Sample records for rapidly reversible decrease

  1. Reversion phenomena of Cu-Cr alloys

    NASA Technical Reports Server (NTRS)

    Nishikawa, S.; Nagata, K.; Kobayashi, S.

    1985-01-01

    Cu-Cr alloys which were given various aging and reversion treatments were investigated in terms of electrical resistivity and hardness. Transmission electron microscopy was one technique employed. Some results obtained are as follows: the increment of electrical resistivity after the reversion at a constant temperature decreases as the aging temperature rises. In a constant aging condition, the increment of electrical resistivity after the reversion increases, and the time required for a maximum reversion becomes shorter as the reversion temperature rises. The reversion phenomena can be repeated, but its amount decreases rapidly by repetition. At first, the amount of reversion increases with aging time and reaches its maximum, and then tends to decrease again. Hardness changes by the reversion are very small, but the hardness tends to soften slightly. Any changes in transmission electron micrographs by the reversion treatment cannot be detected.

  2. Photoinduced local heating in silica photonic crystals for fast and reversible switching.

    PubMed

    Gallego-Gómez, Francisco; Blanco, Alvaro; López, Cefe

    2012-12-04

    Fast and reversible photonic-bandgap tunability is achieved in silica artificial opals by local heating. The effect is fully reversible as heat rapidly dissipates through the non-irradiated structure without active cooling and water is readsorbed. The performance is strongly enhanced by decreasing the photoirradiated opal volume, allowing bandgap shifts of 12 nm and response times of 20 ms. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Changes in earth's dipole.

    PubMed

    Olson, Peter; Amit, Hagay

    2006-11-01

    The dipole moment of Earth's magnetic field has decreased by nearly 9% over the past 150 years and by about 30% over the past 2,000 years according to archeomagnetic measurements. Here, we explore the causes and the implications of this rapid change. Maps of the geomagnetic field on the core-mantle boundary derived from ground-based and satellite measurements reveal that most of the present episode of dipole moment decrease originates in the southern hemisphere. Weakening and equatorward advection of normal polarity magnetic field by the core flow, combined with proliferation and growth of regions where the magnetic polarity is reversed, are reducing the dipole moment on the core-mantle boundary. Growth of these reversed flux regions has occurred over the past century or longer and is associated with the expansion of the South Atlantic Anomaly, a low-intensity region in the geomagnetic field that presents a radiation hazard at satellite altitudes. We address the speculation that the present episode of dipole moment decrease is a precursor to the next geomagnetic polarity reversal. The paleomagnetic record contains a broad spectrum of dipole moment fluctuations with polarity reversals typically occurring during dipole moment lows. However, the dipole moment is stronger today than its long time average, indicating that polarity reversal is not likely unless the current episode of moment decrease continues for a thousand years or more.

  4. Spontaneous breaking of time-reversal symmetry in strongly interacting two-dimensional electron layers in silicon and germanium.

    PubMed

    Shamim, S; Mahapatra, S; Scappucci, G; Klesse, W M; Simmons, M Y; Ghosh, A

    2014-06-13

    We report experimental evidence of a remarkable spontaneous time-reversal symmetry breaking in two-dimensional electron systems formed by atomically confined doping of phosphorus (P) atoms inside bulk crystalline silicon (Si) and germanium (Ge). Weak localization corrections to the conductivity and the universal conductance fluctuations were both found to decrease rapidly with decreasing doping in the Si:P and Ge:P delta layers, suggesting an effect driven by Coulomb interactions. In-plane magnetotransport measurements indicate the presence of intrinsic local spin fluctuations at low doping, providing a microscopic mechanism for spontaneous lifting of the time-reversal symmetry. Our experiments suggest the emergence of a new many-body quantum state when two-dimensional electrons are confined to narrow half-filled impurity bands.

  5. Andexanet alfa effectively reverses edoxaban anticoagulation effects and associated bleeding in a rabbit acute hemorrhage model

    PubMed Central

    Lu, Genmin; Pine, Polly; Leeds, Janet M.; DeGuzman, Francis; Pratikhya, Pratikhya; Lin, Joyce; Malinowski, John; Hollenbach, Stanley J.; Curnutte, John T.

    2018-01-01

    Introduction Increasing use of factor Xa (FXa) inhibitors necessitates effective reversal agents to manage bleeding. Andexanet alfa, a novel modified recombinant human FXa, rapidly reverses the anticoagulation effects of direct and indirect FXa inhibitors. Objective To evaluate the ability of andexanet to reverse anticoagulation in vitro and reduce bleeding in rabbits administered edoxaban. Materials and methods In vitro studies characterized the interaction of andexanet with edoxaban and its ability to reverse edoxaban-mediated anti-FXa activity. In a rabbit model of surgically induced, acute hemorrhage, animals received edoxaban vehicle+andexanet vehicle (control), edoxaban (1 mg/kg)+andexanet vehicle, edoxaban+andexanet (75 mg, 5-minute infusion, 20 minutes after edoxaban), or edoxaban vehicle+andexanet prior to injury. Results Andexanet bound edoxaban with high affinity similar to FXa. Andexanet rapidly and dose-dependently reversed the effects of edoxaban on FXa activity and coagulation pharmacodynamic parameters in vitro. In edoxaban-anticoagulated rabbits, andexanet reduced anti-FXa activity by 82% (from 548±87 to 100±41 ng/ml; P<0.0001), mean unbound edoxaban plasma concentration by ~80% (from 100±10 to 21±6 ng/ml; P<0.0001), and blood loss by 80% vs. vehicle (adjusted for control, 2.6 vs. 12.9 g; P = 0.003). The reduction in blood loss correlated with the decrease in anti-FXa activity (r = 0.6993, P<0.0001) and unbound edoxaban (r = 0.5951, P = 0.0035). Conclusion These data demonstrate that andexanet rapidly reversed the anticoagulant effects of edoxaban, suggesting it could be clinically valuable for the management of acute and surgery-related bleeding. Correlation of blood loss with anti-FXa activity supports the use of anti-FXa activity as a biomarker for assessing anticoagulation reversal in clinical trials. PMID:29590221

  6. Nonbehavioral Selection for Pawns, Mutants of PARAMECIUM AURELIA with Decreased Excitability

    PubMed Central

    Schein, Stanley J.

    1976-01-01

    The reversal response in Paramecium aurelia is mediated by calcium which carries the inward current during excitation. Electrophysiological studies indicate that strontium and barium can also carry the inward current. Exposure to high concentrations of barium rapidly paralyzes and later kills wild-type paramecia. Following mutagenesis with nitrosoguanidine, seven mutants which continued to swim in the `high-barium' solution were selected. All of the mutants show decreased reversal behavior, with phenotypes ranging from extremely non-reversing (`extreme' pawns) to nearly wild-type reversal behavior (`partial' pawns). The mutations fall into three complementation groups, identical to the pwA, pwB, and pwC genes of Kung et al. (1975). All of the pwA and pwB mutants withstand longer exposure to barium, the pwB mutants surviving longer than the pwA mutants. Among mutants of each gene, survival is correlated with loss of reversal behavior. Double mutants (A–B, A–C, B–C), identified in the exautogamous progeny of crosses between `partial' mutants, exhibited a more extreme non-reversing phenotype than either of their single-mutant (`partial' pawn) parents.———Inability to reverse could be expected from an alteration in the calcium-activated reversal mechanism or in excitation. A normal calcium-activated structure was demonstrated in all pawns by chlorpromazine treatment. In a separate report (Schein, Bennett and Katz 1976) the results of electrophysiological investigations directly demonstrate decreased excitability in all of the mutants, a decrease due to an altered calcium activation. The studies of the genetics, the survival in barium and the electro-physiology of the pawns demonstrate that the pwA and pwB genes have different effects on calcium activation. PMID:1001878

  7. Effects of cooling rate on particle rearrangement statistics: Rapidly cooled glasses are more ductile and less reversible.

    PubMed

    Fan, Meng; Wang, Minglei; Zhang, Kai; Liu, Yanhui; Schroers, Jan; Shattuck, Mark D; O'Hern, Corey S

    2017-02-01

    Amorphous solids, such as metallic, polymeric, and colloidal glasses, display complex spatiotemporal response to applied deformations. In contrast to crystalline solids, during loading, amorphous solids exhibit a smooth crossover from elastic response to plastic flow. In this study, we investigate the mechanical response of binary Lennard-Jones glasses to athermal, quasistatic pure shear as a function of the cooling rate used to prepare them. We find several key results concerning the connection between strain-induced particle rearrangements and mechanical response. We show that the energy loss per strain dU_{loss}/dγ caused by particle rearrangements for more rapidly cooled glasses is larger than that for slowly cooled glasses. We also find that the cumulative energy loss U_{loss} can be used to predict the ductility of glasses even in the putative linear regime of stress versus strain. U_{loss} increases (and the ratio of shear to bulk moduli decreases) with increasing cooling rate, indicating enhanced ductility. In addition, we characterized the degree of reversibility of particle motion during a single shear cycle. We find that irreversible particle motion occurs even in the linear regime of stress versus strain. However, slowly cooled glasses, which undergo smaller rearrangements, are more reversible during a single shear cycle than rapidly cooled glasses. Thus, we show that more ductile glasses are also less reversible.

  8. Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit

    PubMed Central

    Chao, Michael Y.; Komatsu, Hidetoshi; Fukuto, Hana S.; Dionne, Heather M.; Hart, Anne C.

    2004-01-01

    Serotonin (5-HT) modulates synaptic efficacy in the nervous system of vertebrates and invertebrates. In the nematode Caenorhabditis elegans, many behaviors are regulated by 5-HT levels, which are in turn regulated by the presence or absence of food. Here, we show that both food and 5-HT signaling modulate chemosensory avoidance response of octanol in C. elegans, and that this modulation is both rapid and reversible. Sensitivity to octanol is decreased when animals are off food or when 5-HT levels are decreased; conversely, sensitivity is increased when animals are on food or have increased 5-HT signaling. Laser microsurgery and behavioral experiments reveal that sensory input from different subsets of octanol-sensing neurons is selectively used, depending on stimulus strength, feeding status, and 5-HT levels. 5-HT directly targets at least one pair of sensory neurons, and 5-HT signaling requires the Gα protein GPA-11. Glutamatergic signaling is required for response to octanol, and the GLR-1 glutamate receptor plays an important role in behavioral response off food but not on food. Our results demonstrate that 5-HT modulation of neuronal activity via G protein signaling underlies behavioral plasticity by rapidly altering the functional circuitry of a chemosensory circuit. PMID:15492222

  9. Effectiveness of hemodialysis in a case of severe valproate overdose.

    PubMed

    Nasa, Prashant; Sehrawat, Deepak; Kansal, Sudha; Chawla, Rajesh

    2011-04-01

    A case of severe sodium valproate overdose is presented in which medicinal management failed to reverse coma of the patient. High-flux hemodialysis was then used to eliminate sodium valproate. This case demonstrated the effectiveness of hemodialysis in not only decreasing valproate levels very rapidly but also as an effective anti-coma management.

  10. Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders.

    PubMed

    Jensen, Brigid K; Monnerie, Hubert; Mannell, Maggie V; Gannon, Patrick J; Espinoza, Cagla Akay; Erickson, Michelle A; Bruce-Keller, Annadora J; Gelman, Benjamin B; Briand, Lisa A; Pierce, R Christopher; Jordan-Sciutto, Kelly L; Grinspan, Judith B

    2015-11-01

    Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors ritonavir or lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed after drug removal. Conversely, nucleoside reverse transcriptase inhibitor zidovudine had no effect. Furthermore, in vivo ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity and have implications for myelination in juvenile HIV patients and myelin maintenance in adults on lifelong therapy.

  11. Effectiveness of hemodialysis in a case of severe valproate overdose

    PubMed Central

    Nasa, Prashant; Sehrawat, Deepak; Kansal, Sudha; Chawla, Rajesh

    2011-01-01

    A case of severe sodium valproate overdose is presented in which medicinal management failed to reverse coma of the patient. High-flux hemodialysis was then used to eliminate sodium valproate. This case demonstrated the effectiveness of hemodialysis in not only decreasing valproate levels very rapidly but also as an effective anti-coma management. PMID:21814378

  12. Dynamical similarity of geomagnetic field reversals.

    PubMed

    Valet, Jean-Pierre; Fournier, Alexandre; Courtillot, Vincent; Herrero-Bervera, Emilio

    2012-10-04

    No consensus has been reached so far on the properties of the geomagnetic field during reversals or on the main features that might reveal its dynamics. A main characteristic of the reversing field is a large decrease in the axial dipole and the dominant role of non-dipole components. Other features strongly depend on whether they are derived from sedimentary or volcanic records. Only thermal remanent magnetization of lava flows can capture faithful records of a rapidly varying non-dipole field, but, because of episodic volcanic activity, sequences of overlying flows yield incomplete records. Here we show that the ten most detailed volcanic records of reversals can be matched in a very satisfactory way, under the assumption of a common duration, revealing common dynamical characteristics. We infer that the reversal process has remained unchanged, with the same time constants and durations, at least since 180 million years ago. We propose that the reversing field is characterized by three successive phases: a precursory event, a 180° polarity switch and a rebound. The first and third phases reflect the emergence of the non-dipole field with large-amplitude secular variation. They are rarely both recorded at the same site owing to the rapidly changing field geometry and last for less than 2,500 years. The actual transit between the two polarities does not last longer than 1,000 years and might therefore result from mechanisms other than those governing normal secular variation. Such changes are too brief to be accurately recorded by most sediments.

  13. Optimizing third molar autotransplantation: applications of reverse-engineered surgical templates and rapid prototyping of three-dimensional teeth.

    PubMed

    Park, Ji-Man; Tatad, Jacquiline Czar I; Landayan, Maria Erika A; Heo, Seong-Joo; Kim, Sun-Jong

    2014-09-01

    The success of autogenous tooth transplantation depends on the vitality of the periodontal ligament attached to the donor tooth, and its viability decreases when it is exposed extraorally. This report describes the case of a 16-year-old patient in whom a rapid prototyped tooth model was performed using cone-beam technology and a surgical template guide for autotransplantation as an effective technique for a critical time-based procedure. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Inhaled hydrogen sulfide: a rapidly reversible inhibitor of cardiac and metabolic function in the mouse.

    PubMed

    Volpato, Gian Paolo; Searles, Robert; Yu, Binglan; Scherrer-Crosbie, Marielle; Bloch, Kenneth D; Ichinose, Fumito; Zapol, Warren M

    2008-04-01

    Breathing hydrogen sulfide (H2S) has been reported to induce a suspended animation-like state with hypothermia and a concomitant metabolic reduction in rodents. However, the impact of H2S breathing on cardiovascular function remains incompletely understood. In this study, the authors investigated the cardiovascular and metabolic effects of inhaled H2S in a murine model. The impact of breathing H2S on cardiovascular function was examined using telemetry and echocardiography in awake mice. The effects of breathing H2S on carbon dioxide production and oxygen consumption were measured at room temperature and in a warmed environment. Breathing H2S at 80 parts per million by volume at 27 degrees C ambient temperature for 6 h markedly reduced heart rate, core body temperature, respiratory rate, and physical activity, whereas blood pressure remained unchanged. Echocardiography demonstrated that H2S exposure decreased both heart rate and cardiac output but preserved stroke volume. Breathing H2S for 6 h at 35 degrees C ambient temperature (to prevent hypothermia) decreased heart rate, physical activity, respiratory rate, and cardiac output without altering stroke volume or body temperature. H2S breathing seems to induce bradycardia by depressing sinus node activity. Breathing H2S for 30 min decreased whole body oxygen consumption and carbon dioxide production at either 27 degrees or 35 degrees C ambient temperature. Both parameters returned to baseline levels within 10 min after the cessation of H2S breathing. Inhalation of H2S at either 27 degrees or 35 degrees C reversibly depresses cardiovascular function without changing blood pressure in mice. Breathing H2S also induces a rapidly reversible reduction of metabolic rate at either body temperature.

  15. Changes in Students' Choice Determinants in Poland: A Comparative Study of Tertiary Business Education between 2008 and 2013

    ERIC Educational Resources Information Center

    Sojkin, Bogdan; Bartkowiak, Pawel; Skuza, Agnieszka

    2015-01-01

    For the last 20 years Polish education faced turbulent changes, first experiencing a rapid increase in the number of students and the dynamic growth of educational institutions, and then facing the reverse trend of decreasing number of students and universities being closed down or facing serious financial problems. Furthermore, forecasts for the…

  16. An insert-based enzymatic cell culture system to rapidly and reversibly induce hypoxia: investigations of hypoxia-induced cell damage, protein expression and phosphorylation in neuronal IMR-32 cells

    PubMed Central

    Huang, Ying; Zitta, Karina; Bein, Berthold; Steinfath, Markus; Albrecht, Martin

    2013-01-01

    SUMMARY Ischemia-reperfusion injury and tissue hypoxia are of high clinical relevance because they are associated with various pathophysiological conditions such as myocardial infarction and stroke. Nevertheless, the underlying mechanisms causing cell damage are still not fully understood, which is at least partially due to the lack of cell culture systems for the induction of rapid and transient hypoxic conditions. The aim of the study was to establish a model that is suitable for the investigation of cellular and molecular effects associated with transient and long-term hypoxia and to gain insights into hypoxia-mediated mechanisms employing a neuronal culture system. A semipermeable membrane insert system in combination with the hypoxia-inducing enzymes glucose oxidase and catalase was employed to rapidly and reversibly generate hypoxic conditions in the culture medium. Hydrogen peroxide assays, glucose measurements and western blotting were performed to validate the system and to evaluate the effects of the generated hypoxia on neuronal IMR-32 cells. Using the insert-based two-enzyme model, hypoxic conditions were rapidly induced in the culture medium. Glucose concentrations gradually decreased, whereas levels of hydrogen peroxide were not altered. Moreover, a rapid and reversible (onoff) generation of hypoxia could be performed by the addition and subsequent removal of the enzyme-containing inserts. Employing neuronal IMR-32 cells, we showed that 3 hours of hypoxia led to morphological signs of cellular damage and significantly increased levels of lactate dehydrogenase (a biochemical marker of cell damage). Hypoxic conditions also increased the amounts of cellular procaspase-3 and catalase as well as phosphorylation of the pro-survival kinase Akt, but not Erk1/2 or STAT5. In summary, we present a novel framework for investigating hypoxia-mediated mechanisms at the cellular level. We claim that the model, the first of its kind, enables researchers to rapidly and reversibly induce hypoxic conditions in vitro without unwanted interference of the hypoxia-inducing agent on the cultured cells. The system could help to further unravel hypoxia-associated mechanisms that are clinically relevant in various tissues and organs. PMID:24046359

  17. Nitric oxide contributes to substance P-induced increases in lung rapidly adapting receptor activity in guinea-pigs.

    PubMed Central

    Joad, J P; Kott, K S; Bonham, A C

    1997-01-01

    1. Substance P induces fluid flux via nitric oxide, and fluid flux stimulates lung rapidly adapting receptors (RARs). We therefore proposed that nitric oxide contributes to substance P-evoked increases in RAR activity. Since substance P decreases dynamic compliance (Cdyn), which can stimulate RARs, we also determined whether nitric oxide contributed to substance P-induced effects on pulmonary function. 2. In anaesthetized guinea-pigs, the effects of substance P on RAR activity, Cdyn, pulmonary resistance (RL), and arterial blood pressure were measured before and after i.v. infusion of NG-methyl-L-arginine (L-NMMA; a nitric oxide synthase inhibitor), or L-NMMA followed by L-arginine (a nitric oxide precursor which reverses the effects of L-NMMA). 3. Substance P-evoked increases in RAR activity were blunted by L-NMMA (P = 0.006) but not by L-NMMA-L-arginine (P = 0.42). 4. Substance P-evoked decreases in Cdyn were slightly inhibited by L-NMMA (P = 0.02) and slightly enhanced by L-NMMA-L-arginine (P = 0.004). However, at the time at which L-NMMA maximally reduced substance P-induced RAR stimulation (the first 30 s), it did not change substance P-induced decreases in Cdyn. 5. Substance P-evoked increases in RL were not changed by L-NMMA (P = 0.10) and were enhanced by L-NMMA-L-arginine (P = 0.03). 6. L-NMMA-evoked increases in mean arterial blood pressure were reversed by L-arginine. Substance P-evoked decreases in mean arterial blood pressure were not changed by L-NMMA or by L-NMMA-L-arginine. 7. We conclude that nitric oxide contributes to substance P-evoked increases in RAR activity and that the increases are most probably independent of decreases in Cdyn. PMID:9379417

  18. Measurement of irradiation effects in a RPV steel by ball indentation technique and magnetic Barkhausen noise

    NASA Astrophysics Data System (ADS)

    Kim, In-Sup; Park, Duck-Gun; Byun, Thak-Sang; Hong, Jun-Hwa

    1999-12-01

    Effects of neutron dose on the mechanical and magnetic properties of a SA508-3 nuclear pressure vessel steel were investigated by using ball indentation test technique and magnetic Barkhausen noise (BN) measurements. The samples were irradiated in a research reactor up to 1018n/cm2 (E>1 MeV) at 70 °C. The yield strength and flow curve were evaluated from the indentation load-depth curves. The change of mechanical properties showed characteristic trend with respect to neutron dose, namely near plateau, rapid increase and slow increase. On the other hand, the BN varied in a reverse manner, a slow decrease up to a neutron dose of 1016n/cm2, followed by a rapid decrease up to a dose of 1018n/cm2.

  19. The Development of Ni-Containing Cryogenic Steels and Their Industrial Manufacturing

    NASA Astrophysics Data System (ADS)

    Wang, Meng; Xie, Zhang-long; Li, Cheng-gang; Liu, Zheng-yu

    China has become one the largest energy consumer in the world due to the rapid growth of its economy, leading to the steady increase in the consumption of LPG, LEG and LNG in recent years. Therefore, urgent demands for the steels to be able to contain liquefied gases had emerged. Nickel containing cryogenic steels had been mainly used for liquefied gas tanks as ferritic cryogenic materials, but there are still many problems in regard of industrial production. In the present work, the optimized processing routes for 5Ni and 9Ni steels were developed at laboratory. The effect of Ni addition on the microstructure and cryogenic toughness of Ni containing steels was investigated. The results showed that the prior austenite grain size decreased from 19.8µm to 18.2µm and the ductile-brittle transition temperature decreased as Ni content increased from 5% to 9%. The quenched and tempered microstructures in 5Ni and 9Ni steels were consisted of tempered martensite and small amount of reversed austenite, with the microstructure of 5Ni steel only containing only 0.3%reversed austenite and a large amount of dispersive cementite was precipitated on ferritic matrix. With the increase of Ni addition up to 9%, the volume fraction of reversed austenite increased to about 5% and cementite precipitation was eliminated because the reversed austenite had absorbed carbon atoms from the matrix. It has been shown that cementite was harmful to the toughness of the steelas a hard second phase because it was easy for cracks' initiation and propagation when the cementite was precipitated at grain boundaries or lath boundaries. Fine grain size, more reversed austenite and less cementite precipitation are worked out to be the key factors to decrease the ductile-brittle transition temperature of 9Ni steel.

  20. Catheter-Based Renal Sympathetic Denervation Significantly Inhibits Atrial Fibrillation Induced by Electrical Stimulation of the Left Stellate Ganglion and Rapid Atrial Pacing

    PubMed Central

    Po, Sunny S.; Wang, Huan; Zhang, Ling; Zhang, Feng; Wang, Kun; Zhou, Qina

    2013-01-01

    Background Sympathetic activity involves the pathogenesis of atrial fibrillation (AF). Renal sympathetic denervation (RSD) decreases sympathetic renal afferent nerve activity, leading to decreased central sympathetic drive. The aim of this study was to identify the effects of RSD on AF inducibility induced by hyper-sympathetic activity in a canine model. Methods To establish a hyper-sympathetic tone canine model of AF, sixteen dogs were subjected to stimulation of left stellate ganglion (LSG) and rapid atrial pacing (RAP) for 3 hours. Then animals in the RSD group (n = 8) underwent radiofrequency ablation of the renal sympathetic nerve. The control group (n = 8) underwent the same procedure except for ablation. AF inducibility, effective refractory period (ERP), ERP dispersion, heart rate variability and plasma norepinephrine levels were measured at baseline, after stimulation and after ablation. Results LSG stimulation combined RAP significantly induced higher AF induction rate, shorter ERP, larger ERP dispersion at all sites examined and higher plasma norepinephrine levels (P<0.05 in all values), compared to baseline. The increased AF induction rate, shortened ERP, increased ERP dispersion and elevated plasma norepinephrine levels can be almost reversed by RSD, compared to the control group (P<0.05). LSG stimulation combined RAP markedly shortened RR-interval and standard deviation of all RR-intervals (SDNN), Low-frequency (LF), high-frequency (HF) and LF/HF ratio (P<0.05). These changes can be reversed by RSD, compared to the control group (P<0.05). Conclusions RSD significantly reduced AF inducibility and reversed the atrial electrophysiological changes induced by hyper-sympathetic activity. PMID:24223140

  1. cap alpha. /sub 2/-Adrenergic receptor-mediated sensitization of forskolin-stimulated cyclic AMP production

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

    Jones, S.B.; Toews, M.L.; Turner, J.T.

    1987-03-01

    Preincubation of HT29 human colonic adenocarcinoma cells with ..cap alpha../sub 2/-adrenergic agonists resulted in a 10- to 20-fold increase in forskolin-stimulated cyclic AMP production as compared to cells preincubated without agonist. Similar results were obtained using either a (/sup 3/H)adenine prelabeling assay or a cyclic AMP radioimmunoassay to measure cyclic AMP levels. This phenomenon, which is termed sensitization, is ..cap alpha../sub 2/-adrenergic receptor-mediated and rapid in onset and reversal. Yohimbine, an ..cap alpha../sub 2/-adrenergic receptor-selective antagonist, blocked norepinephrine-induced sensitization, whereas prazosin (..cap alpha../sub 1/-adrenergic) and sotalol (..beta..-adrenergic) did not. The time for half-maximal sensitization was 5 min and the half-timemore » for reversal was 10 min. Only a 2-fold sensitization of cyclic AMP production stimulated by vasoactive intestinal peptide was observed, indicating that sensitization is relatively selective for forskolin. Sensitization reflects an increased production of cyclic AMP and not a decreased degradation of cyclic AMP, since incubation with a phosphodiesterase inhibitor and forskolin did not mimic sensitization. Increasing the levels of cyclic AMP during the preincubation had no effect on sensitization, indicating that sensitization is not caused by decreased cyclic AMP levels during the preincubation. This rapid and dramatic sensitization of forskolin-stimulated cyclic AMP production is a previously unreported effect that can be added to the growing list of ..cap alpha../sub 2/-adrenergic responses that are not mediated by a decrease in cyclic AMP.« less

  2. Cytokinin Activity in Water-stressed Shoots 1

    PubMed Central

    Itai, Chanan; Vaadia, Yoash

    1971-01-01

    Water stress applied to the plant shoot through enhanced evaporative demands reduced cytokinin activity in extracts of xylem exudate and leaves. This reduction resembled the changes in cytokinin activity caused by water stress applied to the root. Cytokinin activity in detached wilting leaves decreased rapidly. Recovery took place after several hours in a humid chamber. Experiments with 14C-kinetin indicated that the mechanism of the inactivation and its reversal involve a chemical transformation of the cytokinin molecule. PMID:16657585

  3. Vortex Flux Pinning in Type-Ii Superconductors

    NASA Astrophysics Data System (ADS)

    Hasan, Mohammad-Khair A. M.

    1995-01-01

    Rotational magnetization vector measurements on polycrystalline samples of rm YBa_2Cu _3O_7 (YBCO) and (Ba, K)BiO _3 at various fixed fields (H) and temperatures (T) reveal that the vortex flux density (B) in a rotational state consists of a component B_{rm R}, which rotates rigidly with sample rotation, and a B_{rm F} component, which stays at a fixed frictional angle (theta _{rm F}) relative to H. Also, B_{rm R} decreases and ultimately vanishes with increasing H, while B _{rm F} grows monotonically, implying that the vortex pinning strength have a broad distribution. This has been confirmed by the measurements on YBCO of the remanent flux density B^ {rm rm} which can be decomposed analogously into B_{R} ^{} and B_ {F}^{} at angle theta_{F}^{} relative to H. The quantity Hsin theta_{rm F},, which at equilibrium equals tau_{rm p}/mu (the average pinning torque per vortex of moment mu) decreases with increasing high H. This result and the distribution in the strength of the pinning are shown to be consistent with the collective pinning process of vortex bundling. At fixed H, tau_{rm p} decreases rapidly with increasing T, varying approximately as T^{-0.8} for both samples. For polycrystalline YBCO at 4.2 K, B_ {rm R} and B_{ rm F} are found to relax differently with time. The negative creep sign of B_ {rm R} indicates that the number of rotational vortices decreases with time, whereas B _{rm F} shows a positive creep with a negative change in theta_ {rm F}, which indicates that more frictional vortices enter the sample with a tendency of alignment in the direction of H. For grain-oriented YBCO at 4.2 K, the vortex creep measurements of B along the c-axis at different fields showed that: whenever the hysteretic changes of H are reversed in sign, the vortex flux creep (dB/dlogt) decreases very rapidly to zero, where it lingers before changing sign. At the same turning values of H, (dB/dH) also goes to zero. These properties are attributable to the reversals of the vortex motion which occur at the turning values of H and cause a reversal of frictional pinning forces.

