyl alcohol) (PVA) were prepared by water-in-oil (w/o) emulsion crosslinking method for sustained release of ciprofloxacin hydrochloride (CIPRO). The microspheres were prepared with various ratios of hydrolyzed SAP to PVA and extent of crosslinking density. The prepared microspheres with loose and rigid surfaces were evidenced by scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the IPN formation. Differential scanning calorimetry (DSC) study was performed to understand the dispersion nature of drug after encapsulation. The in vitro drug release study was extensively evaluated depending on the process variables in both acidic and alkaline media. All the formulations exhibited satisfactory physicochemical and in vitro release characteristics. Release data indicated a non-Fickian trend of drug release from the formulations. Based on the results, this study suggest that CIPRO loaded IPN microspheres were suitable for sustained release application. Copyright © 2013 Elsevier Ltd. All rights reserved.

Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

PubMed

Shenderovich, Julia; Feldman, Mark; Kirmayer, David; Al-Quntar, Abed; Steinberg, Doron; Lavy, Eran; Friedman, Michael

2015-05-15

Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

PubMed Central

Kim, Min Soo; Yeom, Dong Woo; Kim, Sung Rae; Yoon, Ho Yub; Kim, Chang Hyun; Son, Ho Yong; Kim, Jin Han; Lee, Sangkil; Choi, Young Wook

2017-01-01

A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD. PMID:28053506

Understanding and Predicting the Process of Software Maintenance Releases

NASA Technical Reports Server (NTRS)

Basili, Victor; Briand, Lionel; Condon, Steven; Kim, Yong-Mi; Melo, Walcelio L.; Valett, Jon D.

1996-01-01

One of the major concerns of any maintenance organization is to understand and estimate the cost of maintenance releases of software systems. Planning the next release so as to maximize the increase in functionality and the improvement in quality are vital to successful maintenance management. The objective of this paper is to present the results of a case study in which an incremental approach was used to better understand the effort distribution of releases and build a predictive effort model for software maintenance releases. This study was conducted in the Flight Dynamics Division (FDD) of NASA Goddard Space Flight Center(GSFC). This paper presents three main results: 1) a predictive effort model developed for the FDD's software maintenance release process; 2) measurement-based lessons learned about the maintenance process in the FDD; and 3) a set of lessons learned about the establishment of a measurement-based software maintenance improvement program. In addition, this study provides insights and guidelines for obtaining similar results in other maintenance organizations.

Reported implementation lessons from a national quality improvement initiative; Productive Ward: Releasing Time to Care™. A qualitative, ward-based team perspective.

PubMed

White, Mark; Butterworth, Tony; Wells, John S G

2017-10-01

To explore the experiences of participants involved in the implementation of the Productive Ward: Releasing Time to Care™ initiative in Ireland, identifying key implementation lessons. A large-scale quality improvement programme Productive Ward: Releasing Time to Care™ was introduced nationwide into Ireland in 2011. We captured accounts from ward-based teams in an implementation phase during 2013-14 to explore their experiences. Semi-structured, in-depth interviews with a purposive sample of 24 members of ward-based teams from nine sites involved in the second national phase of the initiative were conducted. Interviews were analysed and coded under themes, using a seven-stage iterative process. The predominant theme identified was associated with the implementation and management of the initiative and included: project management; training; preparation; information and communication; and participant's negative experiences. The most prominent challenge reported related to other competing clinical priorities. Despite the structured approach of Productive Ward: Releasing Time to Care™, it appears that overstretched and busy clinical environments struggle to provide the right climate and context for ward-based teams to engage and interact actively with quality improvement tools, methods and activities. Findings highlight five key aspects of implementation and management that will help facilitate successful adoption of large-scale, ward-based quality improvement programmes such as Productive Ward: Releasing Time to Care™. Utilising pre-existing implementation or quality frameworks to assess each ward/unit for 'readiness' prior to commencing a quality improvement intervention such as Productive Ward: Releasing Time to Care™ should be considered. © 2017 John Wiley & Sons Ltd.

Release of Gd-ions from peralkaline borosilicate glass in pure water for neutrino detection in Water-Cherenkov Detectors

NASA Astrophysics Data System (ADS)

Dongol, R.; Sundaram, S. K.

2017-09-01

The addition of Gadolinium (Gd)-based salt, specially GdCl3, in the Water Cherenkov Detectors (WCDs) enhances the sensitivity to neutrino detection. However, the unwanted Cl-based byproducts, significantly reduces the transparency of water and sensitivity of WCDs. An alternative method, to introduce Gd-ions in the WCDs, is through Gd-release from a custom designed Gd-doped glass, when in contact with water. This can potentially eliminate the use of Gd-based salts and byproducts. In this work, we report the Gd-ions release for a Gd-doped peralkaline (Na/Al > 1) borosilicate glass, which closely represents photomultiplier tube (PMT) glass composition used in WCDs. The purpose of the paper is to show that the Gd-ion release from a custom designed glass in the form of beads or powders is feasible and could be used as a controlled Gd-source in future WCDs to enhance neutrino detection. In addition, we present our results of Gd-solubility in the base glass composition.