  4. Genistein and tyrphostin AG556 decrease ultra-rapidly activating delayed rectifier K+ current of human atria by inhibiting EGF receptor tyrosine kinase.

    PubMed

    Xiao, Guo-Sheng; Zhang, Yan-Hui; Wu, Wei; Sun, Hai-Ying; Wang, Yan; Li, Gui-Rong

    2017-03-01

    The ultra-rapidly activating delayed rectifier K + current I Kur (encoded by K v 1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). Whole-cell patch voltage clamp technique and immunoprecipitation and Western blotting analysis were used to investigate whether the PTK inhibitors genistein, tyrphostin AG556 (AG556) and PP2 regulate human atrial I Kur and hKv1.5 channels stably expressed in HEK 293 cells. Human atrial I Kur was decreased by genistein (a broad-spectrum PTK inhibitor) and AG556 (a highly selective EGFR TK inhibitor) in a concentration-dependent manner. Inhibition of I Kur induced by 30 μM genistein or 10 μM AG556 was significantly reversed by 1 mM orthovanadate (a protein tyrosine phosphatase inhibitor). Similar results were observed in HEK 293 cells stably expressing hK v 1.5 channels. On the other hand, the Src family kinase inhibitor PP2 (1 μM) slightly enhanced I Kur and hK v 1.5 current, and the current increase was also reversed by orthovanadate. Immunoprecipitation and Western blotting analysis showed that genistein, AG556, and PP2 decreased tyrosine phosphorylation of hK v 1.5 channels and that the decrease was countered by orthovanadate. The PTK inhibitors genistein and AG556 decrease human atrial I Kur and cloned hK v 1.5 channels by inhibiting EGFR TK, whereas the Src kinase inhibitor PP2 increases I Kur and hK v 1.5 current. These results imply that EGFR TK and the soluble Src kinases may have opposite effects on human atrial I Kur . © 2017 The British Pharmacological Society.

  5. An efficient and rapid influenza gene cloning strategy for reverse genetics system.

    PubMed

    Shao, Hongxia; Fan, Zhonglei; Wan, Zhimin; Tian, Xiaoyan; Chen, Hongjun; Perez, Daniel R; Qin, Aijian; Ye, Jianqiang

    2015-09-15

    Influenza reverse genetics plays vital roles in understanding influenza molecular characteristics and vaccine development. However, current influenza reverse genetics heavily depends on restriction enzyme and ligation for gene cloning. The traditional cloning process of influenza eight fragments for virus rescuing generally requires considerable work. To simplify and increase the pace of gene cloning for influenza reverse genetics system, we developed a rapid restriction enzyme-free ExnaseTM II-based in vitro recombination approach for influenza gene cloning. We used this strategy rapidly and successfully to clone influenza eight genes both from viruses PR8 and H9N2 for virus rescuing. Our data demonstrate that the strategy developed here can accelerate the process of influenza gene cloning into reverse genetics system, and shows high potential for applications in both influenza basic and applied research. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Hydrogen production from continuous flow, microbial reverse-electrodialysis electrolysis cells treating fermentation wastewater.

    PubMed

    Watson, Valerie J; Hatzell, Marta; Logan, Bruce E

    2015-11-01

    A microbial reverse-electrodialysis electrolysis cell (MREC) was used to produce hydrogen gas from fermentation wastewater without the need for additional electrical energy. Increasing the number of cell pairs in the reverse electrodialysis stack from 5 to 10 doubled the maximum current produced from 60 A/m(3) to 120 A/m(3) using acetate. However, more rapid COD removal required a decrease in the anolyte hydraulic retention time (HRT) from 24 to 12 h to stabilize anode potentials. Hydrogen production using a fermentation wastewater (10 cell pairs, HRT=8 h) reached 0.9±0.1 L H2/Lreactor/d (1.1±0.1 L H2/g-COD), with 58±5% COD removal and a coulombic efficiency of 74±5%. These results demonstrated that consistent rates of hydrogen gas production could be achieved using an MREC if effluent anolyte COD concentrations are sufficient to produce stable anode potentials. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Control of ion gyroscale fluctuations via electrostatic biasing and sheared E×B flow in the C-2 field reversed configuration

    NASA Astrophysics Data System (ADS)

    Schmitz, L.; Ruskov, E.; Deng, B. H.; Binderbauer, M.; Tajima, T.; Gota, H.; Tuszewski, M.

    2016-03-01

    Control of radial particle and thermal transport is instrumental for achieving and sustaining well-confined high-β plasma in a Field-Reversed Configuration (FRC). Radial profiles of low frequency ion gyro-scale density fluctuations (0.5≤kρs≤40), consistent with drift- or drift-interchange modes, have been measured in the scrape-off layer (SOL) and core of the C-2 Field-Reversed Configuration (FRC), together with the toroidal E×B velocity. It is shown here that axial electrostatic SOL biasing controls and reduces gyro-scale density fluctuations, resulting in very low FRC core fluctuation levels. When the radial E×B flow shearing rate decreases below the turbulence decorrelation rate, fluctuation levels increase substantially, concomitantly with onset of the n=2 instability and rapid loss of diamagnetism. Low turbulence levels, improved energy/particle confinement and substantially increased FRC life times are achieved when E×B shear near the separatrix is maintained via axial SOL biasing using an annular washer gun.

  8. Sex reversal triggers the rapid transition from genetic to temperature-dependent sex.

    PubMed

    Holleley, Clare E; O'Meally, Denis; Sarre, Stephen D; Marshall Graves, Jennifer A; Ezaz, Tariq; Matsubara, Kazumi; Azad, Bhumika; Zhang, Xiuwen; Georges, Arthur

    2015-07-02

    Sex determination in animals is amazingly plastic. Vertebrates display contrasting strategies ranging from complete genetic control of sex (genotypic sex determination) to environmentally determined sex (for example, temperature-dependent sex determination). Phylogenetic analyses suggest frequent evolutionary transitions between genotypic and temperature-dependent sex determination in environmentally sensitive lineages, including reptiles. These transitions are thought to involve a genotypic system becoming sensitive to temperature, with sex determined by gene-environment interactions. Most mechanistic models of transitions invoke a role for sex reversal. Sex reversal has not yet been demonstrated in nature for any amniote, although it occurs in fish and rarely in amphibians. Here we make the first report of reptile sex reversal in the wild, in the Australian bearded dragon (Pogona vitticeps), and use sex-reversed animals to experimentally induce a rapid transition from genotypic to temperature-dependent sex determination. Controlled mating of normal males to sex-reversed females produces viable and fertile offspring whose phenotypic sex is determined solely by temperature (temperature-dependent sex determination). The W sex chromosome is eliminated from this lineage in the first generation. The instantaneous creation of a lineage of ZZ temperature-sensitive animals reveals a novel, climate-induced pathway for the rapid transition between genetic and temperature-dependent sex determination, and adds to concern about adaptation to rapid global climate change.

  9. Reversal of coagulopathy in critically ill patients with traumatic brain injury: recombinant factor VIIa is more cost-effective than plasma.

    PubMed

    Stein, Deborah M; Dutton, Richard P; Kramer, Mary E; Scalea, Thomas M

    2009-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability after trauma. Coagulopathy is common in this patient population and requires rapid reversal to allow for safe neurosurgical intervention and prevent worsening of the primary injury. Typically reversal of coagulopathy is accomplished with the use of plasma. Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) has become increasingly used "off-label" in patients with neurosurgical emergencies to rapidly reverse coagulopathy. We hypothesized that the use of rFVIIa in this patient population would prove to be cost-effective as well as demonstrate clinical benefit. The trauma registry at the R Adams Cowley Shock Trauma Center was used to identify all coagulopatic trauma patients admitted between January 2002 and December 2007 with relatively isolated TBI (head Abbreviated Injury Scale score of >or=4). The medical records of patients were reviewed and demographics, injury-specific data, medications administered, laboratory values, blood product utilization, neurosurgical procedures, length of stay (LOS), discharge disposition, and outcome data were abstracted. Patients who received rFVIIa for reversal of coagulopathy were compared against those who did not receive rFVIIa. t Tests were used to compare differences between continuous variables, and chi2 analysis was used to compare categorical variables. A p value of <0.05 was considered significant for all statistical tests. During a 6-year period, there were 179 patients who met inclusion criteria. One hundred eleven patients (62.0%) were treated with conventional therapy alone whereas 68 (38.0%) received rFVIIa. Baseline characteristics between the two groups were similar except that Injury Severity Score and admission International normalized ratio were higher in the rFVIIa group and the rFVIIa group had a higher percentage of patients with head Abbreviated Injury Scale score of 5 injuries, patients who underwent neurosurgical procedures and patients with preinjury warfarin use. There was no difference in total charges between these groups (mean US $63,403 in the conventionally treated group vs. $66,086). When patients who required admission to the intensive care unit were analyzed (n = 110, 50% received rFVIIa), total mean charges and costs were significantly lower in the group that received rFVIIa (mean US $108,900 vs. $77,907). Hospital LOS, days of mechanical ventilation, and plasma utilization were lower in the rFVIIa group. Mortality and thromboembolic complication rates were not different between the two groups. In this study, we were able to demonstrate a significant economic benefit of the use of rFVIIa for reversal of coagulopathy in severely injured patients with TBI. Not all patients with coagulopathy and an anatomic brain injury benefit, but in patients who are neurologically or physiologically compromised, using rFVIIa decreases total charges and costs of hospitalization. This decrease in overall cost is directly attributable to the significant decrease in LOS and decrease in the need for mechanical ventilation. This study demonstrates that in coagulopathic patients with TBI who require intensive care unit admission, rFVIIa is cost-effective and safe. Prospective studies are needed to confirm these findings and establish clinical effectiveness.

  10. Rapid evaluation of reverse-osmosis membranes

    NASA Technical Reports Server (NTRS)

    Hollahan, J. R.; Wydeven, T.

    1972-01-01

    Simultaneous reverse-osmosis tests conducted with centrifuges having multiple compartment heads are discussed. Equipment for retaining reverse-osmosis membrane is illustrated. Method of conducting tests is described.

  11. Light-Induced Gelling in a Micellar Fluid Based on a Zwitterionic Surfactant.

    NASA Astrophysics Data System (ADS)

    Kumar, Rakesh; Raghavan, Srinivasa

    2007-03-01

    Fluids with photoresponsive rheological properties (i.e. photorheological or PR fluids) can be useful in a range of applications, such as in dampers, sensors, and valves for microfluidic or MEMS devices. Previously, we have demonstrated a cationic surfactant-based PR fluid whose viscosity can be rapidly decreased by UV irradiation. This viscosity decrease was not reversible. Here, we describe a different formulation based on a zwitterionic surfactant that shows a rapid increase in viscosity (gelling) upon exposure to UV radiation. The formulation consists of the zwitterionic surfactant and a photosensitive cinnamic acid derivative. Initially, the viscosity of the fluid is low indicating the presence of small micelles. Upon UV irradiation, the cinnamic acid derivative is photoisomerized from trans to cis. In turn, the small micelles transform into long wormlike micelles, thus increasing the solution viscosity by more than five orders of magnitude. Small angle neutron scattering (SANS) data confirms the dramatic increase in micelle length. Possible reasons for such changes in micelle dimensions will be discussed.

  12. Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos.

    PubMed

    Bolnick, Alan; Abdulhasan, Mohammed; Kilburn, Brian; Xie, Yufen; Howard, Mindie; Andresen, Paul; Shamir, Alexandra M; Dai, Jing; Puscheck, Elizabeth E; Rappolee, Daniel A

    2016-08-01

    The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3,3'-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development. The methods used were as follows: culture post-thaw mouse zygotes to the two-cell embryo stage and test effects after 1-h AMPK agonists' (e.g., Met, Asa, BR-DIM, control hyperosmotic stress) exposure on AMPK-dependent loss of Oct4 and/or Rex1 nuclear potency factors, confirm AMPK dependence by reversing potency loss in two-cell-stage embryos with AMPK inhibitor compound C (CC), test whether Met + Asa (i.e., co-added) or DS BR-DIM decreases development of two-cell to blastocyst stage in an AMPK-dependent (CC-sensitive) manner, and evaluate the level of Rex1 and Oct4 nuclear fluorescence in two-cell-stage embryos and rate of two-cell-stage embryo development to blastocysts. Met, Asa, BR-DIM, or hyperosmotic sorbitol stress induces rapid ~50-85 % Rex1 and/or Oct4 protein loss in two-cell embryos. This loss is ~60-90 % reversible by co-culture with AMPK inhibitor CC. Embryo development from two-cell to blastocyst stage is decreased in culture with either Met + Asa or BR-DIM, and this is either >90 or ~60 % reversible with CC, respectively. These experimental designs here showed that Met-, Asa-, BR-DIM-, or sorbitol stress-induced rapid potency loss in two-cell embryos is AMPK dependent as suggested by inhibition of Rex1 and/or Oct4 protein loss with an AMPK inhibitor. The DS BR-DIM or fertility drugs (e.g., Met + Asa) that are used to enhance maternal metabolism to support fertility can also chronically slow embryo growth and block development in an AMPK-dependent manner.

  13. The effects of the CXCR2 antagonist, MK-7123, on bone marrow functions in healthy subjects.

    PubMed

    Hastrup, Nina; Khalilieh, Sauzanne; Dale, David C; Hanson, Lars G; Magnusson, Peter; Tzontcheva, Anjela; Tseng, Jack; Huyck, Susan; Rosenberg, Elizabeth; Krogsgaard, Kim

    2015-04-01

    The CXCR2 antagonist MK-7123 causes dose-dependent reductions in absolute neutrophil counts (ANC) and decreases neutrophil tissue responses, but its effects on bone marrow functions are not yet known. We conducted a double-blind, randomized study in 18 healthy subjects comparing the effects of either MK-7123 (30mg, po, daily for 28days) or placebo on peripheral blood counts and bone marrow myeloid cell populations. MK-7123 caused a reversible decrease (approximately 50%) in the ANC as demonstrated on days 1 and 28, the first and last days of the treatment period. Bone marrow aspirate smears and biopsy imprints did not differ in the proportion of mature neutrophils in pretreatment, day 28, day 56 or placebo samples. There were no treatment effects on biopsy or aspirate clot cellularity, myeloid to erythroid or myeloid post-mitotic to mitotic ratios; flow-cytometric analyses of aspirate cells; or bone marrow fat to cell balance as assessed by MRI. MK-7123 was generally well tolerated with neutropenia being the most common adverse event; however, there were no clinical symptoms associated with decreased ANCs. These findings indicate that the CXCR2 antagonist MK-7123 causes rapidly reversible decrease in the ANC without measurable myelosuppressive effects. The results support the development of CXCR2 antagonists as potentially useful anti-inflammatory agents, primarily interrupting neutrophil trafficking. Copyright © 2015. Published by Elsevier Ltd.

  14. Reversible Rigidity Control Using Low Melting Temperature Alloys

    NASA Astrophysics Data System (ADS)

    Shan, Wanliang; Lu, Tong; Majidi, Carmel

    2013-03-01

    Inspired by nature, materials able to achieve rapid rigidity changes have important applications for human body protection in military and many other areas. This talk presents the fabrication and design of soft-matter technologies that exhibit rapid reversible rigidity control. Fabricated with a masked deposition technique, the soft-matter composite contains liquid-phase and phase-changing metal alloys embedded in a soft and highly stretchable elastomer. The composite material can reversibly change its rigidity by three orders of magnitude and sustain large deformation.

  15. No Trade-Off between Learning Speed and Associative Flexibility in Bumblebees: A Reversal Learning Test with Multiple Colonies

    PubMed Central

    Raine, Nigel E.; Chittka, Lars

    2012-01-01

    Potential trade-offs between learning speed and memory-related performance could be important factors in the evolution of learning. Here, we test whether rapid learning interferes with the acquisition of new information using a reversal learning paradigm. Bumblebees (Bombus terrestris) were trained to associate yellow with a floral reward. Subsequently the association between colour and reward was reversed, meaning bees then had to learn to visit blue flowers. We demonstrate that individuals that were fast to learn yellow as a predictor of reward were also quick to reverse this association. Furthermore, overnight memory retention tests suggest that faster learning individuals are also better at retaining previously learned information. There is also an effect of relatedness: colonies whose workers were fast to learn the association between yellow and reward also reversed this association rapidly. These results are inconsistent with a trade-off between learning speed and the reversal of a previously made association. On the contrary, they suggest that differences in learning performance and cognitive (behavioural) flexibility could reflect more general differences in colony learning ability. Hence, this study provides additional evidence to support the idea that rapid learning and behavioural flexibility have adaptive value. PMID:23028779

  16. Reverse transcription strand invasion based amplification (RT-SIBA): a method for rapid detection of influenza A and B.

    PubMed

    Eboigbodin, Kevin; Filén, Sanna; Ojalehto, Tuomas; Brummer, Mirko; Elf, Sonja; Pousi, Kirsi; Hoser, Mark

    2016-06-01

    Rapid and accurate diagnosis of influenza viruses plays an important role in infection control, as well as in preventing the misuse of antibiotics. Isothermal nucleic acid amplification methods offer significant advantages over the polymerase chain reaction (PCR), since they are more rapid and do not require the sophisticated instruments needed for thermal cycling. We previously described a novel isothermal nucleic acid amplification method, 'Strand Invasion Based Amplification' (SIBA®), with high analytical sensitivity and specificity, for the detection of DNA. In this study, we describe the development of a variant of the SIBA method, namely, reverse transcription SIBA (RT-SIBA), for the rapid detection of viral RNA targets. The RT-SIBA method includes a reverse transcriptase enzyme that allows one-step reverse transcription of RNA to complementary DNA (cDNA) and simultaneous amplification and detection of the cDNA by SIBA under isothermal reaction conditions. The RT-SIBA method was found to be more sensitive than PCR for the detection of influenza A and B and could detect 100 copies of influenza RNA within 15 min. The development of RT-SIBA will enable rapid and accurate diagnosis of viral RNA targets within point-of-care or central laboratory settings.

  17. Reversal of apixaban anticoagulation by four-factor prothrombin complex concentrates in healthy subjects: a randomized three-period crossover study.

    PubMed

    Song, Y; Wang, Z; Perlstein, I; Wang, J; LaCreta, F; Frost, R J A; Frost, C

    2017-11-01

    Essentials Prothrombin complex concentrates (PCCs) may reverse the effect of factor Xa (FXa) inhibitors. We conducted an open-label, randomized, placebo-controlled, three-period crossover study in 15 subjects. Both PCCs rapidly reversed apixaban-mediated decreases in mean endogenous thrombin potential. Four-factor PCC administration had no effect on apixaban pharmacokinetics or anti-FXa activity. Background Currently, there is no approved reversal agent for direct activated factor Xa (FXa) inhibitors; however, several agents are under investigation, including prothrombin complex concentrates (PCCs). Objective This open-label, randomized, placebo-controlled, three-period crossover study assessed the effect of two four-factor PCCs on apixaban pharmacodynamics and pharmacokinetics in 15 healthy subjects. Methods Subjects received apixaban 10 mg twice daily for 3 days. On day 4, 3 h after apixaban, subjects received a 30-min infusion of 50 IU kg -1 Cofact, Beriplex P/N (Beriplex), or saline. Change in endogenous thrombin potential (ETP), measured with a thrombin generation assay (TGA), was the primary endpoint. Secondary endpoints included changes in other TGA parameters, prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time, anti-FXa activity, apixaban pharmacokinetics, and safety. Results Apixaban-related changes in ETP and several other pharmacodynamic measures occurred following apixaban administration. Both PCCs reversed apixaban's effect on ETP; the differences in adjusted mean change from pre-PCC baseline to end of infusion were 425 nm min (95% confidence interval [CI] 219.8-630.7 nm min; P < 0.001) for Cofact, and 91 nm min (95% CI - 31.3 to 212.4 nm min; P > 0.05) for Beriplex. Both PCCs returned ETP to pre-apixaban baseline levels 4 h after PCC infusion, versus 45 h for placebo. For both PCCs, mean ETP peaked 21 h after PCC initiation, and then slowly decreased over the following 48 h. Both PCCs reversed apixaban's effect on TGA peak height, PT, and INR. Apixaban pharmacokinetic and anti-FXa profiles were consistent across treatments. Conclusions Cofact and Beriplex reversed apixaban's steady-state effects on several coagulation assessments. © 2017 International Society on Thrombosis and Haemostasis.

  18. Development of a rapid diagnostic assay for the detection of tomato chlorotic dwarf viroid based on isothermal reverse-transcription-recombinase polymerase amplification

    USDA-ARS?s Scientific Manuscript database

    A molecular diagnostic assay utilizing reverse transcription-recombinase polymerase amplification (RT-RPA) at an isothermal constant temperature of 39 °C and target-specific primers and probe were developed for the rapid, sensitive, and specific detection of tomato chlorotic dwarf viroid (TCDVd) in ...

  19. Mitomycin C dissolved in a reversible thermosetting gel: target tissue concentrations in the rabbit eye.

    PubMed

    Ichien, K; Yamamoto, T; Kitazawa, Y; Oguri, A; Ando, H; Kondo, Y

    1997-01-01

    To determine whether a new, reversible thermosetting gel enhances mitomycin C transfer to target ocular tissues in the rabbit eye. A 0.1 ml solution of mitomycin C containing 0.22 microgram, 2.9 micrograms, or 28 micrograms of the agent dissolved in a reversible thermosetting gel consisting of methylcellulose, citric acid, and polyethylene glycol was injected subconjunctivally in 30 New Zealand albino rabbits. Scleral and conjunctival tissues were excised at 0.5, 1, 2, 4, or 24 hours after the injection and mitomycin C concentrations in these tissues were determined by high performance liquid chromatography. The concentration over time was approximated to a single exponential curve, and initial mitomycin C concentrations, time constants, and half life values were determined. Finally, the areas under the curves (AUCs) between 0.5 and 24 hours were calculated. The mitomycin C concentrations in the target tissues were dose dependent and decreased rapidly over 24 hours. Both the initial mitomycin C concentrations as well as AUCs in these eyes treated with mitomycin C, dissolved in a reversible thermosetting gel, were higher than those in eyes treated similarly in a previous study in which the gel was not used. Applied subconjunctivally in the rabbit eye, mitomycin C dissolved in the reversible thermosetting gel enhanced transfer of the agent to the sclera and the conjunctiva.

  20. Change in the relative contributions of habit and working memory facilitates serial reversal learning expertise in rhesus monkeys.

    PubMed

    Hassett, Thomas C; Hampton, Robert R

    2017-05-01

    Functionally distinct memory systems likely evolved in response to incompatible demands placed on learning by distinct environmental conditions. Working memory appears adapted, in part, for conditions that change frequently, making rapid acquisition and brief retention of information appropriate. In contrast, habits form gradually over many experiences, adapting organisms to contingencies of reinforcement that are stable over relatively long intervals. Serial reversal learning provides an opportunity to simultaneously examine the processes involved in adapting to rapidly changing and relatively stable contingencies. In serial reversal learning, selecting one of the two simultaneously presented stimuli is positively reinforced, while selection of the other is not. After a preference for the positive stimulus develops, the contingencies of reinforcement reverse. Naïve subjects adapt to such reversals gradually, perseverating in selection of the previously rewarded stimulus. Experts reverse rapidly according to a win-stay, lose-shift response pattern. We assessed whether a change in the relative control of choice by habit and working memory accounts for the development of serial reversal learning expertise. Across three experiments, we applied manipulations intended to attenuate the contribution of working memory but leave the contribution of habit intact. We contrasted performance following long and short intervals in Experiments 1 and 2, and we interposed a competing cognitive load between trials in Experiment 3. These manipulations slowed the acquisition of reversals in expert subjects, but not naïve subjects, indicating that serial reversal learning expertise is facilitated by a shift in the control of choice from passively acquired habit to actively maintained working memory.

  1. Potential reversal of a phase shift: the rapid decrease in the cover of the invasive green macroalga Dictyosphaeria cavernosa Forsskål on coral reefs in Kāne`ohe Bay, Oahu, Hawai`i

    NASA Astrophysics Data System (ADS)

    Stimson, J.; Conklin, E.

    2008-12-01

    The native green macroalga Dictyosphaeria cavernosa dominated most of the reef slope habitat in Kāne‘ohe Bay, Hawai‘i for 40 years prior to 2006 and had displaced corals from the habitats they created. This has been one of the most oft-cited examples of a phase shift occurring on a coral reef. After decades of relatively constant, high abundance of the alga, percent cover declined dramatically throughout the bay between February and June 2006. The sudden decrease in cover of this alga appears to be the result of an unusually protracted cloudy, rainy period in March 2006, which may have reduced irradiance and caused the alga to lose weight. Corals and red macroalgae living at the same depths and in some of the same habitats were apparently not affected by this 42-day period of rain and overcast skies. Competition between corals and D. cavernosa for space on reef slopes has been virtually eliminated by the death of this alga, but the unstable rubble formations, which remain in much of the area formerly covered by D. cavernosa may not be conducive to rapid increase in cover by the remaining corals or to establishment by coral recruits. Two years later, there was still no recovery of D. cavernosa. This represents a rare example of decline in macroalgal dominance on a reef and a partial reversal, possibly only temporary, of a phase shift.

  2. Preparing for the unexpected: special considerations and complications after sugammadex administration.

    PubMed

    Iwasaki, Hajime; Renew, J Ross; Kunisawa, Takayuki; Brull, Sorin J

    2017-10-17

    Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.

  3. A centrifugal method for the evaluation of polymer membranes for reverse osmosis

    NASA Technical Reports Server (NTRS)

    Hollahan, J. R.; Wydeven, T.; Mccullough, R. P.

    1973-01-01

    A rapid and simple method employing the laboratory centrifuge shows promise for evaluation of membrane performance during reverse osmosis. Results are presented for cellulose acetate membranes for rejection of salt and urea dissolved solids. Implications of the study are to rapid screening of membrane performance, use in laboratories with limited facilities, and possible space waste water purification.

  4. Validation of Monte Carlo simulation of mammography with TLD measurement and depth dose calculation with a detailed breast model

    NASA Astrophysics Data System (ADS)

    Wang, Wenjing; Qiu, Rui; Ren, Li; Liu, Huan; Wu, Zhen; Li, Chunyan; Li, Junli

    2017-09-01

    Mean glandular dose (MGD) is not only determined by the compressed breast thickness (CBT) and the glandular content, but also by the distribution of glandular tissues in breast. Depth dose inside the breast in mammography has been widely concerned as glandular dose decreases rapidly with increasing depth. In this study, an experiment using thermo luminescent dosimeters (TLDs) was carried out to validate Monte Carlo simulations of mammography. Percent depth doses (PDDs) at different depth values were measured inside simple breast phantoms of different thicknesses. The experimental values were well consistent with the values calculated by Geant4. Then a detailed breast model with a CBT of 4 cm and a glandular content of 50%, which has been constructed in previous work, was used to study the effects of the distribution of glandular tissues in breast with Geant4. The breast model was reversed in direction of compression to get a reverse model with a different distribution of glandular tissues. Depth dose distributions and glandular tissue dose conversion coefficients were calculated. It revealed that the conversion coefficients were about 10% larger when the breast model was reversed, for glandular tissues in the reverse model are concentrated in the upper part of the model.

  5. Reversal of multidrug resistance by surfactants.

    PubMed Central

    Woodcock, D. M.; Linsenmeyer, M. E.; Chojnowski, G.; Kriegler, A. B.; Nink, V.; Webster, L. K.; Sawyer, W. H.

    1992-01-01

    Cremophor EL, a pharmacologically inactive solubilising agent, has been shown to reverse multidrug resistance (MDR). Using flow cytometric evaluation of equilibrium intracellular levels of daunorubicin (DNR), we found that eight other surface active agents will also reverse MDR. All the active detergents contain polyethoxylated moieties but have no similarities in their hydrophobic components. The properties of three polyethoxylated surfactants that showed the lowest toxicities, Cremophor, Tween 80 and Solutol HS15, were examined in more detail. The concentrations of Tween 80 and Solutol required to reverse DNR exclusion were 10-fold lower than for Cremophor. However while concentrations greater than or equal to 1:10(2) of the former two surfactants resulted in breakdown of cells, even 1:10 of Cremophor did not lyse cells. Studies of the effects of Cremophor on the uptake and efflux of DNR in normal and MDR cell types showed that Cremophor increases intracellular DNR primarily by locking the rapid efflux from the cells. This blockage of drug efflux may be mediated by a substantial alteration in the fluidity of cell membranes induced by Cremophor, as shown by decreased fluorescence anisotropy of a membrane probe. Consistent with these data, coinjection of adriamycin plus Cremophor into mice carrying a multidrug resistant P388 transplantable tumour significantly increased the survival time of the mice compared with adriamycin treatment alone. PMID:1637678

  6. Chemical osmosis, reverse chemical osmosis, and the origin of subsurface brines

    NASA Astrophysics Data System (ADS)

    Graf, Donald L.

    1982-08-01

    Calculations using recently-tabulated values of density and osmotic coefficient for NaCl-H 2O indicate that overpressuring is more than adequate to overcome chemical osmosis and drive reverse chemical osmosis in sedimentary sequences. The best-demonstrated overpressuring mechanism is the rapid deposition of fine-grained sediments. The dehydration of gypsum contributes to overpressuring for brief time intervals at shallow depths, whereas water evolved during the protracted conversion of smectite to illite is probably a subordinate, but continuing contributor to overpressuring at greater depth. Occurrences of overpressuring in sedimentary sections older than Cretaceous indicate that post-depositional mechanisms such as tectonic compression and aquathermal pressuring must also operate. The latter may be of major importance in geothermal areas with adequate low-permeability seals, and a nontrivial contributor in areas of normal geothermal gradient because of shales that sharply decrease normal fluid flow. The strongest arguments for the importance to present-day brine compositions of membrane concentration of sea-water solutes are (1) the correlation of δD values of water molecules of pore fluid with those of local meteoric water, (2) the need for major sources of Mg 2+ and Cl - in apparently evaporite-free basins. Even where dissolution of halite is a major contributor of solute, reverse chemical osmosis still operates to leak relatively dilute water. Of the associated diagenetic chemical reactions, that of Mg 2+ with limestone to form dolomite is particularly effective in generating concentrated Cl - brines rich in Ca 2+. It decreases the concentration of Mg 2+, increases that of Ca 2+, and decreases those of both SO 42- and CO 32- by precipitating CaCO 3 and CaSO 4 because of the Ca 2+ common-ion effect.

  7. Reversible Ca2+-induced fast-to-slow transition in primary skeletal muscle culture cells at the mRNA level

    PubMed Central

    Meißner, Joachim D; Kubis, Hans-Peter; Scheibe, Renate J; Gros, Gerolf

    2000-01-01

    The adult fast character and a Ca2+-inducible reversible transition from a fast to a slow type of rabbit myotube in a primary culture were demonstrated at the mRNA level by Northern blot analysis with probes specific for different myosin heavy chain (MyHC) isoforms and enzymes of energy metabolism. No non-adult MyHC isoform mRNA was detected after 22 days of culture. After 4 weeks of culture the fast MyHCIId mRNA was strongly expressed while MyHCI mRNA was virtually absent, indicating the fast adult character of the myotubes in the primary skeletal muscle culture. The data show that a fast-to-slow transition occurred in the myotubes at the level of MyHC isoform gene expression after treatment with the Ca2+ ionophore A23187. The effects of ionophore treatment were decreased levels of fast MyHCII mRNA and an augmented expression of the slow MyHCI gene. Changes in gene expression started very rapidly 1 day after the onset of ionophore treatment. Levels of citrate synthase mRNA increased and levels of glyceraldehyde 3-phosphate dehydrogenase mRNA decreased during ionophore treatment. This points to a shift from anaerobic to oxidative energy metabolism in the primary skeletal muscle culture cells at the level of gene expression. Withdrawal of the Ca2+ ionophore led to a return to increased levels of MyHCII mRNA and decreased levels of MyHCI mRNA, indicating a slow-to-fast transition in the myotubes and the reversibility of the effect of ionophore on MyHC isoform gene expression. PMID:10673542

  8. A novel technique for presurgical nasoalveolar molding using computer-aided reverse engineering and rapid prototyping.

    PubMed

    Yu, Quan; Gong, Xin; Wang, Guo-Min; Yu, Zhe-Yuan; Qian, Yu-Fen; Shen, Gang

    2011-01-01

    To establish a new method of presurgical nasoalveolar molding (NAM) using computer-aided reverse engineering and rapid prototyping technique in infants with unilateral cleft lip and palate (UCLP). Five infants (2 males and 3 females with mean age of 1.2 w) with complete UCLP were recruited. All patients were subjected to NAM before the cleft lip repair. The upper denture casts were recorded using a three-dimensional laser scanner within 2 weeks after birth in UCLP infants. A digital model was constructed and analyzed to simulate the NAM procedure with reverse engineering software. The digital geometrical data were exported to print the solid model with rapid prototyping system. The whole set of appliances was fabricated based on these solid models. Laser scanning and digital model construction simplified the NAM procedure and estimated the treatment objective. The appliances were fabricated based on the rapid prototyping technique, and for each patient, the complete set of appliances could be obtained at one time. By the end of presurgical NAM treatment, the cleft was narrowed, and the malformation of nasoalveolar segments was aligned normally. We have developed a novel technique of presurgical NAM based on a computer-aided design. The accurate digital denture model of UCLP infants could be obtained with laser scanning. The treatment design and appliance fabrication could be simplified with a computer-aided reverse engineering and rapid prototyping technique.

  9. Visually induced self-motion sensation adapts rapidly to left-right reversal of vision

    NASA Technical Reports Server (NTRS)

    Oman, C. M.; Bock, O. L.

    1981-01-01

    Three experiments were conducted using 15 adult volunteers with no overt oculomotor or vestibular disorders. In all experiments, left-right vision reversal was achieved using prism goggles, which permitted a binocular field of vision subtending approximately 45 deg horizontally and 28 deg vertically. In all experiments, circularvection (CV) was tested before and immediately after a period of exposure to reversed vision. After one to three hours of active movement while wearing vision-reversing goggles, 10 of 15 (stationary) human subjects viewing a moving stripe display experienced a self-rotation illusion in the same direction as seen stripe motion, rather than in the opposite (normal) direction, demonstrating that the central neural pathways that process visual self-rotation cues can undergo rapid adaptive modification.

  10. [First confirmed case of laryngeal diphtheria in Djibouti].

    PubMed

    Koeck, J L; Merle, C; Bimet, F; Kiredjian, M; Goullin, B; Teyssou, R

    2000-01-01

    The first bacteriologically confirmed case of laryngeal diphtheria in Djibouti was reported in 1998. It involved a three-year-old native-born infant who had been vaccinated during the first year of life with three doses of a combined vaccine against diphtheria, tetanus, poliomyelitis, and pertussis. A rapid clinical improvement was observed under erythromycin treatment. Other cases of laryngeal diphtheria have been observed. It is important to reverse decreasing vaccinal coverage in Djibouti and to warn incoming travelers of the need to be adequate immunized against diphtheria. Enhanced epidemiologic surveillance of this disease is also needed.

  11. Mixed-mode isolation of triazine metabolites from soil and aquifer sediments using automated solid-phase extraction

    USGS Publications Warehouse

    Mills, M.S.; Thurman, E.M.

    1992-01-01

    Reversed-phase isolation and ion-exchange purification were combined in the automated solid-phase extraction of two polar s-triazine metabolites, 2-amino-4-chloro-6-(isopropylamino)-s-triazine (deethylatrazine) and 2-amino-4-chloro-6-(ethylamino)-s-triazine (deisopropylatrazine) from clay-loam and slit-loam soils and sandy aquifer sediments. First, methanol/ water (4/1, v/v) soil extracts were transferred to an automated workstation following evaporation of the methanol phase for the rapid reversed-phase isolation of the metabolites on an octadecylresin (C18). The retention of the triazine metabolites on C18 decreased substantially when trace methanol concentrations (1%) remained. Furthermore, the retention on C18 increased with decreasing aqueous solubility and increasing alkyl-chain length of the metabolites and parent herbicides, indicating a reversed-phase interaction. The analytes were eluted with ethyl acetate, which left much of the soil organic-matter impurities on the resin. Second, the small-volume organic eluate was purified on an anion-exchange resin (0.5 mL/min) to extract the remaining soil pigments that could foul the ion source of the GC/MS system. Recoveries of the analytes were 75%, using deuterated atrazine as a surrogate, and were comparable to recoveries by soxhlet extraction. The detection limit was 0.1 ??g/kg with a coefficient of variation of 15%. The ease and efficiency of this automated method makes it viable, practical technique for studying triazine metabolites in the environment.

  12. A possible mechanism of current termination in a reversed field pinch

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

    Nagata, A.; Masamune, S.; Arimoto, H.

    1989-10-01

    A rapid growth of magnetic fluctuations resulting from the {ital m}=1 and {ital m}=2 modes and succeeding stop of rotation of these modes have been found as the precursor phenomena of current termination in the STP-3(M) (Trans. Inst. Elec. Eng. Jpn. {bold 107}-{bold B}, 469 (1987)) reversed field pinch. By deepening the field reversal at the wall, these precursors disappear and the current duration becomes much longer. It is found that sudden current termination is caused by a rapid growth of resistive tearing modes mainly because of nonlinear coupling of the {ital m}=1 mode.

  13. Supplementary Investigation in the Langley 20-Foot Free-Spinning Tunnel of the Spin and Recovery Characteristics of a 0.057-Scale Model of the Chance Vought XFU-1 Airplane, Ted No. NACA DE 311

    NASA Technical Reports Server (NTRS)

    Berman, Theodore

    1948-01-01

    An investigation has been conducted in the Langley 20-foot free-spinning tunnel to determine the effects of decreasing the rudder deflection, of decreasing the rudder span, and of differential rudder movements on the spin and recovery characteristics of a 0.057-scale model of the Chance Vought XF7U-1 airplane. The results indicated that decreasing the rudder span or the rudder deflections, individually or jointly, did not seriously alter the spin or recovery characteristics of the model; and recovery by normal use of controls (full rapid rudder reversal followed l/2 to 1 turn later by movement of the stick forward of neutral) remained satisfactory. Linking the original rudders so that the inboard rudder moves from full with the spin to neutral while the outboard rudder moves from neutral to full against the spin will also result in satisfactory spin and recovery characteristics. Calculations of rudder-pedal forces for recovery showed that the expected forces would probably be within the capabilities of a pilot but that it would be advisable to install some type of boost in the control system to insure easy and rapid movement of the rudders.

  14. Decreased glutamate, glutamine and citrulline concentrations in plasma and muscle in endotoxemia cannot be reversed by glutamate or glutamine supplementation: a primary intestinal defect?

    PubMed

    Boutry, Claire; Matsumoto, Hideki; Bos, Cécile; Moinard, Christophe; Cynober, Luc; Yin, Yulong; Tomé, Daniel; Blachier, François

    2012-10-01

    Endotoxemia affects intestinal physiology. A decrease of circulating citrulline concentration is considered as a reflection of the intestinal function. Citrulline can be produced in enterocytes notably from glutamate and glutamine. The aim of this work was to determine if glutamate, glutamine and citrulline concentrations in blood, intestine and muscle are decreased by endotoxemia, and if supplementation with glutamate or glutamine can restore normal concentrations. We induced endotoxemia in rats by an intraperitoneal injection of 0.3 mg kg(-1) lipopolysaccharide (LPS). This led to a rapid anorexia, negative nitrogen balance and a transient increase of the circulating level of IL-6 and TNF-α. When compared with the values measured in pair fed (PF) animals, almost all circulating amino acids (AA) including citrulline decreased, suggesting a decrease of intestinal function. However, at D2 after LPS injection, most circulating AA concentrations were closed to the values recorded in the PF group. At that time, among AA, only glutamate, glutamine and citrulline were decreased in gastrocnemius muscle without change in intestinal mucosa. A supplementation with 4% monosodium glutamate (MSG) or an isomolar amount of glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscle. However, MSG supplementation led to an accumulation of glutamate in the intestinal mucosa. In conclusion, endotoxemia rapidly but transiently decreased the circulating concentrations of almost all AA and more durably of glutamate, glutamine and citrulline in muscle. Supplementation with glutamate or glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscles. The implication of a loss of the intestinal capacity for AA absorption and/or metabolism in endotoxemia (as judged from decreased citrulline plasma concentration) for explaining such results are discussed.

  15. Preclinical Evidence of Rapid-Onset Antidepressant-Like Effect in Radix Polygalae Extract

    PubMed Central

    Park, Hyunwoo; Kim, Yoorim; Park, Sung Hyun; Swanberg, Kelley; Shin, Joo-Yeon; Ha, Sang-Kyu; Cho, Yoonju; Bang, Soo-Yong; Lew, Jae-Hwan; Cho, Seung-Hun; Maeng, Sungho

    2014-01-01

    Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain circuits of depression and may be worthy of further evaluation as a safe substitute to other rapid-onset antidepressants known to have unacceptable side effects. PMID:24520403

  16. Reverse engineering of aircraft wing data using a partial differential equation surface model

    NASA Astrophysics Data System (ADS)

    Huband, Jacalyn Mann

    Reverse engineering is a multi-step process used in industry to determine a production representation of an existing physical object. This representation is in the form of mathematical equations that are compatible with computer-aided design and computer-aided manufacturing (CAD/CAM) equipment. The four basic steps to the reverse engineering process are data acquisition, data separation, surface or curve fitting, and CAD/CAM production. The surface fitting step determines the design representation of the object, and thus is critical to the success or failure of the reverse engineering process. Although surface fitting methods described in the literature are used to model a variety of surfaces, they are not suitable for reversing aircraft wings. In this dissertation, we develop and demonstrate a new strategy for reversing a mathematical representation of an aircraft wing. The basis of our strategy is to take an aircraft design model and determine if an inverse model can be derived. A candidate design model for this research is the partial differential equation (PDE) surface model, proposed by Bloor and Wilson and used in the Rapid Airplane Parameter Input Design (RAPID) tool at the NASA-LaRC Geolab. There are several basic mathematical problems involved in reversing the PDE surface model: (i) deriving a computational approximation of the surface function; (ii) determining a radial parametrization of the wing; (iii) choosing mathematical models or classes of functions for representation of the boundary functions; (iv) fitting the boundary data points by the chosen boundary functions; and (v) simultaneously solving for the axial parameterization and the derivative boundary functions. The study of the techniques to solve the above mathematical problems has culminated in a reverse PDE surface model and two reverse PDE surface algorithms. One reverse PDE surface algorithm recovers engineering design parameters for the RAPID tool from aircraft wing data and the other generates a PDE surface model with spline boundary functions from an arbitrary set of grid points. Our numerical tests show that the reverse PDE surface model and the reverse PDE surface algorithms can be used for the reverse engineering of aircraft wing data.

  17. Spurious behavior in volcanic records of geomagnetic field reversals

    NASA Astrophysics Data System (ADS)

    Carlut, Julie; Vella, Jerome; Valet, Jean-Pierre; Soler, Vicente; Legoff, Maxime

    2016-04-01

    Very large directional variations of magnetization have been reported in several lava flows recording a geomagnetic reversal. Such behavior could reflect real geomagnetic changes or be caused by artifacts due to post-emplacement alteration and/or non-ideal magnetic behavior. More recently, a high resolution paleomagnetic record from sediments pleads also for an extremely rapid reversal process during the last reversal. Assuming that the geomagnetic field would have moved by tens of degrees during cooling of moderate thickness lava flows implies brief episodes of rapid changes by a few degrees per day that are difficult to reconcile with the rate of liquid motions at the core surface. Systematical mineralogical bias is a most likely explanation to promote such behavior as recently reconsidered by Coe et al., 2014 for the rapid field changes recorded at Steens Mountain. We resampled three lava flows at La Palma island (Canarias) that are sandwiched between reverse polarity and normal polarity flows associated with the last reversal. The results show an evolution of the magnetization direction from top to bottom. Thermal demagnetization experiments were conducted using different heating and cooling rates. Similarly, continuous demagnetization and measurements. In both cases, we did not notice any remagnetization associated with mineralogical transformations during the experiments. Magnetic grain sizes do not show any correlation with the amplitude of the deviations. Microscopic observations indicate poor exsolution, which could suggests post-cooling thermochemical remagnetization processes.

  18. Mitomycin C dissolved in a reversible thermosetting gel: target tissue concentrations in the rabbit eye

    PubMed Central

    Ichien, K.; Yamamoto, T.; Kitazawa, Y.; Oguri, A.; Ando, H.; Kondo, Y.

    1997-01-01

    AIMS—To determine whether a new, reversible thermosetting gel enhances mitomycin C transfer to target ocular tissues in the rabbit eye.
METHODS—A 0.1 ml solution of mitomycin C containing 0.22 µg, 2.9 µg, or 28 µg of the agent dissolved in a reversible thermosetting gel consisting of methylcellulose, citric acid, and polyethylene glycol was injected subconjunctivally in 30 New Zealand albino rabbits. Scleral and conjunctival tissues were excised at 0.5, 1, 2, 4, or 24 hours after the injection and mitomycin C concentrations in these tissues were determined by high performance liquid chromatography. The concentration over time was approximated to a single exponential curve, and initial mitomycin C concentrations, time constants, and half life values were determined. Finally, the areas under the curves (AUCs) between 0.5 and 24 hours were calculated.
RESULTS—The mitomycin C concentrations in the target tissues were dose dependent and decreased rapidly over 24 hours. Both the initial mitomycin C concentrations as well as AUCs in these eyes treated with mitomycin C, dissolved in a reversible thermosetting gel, were higher than those in eyes treated similarly in a previous study in which the gel was not used.
CONCLUSION—Applied subconjunctivally in the rabbit eye, mitomycin C dissolved in the reversible thermosetting gel enhanced transfer of the agent to the sclera and the conjunctiva.

 PMID:9135413

  19. Rapid group-, serotype-, and vaccine strain-specific identification of poliovirus isolates by real-time reverse transcription-PCR using degenerate primers and probes containing deoxyinosine residues.

    PubMed

    Kilpatrick, David R; Yang, Chen-Fu; Ching, Karen; Vincent, Annelet; Iber, Jane; Campagnoli, Ray; Mandelbaum, Mark; De, Lina; Yang, Su-Ju; Nix, Allan; Kew, Olen M

    2009-06-01

    We have adapted our previously described poliovirus diagnostic reverse transcription-PCR (RT-PCR) assays to a real-time RT-PCR (rRT-PCR) format. Our highly specific assays and rRT-PCR reagents are designed for use in the WHO Global Polio Laboratory Network for rapid and large-scale identification of poliovirus field isolates.

  20. Platelet Dynamics during Natural and Pharmacologically Induced Torpor and Forced Hypothermia

    PubMed Central

    de Vrij, Edwin L.; Vogelaar, Pieter C.; Goris, Maaike; Houwertjes, Martin C.; Herwig, Annika; Dugbartey, George J.; Boerema, Ate S.; Strijkstra, Arjen M.; Bouma, Hjalmar R.; Henning, Robert H.

    2014-01-01

    Hibernation is an energy-conserving behavior in winter characterized by two phases: torpor and arousal. During torpor, markedly reduced metabolic activity results in inactivity and decreased body temperature. Arousal periods intersperse the torpor bouts and feature increased metabolism and euthermic body temperature. Alterations in physiological parameters, such as suppression of hemostasis, are thought to allow hibernators to survive periods of torpor and arousal without organ injury. While the state of torpor is potentially procoagulant, due to low blood flow, increased viscosity, immobility, hypoxia, and low body temperature, organ injury due to thromboembolism is absent. To investigate platelet dynamics during hibernation, we measured platelet count and function during and after natural torpor, pharmacologically induced torpor and forced hypothermia. Splenectomies were performed to unravel potential storage sites of platelets during torpor. Here we show that decreasing body temperature drives thrombocytopenia during torpor in hamster with maintained functionality of circulating platelets. Interestingly, hamster platelets during torpor do not express P-selectin, but expression is induced by treatment with ADP. Platelet count rapidly restores during arousal and rewarming. Platelet dynamics in hibernation are not affected by splenectomy before or during torpor. Reversible thrombocytopenia was also induced by forced hypothermia in both hibernating (hamster) and non-hibernating (rat and mouse) species without changing platelet function. Pharmacological torpor induced by injection of 5′-AMP in mice did not induce thrombocytopenia, possibly because 5′-AMP inhibits platelet function. The rapidness of changes in the numbers of circulating platelets, as well as marginal changes in immature platelet fractions upon arousal, strongly suggest that storage-and-release underlies the reversible thrombocytopenia during natural torpor. Possibly, margination of platelets, dependent on intrinsic platelet functionality, governs clearance of circulating platelets during torpor. PMID:24722364

  1. Methylene blue does not reverse existing neurofibrillary tangle pathology in the rTg4510 mouse model of tauopathy.

    PubMed

    Spires-Jones, Tara L; Friedman, Taylor; Pitstick, Rose; Polydoro, Manuela; Roe, Allyson; Carlson, George A; Hyman, Bradley T

    2014-03-06

    Alzheimer's disease is characterized pathologically by aggregation of amyloid beta into senile plaques and aggregation of pathologically modified tau into neurofibrillary tangles. While changes in amyloid processing are strongly implicated in disease initiation, the recent failure of amyloid-based therapies has highlighted the importance of tau as a therapeutic target. "Tangle busting" compounds including methylene blue and analogous molecules are currently being evaluated as therapeutics in Alzheimer's disease. Previous studies indicated that methylene blue can reverse tau aggregation in vitro after 10 min, and subsequent studies suggested that high levels of drug reduce tau protein levels (assessed biochemically) in vivo. Here, we tested whether methylene blue could remove established neurofibrillary tangles in the rTg4510 model of tauopathy, which develops robust tangle pathology. We find that 6 weeks of methylene blue dosing in the water from 16 months to 17.5 months of age decreases soluble tau but does not remove sarkosyl insoluble tau, or histologically defined PHF1 or Gallyas positive tangle pathology. These data indicate that methylene blue treatment will likely not rapidly reverse existing tangle pathology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Methylene blue does not reverse existing neurofibrillary tangle pathology in the rTg4510 mouse model of tauopathy

    PubMed Central

    Spires-Jones, Tara L; Friedman, Taylor; Pitstick, Rose; Polydoro, Manuela; Roe, Allyson; Carlson, George A; Hyman, Bradley T

    2014-01-01

    Alzheimer's disease is characterized pathologically by aggregation of amyloid beta into senile plaques and aggregation of pathologically modified tau into neurofibrillary tangles. While changes in amyloid processing are strongly implicated in disease initiation, the recent failure of amyloid-based therapies has highlighted the importance of tau as a therapeutic target. “Tangle busting” compounds including methylene blue and analogous molecules are currently being evaluated as therapeutics in Alzheimer's disease. Previous studies indicated that methylene blue can reverse tau aggregation in vitro after 10 minutes, and subsequent studies suggested that high levels of drug reduce tau protein levels (assessed biochemically) in vivo. Here, we tested whether methylene blue could remove established neurofibrillary tangles in the rTg4510 model of tauopathy, which develops robust tangle pathology. We find that 6 weeks of methylene blue dosing in the water from 16 months to 17.5 months of age decreases soluble tau but does not remove sarkosyl insoluble tau, or histologically defined PHF1 or Gallyas positive tangle pathology. These data indicate that methylene blue treatment will likely not rapidly reverse existing tangle pathology. PMID:24462887

  3. Evidence for rapid uptake of D-galacturonic acid in the yeast Saccharomyces cerevisiae by a channel-type transport system.

    PubMed

    Souffriau, Ben; den Abt, Tom; Thevelein, Johan M

    2012-07-30

    D-Galacturonic acid is a major component of pectins but cannot be metabolized by Saccharomyces cerevisiae. It is assumed not to be taken up. We show that yeast displays surprisingly rapid low-affinity uptake of D-galacturonic acid, strongly increasing with decreasing extracellular pH and without saturation up to 1.5 M. There was no intracellular concentration above the extracellular level and transport was reversible. Among more than 160 single and multiple deletion mutants in channels and transporters, no strain was affected in D-galacturonic acid uptake. The uptake was not inhibited by any compound tested as candidate competitive inhibitor, including D-glucuronic acid, which was also transported. The characteristics of D-galacturonic acid uptake are consistent with involvement of a channel-type system, probably encoded by multiple genes. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Exciton-controlled fluorescence: application to hybridization-sensitive fluorescent DNA probe.

    PubMed

    Okamoto, Akimitsu; Ikeda, Shuji; Kubota, Takeshi; Yuki, Mizue; Yanagisawa, Hiroyuki

    2009-01-01

    A hybridization-sensitive fluorescent probe has been designed for nucleic acid detection, using the concept of fluorescence quenching caused by the intramolecular excitonic interaction of fluorescence dyes. We synthesized a doubly thiazole orange-labeled nucleotide showing high fluorescence intensity for a hybrid with the target nucleic acid and effective quenching for the single-stranded state. This exciton-controlled fluorescent probe was applied to living HeLa cells using microinjection to visualize intracellular mRNA localization. Immediately after injection of the probe into the cell, fluorescence was observed from the probe hybridizing with the target RNA. This fluorescence rapidly decreased upon addition of a competitor DNA. Multicoloring of this probe resulted in the simple simultaneous detection of plural target nucleic acid sequences. This probe realized a large, rapid, reversible change in fluorescence intensity in sensitive response to the amount of target nucleic acid, and facilitated spatiotemporal monitoring of the behavior of intracellular RNA.

  5. Rapidly reversible redox transformation in nanophase manganese oxides at room temperature triggered by changes in hydration

    PubMed Central

    Birkner, Nancy; Navrotsky, Alexandra

    2014-01-01

    Chemisorption of water onto anhydrous nanophase manganese oxide surfaces promotes rapidly reversible redox phase changes as confirmed by calorimetry, X-ray diffraction, and titration for manganese average oxidation state. Surface reduction of bixbyite (Mn2O3) to hausmannite (Mn3O4) occurs in nanoparticles under conditions where no such reactions are seen or expected on grounds of bulk thermodynamics in coarse-grained materials. Additionally, transformation does not occur on nanosurfaces passivated by at least 2% coverage of what is likely an amorphous manganese oxide layer. The transformation is due to thermodynamic control arising from differences in surface energies of the two phases (Mn2O3 and Mn3O4) under wet and dry conditions. Such reversible and rapid transformation near room temperature may affect the behavior of manganese oxides in technological applications and in geologic and environmental settings. PMID:24733903

  6. Rapidly reversible redox transformation in nanophase manganese oxides at room temperature triggered by changes in hydration.

    PubMed

    Birkner, Nancy; Navrotsky, Alexandra

    2014-04-29

    Chemisorption of water onto anhydrous nanophase manganese oxide surfaces promotes rapidly reversible redox phase changes as confirmed by calorimetry, X-ray diffraction, and titration for manganese average oxidation state. Surface reduction of bixbyite (Mn2O3) to hausmannite (Mn3O4) occurs in nanoparticles under conditions where no such reactions are seen or expected on grounds of bulk thermodynamics in coarse-grained materials. Additionally, transformation does not occur on nanosurfaces passivated by at least 2% coverage of what is likely an amorphous manganese oxide layer. The transformation is due to thermodynamic control arising from differences in surface energies of the two phases (Mn2O3 and Mn3O4) under wet and dry conditions. Such reversible and rapid transformation near room temperature may affect the behavior of manganese oxides in technological applications and in geologic and environmental settings.

  7. Complete and rapid reversal of the body color pattern in juveniles of the convict surgeonfish Acanthurus triostegus at Moorea Island (French Polynesia)

    NASA Astrophysics Data System (ADS)

    Besson, Marc; Salis, Pauline; Laudet, Vincent; Lecchini, David

    2018-03-01

    Color polymorphism is widespread in animals and can be associated with temporary adjustments to environmental variables (phenotypic plasticity). In teleost fishes, one of the most remarkable examples of color plasticity is background adaptation in flatfishes. However, such rapid and complete changes in body color and pattern remain relatively unreported in other species. The convict surgeonfish Acanthurus triostegus is a gregarious species whose body color pattern consists of black vertical bars on a whitish body. Here, we describe an entirely reverse body color pattern (white vertical bars on a blackish body) that we observed in some A. triostegus juveniles in a nursery area at Moorea Island, French Polynesia. In aquaria, we determined that change from one color pattern to the other is rapid, reversible, and corresponds to phenotypic plasticity associated with aggressive behavior.

  8. Salinity inhibits post transcriptional processing of chloroplast 16S rRNA in shoot cultures of jojoba (Simmondsia chinesis).

    PubMed

    Mizrahi-Aviv, Ela; Mills, David; Benzioni, Aliza; Bar-Zvi, Dudy

    2005-03-01

    Chloroplast metabolism is rapidly affected by salt stress. Photosynthesis is one of the first processes known to be affected by salinity. Here, we report that salinity inhibits chloroplast post-transcriptional RNA processing. A differentially expressed 680-bp cDNA, containing the 3' sequence of 16S rRNA, transcribed intergenic spacer, exon 1 and intron of tRNA(Ile), was isolated by differential display reverse transcriptase PCR from salt-grown jojoba (Simmondsia chinesis) shoot cultures. Northern blot analysis indicated that although most rRNA appears to be fully processed, partially processed chloroplast 16S rRNA accumulates in salt-grown cultures. Thus, salinity appears to decrease the processing of the rrn transcript. The possible effect of this decreased processing on physiological processes is, as yet, unknown.

  9. Cranioplasty prosthesis manufacturing based on reverse engineering technology

    PubMed Central

    Chrzan, Robert; Urbanik, Andrzej; Karbowski, Krzysztof; Moskała, Marek; Polak, Jarosław; Pyrich, Marek

    2012-01-01

    Summary Background Most patients with large focal skull bone loss after craniectomy are referred for cranioplasty. Reverse engineering is a technology which creates a computer-aided design (CAD) model of a real structure. Rapid prototyping is a technology which produces physical objects from virtual CAD models. The aim of this study was to assess the clinical usefulness of these technologies in cranioplasty prosthesis manufacturing. Material/Methods CT was performed on 19 patients with focal skull bone loss after craniectomy, using a dedicated protocol. A material model of skull deficit was produced using computer numerical control (CNC) milling, and individually pre-operatively adjusted polypropylene-polyester prosthesis was prepared. In a control group of 20 patients a prosthesis was manually adjusted to each patient by a neurosurgeon during surgery, without using CT-based reverse engineering/rapid prototyping. In each case, the prosthesis was implanted into the patient. The mean operating times in both groups were compared. Results In the group of patients with reverse engineering/rapid prototyping-based cranioplasty, the mean operating time was shorter (120.3 min) compared to that in the control group (136.5 min). The neurosurgeons found the new technology particularly useful in more complicated bone deficits with different curvatures in various planes. Conclusions Reverse engineering and rapid prototyping may reduce the time needed for cranioplasty neurosurgery and improve the prosthesis fitting. Such technologies may utilize data obtained by commonly used spiral CT scanners. The manufacturing of individually adjusted prostheses should be commonly used in patients planned for cranioplasty with synthetic material. PMID:22207125

  10. The behavioural consequences of sex reversal in dragons

    PubMed Central

    Li, Hong; Holleley, Clare E.; Elphick, Melanie; Georges, Arthur

    2016-01-01

    Sex differences in morphology, physiology, and behaviour are caused by sex-linked genes, as well as by circulating sex-steroid levels. Thus, a shift from genotypic to environmental sex determination may create an organism that exhibits a mixture of male-like and female-like traits. We studied a lizard species (Central Bearded Dragon, Pogona vitticeps), in which the high-temperature incubation of eggs transforms genetically male individuals into functional females. Although they are reproductively female, sex-reversed dragons (individuals with ZZ genotype reversed to female phenotype) resemble genetic males rather than females in morphology (relative tail length), general behaviour (boldness and activity level), and thermoregulatory tactics. Indeed, sex-reversed ‘females’ are more male-like in some behavioural traits than are genetic males. This novel phenotype may impose strong selection on the frequency of sex reversal within natural populations, facilitating rapid shifts in sex-determining systems. A single period of high incubation temperatures (generating thermally induced sex reversal) can produce functionally female individuals with male-like (or novel) traits that enhance individual fitness, allowing the new temperature-dependent sex-determining system to rapidly replace the previous genetically based one.

  11. Depth-related response of macroinvertebrates to the reversal of eutrophication in a Mediterranean lake: Implications for ecological assessment.

    PubMed

    Bazzanti, Marcello; Mastrantuono, Luciana; Pilotto, Francesca

    2017-02-01

    A better management of nutrient inflows into lakes has led to an improvement in their conditions (i.e. reversal of eutrophication) and the effects of this on macroinvertebrate communities that inhabit different lake-depth zones is largely unknown. This paper reports a comparison of macroinvertebrate communities living in the eulittoral, infralittoral and sublittoral/profundal zones of Lake Nemi (Central Italy) before and after its natural recovery from eutrophication following the deviation of domestic wastewater. The infralittoral zone responded more rapidly than the other two depth-zones to the improved ecological conditions, as shown by larger differences in community composition between the two periods. In the eulittoral sand, the combined effects of hydromorphological pressures and reversal of eutrophication hindered the biotic response. In the eulittoral and infralittoral zones, typical taxa of mesotrophic waters appeared or increased their abundances after the eutrophication reversal. Benthic invertebrate response was slower in the sublittoral/profundal zone due to deoxygenation that continued to prevail in the deepest area of the lake during summer. However, both tolerant and more sensitive taxa were collected there for the first time. After the reversal of eutrophication, the percentage of molluscan+large crustaceans increased in the infralittoral zone, whereas the oligochaete/chironomid ratio decreased in both sublittoral/profundal and infralittoral zones. Functional feeding metrics (percentages of filter-feeders, collector-gatherers, miners and scrapers/grazers) differently tracked the reversal of eutrophication in the three depth-zones probably according to the effects of the reduction of nutrients on food-web structure influencing macroinvertebrates. Biological Monitoring Working Party (BMWP) and the Average Score Per Taxon (ASPT) seemed to respond to eutrophication reversal only in the sublittoral/profundal zone, where deoxygenation plays a major role as a structuring agent of the community. Our results suggest that the effects of reversal of eutrophication can be better assessed by examining the response of the communities belonging to each zone individually. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

    PubMed Central

    Piston, David W.

    2015-01-01

    Traditional therapies for type 1 diabetes (T1D) involve insulin replacement or islet/pancreas transplantation and have numerous limitations. Our previous work demonstrated the ability of embryonic brown adipose tissue (BAT) transplants to establish normoglycemia without insulin in chemically induced models of insulin-deficient diabetes. The current study sought to extend the technique to an autoimmune-mediated T1D model and document the underlying mechanisms. In nonobese diabetic (NOD) mice, BAT transplants result in complete reversal of T1D associated with rapid and long-lasting euglycemia. In addition, BAT transplants placed prior to the onset of diabetes on NOD mice can prevent or significantly delay the onset of diabetes. As with streptozotocin (STZ)-diabetic models, euglycemia is independent of insulin and strongly correlates with decrease of inflammation and increase of adipokines. Plasma insulin-like growth factor-I (IGF-I) is the first hormone to increase following BAT transplants. Adipose tissue of transplant recipients consistently express IGF-I compared with little or no expression in controls, and plasma IGF-I levels show a direct negative correlation with glucose, glucagon, and inflammatory cytokines. Adipogenic and anti-inflammatory properties of IGF-I may stimulate regeneration of new healthy white adipose tissue, which in turn secretes hypoglycemic adipokines that substitute for insulin. IGF-I can also directly decrease blood glucose through activating insulin receptor. These data demonstrate the potential for insulin-independent reversal of autoimmune-induced T1D with BAT transplants and implicate IGF-I as a likely mediator in the resulting equilibrium. PMID:25898954

  13. Reverse transcription loop-mediated isothermal amplification (RT-LAMP), a light for mammalian transcript analysis in low-input laboratories.

    PubMed

    Pandey, Mamta; Singh, Dheer; Onteru, Suneel K

    2018-06-01

    Transcript analysis is usually performed by costly, time-consuming, and expertise intensive methods, like real time-PCR, microarray, etc. However, they are not much feasible in low-input laboratories. Therefore, we implemented the reverse transcription loop-mediated isothermal amplification (RT-LAMP) as a means of mammalian transcript analysis. Particularly, RT-LAMP was developed for buffalo aromatase cytochrome P450 (CYP19) transcript, to study its expression in 3D-cultured buffalo granulosa cells, which were exposed to lipopolysaccharide (LPS). The CYP19-RT-LAMP assay rapidly identified the LPS-induced downregulation of the CYP19 gene within 30 min at 63°C in a water bath. The assay was visualized via unaided eye by observing the change in turbidity and fluorescence, which were decreased by increasing the LPS exposure time to granulosa cells. Overall, the developed CYP19-RT-LAMP assay provided a hope on the application of RT-LAMP for mammalian transcript analysis in low-input laboratories. © 2017 Wiley Periodicals, Inc.

  14. Biphasic effects of selective serotonin reuptake inhibitors on anxiety: rapid reversal of escitalopram's anxiogenic effects in the novelty-induced hypophagia test in mice?

    PubMed

    Koek, Wouter; Mitchell, Nathan C; Daws, Lynette C

    2018-06-01

    In humans, chronic treatment with selective serotonin reuptake inhibitors (SSRIs) decreases anxiety, unlike acute treatment, which can increase anxiety. Although this biphasic pattern is observed clinically, preclinical demonstrations are rare. In an animal model of antidepressant-induced anxiolytic effects, the novelty-induced hypophagia (NIH) test, a single administration of the SSRI citalopram reportedly elicited anxiogenic-like effects, whereas three administrations over 24 h were sufficient to produce anxiolytic-like effects. Extending these findings, the present study examined the effects of acute and repeated escitalopram in a similar NIH test in a commonly used mouse strain (i.e. C57BL/6J), analyzing results with a method (i.e. survival analysis) that can model the skewed distribution of latencies to consume food and that can deal with censored data (i.e. when consumption does not occur during the test). Saline-treated mice showed robust NIH. Acute escitalopram enhanced NIH, but did so only at a dose (i.e. 32 mg/kg) that similarly enhanced hypophagia in a familiar environment. The effects of escitalopram on NIH did not significantly change after repeated (three times) administration over 24 h. Additional studies are necessary to delineate the conditions under which rapid reversal of SSRI-induced anxiety can be modeled in animals using the NIH test.

  15. Rapid Measurement of Room Temperature Ionic Liquid Electrochemical Gas Sensor using Transient Double Potential Amperometry

    PubMed Central

    Wan, Hao; Yin, Heyu; Mason, Andrew J.

    2016-01-01

    Intense study on gas sensors has been conducted to implement fast gas sensing with high sensitivity, reliability and long lifetime. This paper presents a rapid amperometric method for gas sensing based on a room temperature ionic liquid electrochemical gas sensor. To implement a miniaturized sensor with a fast response time, a three electrode system with gold interdigitated electrodes was fabricated by photolithography on a porous polytetrafluoroethylene substrate that greatly enhances gas diffusion. Furthermore, based on the reversible reaction of oxygen, a new transient double potential amperometry (DPA) was explored for electrochemical analysis to decrease the measurement time and reverse reaction by-products that could cause current drift. Parameters in transient DPA including oxidation potential, oxidation period, reduction period and sample point were investigated to study their influence on the performance of the sensor. Oxygen measurement could be accomplished in 4 s, and the sensor presented a sensitivity of 0.2863 μA/[%O2] and a linearity of 0.9943 when tested in air samples with different oxygen concentrations. Repeatability and long-term stability were also investigated, and the sensor was shown to exhibit good reliability. In comparison to conventional constant potential amperometry, transient DPA was shown to reduce relative standard deviation by 63.2%. With transient DPA, the sensitivity, linearity, repeatability, measurement time and current drift characteristics demonstrated by the presented gas sensor are promising for acute exposure applications. PMID:28603384

  16. Rapid Measurement of Room Temperature Ionic Liquid Electrochemical Gas Sensor using Transient Double Potential Amperometry.

    PubMed

    Wan, Hao; Yin, Heyu; Mason, Andrew J

    2017-04-01

    Intense study on gas sensors has been conducted to implement fast gas sensing with high sensitivity, reliability and long lifetime. This paper presents a rapid amperometric method for gas sensing based on a room temperature ionic liquid electrochemical gas sensor. To implement a miniaturized sensor with a fast response time, a three electrode system with gold interdigitated electrodes was fabricated by photolithography on a porous polytetrafluoroethylene substrate that greatly enhances gas diffusion. Furthermore, based on the reversible reaction of oxygen, a new transient double potential amperometry (DPA) was explored for electrochemical analysis to decrease the measurement time and reverse reaction by-products that could cause current drift. Parameters in transient DPA including oxidation potential, oxidation period, reduction period and sample point were investigated to study their influence on the performance of the sensor. Oxygen measurement could be accomplished in 4 s, and the sensor presented a sensitivity of 0.2863 μA/[%O 2 ] and a linearity of 0.9943 when tested in air samples with different oxygen concentrations. Repeatability and long-term stability were also investigated, and the sensor was shown to exhibit good reliability. In comparison to conventional constant potential amperometry, transient DPA was shown to reduce relative standard deviation by 63.2%. With transient DPA, the sensitivity, linearity, repeatability, measurement time and current drift characteristics demonstrated by the presented gas sensor are promising for acute exposure applications.

  17. Tumors acquire inhibitor of apoptosis protein (IAP)-mediated apoptosis resistance through altered specificity of cytosolic proteolysis.

    PubMed

    Hong, Xu; Lei, Lu; Glas, Rickard

    2003-06-16

    Many tumors overexpress members of the inhibitor of apoptosis protein (IAP) family. IAPs contribute to tumor cell apoptosis resistance by the inhibition of caspases, and are degraded by the proteasome to allow further progression of apoptosis. Here we show that tumor cells can alter the specificity of cytosolic proteolysis in order to acquire apoptosis resistance, which promotes formation of rapidly growing tumors. Survival of tumor cells with low proteasomal activity can occur in the presence of high expression of Tri-peptidyl-peptidase II (TPP II), a large subtilisin-like peptidase that complements proteasomal activity. We find that this state leaves tumor cells unable of effectively degrading IAPs, and that cells in this state form rapidly growing tumors in vivo. We also find, in studies of apoptosis resistant cells derived from large in vivo tumors, that these have acquired an altered peptidase activity, with up-regulation of TPP II activity and decreased proteasomal activity. Importantly, we find that growth of subcutaneous tumors is limited by maintenance of the apoptosis resistant phenotype. The apoptosis resistant phenotype was reversed by increased expression of Smac/DIABLO, an antagonist of IAP molecules. Our data suggest a reversible mechanism in regulation of apoptosis resistance that drives tumor progression in vivo. These data are relevant in relation to the multitude of therapy-resistant clinical tumors that have increased levels of IAP molecules.

  18. Kinetic analysis of enzyme systems with suicide substrate in the presence of a reversible competitive inhibitor, tested by simulated progress curves.

    PubMed

    Moruno-Dávila, M A; Garrido-del Solo, C; García-Moreno, M; Havsteen, B H; Garcia-Sevilla, F; Garcia-Cánovas, F; Varón, R

    2001-02-01

    The use of suicide substrates remains a very important and useful method in enzymology for studying enzyme mechanisms and designing potential drugs. Suicide substrates act as modified substrates for the target enzymes and bind to the active site. Therefore the presence of a competitive reversible inhibitor decreases the rate of substrate-induced inactivation and protects the enzyme from this inactivation. This lowering on the inactivation rate has evident physiological advantages, since it allows the easy acquisition of experimental data and facilitates kinetic data analysis by providing another variable (inhibitor concentration). However despite the importance of the simultaneous action of a suicide substrate and a competitive reversible inhibition, to date no corresponding kinetic analysis has been carried out. Therefore we present a general kinetic analysis of a Michaelis-Menten reaction mechanism with double inhibition caused by both, a suicide substrate and a competitive reversible inhibitor. We assume rapid equilibrium of the reversible reaction steps involved, while the time course equations for the reaction product have been derived with the assumption of a limiting enzyme. The goodness of the analytical solutions has been tested by comparison with the simulated curves obtained by numerical integration. A kinetic data analysis to determine the corresponding kinetic parameters from the time progress curve of the product is suggested. In conclusion, we present a complete kinetic analysis of an enzyme reaction mechanism as described above in an attempt to fill a gap in the theoretical treatment of this type of system.

  19. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myoribers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postmitotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  20. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  1. Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.

    PubMed

    Fan, Jinqi; Zou, Lili; Cui, Kun; Woo, Kamsang; Du, Huaan; Chen, Shaojie; Ling, Zhiyu; Zhang, Quanjun; Zhang, Bo; Lan, Xianbin; Su, Li; Zrenner, Bernhard; Yin, Yuehui

    2015-01-01

    The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1-7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-β1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin-angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF.

  2. Evidence for biofilm acid neutralization by baking soda.

    PubMed

    Zero, Domenick T

    2017-11-01

    The generating of acids from the microbial metabolism of dietary sugars and the subsequent decrease in biofilm pH below the pH at which tooth mineral begins to demineralize (critical pH) are the key elements of the dental caries process. Caries preventive strategies that rapidly neutralize biofilm acids can prevent demineralization and favor remineralization and may help prevent the development of sugar-induced dysbiosis that shifts the biofilm toward increased cariogenic potential. Although the neutralizing ability of sodium bicarbonate (baking soda) has been known for many years, its anticaries potential as an additive to fluoride dentifrice has received only limited investigation. There is evidence that baking soda rapidly can reverse the biofilm pH decrease after a sugar challenge; however, the timing of when it is used in relation to a dietary sugar exposure is critical in that the sooner its used the greater the benefit in preventing a sustained biofilm pH decrease and subsequent demineralization. Furthermore, the effectiveness of baking soda in elevating biofilm pH appears to depend on concentration. Thus, the concentration of baking soda in marketed dentifrice products, which ranges from 10% to 65%, may affect their biofilm pH neutralizing performance. People with hyposalivation particularly may benefit from using fluoride dentifrice containing baking soda because of their diminished ability to clear dietary sugars and buffer biofilm acids. Although promising, there is the need for more evidence that strategies that modify the oral ecology, such as baking soda, can alter the cariogenic (acidogenic and aciduric) properties of biofilm microorganisms. The acid neutralization of dental biofilm by using fluoride dentifrice that contains baking soda has potential for helping counteract modern high-sugar diets by rapidly neutralizing biofilm-generated acid, especially in people with hyposalivation. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

  3. Cysteine reversal of the novel neuromuscular blocking drug CW002 in dogs: pharmacodynamics, acute cardiovascular effects, and preliminary toxicology.

    PubMed

    Sunaga, Hiroshi; Malhotra, Jaideep K; Yoon, Edward; Savarese, John J; Heerdt, Paul M

    2010-04-01

    CW002 is a neuromuscular blocking drug that is inactivated by endogenous L-cysteine. This study determined the exogenous L-cysteine dose-response relationship for CW002 reversal along with acute cardiovascular effects and organ toxicity in dogs. Six dogs were each studied four times during isoflurane-nitrous oxide anesthesia and recording of muscle twitch, arterial pressure, and heart rate. CW002 (0.08 mg/kg or 9 x ED95) was injected, and the time to spontaneous muscle recovery was determined. CW002 was then administered again followed 1 min later by 10, 20, 50, or 100 mg/kg L-cysteine (1 dose/experiment). After twitch recovery, CW002 was given a third time to determine whether residual L-cysteine influenced duration. Preliminary toxicology was performed in an additional group of dogs that received CW002 followed by vehicle (n = 8) or 200 mg/kg L-cysteine (n = 8). Animals were awakened and observed for 2 or 14 days before sacrificing and anatomic, biochemical, and histopathologic analyses. L-cysteine at all doses accelerated recovery from CW002, with both 50 and 100 mg/kg decreasing median duration from more than 70 min to less than 5 min. After reversal, duration of a subsequent CW002 dose was also decreased in a dose-dependent manner. Over the studied dose range, L-cysteine had less than 10% effect on blood pressure and heart rate. Animals receiving a single 200-mg/kg dose of L-cysteine showed no clinical, anatomic, biochemical, or histologic evidence of organ toxicity. The optimal L-cysteine dose for rapidly reversing the neuromuscular blockade produced by a large dose of CW002 in dogs is approximately 50 mg/kg, which has no concomitant hemodynamic effect. A dose of 200 mg/kg had no evident organ toxicity.

  4. Inverse agonist abolishes desensitization of a constitutively active mutant of thyrotropin-releasing hormone receptor: role of cellular calcium and protein kinase C

    PubMed Central

    Grimberg, Hagit; Zaltsman, Ilona; Lupu-Meiri, Monica; Gershengorn, Marvin C; Oron, Yoram

    1999-01-01

    C335Stop is a constitutively active mutant of the TRH receptor (TRH-R). To investigate the mechanism of the decreased responsiveness of C335Stop TRH-R, we studied cellular Ca2+ concentrations ([Ca2+]i) in AtT20 cells stably transfected with C335Stop TRH-R cDNA, or Ca2+-activated chloride currents in Xenopus laevis oocytes expressing this mutant receptor after injection of cRNA. The competitive TRH-R binding antagonist, chlorodiazepoxide (CDE), was used as an inverse agonist to study the contribution of constitutive activity to desensitization. Acute treatment with CDE resulted in a rapid (within minutes) decrease in [Ca2+]i and an increase in the response amplitude to TRH with no measurable change in receptor density. Conversely, removal of chronically administered CDE caused a rapid increase in [Ca2+]i and a decrease in TRH response amplitude. CDE abolished heterologous desensitization induced by C335Stop TRH-R on muscarinic m1-receptor (m1-R) co-expressed in Xenopus oocytes. Chelation of extracellular calcium with EGTA caused a rapid decrease in [Ca2+]i and a concomitant increase in the response to TRH in AtT20 cells expressing C335Stop TRH-Rs. Chelerythrine, a specific inhibitor of protein kinase C (PKC), reversed the heterologous desensitization of the response to acetylcholine (ACh). The phosphoserine/phosphothreonine phosphatase inhibitor, okadaic acid, abolished the effect of chelerythrine. Down-regulation of PKC by chronic exposure to phorbol 12-myristate 13-acetate (PMA) or acute inhibition with chelerythrine caused a partial resensitization of the response to TRH. Western analysis indicated that the α subtype of protein kinase C was down-regulated in cells expressing C335Stop TRH-Rs. Following a 5 min exposure to PMA, the residual αPKC translocated to the particular fraction. We propose that cells expressing the constitutively active mutant TRH-R rapidly desensitize their response, utilizing a mechanism mediated by an increase in [Ca2+]i and PKC. PMID:10204996

  5. Kinetics of imidization and crosslinking in PMR-polyimide resin

    NASA Technical Reports Server (NTRS)

    Lauver, R. W.

    1977-01-01

    Infrared spectroscopy and differential scanning calorimetry were employed to study the imidization and crosslinking kinetics of norbornenyl-capped, addition-type polyimide resins (designated PMR for polymerization of monomer reactants). The spectral and thermal analyses were performed on resin specimens which had been isothermally aged at temperatures appropriate for imidization (120 to 204 C) and crosslinking (275 to 325 C). Imidization occurs rapidly (approximately 0.01/min) at short times, while at times longer than approximately 0.5 hour, the rate decreases significantly (approximately 0.0001/min). The crosslinking reaction exhibits first order kinetics during the initial portion of the reaction and its rate appears to be limited by the reversion of the norbornenyl Diels-Alder adduct. The total heat evolved per mole of endcap during crosslinking shows an inverse dependence on the molecular weight of the imide prepolymers. This reflects the effect of endcap dilution and decreased mobility of the larger oligomers.

  6. A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer-based chemical sensor

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

    Bryant, M. J.; Skelton, J. M.; Hatcher, L. E.

    Selective, robust and cost-effective chemical sensors for detecting small volatile-organic compounds (VOCs) have widespread applications in industry, healthcare and environmental monitoring. Here we design a Pt(II) pincer-Type material with selective absorptive and emissive responses to methanol and water. The yellow anhydrous form converts reversibly on a subsecond timescale to a red hydrate in the presence of parts-per-Thousand levels of atmospheric water vapour. Exposure to methanol induces a similarly-rapid and reversible colour change to a blue methanol solvate. Stable smart coatings on glass demonstrate robust switching over 10 4 cycles, and flexible microporous polymer membranes incorporating microcrystals of the complex showmore » identical vapochromic behaviour. The rapid vapochromic response can be rationalised from the crystal structure, and in combination with quantum-chemical modelling, we provide a complete microscopic picture of the switching mechanism. We discuss how this multiscale design approach can be used to obtain new compounds with tailored VOC selectivity and spectral responses.« less

  7. A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer-based chemical sensor

    DOE PAGES

    Bryant, M. J.; Skelton, J. M.; Hatcher, L. E.; ...

    2017-11-27

    Selective, robust and cost-effective chemical sensors for detecting small volatile-organic compounds (VOCs) have widespread applications in industry, healthcare and environmental monitoring. Here we design a Pt(II) pincer-Type material with selective absorptive and emissive responses to methanol and water. The yellow anhydrous form converts reversibly on a subsecond timescale to a red hydrate in the presence of parts-per-Thousand levels of atmospheric water vapour. Exposure to methanol induces a similarly-rapid and reversible colour change to a blue methanol solvate. Stable smart coatings on glass demonstrate robust switching over 10 4 cycles, and flexible microporous polymer membranes incorporating microcrystals of the complex showmore » identical vapochromic behaviour. The rapid vapochromic response can be rationalised from the crystal structure, and in combination with quantum-chemical modelling, we provide a complete microscopic picture of the switching mechanism. We discuss how this multiscale design approach can be used to obtain new compounds with tailored VOC selectivity and spectral responses.« less

  8. Pre-stimulus EEG oscillations correlate with perceptual alternation of speech forms.

    PubMed

    Barraza, Paulo; Jaume-Guazzini, Francisco; Rodríguez, Eugenio

    2016-05-27

    Speech perception is often seen as a passive process guided by physical stimulus properties. However, ongoing brain dynamics could influence the subsequent perceptual organization of the speech, to an as yet unknown extent. To elucidate this issue, we analyzed EEG oscillatory activity before and immediately after the repetitive auditory presentation of words inducing the so-called verbal transformation effect (VTE), or spontaneous alternation of meanings due to its rapid repetition. Subjects indicated whether the meaning of the bistable word changed or not. For the Reversal more than for the Stable condition, results show a pre-stimulus local alpha desynchronization (300-50ms), followed by an early post-stimulus increase of local beta synchrony (0-80ms), and then a late increase and decrease of local alpha (200-340ms) and beta (360-440ms) synchrony respectively. Additionally, the ERPs showed that reversal positivity (RP) and reversal negativity components (RN), along with a late positivity complex (LPC) correlate with switching between verbal forms. Our results show how the ongoing dynamics brain is actively involved in the perceptual organization of the speech, destabilizing verbal perceptual states, and facilitating the perceptual regrouping of the elements composing the linguistic auditory stimulus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Bole girdling affects metabolic properties and root, trunk and branch hydraulics of young ponderosa pine trees.

    PubMed

    Domec, Jean-Christophe; Pruyn, Michele L

    2008-10-01

    Effects of trunk girdling on seasonal patterns of xylem water status, water transport and woody tissue metabolic properties were investigated in ponderosa pine (Pinus ponderosa Dougl. ex P. Laws.) trees. At the onset of summer, there was a sharp decrease in stomatal conductance (g(s)) in girdled trees followed by a full recovery after the first major rainfall in September. Eliminating the root as a carbohydrate sink by girdling induced a rapid reversible reduction in g(s). Respiratory potential (a laboratory measure of tissue-level respiration) increased above the girdle (branches and upper trunk) and decreased below the girdle (lower trunk and roots) relative to control trees during the growing season, but the effect was reversed after the first major rainfall. The increase in branch respiratory potential induced by girdling suggests that the decrease in g(s) was caused by the accumulation of carbohydrates above the girdle, which is consistent with an observed increase in leaf mass per area in the girdled trees. Trunk girdling did not affect native xylem embolism or xylem conductivity. Both treated and control trunks experienced loss of xylem conductivity ranging from 10% in spring to 30% in summer. Girdling reduced xylem growth and sapwood to leaf area ratio, which in turn reduced branch leaf specific conductivity (LSC). The girdling-induced reductions in g(s) and transpiration were associated with a decrease in leaf hydraulic conductance. Two years after girdling, when root-to-shoot phloem continuity had been restored, girdled trees had a reduced density of new wood, which increased xylem conductivity and whole-tree LSC, but also vulnerability to embolism.

  10. Rapid and reliable diagnostic method to detect Zika virus by real-time fluorescence reverse transcription loop-mediated isothermal amplification.

    PubMed

    Guo, Xu-Guang; Zhou, Yong-Zhuo; Li, Qin; Wang, Wei; Wen, Jin-Zhou; Zheng, Lei; Wang, Qian

    2018-04-18

    To detect Zika virus more rapidly and accurately, we developed a novel method that utilized a real-time fluorescence reverse transcription loop-mediated isothermal amplification (LAMP) technique. The NS5 gene was amplified by a set of six specific primers that recognized six distinct sequences. The amplification process, including 60 min of thermostatic reaction with Bst DNA polymerase following real-time fluorescence reverse transcriptase using genomic Zika virus standard strain (MR766), was conducted through fluorescent signaling. Among the six pairs of primers that we designate here, NS5 was the most efficient with a high sensitivity of up to 3.3 ng/μl and reproducible specificity on eight pathogen samples that were used as negative controls. The real-time fluorescence reverse transcription LAMP detection process can be completed within 35 min. Our study demonstrated that real-time fluorescence reverse transcription LAMP could be highly beneficial and convenient clinical application to detect Zika virus due to its high specificity and stability.

  11. Nitrite therapy after cardiac arrest reduces ROS generation, improves cardiac and neurological function and enhances survival via reversible inhibition of mitochondrial complex I

    PubMed Central

    Dezfulian, Cameron; Shiva, Sruti; Alekseyenko, Aleksey; Pendyal, Akshay; Beiser, DG; Munasinghe, Jeeva P.; Anderson, Stasia A.; Chesley, Christopher F.; Hoek, TL Vanden; Gladwin, Mark T.

    2009-01-01

    Background Three-fourths of cardiac arrest survivors die prior to hospital discharge or suffer significant neurological injury. Excepting therapeutic hypothermia and revascularization, no novel therapies have been developed that improve survival or cardiac and neurological function after resuscitation. Nitrite (NO2−) increases cellular resilience to focal ischemia-reperfusion injury in multiple organs. We hypothesized that nitrite therapy may improve outcomes after the unique global ischemia-reperfusion insult of cardiopulmonary arrest. Methods and Results We developed a mouse model of cardiac arrest characterized by 12-minutes of normothermic asystole and a high cardiopulmonary resuscitation (CPR) rate. In this model, global ischemia and CPR was associated with blood and organ nitrite depletion, reversible myocardial dysfunction, impaired alveolar gas exchange, neurological injury and an approximate 50% mortality. A single low dose of intravenous nitrite (50 nmol=1.85 μmol/kg=0.13 mg/kg) compared to blinded saline placebo given at CPR initiation with epinephrine improved cardiac function, survival and neurological outcomes. From a mechanistic standpoint, nitrite treatment restored intracardiac nitrite and increased S-nitrosothiol levels, decreased pathological cardiac mitochondrial oxygen consumption due to reactive oxygen species formation and prevented oxidative enzymatic injury via reversible specific inhibition of respiratory chain complex I. Conclusion Nitrite therapy after resuscitation from 12-minutes of asystole rapidly and reversibly modulated mitochondrial reactive oxygen species generation during early reperfusion, limiting acute cardiac dysfunction and death, as well as neurological impairment in survivors. PMID:19704094

  12. Dynamics of high-bypass-engine thrust reversal using a variable-pitch fan

    NASA Technical Reports Server (NTRS)

    Schaefer, J. W.; Sagerser, D. R.; Stakolich, E. G.

    1977-01-01

    The test program demonstrated that successful and rapid forward-to reverse-thrust transients can be performed without any significant engine operational limitations for fan blade pitch changes through either feather pitch or flat pitch. For through-feather-pitch operation with a flight inlet, fan stall problems were encountered, and a fan blade overshoot technique was used to establish reverse thrust.

  13. Application of wide-field optical coherence tomography to monitoring of viability of rat brain in vivo

    NASA Astrophysics Data System (ADS)

    Sato, Manabu; Nishidate, Izumi

    2014-05-01

    We investigated the feasibility of OCT in monitoring the viability of the brain. It was confirmed that after an overdose of pentobarbital sodium salt for an euthanasia, the OCT signal intensity increased before cardiac arrest and finally became 2.7 times, and by periodically changing the tissue temperature from 20 to 32 °C in vivo, average correlation coefficients between the ratio of signal intensity (RSI) and temperature were determined to be -0:42 to -0:50. RSI reversibly changed with subsequent variations of temperatures and finally increased rapidly just before cardiac arrest. These results indicate that RSI could correspond to decreases in viability.

  14. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device.

    PubMed

    Germain, Todd; Ansari, Megan; Pappas, Dimitri

    2016-09-14

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS

    PubMed Central

    Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y.; Robb, Ellen L.; Logan, Angela; Nadtochiy, Sergiy M.; Ord, Emily N. J.; Smith, Anthony C.; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J.; James, Andrew M.; Rogatti, Sebastian; Hartley, Richard C.; Eaton, Simon; Costa, Ana S.H.; Brookes, Paul S.; Davidson, Sean M.; Duchen, Michael R.; Saeb-Parsy, Kourosh; Shattock, Michael J.; Robinson, Alan J.; Work, Lorraine M.; Frezza, Christian; Krieg, Thomas; Murphy, Michael P.

    2014-01-01

    Ischaemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death, and aberrant immune responses through generation of mitochondrial reactive oxygen species (ROS)1-5. Although mitochondrial ROS production in IR is established, it has generally been considered a non-specific response to reperfusion1,3. Here, we developed a comparative in vivo metabolomic analysis and unexpectedly identified widely conserved metabolic pathways responsible for mitochondrial ROS production during IR. We showed that selective accumulation of the citric acid cycle (CAC) intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase (SDH), which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. Upon reperfusion, the accumulated succinate is rapidly re-oxidised by SDH, driving extensive ROS generation by reverse electron transport (RET) at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo IR injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of IR injury. Furthermore, these findings reveal a novel pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation upon subsequent reperfusion is a potential therapeutic target to decrease IR injury in a range of pathologies. PMID:25383517

  16. Rapid and reversible epigenome editing by endogenous chromatin regulators.

    PubMed

    Braun, Simon M G; Kirkland, Jacob G; Chory, Emma J; Husmann, Dylan; Calarco, Joseph P; Crabtree, Gerald R

    2017-09-15

    Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells. Furthermore, Hp1/Suv39h1 heterochromatin complex recruitment to active promoters deposits H3K9me3 domains, resulting in gene silencing that can be reversed upon washout of the chemical dimerizer. This inducible recruitment strategy provides precise kinetic information to model epigenetic memory and plasticity. It is broadly applicable to mechanistic studies of chromatin in mammalian cells and is particularly suited to the analysis of endogenous multi-subunit chromatin regulator complexes.Understanding the link between epigenetic marks and gene regulation requires the development of new tools to directly manipulate chromatin. Here the authors demonstrate a Cas9-based system to recruit chromatin remodelers to loci of interest, allowing rapid, reversible manipulation of epigenetic states.

  17. No impact of repeated extinction exposures on operant responding maintained by different reinforcer rates.

    PubMed

    Bai, John Y H; Podlesnik, Christopher A

    2017-05-01

    Greater rates of intermittent reinforcement in the presence of discriminative stimuli generally produce greater resistance to extinction, consistent with predictions of behavioral momentum theory. Other studies reveal more rapid extinction with higher rates of reinforcers - the partial reinforcement extinction effect. Further, repeated extinction often produces more rapid decreases in operant responding due to learning a discrimination between training and extinction contingencies. The present study examined extinction repeatedly with training with different rates of intermittent reinforcement in a multiple schedule. We assessed whether repeated extinction would reverse the pattern of greater resistance to extinction with greater reinforcer rates. Counter to this prediction, resistance to extinction was consistently greater across twelve assessments of training followed by six successive sessions of extinction. Moreover, patterns of responding during extinction resembled those observed during satiation tests, which should not alter discrimination processes with repeated testing. These findings join others suggesting operant responding in extinction can be durable across repeated tests. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Intracellular fluid flow in rapidly moving cells

    PubMed Central

    Keren, Kinneret; Yam, Patricia T.; Kinkhabwala, Anika; Mogilner, Alex; Theriot, Julie A.

    2010-01-01

    Cytosolic fluid dynamics have been implicated in cell motility1–5 because of the hydrodynamic forces they induce and because of their influence on transport of components of the actin machinery to the leading edge. To investigate the existence and the direction of fluid flow in rapidly moving cells, we introduced inert quantum dots into the lamellipodia of fish epithelial keratocytes and analysed their distribution and motion. Our results indicate that fluid flow is directed from the cell body towards the leading edge in the cell frame of reference, at about 40% of cell speed. We propose that this forward-directed flow is driven by increased hydrostatic pressure generated at the rear of the cell by myosin contraction, and show that inhibition of myosin II activity by blebbistatin reverses the direction of fluid flow and leads to a decrease in keratocyte speed. We present a physical model for fluid pressure and flow in moving cells that quantitatively accounts for our experimental data. PMID:19767741

  19. Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2*

    PubMed Central

    Wiemhoefer, Anne; Stargardt, Anita; van der Linden, Wouter A.; Renner, Maria C.; van Kesteren, Ronald E.; Stap, Jan; Raspe, Marcel A.; Tomkinson, Birgitta; Kessels, Helmut W.; Ovaa, Huib; Overkleeft, Herman S.; Florea, Bogdan; Reits, Eric A.

    2015-01-01

    Tripeptidyl peptidase II (TPP2) is a serine peptidase involved in various biological processes, including antigen processing, cell growth, DNA repair, and neuropeptide mediated signaling. The underlying mechanisms of how a peptidase can influence this multitude of processes still remain unknown. We identified rapid proteomic changes in neuroblastoma cells following selective TPP2 inhibition using the known reversible inhibitor butabindide, as well as a new, more potent, and irreversible peptide phosphonate inhibitor. Our data show that TPP2 inhibition indirectly but rapidly decreases the levels of active, di-phosphorylated extracellular signal-regulated kinase 1 (ERK1) and ERK2 in the nucleus, thereby down-regulating signal transduction downstream of growth factors and mitogenic stimuli. We conclude that TPP2 mediates many important cellular functions by controlling ERK1 and ERK2 phosphorylation. For instance, we show that TPP2 inhibition of neurons in the hippocampus leads to an excessive strengthening of synapses, indicating that TPP2 activity is crucial for normal brain function. PMID:26041847

  20. Obesity-induced decreases in muscle performance are not reversed by weight loss.

    PubMed

    Seebacher, F; Tallis, J; McShea, K; James, R S

    2017-08-01

    Obesity can affect muscle phenotypes, and may thereby constrain movement and energy expenditure. Weight loss is a common and intuitive intervention for obesity, but it is not known whether the effects of obesity on muscle function are reversible by weight loss. Here we tested whether obesity-induced changes in muscle metabolic and contractile phenotypes are reversible by weight loss. We used zebrafish (Danio rerio) in a factorial design to compare energy metabolism, locomotor capacity, muscle isometric force and work-loop power output, and myosin heavy chain (MHC) composition between lean fish, diet-induced obese fish, and fish that were obese and then returned to lean body mass following diet restriction. Obesity increased resting metabolic rates (P<0.001) and decreased maximal metabolic rates (P=0.030), but these changes were reversible by weight loss, and were not associated with changes in muscle citrate synthase activity. In contrast, obesity-induced decreases in locomotor performance (P=0.0034), and isolated muscle isometric stress (P=0.01), work-loop power output (P<0.001) and relaxation rates (P=0.012) were not reversed by weight loss. Similarly, obesity-induced decreases in concentrations of fast and slow MHCs, and a shift toward fast MHCs were not reversed by weight loss. Obesity-induced changes in locomotor performance and muscle contractile function were not reversible by weight loss. These results show that weight loss alone may not be a sufficient intervention.

  1. ATP-induced current in isolated outer hair cells of guinea pig cochlea.

    PubMed

    Nakagawa, T; Akaike, N; Kimitsuki, T; Komune, S; Arima, T

    1990-05-01

    1. Electrical and pharmacologic properties of ATP-induced current in outer hair cells isolated from guinea pig cochlea were investigated in the whole-cell recording mode by the use of a conventional patch-clamp technique. 2. Under current-clamp conditions, rapid application of ATP depolarized the outer hair cells resulting in an increase in conductance. The ATP-induced response did not show any desensitization during a continuous application. 3. At a holding potential of -70 mV, the ATP-induced inward current increased in a sigmoidal fashion over the concentration range between 3 microM and 1 mM. The half-maximum concentration (EC50) was 12 microM and the Hill coefficient was 0.93. 4. The ATP-induced current had a reversal potential near 6 mV, which was close to the theoretical value (1 mV) calculated from the Goldman-Hodgkin-Katz equation for permeable intra- and extracellular cations. 5. In the current-voltage (I-V) relationship for the ATP response, a slight inward-going rectification was observed at more positive potentials than the reversal potential. 6. The substitution of extracellular Na+ by equimolar choline+ shifted the reversal potential of the ATP-induced current to more negative values. The substitution of Cs+ in the internal solution by N-methyl-D-glucamine+ (NMG+) shifted it in the positive direction. The reversal potential of ATP-induced current was also shifted to positive values with increasing extracellular Ca2+ concentration. A decrease of intracellular Cl- by gluconate- did not affect the reversal potential, thereby indicating that the ATP-induced current is carried through a large cation channel.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Ketamine Corrects Stress-Induced Cognitive Dysfunction through JAK2/STAT3 Signaling in the Orbitofrontal Cortex

    PubMed Central

    Patton, Michael S; Lodge, Daniel J; Morilak, David A; Girotti, Milena

    2017-01-01

    Deficits in cognitive flexibility are prominent in stress-related psychiatric disorders, including depression. Ketamine has rapid antidepressant efficacy, but it is unknown if ketamine improves cognitive symptoms. In rats, 2 weeks chronic intermittent cold (CIC) stress impairs reversal learning, a form of cognitive flexibility mediated by the orbitofrontal cortex (OFC) that we have used previously to model cognitive dysfunction in depression. We have shown that activating JAK2/STAT3 signaling in the OFC rescued the CIC stress-induced reversal learning deficit. Thus, in the present study we determined whether ketamine also corrects the stress-induced reversal learning deficit, and if JAK2/STAT3 signaling is involved in this effect. A single injection of ketamine (10 mg/kg, i.p.) 24 h prior to testing rescued the CIC stress-induced reversal learning deficit. CIC stress decreased JAK2 phosphorylation in the OFC, and ketamine restored pJAK2 levels within 2 h post injection. The JAK2 inhibitor AG490 given systemically or into the OFC at the time of ketamine injection prevented its beneficial effect on reversal learning. We then tested the role of JAK2/STAT3 in ketamine-induced plasticity in the OFC. Ketamine depressed local field potentials evoked in the OFC by excitatory thalamic afferent stimulation, and this was prevented by JAK2 inhibition in the OFC. Further, in both the OFC and primary cortical neurons in culture, ketamine increased expression of the neural plasticity-related protein Arc, and this was prevented by JAK2 inhibition. These results suggest that the JAK2/STAT3 signaling pathway is a novel mechanism by which ketamine exerts its therapeutic effects on stress-induced cognitive dysfunction in the OFC. PMID:27748739

  3. Tension responses to rapid pressure release in glycerinated rabbit muscle fibers.

    PubMed Central

    Fortune, N S; Geeves, M A; Ranatunga, K W

    1991-01-01

    We have previously shown that the isometric tension of a fully calcium-activated skinned rabbit psoas muscle fiber is reversibly depressed by increased hydrostatic pressure. We report here the characterization of tension transients induced by a rapid (less than 1-ms) release of increased pressure at 12 degrees C. The tension transient consists of three clear phases, an initial further decrease of tension in phase with pressure change followed by two phases of tension increase back to the level recorded at ambient pressure. The mean reciprocal relaxation time for phase 2 (1/tau 2) was approximately 17 s-1 and that for phase 3 (1/tau 3) was 3 s-1. The presence of 20 mM inorganic phosphate markedly increased 1/tau 2 to approximately 52 s-1 and decreased 1/tau 3 to approximately 1.7 s-1. These observations are interpreted in terms of a pressure-sensitive transition between two attached crossbridge states of low (or zero) and higher force. This is compatible with the pressure-sensitive isomerization of actomyosin previously observed in solution. The results presented allow us to propose a coupling between a specific pressure-sensitive isomerization of purified actomyosin, the phosphate release step of the ATPase pathway, and the force-generating event of the cross-bridge cycle. PMID:1871140

  4. Electrochemical treatment of reverse osmosis concentrate on boron-doped electrodes in undivided and divided cell configurations.

    PubMed

    Bagastyo, Arseto Y; Batstone, Damien J; Kristiana, Ina; Escher, Beate I; Joll, Cynthia; Radjenovic, Jelena

    2014-08-30

    An undivided electrolytic cell may offer lower electrochlorination through reduction of chlorine/hypochlorite at the cathode. This study investigated the performance of electrooxidation of reverse osmosis concentrate using boron-doped diamond electrodes in membrane-divided and undivided cells. In both cell configurations, similar extents of chemical oxygen demand and dissolved organic carbon removal were obtained. Continuous formation of chlorinated organic compounds was observed regardless of the membrane presence. However, halogenation of the organic matter did not result in a corresponding increase in toxicity (Vibrio fischeri bioassay performed on extracted samples), with toxicity decreasing slightly until 10AhL(-1), and generally remaining near the initial baseline-toxicity equivalent concentration (TEQ) of the raw concentrate (i.e., ∼2mgL(-1)). The exception was a high range toxicity measure in the undivided cell (i.e., TEQ=11mgL(-1) at 2.4AhL(-1)), which rapidly decreased to 4mgL(-1). The discrepancy between the halogenated organic matter and toxicity patterns may be a consequence of volatile and/or polar halogenated by-products formed in oxidation by OH electrogenerated at the anode. The undivided cell exhibited lower energy compared to the divided cell, 0.25kWhgCOD(-1) and 0.34kWhgCOD(-1), respectively, yet it did not demonstrate any improvement regarding by-products formation. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Survey of Propulsion Systems for High Capacity Personal Rapid Transit

    DOT National Transportation Integrated Search

    1975-07-01

    The high-capacity personal rapid transit (HCPRT) system must operate with very short headways. To achieve safe operation at these headways, the propulsion system should meet certain unconventional requirements. They include reversible thrust capabili...

  6. High Throughput Determination of Critical Human Dosing Parameters (SOT)

    EPA Science Inventory

    High throughput toxicokinetics (HTTK) is a rapid approach that uses in vitro data to estimate TK for hundreds of environmental chemicals. Reverse dosimetry (i.e., reverse toxicokinetics or RTK) based on HTTK data converts high throughput in vitro toxicity screening (HTS) data int...

  7. High Throughput Determinations of Critical Dosing Parameters (IVIVE workshop)

    EPA Science Inventory

    High throughput toxicokinetics (HTTK) is an approach that allows for rapid estimations of TK for hundreds of environmental chemicals. HTTK-based reverse dosimetry (i.e, reverse toxicokinetics or RTK) is used in order to convert high throughput in vitro toxicity screening (HTS) da...

  8. RNA Virus Reverse Genetics and Vaccine Design

    PubMed Central

    Stobart, Christopher C.; Moore, Martin L.

    2014-01-01

    RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines. PMID:24967693

  9. Annual reversible plasticity of feeding structures: cyclical changes of jaw allometry in a sea urchin

    PubMed Central

    Ebert, Thomas A.; Hernández, José Carlos; Clemente, Sabrina

    2014-01-01

    A wide variety of organisms show morphologically plastic responses to environmental stressors but in general these changes are not reversible. Though less common, reversible morphological structures are shown by a range of species in response to changes in predators, competitors or food. Theoretical analysis indicates that reversible plasticity increases fitness if organisms are long-lived relative to the frequency of changes in the stressor and morphological changes are rapid. Many sea urchin species show differences in the sizes of jaws (demi-pyramids) of the feeding apparatus, Aristotle's lantern, relative to overall body size, and these differences have been correlated with available food. The question addressed here is whether reversible changes of relative jaw size occur in the field as available food changes with season. Monthly samples of the North American Pacific coast sea urchin Strongylocentrotus purpuratus were collected from Gregory Point on the Oregon (USA) coast and showed an annual cycle of relative jaw size together with a linear trend from 2007 to 2009. Strongylocentrotus purpuratus is a long-lived species and under field conditions individuals experience multiple episodes of changes in food resources both seasonally and from year to year. Their rapid and reversible jaw plasticity fits well with theoretical expectations. PMID:24500161

  10. Rapid detection of avian influenza virus a and subtype H5N1 by single step multiplex reverse transcription-polymerase chain reaction.

    PubMed

    Wei, Hui-Ling; Bai, Gui-Rong; Mweene, Aaron S; Zhou, Ying-Chun; Cong, Yan-Long; Pu, Juan; Wang, Shuai; Kida, Hiroshi; Liu, Jin-Hua

    2006-06-01

    Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) virus caused great economic losses to the poultry industry and resulted in human deaths in Thailand and Viet Nam in 2004. Rapid typing and subtyping of H5N1 viruses, especially from clinical specimens, are desirable for taking prompt control measures to prevent the spread of the disease. Here, we developed a set of oligonucleotide primers able to detect, type and subtype H5 and N1 influenza viruses in a single step multiplex reverse transcription-polymerase chain reaction (RT-PCR). RNA was extracted from allantoic fluid or from specimens with guanidinium isothiocyanate reagent. Reverse transcription and PCR were carried out with a mixture of primers specific for influenza viruses of type A, subtype H5 and N1 in a single reaction system under identical conditions. The amplified DNA fragments were analyzed by agarose gel electrophoresis. All the H5N1 viruses tested in the study and the experimental specimens presented three specific bands by the method established here. The results presented here suggest that the method described below is rapid and specific and, therefore, could be valuable in the rapid detection of H5N1 influenza viruses in clinics.

  11. Carbon Tetrachloride at Hepatotoxic Levels Blocks Reversibly Gap Junctions between Rat Hepatocytes

    NASA Astrophysics Data System (ADS)

    Saez, J. C.; Bennett, M. V. L.; Spray, D. C.

    1987-05-01

    Electrical coupling and dye coupling between pairs of rat hepatocytes were reversibly reduced by brief exposure to halogenated methanes (CBrCl3, CCl4, and CHCl3). The potency of different halomethanes in uncoupling hepatocytes was comparable to their hepatotoxicity in vivo, and the rank order was the same as that of their tendency to form free radicals. The effect of carbon tetrachloride (CCl4) on hepatocytes was substantially reduced by prior treatment with SKF 525A, an inhibitor of cytochrome P-450, and by exposure to the reducing reagent β -mercaptoethanol. Halomethane uncoupling occurred with or without extracellular calcium and did not change intracellular concentrations of calcium and hydrogen ions or the phosphorylation state of the main gap-junctional protein. Thus the uncoupling appears to depend on cytochrome P-450 oxidative metabolism in which free radicals are generated and may result from oxidation of the gap-junctional protein or of a regulatory molecule that leads to closure of gap-junctional channels. Decreases in junctional conductance may be a rapid cellular response to injury that protects healthy cells by uncoupling them from unhealthy ones.

  12. Orientation dependent cyclic stability of the elastocaloric effect in textured Ni-Mn-Ga alloys

    NASA Astrophysics Data System (ADS)

    Wei, Longsha; Zhang, Xuexi; Liu, Jian; Geng, Lin

    2018-05-01

    High-performance elastocaloric materials require a large reversible elastocaloric effect and long life cyclic stability. Here, we fabricated textured polycrystalline Ni50.4Mn27.3Ga22.3 alloys by cost-effective casting method to create a <001> texture. A strong correlation between the cyclic stability and the crystal orientation was demonstrated. A large reversible adiabatic temperature change ΔT ˜6 K was obtained when the external stress was applied parallel to <001> direction. However, the ΔT decreased rapidly after 50 cycles, showing an unstable elastocaloric effect (eCE). On the other hand, when the external stress was applied perpendicular to <001>, the adiabatic ΔT was smaller ˜4 K, but was stable over 100 cycles. This significantly enhanced eCE stability was related to the high yield strength, low transformation strain and much higher crack initiation-propagation resistances perpendicular to <001> direction. This study provides a feasible strategy for optimizing the eCE property by creation of the texture structure in polycrystalline Ni-Mn-Ga and Ni-Mn-X (X= In, Sn, Sb) alloys.

  13. Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes

    PubMed Central

    Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

    2016-01-01

    Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes. DOI: http://dx.doi.org/10.7554/eLife.19267.001 PMID:27627745

  14. Character Decomposition and Transposition Processes of Chinese Compound Words in Rapid Serial Visual Presentation.

    PubMed

    Cao, Hong-Wen; Yang, Ke-Yu; Yan, Hong-Mei

    2017-01-01

    Character order information is encoded at the initial stage of Chinese word processing, however, its time course remains underspecified. In this study, we assess the exact time course of the character decomposition and transposition processes of two-character Chinese compound words (canonical, transposed, or reversible words) compared with pseudowords using dual-target rapid serial visual presentation (RSVP) of stimuli appearing at 30 ms per character with no inter-stimulus interval. The results indicate that Chinese readers can identify words with character transpositions in rapid succession; however, a transposition cost is involved in identifying transposed words compared to canonical words. In RSVP reading, character order of words is more likely to be reversed during the period from 30 to 180 ms for canonical and reversible words, but the period from 30 to 240 ms for transposed words. Taken together, the findings demonstrate that the holistic representation of the base word is activated, however, the order of the two constituent characters is not strictly processed during the very early stage of visual word processing.

  15. Cardioprotection by modulation of mitochondrial respiration during ischemia–reperfusion: Role of apoptosis-inducing factor

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

    Xu, Aijun; Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030; Szczepanek, Karol

    Highlights: •Blockade of electron transport prevents the loss of AIF from mitochondria during IR. •Blockade of electron transport decreases caspase-independent cell death during IR. •Mitochondrial AIF content is down-regulated in Harlequin mice. •Blockade of electron transport protects Harlequin mouse hearts during IR. •Amobarbital protection is partially dependent on mitochondrial AIF content. -- Abstract: The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death.more » We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia–reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia–reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in reducing cell injury during reperfusion, the protection derived from the BET is not fully dependent on AIF-driven mechanisms.« less

  16. Remagnetization in Some Transitional Flows

    NASA Astrophysics Data System (ADS)

    Valet, J. P.; Carlut, J. H.; Vella, J.; Le Goff, M.; Soler, V.

    2016-12-01

    Very large directional variations of magnetization have been reported in several lava flows recording a geomagnetic reversal. Such behavior could reflect real geomagnetic changes or be caused by artifacts due to post-emplacement alteration and/or non-ideal magnetic behavior. More recently, a high resolution paleomagnetic record from sediments pleads also for an extremely rapid reversal process during the last reversal (Sagnotti et al., 2014). Assuming that the geomagnetic field would have moved by tens of degrees during cooling of moderate thickness lava flows implies brief episodes of rapid changes by a few degrees per day that are difficult to reconcile with the rate of liquid motions at the core surface. Systematical mineralogical bias is a most likely explanation to promote such behavior as recently reconsidered by Coe et al., 2014 for the rapid field changes recorded at Steens Mountain. We resampled two lava flows at La Palma island (Canarias) that are sandwiched between reverse polarity and normal polarity flows associated with the last geomagnetic reversal. The results show an evolution of the magnetization direction from top to bottom. Hysteresis, coercivity and thermomagnetic parameters do not show important variations and no correlation with the amplitude of the deviations could be established. Thermal demagnetization experiments conducted using continuous demagnetization (TRIAXE method) did not allow the detection of dubious behavior. Experimental evidences finally indicate that critical thermal activation of some of the magnetic grains during the moderate baking by the above flow may be responsible for the directional swing. Microscopic observations indicate poor exsolution, which suggest a link between Ti-rich magnetite and thermoviscous remagnetization.

  17. The savory method can not green deserts or reverse climate change

    USDA-ARS?s Scientific Manuscript database

    Mr. Allan Savory addressed one of the major environmental challenges of our time – rapidly increasing atmospheric CO2 concentrations and climate warming - in a video presentation entitled, "How to green the world's deserts and reverse climate change" that was presented at the 2013 TED (Technology, E...

  18. Using habit reversal to decrease filled pauses in public speaking.

    PubMed

    Mancuso, Carolyn; Miltenberger, Raymond G

    2016-03-01

    This study evaluated the effectiveness of simplified habit reversal in reducing filled pauses that occur during public speaking. Filled pauses consist of "uh," "um," or "er"; clicking sounds; and misuse of the word "like." After baseline, participants received habit reversal training that consisted of awareness training and competing response training. During postintervention assessments, all 6 participants exhibited an immediate decrease in filled pauses. © 2015 Society for the Experimental Analysis of Behavior.

  19. Na+/Ca2+ exchange and regulation of cytoplasmic concentration of calcium in rat cerebellar neurons treated with glutamate.

    PubMed

    Storozhevykh, T P; Sorokina, E G; Vabnitz, A V; Senilova, Ya E; Tukhbatova, G R; Pinelis, V G

    2007-07-01

    In the present work, the forward and/or reversed Na+/Ca2+ exchange in cerebellar granular cells was suppressed by substitution of Na+o by Li+ before, during, and after exposure to glutamate for varied time and also using the inhibitor KB-R7943 of the reversed exchange. After glutamate challenge for 1 min, Na+o/Li+ substitution did not influence the recovery of low [Ca2+]i in a calcium-free medium. A 1-h incubation with 100 microM glutamate induced in the neurons a biphasic and irreversible [Ca2+]i rise (delayed calcium deregulation (DCD)), enhancement of [Na+]i, and decrease in the mitochondrial potential. If Na+o had been substituted by Li+ before the application of glutamate, i.e. the exchange reversal was suppressed during the exposure to glutamate, the number of cells with DCD was nearly fourfold lowered. However, addition of the Na+/K+-ATPase inhibitor ouabain (0.5 mM) not preventing the exchange reversal also decreased DCD in the presence of glutamate. Both exposures decreased the glutamate-caused loss of intracellular ATP. Glucose deprivation partially abolished protective effects of the Na+o/Li+ substitution and ouabain. KB-R7943 (10 microM) increased 7.4-fold the number of cells with the [Ca2+]i decreased to the basal level after the exposure to glutamate. Thus, reversal of the Na+/Ca2+ exchange reinforced the glutamate-caused perturbations of calcium homeostasis in the neurons and slowed the recovery of the decreased [Ca2+]i in the post-glutamate period. However, for development of DCD, in addition to the exchange reversal, other factors are required, in particular a decrease in the intracellular concentration of ATP.

  20. Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants.

    PubMed

    Weitz, Jeffrey I; Pollack, Charles V

    2015-11-25

    Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers.

  1. Optical diagnosis of the progression and reversal of CCl4-induced liver injury in rodent model using minimally invasive autofluorescence spectroscopy.

    PubMed

    Nazeer, Shaiju S; Sandhyamani, S; Jayasree, Ramapurath S

    2015-06-07

    Worldwide, liver cancer is the fifth most common cancer in men and seventh most common cancer in women. Intoxicant-induced liver injury is one of the major causes for severe structural damage with fibrosis and functional derangement of the liver leading to cancer in its later stages. This report focuses on the minimally invasive autofluorescence spectroscopic (AFS) studies on intoxicant, carbon tetrachloride (CCl4)-induced liver damage in a rodent model. Different stages of liver damage, including the reversed stage, on stoppage of the intoxicant are examined. Emission from prominent fluorophores, such as collagen, nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FAD), and variations in redox ratio have been studied. A direct correlation between the severity of the disease and the levels of collagen and redox ratio was observed. On withdrawal of the intoxicant, a gradual reversal of the disease to normal conditions was observed as indicated by the decrease in collagen levels and redox ratio. Multivariate statistical techniques and principal component analysis followed by linear discriminant analysis (PC-LDA) were used to develop diagnostic algorithms for distinguishing different stages of the liver disease based on spectral features. The PC-LDA modeling on a minimally invasive AFS dataset yielded diagnostic sensitivities of 93%, 87% and 87% and specificities of 90%, 98% and 98% for pairwise classification among normal, fibrosis, cirrhosis and reversal conditions. We conclude that AFS along with PC-LDA algorithm has the potential for rapid and accurate minimally invasive diagnosis and detection of structural changes due to liver injury resulting from various intoxicants.

  2. Aminocaproic Acid and Tranexamic Acid Fail to Reverse Dabigatran-Induced Coagulopathy.

    PubMed

    Levine, Michael; Huang, Margaret; Henderson, Sean O; Carmelli, Guy; Thomas, Stephen H

    In recent years, dabigatran has emerged as a popular alternative to warfarin for treatment of atrial fibrillation. If rapid reversal is required, however, no reversal agent has clearly been established. The primary purpose of this manuscript was to evaluate the efficacy of tranexamic acid and aminocaproic acid as agents to reverse dabigatran-induced coagulopathy. Rats were randomly assigned to 6 groups. Each rat received either dabigatran or oral placebo, followed by saline, tranexamic acid, or aminocaproic acid. An activated clotting test was used to measure the coagulopathy. Neither tranexamic acid nor aminocaproic acid successfully reversed dabigatran-induced coagulopathy. In this rodent model of dabigatran-induced coagulopathy, neither tranexamic acid nor aminocaproic acid were able to reverse the coagulopathy.

  3. Reversal of diabetic peripheral neuropathy with phototherapy (MIRE) decreases falls and the fear of falling and improves activities of daily living in seniors.

    PubMed

    Powell, Mark W; Carnegie, Dale H; Burke, Thomas J

    2006-01-01

    to determine whether restoration of sensation, impaired due to diabetic peripheral neuropathy (DPN), would reduce the number of falls and the fear of falling and improve activities of daily living (ADL) in a Medicare-aged population. retrospective cohort study of patients with documented, monochromatic near-infrared phototherapy (MIRE)-mediated, symptomatic reversal of DPN. responses to a health status questionnaire following symptomatic reversal of DPN. 252 patients (mean age 76 years) provided health information following symptomatic reversal of diabetic neuropathy (mean duration 8.6 months). incidence of falls and fear of falling decreased within 1 month after reversal of peripheral neuropathy and remained low after 1 year. Likewise, improved ADL were evident soon after reversal of peripheral neuropathy and showed further improvement after 1 year. Overall, reversal of peripheral neuropathy in a clinician's office and subsequent use of MIRE at home was associated with a 78% reduction in falls, a 79% decrease in balance-related fear of falling and a 72% increase in ADL (P < 0.0002 for all results). reversal of peripheral neuropathy is associated with an immediate reduction in the absolute number of falls, a reduced fear of falling and improved ADL. These results suggest that symptomatic reversal of diabetic neuropathy will have a substantial favourable, long-term socioeconomic impact on patients with DPN and the Medicare system, and improve the quality of life for elderly patients with diabetes and peripheral neuropathy.

  4. Tracking the Chemical and Structural Evolution of the TiS2 Electrode in the Lithium-Ion Cell Using Operando X-ray Absorption Spectroscopy.

    PubMed

    Zhang, Liang; Sun, Dan; Kang, Jun; Wang, Hsiao-Tsu; Hsieh, Shang-Hsien; Pong, Way-Faung; Bechtel, Hans A; Feng, Jun; Wang, Lin-Wang; Cairns, Elton J; Guo, Jinghua

    2018-06-06

    As the lightest and cheapest transition metal dichalcogenide, TiS 2 possesses great potential as an electrode material for lithium batteries due to the advantages of high energy density storage capability, fast ion diffusion rate, and low volume expansion. Despite the extensive investigation of its electrochemical properties, the fundamental discharge-charge reaction mechanism of the TiS 2 electrode is still elusive. Here, by a combination of ex situ and operando X-ray absorption spectroscopy with density functional theory calculations, we have clearly elucidated the evolution of the structural and chemical properties of TiS 2 during the discharge-charge processes. The lithium intercalation reaction is highly reversible and both Ti and sulfur are involved in the redox reaction during the discharge and charge processes. In contrast, the conversion reaction of TiS 2 is partially reversible in the first cycle. However, Ti-O related compounds are developed during electrochemical cycling over extended cycles, which results in the decrease of the conversion reaction reversibility and the rapid capacity fading. In addition, the solid electrolyte interphase formed on the electrode surface is found to be highly dynamic in the initial cycles and then gradually becomes more stable upon further cycling. Such understanding is important for the future design and optimization of TiS 2 based electrodes for lithium batteries.

  5. Glucocorticoid acts on a putative G protein-coupled receptor to rapidly regulate the activity of NMDA receptors in hippocampal neurons.

    PubMed

    Zhang, Yanmin; Sheng, Hui; Qi, Jinshun; Ma, Bei; Sun, Jihu; Li, Shaofeng; Ni, Xin

    2012-04-01

    Glucocorticoids (GCs) have been demonstrated to act through both genomic and nongenomic mechanisms. The present study demonstrated that corticosterone rapidly suppressed the activity of N-methyl-D-aspartate (NMDA) receptors in cultured hippocampal neurons. The effect was maintained with corticosterone conjugated to bovine serum albumin and blocked by inhibition of G protein activity with intracellular GDP-β-S application. Corticosterone increased GTP-bound G(s) protein and cyclic AMP (cAMP) production, activated phospholipase Cβ(3) (PLC-β(3)), and induced inositol-1,4,5-triphosphate (IP(3)) production. Blocking PLC and the downstream cascades with PLC inhibitor, IP(3) receptor antagonist, Ca(2+) chelator, and protein kinase C (PKC) inhibitors prevented the actions of corticosterone. Blocking adenylate cyclase (AC) and protein kinase A (PKA) caused a decrease in NMDA-evoked currents. Application of corticosterone partly reversed the inhibition of NMDA currents caused by blockage of AC and PKA. Intracerebroventricular administration of corticosterone significantly suppressed long-term potentiation (LTP) in the CA1 region of the hippocampus within 30 min in vivo, implicating the possibly physiological significance of rapid effects of GC on NMDA receptors. Taken together, our results indicate that GCs act on a putative G protein-coupled receptor to activate multiple signaling pathways in hippocampal neurons, and the rapid suppression of NMDA activity by GCs is dependent on PLC and downstream signaling.

  6. Reversible blindness associated with alcoholic ketoacidosis.

    PubMed

    Yanagawa, Youichi; Kiyozumi, Teturou; Hatanaka, Kousuke; Itoh, Toshitaka; Sakamoto, Toshihisa; Okada, Yoshiaki

    2004-04-01

    To report a case of reversible blindness associated with severe alcoholic ketoacidosis. Observational case report. A 44-year-old male presented with gradual bilateral blindness that developed within a 24-hour period. He suffered from ethanol-induced severe ketoacidosis and shock and was resuscitated with epinephrine and sodium bicarbonate. The treatment of acidosis led to a rapid resolution of the patient's blindness. It is important to understand the role of severe acidosis as the sole causative factor of reversible bilateral blindness.

  7. Exercise training improves obesity‐related lymphatic dysfunction

    PubMed Central

    Hespe, Geoffrey E.; Kataru, Raghu P.; Savetsky, Ira L.; García Nores, Gabriela D.; Torrisi, Jeremy S.; Nitti, Matthew D.; Gardenier, Jason C.; Zhou, Jie; Yu, Jessie Z.; Jones, Lee W.

    2016-01-01

    Key points Obesity results in perilymphatic inflammation and lymphatic dysfunction.Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells.Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Abstract Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti‐inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic specific genes, including VEGFR‐3 and Prox1. Taken together, our findings suggest that obesity impairs lymphatic function via multiple mechanisms and that these pathological changes can be reversed, in part, with aerobic exercise, independent of weight loss. In addition, our study shows that obesity‐induced lymphatic endothelial cell gene expression changes are reversible with behavioural modifications. PMID:26931178

  8. Magnetic alloy nanowire arrays with different lengths: Insights into the crossover angle of magnetization reversal process

    NASA Astrophysics Data System (ADS)

    Samanifar, S.; Alikhani, M.; Almasi Kashi, M.; Ramazani, A.; Montazer, A. H.

    2017-05-01

    Nanoscale magnetic alloy wires are being actively investigated, providing fundamental insights into tuning properties in magnetic data storage and processing technologies. However, previous studies give trivial information about the crossover angle of magnetization reversal process in alloy nanowires (NWs). Here, magnetic alloy NW arrays with different compositions, composed of Fe, Co and Ni have been electrochemically deposited into hard-anodic aluminum oxide templates with a pore diameter of approximately 150 nm. Under optimized conditions of alumina barrier layer and deposition bath concentrations, the resulting alloy NWs with aspect ratio and saturation magnetization (Ms) up to 550 and 1900 emu cm-3, respectively, are systematically investigated in terms of composition, crystalline structure and magnetic properties. Using angular dependence of coercivity extracted from hysteresis loops, the reversal processes are evaluated, indicating non-monotonic behavior. The crossover angle (θc) is found to depend on NW length and Ms. At a constant Ms, increasing NW length decreases θc, thereby decreasing the involvement of vortex mode during the magnetization reversal process. On the other hand, decreasing Ms decreases θc in large aspect ratio (>300) alloy NWs. Phenomenologically, it is newly found that increasing Ni content in the composition decreases θc. The angular first-order reversal curve (AFORC) measurements including the irreversibility of magnetization are also investigated to gain a more detailed insight into θc.

  9. One-Step and Stepwise Magnification of a BOBBED LETHAL Chromosome in DROSOPHILA MELANOGASTER

    PubMed Central

    Endow, Sharyn A.; Komma, Donald J.

    1986-01-01

    Bobbed lethal (bbl) chromosomes carry too few ribosomal genes for homozygous flies to be viable. Reversion of bbl chromosomes to bb or nearly bb + occurs under magnifying conditions at a low frequency in a single generation. These reversions occur too rapidly to be accounted for by single unequal sister chromatid exchanges and seem unlikely to be due to multiple sister strand exchanges within a given cell lineage. Analysis of several one-step revertants indicates that they are X-Y recombinant chromosomes which probably arise from X-Y recombination at bb. The addition of ribosomal genes from the Y chromosome to the bbl chromosome explains the more rapid reversion of the bbl chromosome than is permitted by single events of unequal sister chromatid exchange. Analysis of stepwise bbl magnified chromosomes, which were selected over a period of 4–9 magnifying generations, shows ribosomal gene patterns that are closely similar to each other. Similarity in rDNA pattern among stepwise magnified products of the same parental chromosome is consistent with reversion by a mechanism of unequal sister strand exchange. PMID:3095184

  10. Acute shallowing of the anterior chamber.

    PubMed Central

    Mapstone, R

    1981-01-01

    In aging eyes phenylephrine drops have no significant effect on the depth of the anterior chamber, whereas pilocarpine drops produce a significant shallowing. If both drugs are instilled simultaneously, a significantly greater decrease in anterior chamber depth occurs. The effect is seen in normal, glaucomatous, and hypertensive eyes, and in eyes with shallow anterior chambers. It did not occur in eyes that had had an iridectomy. During the course of a positive provocative test an acute reduction in anterior depth occurs which is reversed when the angle opens and pressure returns to normal levels. It is concluded that the depth of the anterior chamber is not a static dimension but that changes can occur which are rapid and transient. The mechanism of shallowing and deepening depends on an increase or a decrease in the pupil block force. It is a necessary consequence too that eyes with nonshallow anterior chambers can get closed-angle glaucoma and that this possibility cannot be detected by a conventional gonioscopic approach. PMID:6455153

  11. Sugammadex: A Review of Neuromuscular Blockade Reversal.

    PubMed

    Keating, Gillian M

    2016-07-01

    Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade.

  12. Rapid and reversible photoinduced switching of a rotaxane crystal

    NASA Astrophysics Data System (ADS)

    Chen, Kai-Jen; Tsai, Ya-Ching; Suzaki, Yuji; Osakada, Kohtaro; Miura, Atsushi; Horie, Masaki

    2016-11-01

    Crystalline phase transitions caused by external stimuli have been used to detect physical changes in the solid-state properties. This study presents the mechanical switching of crystals of ferrocene-containing rotaxane controlled by focused laser light. The expansion and contraction of the crystals can be driven by turning on and off laser light at 445 nm. The irradiation-induced expansion of the crystal involves elongation along the a, b and c axes at 30 °C, whereas heating of the crystal at 105 °C causes the shortening of c axis. The expansions reversibly occur and have the advantage of a rapid relaxation (reverse) process. Single-crystal X-ray crystallography reveals the detailed structural changes of the molecules, corresponding to a change in the size of the crystals on laser irradiation. This molecular crystal behaviour induced by laser irradiation, is demonstrated for the remote control of objects, namely, microparticle transport and microswitching in an electric circuit.

  13. Virus-induced gene silencing (VIGS) in barley seedling leaves

    USDA-ARS?s Scientific Manuscript database

    Virus-induced gene silencing (VIGS) is one of the most potent reverse genetics technologies for gene functional characterization. This method exploits a dsRNA-mediated antiviral defense mechanism in plants. Using this method allows researchers to generate rapid phenotypic data in a relatively rapid ...

  14. Reversible Cryopreservation of Living Cells Using an Electron Microscopy Cryo-Fixation Method.

    PubMed

    Huebinger, Jan; Han, Hong-Mei; Grabenbauer, Markus

    2016-01-01

    Rapid cooling of aqueous solutions is a useful approach for two important biological applications: (I) cryopreservation of cells and tissues for long-term storage, and (II) cryofixation for ultrastructural investigations by electron and cryo-electron microscopy. Usually, both approaches are very different in methodology. Here we show that a novel, fast and easy to use cryofixation technique called self-pressurized rapid freezing (SPRF) is-after some adaptations-also a useful and versatile technique for cryopreservation. Sealed metal tubes with high thermal diffusivity containing the samples are plunged into liquid cryogen. Internal pressure builds up reducing ice crystal formation and therefore supporting reversible cryopreservation through vitrification of cells. After rapid rewarming of pressurized samples, viability rates of > 90% can be reached, comparable to best-performing of the established rapid cooling devices tested. In addition, the small SPRF tubes allow for space-saving sample storage and the sealed containers prevent contamination from or into the cryogen during freezing, storage, or thawing.

  15. A temperature reversal within the rapid Younger Dryas-Holocene warming in the North Atlantic?

    NASA Astrophysics Data System (ADS)

    Vincent, Jessie H.; Cwynar, Les C.

    2016-12-01

    The onset of the Holocene has been generally considered rapid and uninterrupted in the circum-Atlantic region. Loss-on-ignition (LOI - an index of organic carbon) profiles from 18 lateglacial-aged lakes in Nova Scotia, Canada, together with chironomid-inferred temperature reconstructions at 5 sites, demonstrate that the rapid warming from the Younger Dryas (GS-1) to the Holocene was interrupted by a cooling of 1.6-6.4 °C in summer surface lake water temperature. The resulting inflection or reversal on the rising temperature curve has also been identified at 35 sites outside Nova Scotia from terrestrial and marine settings, indicating that this cool step is a robust feature throughout the North Atlantic and is likely the result of major oceanic and atmospheric reorganization of the Holocene climate system.

  16. Inhaled Hydrogen Sulfide

    PubMed Central

    Volpato, Gian Paolo; Searles, Robert; Yu, Binglan; Scherrer-Crosbie, Marielle; Bloch, Kenneth D.; Ichinose, Fumito; Zapol, Warren M.

    2010-01-01

    Background Breathing hydrogen sulfide (H2S) has been reported to induce a suspended animation–like state with hypothermia and a concomitant metabolic reduction in rodents. However, the impact of H2S breathing on cardiovascular function remains incompletely understood. In this study, the authors investigated the cardiovascular and metabolic effects of inhaled H2S in a murine model. Methods The impact of breathing H2S on cardiovascular function was examined using telemetry and echocardiography in awake mice. The effects of breathing H2S on carbon dioxide production and oxygen consumption were measured at room temperature and in a warmed environment. Results Breathing H2S at 80 parts per million by volume at 27°C ambient temperature for 6 h markedly reduced heart rate, core body temperature, respiratory rate, and physical activity, whereas blood pressure remained unchanged. Echocardiography demonstrated that H2S exposure decreased both heart rate and cardiac output but preserved stroke volume. Breathing H2S for 6 h at 35°C ambient temperature (to prevent hypothermia) decreased heart rate, physical activity, respiratory rate, and cardiac output without altering stroke volume or body temperature. H2S breathing seems to induce bradycardia by depressing sinus node activity. Breathing H2S for 30 min decreased whole body oxygen consumption and carbon dioxide production at either 27° or 35°C ambient temperature. Both parameters returned to baseline levels within 10 min after the cessation of H2S breathing. Conclusions Inhalation of H2S at either 27° or 35°C reversibly depresses cardiovascular function without changing blood pressure in mice. Breathing H2S also induces a rapidly reversible reduction of metabolic rate at either body temperature. PMID:18362598

  17. Rapid preparation of lecture slides.

    PubMed

    Persson, A V; Frusha, J D; Chevalier, R J

    1985-02-01

    When lecture slides must be prepared at a moment's notice, these methods of rapid preparation will allow you to create good quality slides. Although rush jobs are usually associated with higher costs, using these methods will keep the price per slide to a minimum. An investment must be made for the initial equipment, but the cost per slide is much less than that of slides produced by the standard methods. Type produced by typewriters or computer printers is adequate for most slides, but better slides can be produced with KroyType or Letraset letters. The KL film is preferred for reverse slides of text or line drawings, and the RPC film for production of radiographic slides. If an X-omat developer is not available, Polaroid film is a good alternative for rapid production of slides. The KL reverse slide projects best and can be colored, but RPC film produces a good positive slide of typed material. We have also photographed from a computer terminal screen using the KL film to make positive slides, the Polaroid continuous tone film for reverse slides, and Polaroid color film for color slides of material composed on a computer terminal with multicolor and graphics capabilities.

  18. In vivo biosynthesis of L-(/sup 35/S)Cys-arginine vasopressin, -oxytocin, and -somatostatin: rapid estimation using reversed phase high pressure liquid chromatography. [Rats

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

    Franco-Bourland, R.E.; Fernstrom, J.D.

    1981-01-01

    L(/sup 35/S)Cys-arginine vasopressin, -oxytocin, and -somatostatin were purified from hypothalami and neurohypophyses 4 h after rats received L(/sup 35/S)Cys via the third ventricle. After acetic acid extraction, Sephadex G-25 filtration, and chemoadsorption to C18-silica (Sep-Pak cartridges), the labeled peptides were rapidly separated by gradient elution, reversed phase, high pressure liquid chromatography (HPLC). The identity and isotopic purity of the labeled peptides were determined by several reversed phase HPLC procedures in conjunction with chemical modification. The labeled peptide fractions were at least 50% radiochemically pure. Using this HPLC isolation procedure, incorporation of L-(/sup 35/S)Cys into each peptide was determined in hydratedmore » and dehydrated rats. Label incorporation into arginine vasopressin and oxytocin in the hypothalamus and the neurohypophysis of dehydrated rats was 2-3 times greater than that in hydrated rats. Incorporation of label into hypothalamic and neurohypophyseal somatostatin was unaffected by the hydration state of the animal. This procedure thus provides a very rapid, but sensitive, set of techniques for studying the control of small peptide biosynthesis in the brain.« less

  19. Real-life experience with the specific reversal agent idarucizumab for the management of emergency situations in dabigatran-treated patients: a series of 11 cases.

    PubMed

    Vosko, Milan R; Bocksrucker, Christof; Drwiła, Rafał; Dulíček, Petr; Hauer, Tomas; Mutzenbach, Johannes; Schlimp, Christoph J; Špinler, David; Wolf, Thomas; Zugwitz, Daša

    2017-04-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) have a favorable benefit-risk profile compared with vitamin K antagonists. However, the lack of specific reversal agents has made the management of some patients receiving long-term treatment with NOACs problematic in emergency situations such as major bleeding events or urgent procedures. Idarucizumab, a fully humanized Fab antibody fragment that binds specifically and with high affinity to dabigatran, was recently approved for use in adult patients treated with dabigatran when rapid reversal of its anticoagulant effect is required. Clinical experience with idarucizumab is currently limited. We report 11 real-life clinical cases in which idarucizumab was used after multidisciplinary consultation in a variety of emergency situations including severe postoperative bleeding, emergency high-bleeding-risk surgery (hip/spine surgery and neurosurgery), invasive diagnostic testing (lumbar puncture), intracranial bleeding (pre-pontine subarachnoid hemorrhage and lobar intracerebral hemorrhage) and thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke. This case series illustrates the role of idarucizumab in improving patient safety in rare emergency situations requiring rapid reversal of the anticoagulant effect of dabigatran, while highlighting the importance of information and education about the availability and appropriate use of this recently approved specific reversal agent.

  20. Inhibition of the reverse mode of the Na+/Ca2+ exchange by KB-R7943 augments arrhythmogenicity in the canine heart during rapid heart rates.

    PubMed

    Shinada, Takuro; Hirayama, Yoshiyuki; Maruyama, Mitsunori; Ohara, Toshihiko; Yashima, Masaaki; Kobayashi, Yoshinori; Atarashi, Hirotsugu; Takano, Teruo

    2005-07-01

    To test the hypothesis that the reverse mode of the Na+/Ca2+ exchange augmented by a rapid heart rate has an antiarrhythmic effect by shortening the action potential duration, we examined the effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate), a selective inhibitor of the reverse mode of the Na+/Ca2+ exchange, to attenuate this effect. We recorded the electrocardiogram, monophasic action potential (MAP), and left ventricular pressure in canine beating hearts. In comparison to the control, KB-R7943 significantly increased the QTc value and MAP duration. MAP alternans and left ventricular pressure alternans were observed after changing the cycle length to 300 milliseconds in the control studies. KB-R7943 magnified both types of alternans and produced spatially discordant alternans between right and left ventricles. Early after-depolarizations and nonsustained ventricular tachycardia occurred in the presence of KB-R7943. Our data suggest that the reverse mode of the Na+/Ca2+ exchange may contribute to suppression of arrhythmias by abbreviating action potential duration under pathophysiological conditions. This conclusion is based on further confirmation by future studies of the specificity of KB-R7943 for block of the reverse mode of the Na+/Ca2+ exchange.

  1. Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.

    PubMed

    Starkman, M N; Giordani, B; Gebarski, S S; Berent, S; Schork, M A; Schteingart, D E

    1999-12-15

    Decreased hippocampal volume is observed in patients with Cushing's syndrome and other conditions associated with elevated cortisol levels, stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for reversibility of human hippocampal atrophy. The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment. Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease. Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.

  2. Hexamethonium reverses the lethal cardiopulmonary damages in a rat model of brainstem lesions mimicking fatal enterovirus 71 encephalitis.

    PubMed

    Lu, Wen-Hsien; Hsieh, Kai-Sheng; Lu, Pei-Jung; Wu, Yi-Shan; Ho, Wen-Yu; Lai, Chi-Cheng; Wang, Jyh-Seng; Ger, Luo-Ping; Hsiao, Michael; Tseng, Ching-Jiunn

    2013-05-01

    Among enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. However, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. We investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model. Treatment study. Research laboratory. Sprague-Dawley rats. We microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker. The time course of changes in the heart and lungs of rats with brainstem lesions were investigated. Rats were administered 6-hydroxydopamine to induce brainstem lesions, causing acute hypertension in 10 minutes and acute elevations of catecholamines accompanied by acute cardiac dysfunction and increased strong expressions of connexin 43 gap junction protein in heart and lung specimens by immunohistochemical staining within 3 hours. Severe pulmonary hemorrhagic edema was produced within 6 hours, and the rats expired rapidly within 7 hours. After hexamethonium treatment, it was found that the acute hypertension induced by 6-hydroxydopamine lesions was immediately reversed and the acute high rise of catecholamine serum level was significantly attenuated within 3 hours, accompanied by preserved cardiac output and decreased expressions of connexin 43 in the heart and lungs. No pulmonary edema occurred and the rats survived for more than 14 hours. Early hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.

  3. The Role of Reversed Equatorial Zonal Transport in Terminating an ENSO Event

    NASA Astrophysics Data System (ADS)

    Chen, H. C.; Hu, Z. Z.; Huang, B.; Sui, C. H.

    2016-02-01

    In this study, we demonstrate that a sudden reversal of anomalous equatorial zonal current at the peaking ENSO phase triggers the rapid termination of an ENSO event. Throughout an ENSO cycle, the anomalous equatorial zonal current is strongly controlled by the concavity of the anomalous thermocline meridional structure near the equator. During the ENSO developing phase, the anomalous zonal current in the central and eastern Pacific generally enhances the ENSO growth through its zonal SST advection. In the mature phase of ENSO, however, the equatorial thermocline depth anomalies are reflected in the eastern Pacific and slowly propagate westward off the equator in both hemispheres. As a result, the concavity of the thermocline anomalies near the equator is reversed, i.e., the off-equatorial thermocline depth anomalies become higher than that on the equator for El Niño events and lower for La Niño events. This meridional change of thermocline structure reverses zonal transport rapidly in the central-to-eastern equatorial Pacific, which weakens the ENSO SST anomalies by reversed advection. More importantly, the reversed zonal mass transport weakens the existing zonal tilting of equatorial thermocline and suppresses the thermocline feedback. Both processes are concentrated in the eastern equatorial Pacific and can be effective on subseasonal time scales. These current reversal effects are built-in to the ENSO peak phase and independent of the zonal wind effect on thermocline slope. It functions as an oceanic control on ENSO evolution during both El Niño and La Niña events.

  4. Reversal of the toxic effects of cachectin by concurrent insulin administration.

    PubMed

    Fraker, D L; Merino, M J; Norton, J A

    1989-06-01

    Rats treated with recombinant human tumor necrosis factor-cachectin, 100 micrograms/kg ip twice daily for 5 consecutive days, had a 56% decrease in food intake, a 54% decrease in nitrogen balance, and a 23-g decrease in body weight gain vs. saline-treated controls. Concurrent neutral protamine hagedorn insulin administration of 2 U/100 g sc twice daily reversed all of these changes to control levels without causing any treatment deaths. The improvement seen with insulin was dose independent. Five days of cachectin treatment caused a severe interstitial pneumonitis, periportal inflammation in the liver, and an increase in wet organ weight in the heart, lungs, kidney, and spleen. Concurrent insulin treatment led to near total reversal of these histopathologic changes. Cachectin treatment did not significantly change blood glucose levels from control values of 130-140 mg/dl, but insulin plus cachectin caused a significant decrease in blood glucose from 1 through 12 h after injection. Administration of high-dose insulin can near totally reverse the nutritional and histopathologic toxicity of sublethal doses of cachectin in rats.

  5. Rapid Amorphization in Metastable CoSeO3·H2O Nanosheets for Ultrafast Lithiation Kinetics.

    PubMed

    Jiang, Yingchang; Song, Yun; Pan, Zhichang; Meng, Yu; Jiang, Le; Wu, Zeyi; Yang, Peiyu; Gu, Qinfen; Sun, Dalin; Hu, Linfeng

    2018-05-02

    The realization of high-performance anode materials with high capacity at fast lithiation kinetics and excellent cycle stability remains a significant but critical challenge for high-power applications such as electric vehicles. Two-dimensional nanostructures have attracted considerable research interest in electrochemical energy storage devices owing to their intriguing surface effect and significantly decreased ion-diffusion pathway. Here we describe rationally designed metastable CoSeO 3 ·H 2 O nanosheets synthesized by a facile hydrothermal method for use as a Li ion battery anode. This crystalline nanosheet can be steadily converted into amorphous phase at the beginning of the first Li + discharge cycling, leading to ultrahigh reversible capacities of 1100 and 515 mAh g -1 after 1000 cycles at a high rate of 3 and 10 A g -1 , respectively. The as-obtained amorphous structure experiences an isotropic stress, which can significantly reduce the risk of fracture during electrochemical cycling. Our study offers a precious opportunity to reveal the ultrafast lithiation kinetics associated with the rapid amorphization mechanism in layered cobalt selenide nanosheets.

  6. Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2.

    PubMed

    Wiemhoefer, Anne; Stargardt, Anita; van der Linden, Wouter A; Renner, Maria C; van Kesteren, Ronald E; Stap, Jan; Raspe, Marcel A; Tomkinson, Birgitta; Kessels, Helmut W; Ovaa, Huib; Overkleeft, Herman S; Florea, Bogdan; Reits, Eric A

    2015-08-01

    Tripeptidyl peptidase II (TPP2) is a serine peptidase involved in various biological processes, including antigen processing, cell growth, DNA repair, and neuropeptide mediated signaling. The underlying mechanisms of how a peptidase can influence this multitude of processes still remain unknown. We identified rapid proteomic changes in neuroblastoma cells following selective TPP2 inhibition using the known reversible inhibitor butabindide, as well as a new, more potent, and irreversible peptide phosphonate inhibitor. Our data show that TPP2 inhibition indirectly but rapidly decreases the levels of active, di-phosphorylated extracellular signal-regulated kinase 1 (ERK1) and ERK2 in the nucleus, thereby down-regulating signal transduction downstream of growth factors and mitogenic stimuli. We conclude that TPP2 mediates many important cellular functions by controlling ERK1 and ERK2 phosphorylation. For instance, we show that TPP2 inhibition of neurons in the hippocampus leads to an excessive strengthening of synapses, indicating that TPP2 activity is crucial for normal brain function. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. An Escherichia coli Expression Assay and Screen for Human Immunodeficiency Virus Protease Variants with Decreased Susceptibility to Indinavir

    PubMed Central

    Melnick, Laurence; Yang, Shiow-Shong; Rossi, Rick; Zepp, Charlie; Heefner, Donald

    1998-01-01

    We have developed a recombinant Escherichia coli screening system for the rapid detection and identification of amino acid substitutions in the human immunodeficiency virus (HIV) protease associated with decreased susceptibility to the protease inhibitor indinavir (MK-639; Merck & Co.). The assay depends upon the correct processing of a segment of the HIV-1 HXB2 gag-pol polyprotein followed by detection of HIV reverse transcriptase activity by a highly sensitive, colorimetric enzyme-linked immunosorbent assay. The highly sensitive system detects the contributions of single substitutions such as I84V, L90M, and L63P. The combination of single substitutions further decreases the sensitivity to indinavir. We constructed a library of HIV protease variant genes containing dispersed mutations and, using the E. coli recombinant system, screened for mutants with decreased indinavir sensitivity. The discovered HIV protease variants contain amino acid substitutions commonly associated with indinavir resistance in clinical isolates, including the substitutions L90M, L63P, I64V, V82A, L24I, and I54T. One substitution, W6R, is also frequently found by the screen and has not been reported elsewhere. Of a total of 12,000 isolates that were screened, 12 protease variants with decreased sensitivity to indinavir were found. The L63P substitution, which is also associated with indinavir resistance, increases the stability of the isolated protease relative to that of the native HXB2 protease. The rapidity, sensitivity, and accuracy of this screen also make it useful for screening for novel inhibitors. We have found the approach described here to be useful for the detection of amino acid substitutions in HIV protease that have been associated with drug resistance as well as for the screening of novel compounds for inhibitory activity. PMID:9835523

  8. Early reversible acute kidney injury is associated with improved survival in septic shock.

    PubMed

    Sood, Manish M; Shafer, Leigh Anne; Ho, Julie; Reslerova, Martina; Martinka, Greg; Keenan, Sean; Dial, Sandra; Wood, Gordon; Rigatto, Claudio; Kumar, Anand

    2014-10-01

    The fact that acute kidney injury (AKI) is associated with worse clinical outcomes forms the basis of most AKI prognostic scoring systems. However, early reversibility of renal dysfunction in acute illness is not considered in such systems. We sought to determine whether early (≤24 hours after shock documentation) reversibility of AKI was independently associated with in-hospital mortality in septic shock. Patient information was derived from an international database of septic shock cases from 28 different institutions in Canada, the United States and Saudi Arabia. Data from a final cohort of 5443 patients admitted with septic shock between Jan 1996 and Dec 2009 was analyzed. The following 4 definitions were used in regards to AKI status: (1) reversible AKI = AKI of any RIFLE severity prevalent at shock diagnosis or incident at 6 hours post-diagnosis that reverses by 24 hours, (2) persistent AKI = AKI prevalent at shock diagnosis and persisting during the entire 24 hours post-shock diagnosis, (3) new AKI = AKI incident between 6 and 24 hours post-shock diagnosis, and (4) improved AKI = AKI prevalent at shock diagnosis or incident at 6 hours post followed by improvement of AKI severity across at least one RIFLE category over the first 24 hours. Cox proportional hazards were used to determine the association between AKI status and in-hospital mortality. During the first 24 hours, reversible AKI occurred in 13.0%, persistent AKI in 54.9%, new AKI in 11.7%, and no AKI in 22.4%. In adjusted analyses, reversible AKI was associated with improved survival (HR, 0.64; 95% CI, 0.53-0.77) compared to no AKI (referent), persistent AKI (HR, 0.99; 95% CI, 0.88-1.11), and new AKI (HR, 1.41; 95% CI, 1.22-1.62). Improved AKI occurred in 19.1% with improvement across any RIFLE category associated with a significant decrease in mortality (HR, 0.53; 95% CI, 0.45-0.63). More rapid antimicrobial administration, lower Acute Physiology and Chronic Health Evaluation II score, lower age, and a smaller number of failed organs (excluding renal) on the day of shock as well as community-acquired infection were independently associated with reversible AKI. In septic shock, reversible AKI within the first 24 hours of admission confers a survival benefit compared to no, new, or persistent AKI. Prognostic AKI classification schemes should consider integration of early AKI reversibility into the scoring system. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Neutral Red and Ferroin as Reversible and Rapid Redox Materials for Redox Flow Batteries.

    PubMed

    Hong, Jeehoon; Kim, Ketack

    2018-06-11

    Neutral red and ferroin are used as redox indicators (RINs) in potentiometric titrations. The rapid response and reversibility that are prerequisites for RINs are also desirable properties for the active materials in redox flow batteries (RFBs). This study describes the electrochemical properties of ferroin and neutral red as a redox pair. The rapid reaction rates of the RINs allow a cell to run at a rate of 4 C with 89 % capacity retention after the 100 th  cycle. The diffusion coefficients, electrode reaction rates, and solubilities of the RINs were determined. The electron-transfer rate constants of ferroin and neutral red are 0.11 and 0.027 cm s -1 , respectively, which are greater than those of the components of all-vanadium and Zn/Br 2 cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. A rapid monitoring method for inorganic arsenic in rice flour using reversed phase-high performance liquid chromatography-inductively coupled plasma mass spectrometry.

    PubMed

    Narukawa, Tomohiro; Chiba, Koichi; Sinaviwat, Savarin; Feldmann, Jörg

    2017-01-06

    A new rapid monitoring method by means of high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) following the heat-assisted extraction was developed for measurement of total inorganic arsenic species in rice flour. As(III) and As(V) eluted at the same retention time and completely separated from organoarsenic species by an isocratic elution program on a reversed phase column. Therefore, neither ambiguous oxidation of arsenite to arsenate nor the integration of two peaks were necessary to determine directly the target analyte inorganic arsenic. Rapid injection allowed measuring 3 replicates within 6min and this combined with a quantitative extraction of all arsenic species from rice flour by a 15min HNO 3 -H 2 O 2 extraction makes this the fastest laboratory based method for inorganic arsenic in rice flour. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Rapid and sensitive detection of Lily symptomless virus by reverse transcription loop-mediated isothermal amplification.

    PubMed

    He, Xiangfeng; Xue, Fei; Xu, Shufa; Wang, Wenhe

    2016-12-01

    Lily symptomless virus (LSV) is one of the most prevalent viruses that infect lily plants worldwide. A rapid and sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for detection of LSV, using two primer pairs that specifically amplified the conserved sequence of LSV coat protein. The optimum reaction conditions were as follows: 4mM MgCl 2 and 0.8M betaine with incubation at 64°C for 30min. The limit of detection of LSV from infected lily leaves was 10-fold higher for RT-LAMP than for conventional RT-PCR. Moreover, RT-LAMP detected LSV in not only symptomatic, but also in symptomless tissues of infected plants. These findings indicate that our RT-LAMP method for LSV can serve as a low-cost, simple, and rapid alternative to conventional detection assays. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A rapid reversed-phase thin layer chromatographic protocol for detection of adulteration in ghee (clarified milk fat) with vegetable oils.

    PubMed

    Rani, Anupama; Sharma, Vivek; Arora, Sumit; Lal, Darshan; Kumar, Anil

    2015-04-01

    Detection of milk fat adulteration with foreign fats/oils continues to be a challenge for the dairy industry as well as food testing laboratories, especially in the present scenario of rampant adulteration using the scientific knowledge by unscrupulous persons involved in the trade. In the present investigation a rapid reversed-phase thin layer chromatographic (RP-TLC) protocol was standardized to ascertain the purity of milk fat. RP-TLC protocol did not show any false positive results in the genuine ghee (clarified butter fat) samples of known origin. Adulteration of ghee with coconut oil up to 7. 5 %, soybean oil, sunflower oil and groundnut oil up to 1 %, while, designer oil up to 2 % level could be detected using the standardized RP-TLC protocol. The protocol standardized is rapid and convenient to use.

  13. Spatial reversal learning in preclinical scrapie-inoculated mice.

    PubMed

    Lysons, A M; Woollard, S J

    1996-04-10

    Acquisition and reversal of a two-choice spatial discrimination were tested in scrapie-inoculated mice. Both acquisition and reversal were normal in mice tested 138 and 103 days prior to the onset of clinical symptoms. At 65 days before onset of clinical symptoms, scrapie-inoculated mice required more trails to criterion in reversal learning, but this effect was not significant in a second experiment (68 days preclinical) and was transient: no effect was seen 33 days before symptoms. However, the course of reversal learning was abnormal in all three late preclinical groups (68, 65 and 33 days before symptoms). Reversal learning in these three groups was characterized by a rapid extinction of the original discrimination, followed by a period, absent in controls, during which performance showed no further improvement. This effect corresponds in time of onset to the appearance of characteristic neuropathological features.

  14. Canine model of nasal congestion and allergic rhinitis.

    PubMed

    Tiniakov, Ruslan L; Tiniakova, Olga P; McLeod, Robbie L; Hey, John A; Yeates, Donovan B

    2003-05-01

    The ragweed- and histamine-induced decreases in nasal patency in cohorts of ragweed-sensitized and nonsensitized dogs were assessed. The volume of nasal airways (V(NA)) was assessed by acoustic rhinometry and resistance to airflow (R(NA)) by anterior rhinomanometry. Histamine delivered to the nasal passages of five dogs caused a rapid and prolonged increase in R(NA) (0.75 +/- 0.26 to 3.56 +/- 0.50 cmH(2)O. l(-1). min), an effect that was reversed by intranasal delivery of aerosolized phenylephrine. Ragweed challenge in five ragweed-sensitized dogs increased R(NA) from 0.16 +/- 0.02 to 0.53 +/- 0.07 cmH(2)O. l(-1). min and decreased V(NA) from 12.5 +/- 1.9 to 3.9 +/- 0.3 cm(3), whereas administration of saline aerosol neither increased R(NA) nor decreased V(NA). Prior administration of d-pseudoephedrine (30 mg po) attenuated the ragweed-induced increase in R(NA) and decrease in V(NA). Ragweed challenge changed neither R(NA) nor V(NA) in four nonsensitized dogs. Mediator-induced nasal congestion and allergen-induced allergic rhinitis in ragweed-sensitized dogs, which exhibit symptoms similar to human disease, can be used in the evaluation of safety and efficacy of antiallergic activity of potential drugs.

  15. BDNF pathway is involved in the protective effects of SS-31 on isoflurane-induced cognitive deficits in aging mice.

    PubMed

    Wu, Jing; Zhang, Mingqiang; Li, Huihui; Sun, Xiaoru; Hao, Shuangying; Ji, Muhuo; Yang, Jianjun; Li, Kuanyu

    2016-05-15

    Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation. Behavioral tests were evaluated by the open field test and fear conditioning test 24h after the experiment. We showed that cognitive deficits induced by exposure of the aging mice to isoflurane were accompanied by mitochondrial dysfunction in hippocampus due to loss of the enzymatic activity of complex I. This loss resulted in the increase of reactive oxygen species production, decrease of ATP production and mitochondrial membrane potential, and opening of mitochondrial permeability transition pore. Further, we provided evidence that the BDNF signaling pathway was involved in this process to regulate synaptic plasticity-related proteins, for instance, downregulation of synapsin 1, PSD-95 and p-CREB, and upregulation of NR2A, NR2B, CaMKIIα and CaMKIIβ. Of note, the isoflurane-induced cognitive deficits were rescued by SS-31 through reversal of mitochondrial dysfunction, which facilitated the regulation of BDNF signaling including the expression reversal of aforementioned important synaptic-signaling proteins in aging mice. Our data demonstrate that reversing mitochondrial dysfunction by SS-31 enhances BDNF signaling pathway and synaptic plasticity, and provides protective effects on cognitive function, thereby support the notion that SS-31 may have therapeutic benefits for elderly humans undertaking anesthesia. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Improving the quantum cost of reversible Boolean functions using reorder algorithm

    NASA Astrophysics Data System (ADS)

    Ahmed, Taghreed; Younes, Ahmed; Elsayed, Ashraf

    2018-05-01

    This paper introduces a novel algorithm to synthesize a low-cost reversible circuits for any Boolean function with n inputs represented as a Positive Polarity Reed-Muller expansion. The proposed algorithm applies a predefined rules to reorder the terms in the function to minimize the multi-calculation of common parts of the Boolean function to decrease the quantum cost of the reversible circuit. The paper achieves a decrease in the quantum cost and/or the circuit length, on average, when compared with relevant work in the literature.

  17. Reversal of Fortune: Increased Star Formation Efficiencies in the Early Histories of Dwarf Galaxies?

    NASA Astrophysics Data System (ADS)

    Madau, Piero; Weisz, Daniel R.; Conroy, Charlie

    2014-08-01

    On dwarf galaxy scales, the different shapes of the galaxy stellar mass function and the dark halo mass function require a star-formation efficiency (SFE) in these systems that is currently more than 1 dex lower than that of Milky Way-size halos. Here, we argue that this trend may actually be reversed at high redshift. Specifically, by combining the resolved star-formation histories of nearby isolated dwarfs with the simulated mass-growth rates of dark matter halos, we show that the assembly of these systems occurs in two phases: (1) an early, fast halo accretion phase with a rapidly deepening potential well, characterized by a high SFE; and (2) a late, slow halo accretion phase where, perhaps as a consequence of reionization, the SFE is low. Nearby dwarfs have more old stars than predicted by assuming a constant or decreasing SFE with redshift, a behavior that appears to deviate qualitatively from the trends seen among more massive systems. Taken at face value, the data suggest that at sufficiently early epochs, dwarf galaxy halos above the atomic cooling mass limit can be among the most efficient sites of star formation in the universe.

  18. Endocide-Induced Abnormal Growth Forms of Invasive Giant Salvinia (Salvinia molesta).

    PubMed

    Li, Shiyou; Wang, Ping; Su, Zushang; Lozano, Emily; LaMaster, Olivia; Grogan, Jason B; Weng, Yuhui; Decker, Thomas; Findeisen, John; McGarrity, Monica

    2018-05-22

    Giant salvinia (Salvinia molesta) is one of the most noxious invasive species in the world. The fern is known to have primary, secondary, and tertiary growth forms, which are also commonly hypothesized as growth stages. The identification of these forms is primarily based on the size and folding status of the floating leaves. However, we identified 12 forms in the greenhouse and the field. Our experiments showed that the folding of floating leaves is a reversible trait dependent on water access. The floating leaves quickly fold in response to water shortage, reducing water loss and needs, decreasing growth, and avoiding trichome damage. The leaves re-open to allow trichomes repel water and enhance growth when having adequate water supply. Larger secondary or tertiary forms do not produce small-leaf primary forms without high intensity stress. These results do not support the hypothesis that three growth forms represent sequential growth stages. The abnormal small-leaf forms are the result of endocide-induced autotoxicity and some of them never grow into other forms. The development of abnormal forms and reversible leaf folding strategy in response to high stress along with rapid asexual reproduction are major adaptive traits contributing to the invasiveness of S. molesta.

  19. Role of dopamine D2 receptors in optimizing choice strategy in a dynamic and uncertain environment

    PubMed Central

    Kwak, Shinae; Huh, Namjung; Seo, Ji-Seon; Lee, Jung-Eun; Han, Pyung-Lim; Jung, Min W.

    2014-01-01

    In order to investigate roles of dopamine receptor subtypes in reward-based learning, we examined choice behavior of dopamine D1 and D2 receptor-knockout (D1R-KO and D2R-KO, respectively) mice in an instrumental learning task with progressively increasing reversal frequency and a dynamic two-armed bandit task. Performance of D2R-KO mice was progressively impaired in the former as the frequency of reversal increased and profoundly impaired in the latter even with prolonged training, whereas D1R-KO mice showed relatively minor performance deficits. Choice behavior in the dynamic two-armed bandit task was well explained by a hybrid model including win-stay-lose-switch and reinforcement learning terms. A model-based analysis revealed increased win-stay, but impaired value updating and decreased value-dependent action selection in D2R-KO mice, which were detrimental to maximizing rewards in the dynamic two-armed bandit task. These results suggest an important role of dopamine D2 receptors in learning from past choice outcomes for rapid adjustment of choice behavior in a dynamic and uncertain environment. PMID:25389395

  20. Pressure-Responsive, Surfactant-Free CO2-Based Nanostructured Fluids

    PubMed Central

    2017-01-01

    Microemulsions are extensively used in advanced material and chemical processing. However, considerable amounts of surfactant are needed for their formulation, which is a drawback due to both economic and ecological reasons. Here, we describe the nanostructuration of recently discovered surfactant-free, carbon dioxide (CO2)-based microemulsion-like systems in a water/organic-solvent/CO2 pressurized ternary mixture. “Water-rich” nanodomains embedded into a “water-depleted” matrix have been observed and characterized by the combination of Raman spectroscopy, molecular dynamics simulations, and small-angle neutron scattering. These single-phase fluids show a reversible, pressure-responsive nanostructuration; the “water-rich” nanodomains at a given pressure can be instantaneously degraded/expanded by increasing/decreasing the pressure, resulting in a reversible, rapid, and homogeneous mixing/demixing of their content. This pressure-triggered responsiveness, together with other inherent features of these fluids, such as the absence of any contaminant in the ternary mixture (e.g., surfactant), their spontaneous formation, and their solvation capability (enabling the dissolution of both hydrophobic and hydrophilic molecules), make them appealing complex fluid systems to be used in molecular material processing and in chemical engineering. PMID:28846386

  1. Electrochemical oxidation of tramadol in low-salinity reverse osmosis concentrates using boron-doped diamond anodes.

    PubMed

    Lütke Eversloh, Christian; Schulz, Manoj; Wagner, Manfred; Ternes, Thomas A

    2015-04-01

    The electrochemical treatment of low-salinity reverse osmosis (RO) concentrates was investigated using tramadol (100 μM) as a model substance for persistent organic contaminants. Galvanostatic degradation experiments using boron-doped diamond electrodes at different applied currents were conducted in RO concentrates as well as in ultra-pure water containing either sodium chloride or sodium sulfate. Kinetic investigations revealed a significant influence of in-situ generated active chlorine besides direct anodic oxidation. Therefore, tramadol concentrations decreased more rapidly at elevated chloride content. Nevertheless, reduction of total organic carbon (TOC) was found to be comparatively low, demonstrating that transformation rather than mineralization was taking place. Early stage product formation could be attributed to both direct and indirect processes, including demethylation, hydroxylation, dehydration, oxidative aromatic ring cleavage and halogenation reactions. The latter led to various halogenated derivatives and resulted in AOX (adsorbable organic halogens) formation in the lower mg/L-range depending on the treatment conditions. Characterisation of transformation products (TPs) was achieved via MS(n) experiments and additional NMR measurements. Based on identification and quantification of the main TPs in different matrices and on additional potentiostatic electrolysis, a transformation pathway was proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Command Surface of Self-Organizing Structures by Radical Polymers with Cooperative Redox Reactivity.

    PubMed

    Sato, Kan; Mizuma, Takahiro; Nishide, Hiroyuki; Oyaizu, Kenichi

    2017-10-04

    Robust radical-substituted polymers with ideal redox capability were used as "command surfaces" for liquid crystal orientation. The alignment of the smectic liquid crystal electrolytes with low-dimensional ion conduction pathways was reversible and readily switched in response to the redox states of the polymers. In one example, a charge storage device with a cooperative redox effect was fabricated. The bulk ionic conductivity of the cell was significantly decreased only after the electrode was fully charged, due to the anisotropic ionic conductivity of the electrolytes (ratio >10 3 ). The switching enabled both a rapid cell response and long charge retention. Such a cooperative command surface of self-assembled structures will give rise to new highly energy efficient supramolecular-based devices including batteries, charge carriers, and actuators.

  3. Ultrasound-modulated bubble propulsion of chemically powered microengines.

    PubMed

    Xu, Tailin; Soto, Fernando; Gao, Wei; Garcia-Gradilla, Victor; Li, Jinxing; Zhang, Xueji; Wang, Joseph

    2014-06-18

    The use of an ultrasound (US) field for rapid and reversible control of the movement of bubble-propelled chemically powered PEDOT/Ni/Pt microengines is demonstrated. Such operation reflects the US-induced disruption of normal bubble evolution and ejection, essential for efficient propulsion of catalytic microtubular engines. It offers precise speed control, with sharp increases and decreases of the speed at low and high US powers, respectively. A wide range of speeds can thus be generated by tuning the US power. Extremely fast changes in the motor speed (<0.1 s) and reproducible "On/Off" activations are observed, indicating distinct advantages compared to motion control methods based on other external stimuli. Such effective control of the propulsion of chemically powered microengines, including remarkable "braking" ability, holds considerable promise for diverse applications.

  4. Optoelectronic Characterization of Infrared Photodetector Fabricated on Ge-on-Si Substrate.

    PubMed

    Khurelbaatar, Zagarzusem; Kil, Yeon-Ho; Kim, Taek Sung; Shim, Kyu-Hwan; Hong, Hyobong; Choi, Chel-Jong

    2015-10-01

    We report on the optoelectronic characterization of Ge p-i-n infrared photodetector fabricated on Ge-on-Si substrate using rapid thermal chemical vapor deposition (RTCVD). The phosphorous doping concentration and the root mean square (RMS) surface roughness of epitaxial layer was estimated to be 2 x 10(18) cm(-3) and 1.2 nm, respectively. The photodetector were characterized with respect to their dark, photocurrent and responsivities in the wavelength range of 1530-1630 nm. At 1550 nm wavelength, responsivity of 0.32 A/W was measured for a reverse bias of 1 V, corresponding to 25% external quantum efficiency, without an optimal antireflection coating. Responsivity drastically reduced from 1560 nm wavelength which could be attributed to decreased absorption of Ge at room temperature.

  5. Exercise training improves obesity-related lymphatic dysfunction.

    PubMed

    Hespe, Geoffrey E; Kataru, Raghu P; Savetsky, Ira L; García Nores, Gabriela D; Torrisi, Jeremy S; Nitti, Matthew D; Gardenier, Jason C; Zhou, Jie; Yu, Jessie Z; Jones, Lee W; Mehrara, Babak J

    2016-08-01

    Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti-inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic specific genes, including VEGFR-3 and Prox1. Taken together, our findings suggest that obesity impairs lymphatic function via multiple mechanisms and that these pathological changes can be reversed, in part, with aerobic exercise, independent of weight loss. In addition, our study shows that obesity-induced lymphatic endothelial cell gene expression changes are reversible with behavioural modifications. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  6. ARC-1969-AC74-1058-29

    NASA Image and Video Library

    1974-03-13

    United Airlines DC-8 (N8099U) Two Segment Evaluation. In-Flight Thrust Reversing, Steep Approach Research. The thrust reversing concept was applied to the DC-8 Commercial transport to achieve the rapid descent capability required for FAA certificaiton. Note: Used in publication in Flight Research at Ames; 57 Years of Development and Validation of Aeronautical Technology NASA SP-1998-3300 fig 96

  7. Do we really need sugammadex as an antagonist of muscle relaxants in anesthesia?

    PubMed

    Meistelman, Claude; Donati, François

    2016-08-01

    Sugammadex is a selective relaxant-binding agent that is designed to encapsulate rocuronium and chemically similar steroidal muscle relaxants such as vecuronium. This review summarizes recent information on the use of sugammadex in clinical practice. The main advantages of sugammadex when compared with conventional anticholinesterase agents are a much faster recovery time and its unique ability to reverse rapidly and efficiently, for the first time, deep levels of neuromuscular blockade. However, there is paucity of evidence-based studies on the benefit of deep neuromuscular block, and then routine administration of sugammadex to reverse any level of block, for example, during laparoscopic surgery. It appears that reduction of costs depends mainly on organizational factors. Finally it must be remembered that sugammadex only works with steroidal nondepolarizing muscle relaxants; therefore neostigmine should not be withdrawn because it is the only reversal agent effective against atracurium or cisatracurium. Sugammadex offers a significantly faster and more predictable recovery profile than neostigmine. It is now possible to reverse rapidly and efficiently any level of neuromuscular blockade and to avoid the risk of adverse events because of residual paralysis such as critical respiratory events during recovery from anesthesia.

  8. Rapid and reversible impairments of short- and long-term social recognition memory are caused by acute isolation of adult rats via distinct mechanisms.

    PubMed

    Shahar-Gold, Hadar; Gur, Rotem; Wagner, Shlomo

    2013-01-01

    Mammalian social organizations require the ability to recognize and remember individual conspecifics. This social recognition memory (SRM) can be examined in rodents using their innate tendency to investigate novel conspecifics more persistently than familiar ones. Here we used the SRM paradigm to examine the influence of housing conditions on the social memory of adult rats. We found that acute social isolation caused within few days a significant impairment in acquisition of short-term SRM of male and female rats. Moreover, SRM consolidation into long-term memory was blocked following only one day of social isolation. Both impairments were reversible, but with different time courses. Furthermore, only the impairment in SRM consolidation was reversed by systemic administration of arginine-vasopressin (AVP). In contrast to SRM, object recognition memory was not affected by social isolation. We conclude that acute social isolation rapidly induces reversible changes in the brain neuronal and molecular mechanisms underlying SRM, which hamper its acquisition and completely block its consolidation. These changes occur via distinct, AVP sensitive and insensitive mechanisms. Thus, acute social isolation of rats swiftly causes changes in their brain and interferes with their normal social behavior.

  9. Discovery of Rapid and Reversible Water Insertion in Rare Earth Sulfates: A New Process for Thermochemical Heat Storage.

    PubMed

    Hatada, Naoyuki; Shizume, Kunihiko; Uda, Tetsuya

    2017-07-01

    Thermal energy storage based on chemical reactions is a prospective technology for the reduction of fossil-fuel consumption by storing and using waste heat. For widespread application, a critical challenge is to identify appropriate reversible reactions that occur below 250 °C, where abundant low-grade waste heat and solar energy might be available. Here, it is shown that lanthanum sulfate monohydrate La 2 (SO 4 ) 3 ⋅H 2 O undergoes rapid and reversible dehydration/hydration reactions in the temperature range from 50 to 250 °C upon heating/cooling with remarkably small thermal hysteresis (<50 °C), and thus it emerges as a new candidate system for thermal energy storage. Thermogravimetry and X-ray diffraction analyses reveal that the reactions proceed through an unusual mechanism for sulfates: water is removed from, or inserted in La 2 (SO 4 ) 3 ⋅H 2 O with progressive change in hydration number x without phase change. It is also revealed that only a specific structural modification of La 2 (SO 4 ) 3 exhibits this reversible dehydration/hydration behavior. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Formation of reversed austenite during tempering of 14Cr-7Ni-0.3Nb-0.7Mo-0.03C super martensitic stainless steel

    NASA Astrophysics Data System (ADS)

    Park, Eun Seo; Yoo, Dae Kyoung; Sung, Jee Hyun; Kang, Chang Yong; Lee, Jun Hee; Sung, Jang Hyun

    2004-12-01

    Reversed austenite transformation and existence of retained austenite during tempering of the super martensitic stainless steel of Fe-14Cr-7Ni-0.3Nb-0.7Mo-0.03C were studied by means of experiments on microstructure and X-ray diffraction, and tensile and hardness tests. Acicular type retained austenite at the lath boundary of martensite with the interior appeared after solution annealing. This retained austenite still existed, and reversed austenite was not formed, with tempering up to 24h at 450°C. The reversed austenite began to form above 550°C, and the volume fraction of reversed austenite decreased with increasing tempering temperature after showing a maximum value of 19.2% at 650°C. This maximum volume fraction of reversed austenite was responsible for the lowest value of strength and hardness. The Ni contents of plate type reversed austenite and the surrounding matrix increased and decreased respectively, implying that the reversed austenite was formed as a result of nickel diffusion. The orientation relationships between reversed austenite and the surrounding matrix showed a K-S relationship of(bar 11bar 1)_γ //(01bar 1)_m and[011]_γ //[bar 111]_m.

  11. Encoding changes in orbitofrontal cortex in reversal-impaired aged rats.

    PubMed

    Schoenbaum, Geoffrey; Setlow, Barry; Saddoris, Michael P; Gallagher, Michela

    2006-03-01

    Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.

  12. Using Habit Reversal to Decrease Filled Pauses in Public Speaking

    ERIC Educational Resources Information Center

    Mancuso, Carolyn; Miltenberger, Raymond G.

    2016-01-01

    This study evaluated the effectiveness of simplified habit reversal in reducing filled pauses that occur during public speaking. Filled pauses consist of "uh," "um," or "er"; clicking sounds; and misuse of the word "like." After baseline, participants received habit reversal training that consisted of…

  13. Surface contact stimulates the just-in-time deployment of bacterial adhesins.

    PubMed

    Li, Guanglai; Brown, Pamela J B; Tang, Jay X; Xu, Jing; Quardokus, Ellen M; Fuqua, Clay; Brun, Yves V

    2012-01-01

    The attachment of bacteria to surfaces provides advantages such as increasing nutrient access and resistance to environmental stress. Attachment begins with a reversible phase, often mediated by surface structures such as flagella and pili, followed by a transition to irreversible attachment, typically mediated by polysaccharides. Here we show that the interplay between pili and flagellum rotation stimulates the rapid transition between reversible and polysaccharide-mediated irreversible attachment. We found that reversible attachment of Caulobacter crescentus cells is mediated by motile cells bearing pili and that their contact with a surface results in the rapid pili-dependent arrest of flagellum rotation and concurrent stimulation of polar holdfast adhesive polysaccharide. Similar stimulation of polar adhesin production by surface contact occurs in Asticcacaulis biprosthecum and Agrobacterium tumefaciens. Therefore, single bacterial cells respond to their initial contact with surfaces by triggering just-in-time adhesin production. This mechanism restricts stable attachment to intimate surface interactions, thereby maximizing surface attachment, discouraging non-productive self-adherence, and preventing curing of the adhesive. © 2011 Blackwell Publishing Ltd.

  14. Reversal of succinylcholine induced apnea with an organophosphate scavenging recombinant butyrylcholinesterase.

    PubMed

    Geyer, Brian C; Larrimore, Katherine E; Kilbourne, Jacquelyn; Kannan, Latha; Mor, Tsafrir S

    2013-01-01

    Concerns about the safety of paralytics such as succinylcholine to facilitate endotracheal intubation limit their use in prehospital and emergency department settings. The ability to rapidly reverse paralysis and restore respiratory drive would increase the safety margin of an agent, thus permitting the pursuit of alternative intubation strategies. In particular, patients who carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme responsible for succinylcholine hydrolysis, are susceptible to succinylcholine-induced apnea, which manifests as paralysis, lasting hours beyond the normally brief half-life of succinylcholine. We hypothesized that intravenous administration of plant-derived recombinant BChE, which also prevents mortality in nerve agent poisoning, would rapidly reverse the effects of succinylcholine. Recombinant butyrylcholinesterase was produced in transgenic plants and purified. Further analysis involved murine and guinea pig models of succinylcholine toxicity. Animals were treated with lethal and sublethal doses of succinylcholine followed by administration of butyrylcholinesterase or vehicle. In both animal models vital signs and overall survival at specified intervals post succinylcholine administration were assessed. Purified plant-derived recombinant human butyrylcholinesterase can hydrolyze succinylcholine in vitro. Challenge of mice with an LD100 of succinylcholine followed by BChE administration resulted in complete prevention of respiratory inhibition and concomitant mortality. Furthermore, experiments in symptomatic guinea pigs demonstrated extremely rapid succinylcholine detoxification with complete amelioration of symptoms and no apparent complications. Recombinant plant-derived butyrylcholinesterase was capable of counteracting and reversing apnea in two complementary models of lethal succinylcholine toxicity, completely preventing mortality. This study of a protein antidote validates the feasibility of protection and treatment of overdose from succinylcholine as well as other biologically active butyrylcholinesterase substrates.

  15. Intramuscular Cobinamide Sulfite in a Rabbit Model of Sub-Lethal Cyanide Toxicity

    PubMed Central

    Brenner, Matthew; Kim, Jae G.; Mahon, Sari B.; Lee, Jangwoen; Kreuter, Kelly A.; Blackledge, William; Mukai, David; Patterson, Steve; Mohammad, Othman; Sharma, Vijay S.; Boss, Gerry R.

    2009-01-01

    Objective To determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity. Background Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B12) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigated the use of intramuscular cobinamide sulfite to reverse cyanide toxicity induced physiologic changes in a sublethal cyanide exposure animal model. Methods New Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous wave near infrared spectroscopy monitoring of tissue oxy- and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5). Results Intramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system was in a mean of 1032 minutes in the control group and 9 minutes in the cobinamide group with a difference of 1023 minutes (95% confidence interval [CI] 116, 1874 minutes). In muscle tissue, recovery times were 76 and 24 minutes with a difference of 52 minutes (95% CI 7, 98min). Red blood cell cyanide levels returned towards normal significantly faster in cobinamide sulfite-treated animals than in control animals. Conclusions Intramuscular cobinamide sulfite rapidly and effectively reverses the physiologic effects of cyanide poisoning, suggesting that a compact cyanide antidote kit can be developed for mass casualty cyanide exposures. PMID:20045579

  16. Photovoltaic and thermophotovoltaic devices with quantum barriers

    DOEpatents

    Wernsman, Bernard R [Jefferson Hills, PA

    2007-04-10

    A photovoltaic or thermophotovoltaic device includes a diode formed by p-type material and n-type material joined at a p-n junction and including a depletion region adjacent to said p-n junction, and a quantum barrier disposed near or in the depletion region of the p-n junction so as to decrease device reverse saturation current density while maintaining device short circuit current density. In one embodiment, the quantum barrier is disposed on the n-type material side of the p-n junction and decreases the reverse saturation current density due to electrons while in another, the barrier is disposed on the p-type material side of the p-n junction and decreases the reverse saturation current density due to holes. In another embodiment, both types of quantum barriers are used.

  17. Vitamin E Supplementation in Burn Patients

    DTIC Science & Technology

    2013-10-01

    consequences of this severe and rapid depletion are unknown because adipose tissue alpha- tocopherol normally takes years to deplete. Our long- term...proposal were to a) attenuate alpha- tocopherol depletion in burn patients by vitamin E supplementation, b) to prevent or reverse oxidative stress, c...hypothesis is that the administration of high doses of alpha- tocopherol will prevent or restore levels of vitamin E in adipose tissue and reverse

  18. Rapid and Quantitative Detection of Hepatitis A Virus from Green Onion and Strawberry Rinses by Use of Real-Time Reverse Transcription-PCR

    PubMed Central

    Shan, X. C.; Wolffs, P.; Griffiths, M. W.

    2005-01-01

    In this study, an immunomagnetic capture method and a real-time reverse transcription-PCR assay were used to quantify hepatitis A virus (HAV) in green onion and strawberry rinses. This combined protocol detected as low as 0.5 PFU HAV in produce rinses and concentrated HAV levels up to 20-fold. PMID:16151164

  19. A social change perspective on injury prevention in China.

    PubMed

    Ozanne-Smith, Joan; Li, Qingfeng

    2018-05-05

    China has undergone massive social change over the past four decades. Since national estimates became available in 1987, the overall fatal injury rate has decreased. This paper investigates targeted interventions and sociodemographic factors that may have contributed to fatal injury rate changes particularly for road traffic fatality (RTF), suicide and drowning. (1) To review the recent epidemiology of injury in China.(2)To investigate factors influencing trends in overall and specific cause injury mortality rates. Published injury mortality statistics and related literature were reviewed. Factors potentially influencing trends were investigated in the context of rapid development based on literature reviews of targeted interventions, macrolevel and microlevel contextual factors and changes specific to RTF, suicide and drowning. Overall estimated national injury mortality rates in China decreased between 1987 and 2015, despite a rapid rise in RTF. Suicide and drowning rates decreased significantly and falls displaced drowning among the leading causes. The higher female to male suicide ratio reversed. Differences were observed in frequencies and proportions of deaths by major cause by age group and over time. Economic and structural development and related social change in this period include: urbanisation, changes in demographics, life choices (eg, internal migration), education, poverty alleviation, health insurance and relevant regulations/legislation. These factors potentially explain much of the change in fatal injury rates in China. Data limitations persist. Increased investment in data and research would provide realistic opportunities for accelerated progress in implementing effective targeted interventions to further reduce China's injury burden. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. High cytidine deaminase expression in the liver provides sanctuary for cancer cells from decitabine treatment effects.

    PubMed

    Ebrahem, Quteba; Mahfouz, Reda Z; Ng, Kwok Peng; Saunthararajah, Yogen

    2012-10-01

    We document for the first time that sanctuary in an organ which expresses high levels of the enzyme cytidine deaminase (CDA) is a mechanism of cancer cell resistance to cytidine analogues. This mechanism could explain why historically, cytidine analogues have not been successful chemotherapeutics against hepatotropic cancers, despite efficacy in vitro. Importantly, this mechanism of resistance can be readily reversed, without increasing toxicity to sensitive organs, by combining a cytidine analogue with an inhibitor of cytidine deaminase (tetrahydrouridine). Specifically, CDA rapidly metabolizes cytidine analogues into inactive uridine counterparts. Hence, to determine if sheltering/protection of cancer cells in organs which express high levels of CDA (e.g., liver) is a mechanism of resistance, we utilized a murine xenotransplant model of myeloid cancer that is sensitive to epigenetic therapeutic effects of the cytidine analogue decitabine in vitro and hepato-tropic in vivo. Treatment of tumor-bearing mice with decitabine (subcutaneous 0.2mg/kg 2X/week) doubled median survival and significantly decreased extra-hepatic tumor burden, but hepatic tumor burden remained substantial, to which the animals eventually succumbed. Combining a clinically-relevant inhibitor of CDA (tetrahydrouridine) with a lower dose of decitabine (subcutaneous 0.1mg/kg 2X/week) markedly decreased liver tumor burden without blood count or bone marrow evidence of myelotoxicity, and with further improvement in survival. In conclusion, sanctuary in a CDA-rich organ is a mechanism by which otherwise susceptible cancer cells can resist the effects of decitabine epigenetic therapy. This protection can be reversed without increasing myelotoxicity by combining tetrahydrouridine with a lower dose of decitabine.

  1. Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model.

    PubMed

    Speidl, Walter S; Cimmino, Giovanni; Ibanez, Borja; Elmariah, Sammy; Hutter, Randolph; Garcia, Mario J; Fuster, Valentin; Goldman, Martin E; Badimon, Juan J

    2010-08-01

    Aortic stenosis (AS) is associated with significant morbidity and mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces atherosclerotic plaque regression. The aims of this study were to determine the effects of rApoA-I(M) on experimental aortic valve degeneration and its mechanisms of action. New Zealand White rabbits (n = 20) were fed an atherogenic diet for 9 months and then randomized to either placebo or rApoA-I(M). Echocardiography was used to assess the effect of the treatments on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized low-density lipoprotein served to define the effects of rApoA-I(M) on the expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in the rApoA-I(M) animals showed significantly less leaflet thickening, inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular cholesterol content in PAVMF. Recombinant apolipoprotein A-I Milano treatment reverses AS in this experimental rabbit model. The beneficial effects seem to be mediated by enhanced cholesterol removal and by reduced inflammation and calcification.

  2. Sudden collapse of vacuoles in Saintpaulia sp. palisade cells induced by a rapid temperature decrease.

    PubMed

    Kadohama, Noriaki; Goh, Tatsuaki; Ohnishi, Miwa; Fukaki, Hidehiro; Mimura, Tetsuro; Suzuki, Yoshihiro

    2013-01-01

    It is well known that saintpaulia leaf is damaged by the rapid temperature decrease when cold water is irrigated onto the leaf surface. We investigated this temperature sensitivity and the mechanisms of leaf damage in saintpaulia (Saintpaulia sp. cv. 'Iceberg') and other Gesneriaceae plants. Saintpaulia leaves were damaged and discolored when subjected to a rapid decrease in temperature, but not when the temperature was decreased gradually. Sensitivity to rapid temperature decrease increased within 10 to 20 min during pre-incubation at higher temperature. Injury was restricted to the palisade mesophyll cells, where there was an obvious change in the color of the chloroplasts. During a rapid temperature decrease, chlorophyll fluorescence monitored by a pulse amplitude modulated fluorometer diminished and did not recover even after rewarming to the initial temperature. Isolated chloroplasts were not directly affected by the rapid temperature decrease. Intracellular pH was monitored with a pH-dependent fluorescent dye. In palisade mesophyll cells damaged by rapid temperature decrease, the cytosolic pH decreased and the vacuolar membrane collapsed soon after a temperature decrease. In isolated chloroplasts, chlorophyll fluorescence declined when the pH of the medium was lowered. These results suggest that a rapid temperature decrease directly or indirectly affects the vacuolar membrane, resulting in a pH change in the cytosol that subsequently affects the chloroplasts in palisade mesophyll cells. We further confirmed that the same physiological damage occurs in other Gesneriaceae plants. These results strongly suggested that the vacuoles of palisade mesophyll cells collapsed during the initial phase of leaf injury.

  3. Sudden Collapse of Vacuoles in Saintpaulia sp. Palisade Cells Induced by a Rapid Temperature Decrease

    PubMed Central

    Kadohama, Noriaki; Goh, Tatsuaki; Ohnishi, Miwa; Fukaki, Hidehiro; Mimura, Tetsuro; Suzuki, Yoshihiro

    2013-01-01

    It is well known that saintpaulia leaf is damaged by the rapid temperature decrease when cold water is irrigated onto the leaf surface. We investigated this temperature sensitivity and the mechanisms of leaf damage in saintpaulia (Saintpaulia sp. cv. ‘Iceberg’) and other Gesneriaceae plants. Saintpaulia leaves were damaged and discolored when subjected to a rapid decrease in temperature, but not when the temperature was decreased gradually. Sensitivity to rapid temperature decrease increased within 10 to 20 min during pre-incubation at higher temperature. Injury was restricted to the palisade mesophyll cells, where there was an obvious change in the color of the chloroplasts. During a rapid temperature decrease, chlorophyll fluorescence monitored by a pulse amplitude modulated fluorometer diminished and did not recover even after rewarming to the initial temperature. Isolated chloroplasts were not directly affected by the rapid temperature decrease. Intracellular pH was monitored with a pH-dependent fluorescent dye. In palisade mesophyll cells damaged by rapid temperature decrease, the cytosolic pH decreased and the vacuolar membrane collapsed soon after a temperature decrease. In isolated chloroplasts, chlorophyll fluorescence declined when the pH of the medium was lowered. These results suggest that a rapid temperature decrease directly or indirectly affects the vacuolar membrane, resulting in a pH change in the cytosol that subsequently affects the chloroplasts in palisade mesophyll cells. We further confirmed that the same physiological damage occurs in other Gesneriaceae plants. These results strongly suggested that the vacuoles of palisade mesophyll cells collapsed during the initial phase of leaf injury. PMID:23451194

  4. Changes in the Levels of Abscisic Acid and Its Metabolites in Excised Leaf Blades of Xanthium strumarium during and after Water Stress 1

    PubMed Central

    Zeevaart, Jan A. D.

    1980-01-01

    The time course of abscisic acid (ABA) accumulation during water stress and of degradation following rehydration was investigated by analyzing the levels of ABA and its metabolites phaseic acid (PA) and alkalihydrolyzable conjugated ABA in excised leaf blades of Xanthium strumarium. Initial purification was by reverse-phase, preparative, high performance liquid chromatography (HPLC) which did not require prior partitioning. ABA and PA were purified further by analytical HPLC with a μBondapak-NH2 column, and quantified by GLC with an electron capture detector. The ABA content of stressed leaves increased for 4 to 5 hours and then leveled off due to a balance between synthesis and degradation. Since PA accumulated at a constant rate throughout the wilting period, it was concluded that the rate of ABA synthesis decreased after the first 4 to 5 hours stress. Conjugated ABA increased at a low rate during stress. This is interpreted to indicate that free ABA was converted to the conjugated form, rather than the reverse. Following rehydration of wilted leaves, the ABA level immediately ceased increasing; it remained constant for 1 hour and then declined rapidly to the prestress level over a 2- to 3-hour period with a concomitant rise in the PA level. In contrast to the rapid disappearance of ABA after relief of stress, the high PA content of rehydrated leaves declined only slowly. The level of conjugated ABA did not change following rehydration, indicating that conjugation of ABA was irreversible. Detached Xanthium leaves that were subjected to a wilting-recovery-rewilting cycle in darkness, responded to the second wilting period by formation of the same amount of ABA as accumulated after the first stress period. PMID:16661500

  5. Changes in the Levels of Abscisic Acid and Its Metabolites in Excised Leaf Blades of Xanthium strumarium during and after Water Stress.

    PubMed

    Zeevaart, J A

    1980-10-01

    The time course of abscisic acid (ABA) accumulation during water stress and of degradation following rehydration was investigated by analyzing the levels of ABA and its metabolites phaseic acid (PA) and alkalihydrolyzable conjugated ABA in excised leaf blades of Xanthium strumarium. Initial purification was by reverse-phase, preparative, high performance liquid chromatography (HPLC) which did not require prior partitioning. ABA and PA were purified further by analytical HPLC with a muBondapak-NH(2) column, and quantified by GLC with an electron capture detector.The ABA content of stressed leaves increased for 4 to 5 hours and then leveled off due to a balance between synthesis and degradation. Since PA accumulated at a constant rate throughout the wilting period, it was concluded that the rate of ABA synthesis decreased after the first 4 to 5 hours stress. Conjugated ABA increased at a low rate during stress. This is interpreted to indicate that free ABA was converted to the conjugated form, rather than the reverse.Following rehydration of wilted leaves, the ABA level immediately ceased increasing; it remained constant for 1 hour and then declined rapidly to the prestress level over a 2- to 3-hour period with a concomitant rise in the PA level. In contrast to the rapid disappearance of ABA after relief of stress, the high PA content of rehydrated leaves declined only slowly. The level of conjugated ABA did not change following rehydration, indicating that conjugation of ABA was irreversible.Detached Xanthium leaves that were subjected to a wilting-recovery-rewilting cycle in darkness, responded to the second wilting period by formation of the same amount of ABA as accumulated after the first stress period.

  6. Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure

    NASA Technical Reports Server (NTRS)

    Elliott, A. R.; Fu, Z.; Tsukimoto, K.; Prediletto, R.; Mathieu-Costello, O.; West, J. B.

    1992-01-01

    We previously showed that when the pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to determine whether some of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. To test this, the Ptm was raised to 52.5 cmH2O for 1 min of blood perfusion and then reduced to 12.5 cmH2O for 3 min of saline-dextran perfusion, followed by intravascular fixation at the same pressure. In another group of animals, the pressure was elevated for 1 min of blood and 3 min of saline-dextran before being reduced. The results were compared with previous studies in which the capillary pressures were maintained elevated at 52.5 cmH2O during the entire procedure. Control studies were also done at sustained low pressures. The results showed that the number of endothelial and epithelial breaks per millimeter and the total fraction area of the breaks were reduced when the pressure was lowered. For example, the number of endothelial breaks per millimeter decreased from 7.1 +/- 2.1 to 2.4 +/- 0.7, and the number of epithelial breaks per millimeter fell from 11.4 +/- 3.7 to 3.4 +/- 0.7. There was evidence that the breaks that closed were those that were initially small and were associated with an intact basement membrane. The results suggest that cells can move along their underlying matrix by rapid disengagement and reattachment of cell adhesion molecules, causing breaks to open or close within minutes.(ABSTRACT TRUNCATED AT 250 WORDS).

  7. Wind tunnel test of model target thrust reversers for the Pratt and Whitney aircraft JT8D-100 series engines installed on a 727-200 airplane

    NASA Technical Reports Server (NTRS)

    Hambly, D.

    1974-01-01

    The results of a low speed wind tunnel test of 0.046 scale model target thrust reversers installed on a 727-200 model airplane are presented. The full airplane model was mounted on a force balance, except for the nacelles and thrust reversers, which were independently mounted and isolated from it. The installation had the capability of simulating the inlet airflows and of supplying the correct proportions of primary and secondary air to the nozzles. The objectives of the test were to assess the compatibility of the thrust reversers target door design with the engine and airplane. The following measurements were made: hot gas ingestion at the nacelle inlets; model lift, drag, and pitching moment; hot gas impingement on the airplane structure; and qualitative assessment of the rudder effectiveness. The major parameters controlling hot gas ingestion were found to be thrust reverser orientation, engine power setting, and the lip height of the bottom thrust reverser doors on the side nacelles. The thrust reversers tended to increase the model lift, decrease the drag, and decrease the pitching moment.

  8. AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

    PubMed Central

    Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

    2016-01-01

    Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

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

    Gilat, E.; Kadar, T.; Levy, A.

    Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 {+-} 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsantmore » effect (53 {+-} 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in brain damage. The addition of scopolamine to midazolam did not alter the above observation. In summary, nasal midazolam treatment briefly after initiation of OP-induced seizure leads to cessation of EGSA and prevented brain lesions and behavioral deficiencies in the rat model.« less

  10. Lead exposures and biological responses in military weapons systems: Aerosol characteristics and acute lead effects among US Army artillerymen: Final report

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

    Bhattacharyya, M.H.; Stebbings, J.H.; Peterson, D.P.

    1993-03-01

    This study was to determine the concentration and chemical nature of lead (Pb) aerosols produced during the firing of artillery and to determine the exposures and biological responses of crew members exposed to lead aerosols during such firing. The concentrations of lead-containing aerosols at crew positions depended on wind conditions, with higher concentrations when firing into a head wind. Aerosol concentrations were highest in the muzzle blast zone. Concentrations of lead in the blood of crew members rose during the first 12 days of exposure to elevated airborne lead concentrations and then leveled off. There was no rapid decrease inmore » blood lead concentrations after completion of firing. Small decreases in hematocrit and small increases in free erythrocyte porphyrin were correlated with increasing exposure to airborne lead. These changes were reversed by seven weeks after firing. Changes in nerve conduction velocity had borderline statistical significance to airborne lead exposure. In measuring nerve conduction velocity, differences in skin temperature must be taken into account.« less

  11. The V-ATPase membrane domain is a sensor of granular pH that controls the exocytotic machinery.

    PubMed

    Poëa-Guyon, Sandrine; Ammar, Mohamed Raafet; Erard, Marie; Amar, Muriel; Moreau, Alexandre W; Fossier, Philippe; Gleize, Vincent; Vitale, Nicolas; Morel, Nicolas

    2013-10-28

    Several studies have suggested that the V0 domain of the vacuolar-type H(+)-adenosine triphosphatase (V-ATPase) is directly implicated in secretory vesicle exocytosis through a role in membrane fusion. We report in this paper that there was a rapid decrease in neurotransmitter release after acute photoinactivation of the V0 a1-I subunit in neuronal pairs. Likewise, inactivation of the V0 a1-I subunit in chromaffin cells resulted in a decreased frequency and prolonged kinetics of amperometric spikes induced by depolarization, with shortening of the fusion pore open time. Dissipation of the granular pH gradient was associated with an inhibition of exocytosis and correlated with the V1-V0 association status in secretory granules. We thus conclude that V0 serves as a sensor of intragranular pH that controls exocytosis and synaptic transmission via the reversible dissociation of V1 at acidic pH. Hence, the V-ATPase membrane domain would allow the exocytotic machinery to discriminate fully loaded and acidified vesicles from vesicles undergoing neurotransmitter reloading.

  12. The V-ATPase membrane domain is a sensor of granular pH that controls the exocytotic machinery

    PubMed Central

    Poëa-Guyon, Sandrine; Ammar, Mohamed Raafet; Erard, Marie; Amar, Muriel; Moreau, Alexandre W.; Fossier, Philippe; Gleize, Vincent

    2013-01-01

    Several studies have suggested that the V0 domain of the vacuolar-type H+-adenosine triphosphatase (V-ATPase) is directly implicated in secretory vesicle exocytosis through a role in membrane fusion. We report in this paper that there was a rapid decrease in neurotransmitter release after acute photoinactivation of the V0 a1-I subunit in neuronal pairs. Likewise, inactivation of the V0 a1-I subunit in chromaffin cells resulted in a decreased frequency and prolonged kinetics of amperometric spikes induced by depolarization, with shortening of the fusion pore open time. Dissipation of the granular pH gradient was associated with an inhibition of exocytosis and correlated with the V1–V0 association status in secretory granules. We thus conclude that V0 serves as a sensor of intragranular pH that controls exocytosis and synaptic transmission via the reversible dissociation of V1 at acidic pH. Hence, the V-ATPase membrane domain would allow the exocytotic machinery to discriminate fully loaded and acidified vesicles from vesicles undergoing neurotransmitter reloading. PMID:24165939

  13. Model development of supersonic trough wind with shocks

    NASA Technical Reports Server (NTRS)

    Grebowsky, J. M.

    1972-01-01

    The time dependent one dimensional hydrodynamic equations describe the evolution of the thermal plasma flow along closed magnetic field lines outside of the plasmasphere. The convection of the supersonic polar wind onto a closed fieldline results in the assumed formation of collisionless plasma shocks. These shocks move earthward as the field line with its frozen-in plasma remains fixed or contracts with time to smaller L coordinates. The high equatorial plasma temperature (of the order of electron volts) produced by the shock process decreases with time if the flow is isothermal but it will increase if the contraction is under adiabatic conditions. Assuming adiabaticity a peak in the temperature forms at the equator in conjunction with a depression in the ion density. After an initial contraction, if the flux tube drifts to higher L coordinates the direction of the shock motion can be reversed so that the supersonic region will expand along the field line towards the state characterizing the supersonic polar wind. A rapid expansion will lower the equatorial density while the temperature decreases with time under adiabatic but not isothermal conditions.

  14. Effects of anion transport inhibitors and ion substitution on Cl sup minus transport in TAL of Henle's loop

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

    Kondo, Yoshiaki; Yoshitomi, Koji; Imai, Masashi

    1987-12-01

    To identify the mechanism of Cl{sup {minus}} transport across the thin ascending limb of Henle's loop (TAL), the authors examined effects of anion transport inhibitors and ionic substitution in the isolated segments of hamsters using the in vitro microperfusion technique. 4,4{prime}-diisothiocyanostilbene-2,2{prime}-disulfonic acid (DIDS) at 10{sup {minus}3} M changed the NaCl diffusion voltage (V{sub t}) to the orientation that corresponds to the decrease in the Cl{sup {minus}}-Na{sup +} permeability ratio when it was added either to the bath or to the lumen. DIDS, added to the bath or to the lumen decreased the lumen-to-bath flux coefficient for {sup 36}Cl, whereas itmore » had little effect on the flux coefficient for {sup 22}Na. The inhibitory effect of phloretin was rapid and reversible. Phloridzin was ineffective. From these observations, they conclude that Cl{sup {minus}} transport across the TAL is distinct from Na{sup +} and is not coupled with Na{sup +}, K{sup +}, or HCO{sup {minus}}{sub 3}.« less

  15. Artificial Photosynthetic Reaction Center Exhibiting Acid-Responsive Regulation of Photoinduced Charge Separation

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

    Pahk, Ian; Kodis, Gerdenis; Fleming, Graham R.

    Charge separation (CS) is the primary light-driven reaction in photosynthesis whereas onphotochemical quenching (NPQ) is a photoprotective regulatory mechanism employed by many photosynthetic organisms to dynamically modulate energy flow within the photosynthetic apparatus in response to fluctuating light conditions. Activated by decreases in lumen pH produced during periods of high photon flux, NPQ induces rapid thermal dissipation of excess excitation energy. As a result, the rate of CS decreases, thereby limiting the accumulation of potentially deleterious reactive intermediates and byproducts. In this article, a molecular triad that functionally mimics the effects of NPQ associated with an artificial photosynthetic reaction centermore » is described. Steady-state absorption and emission, time-resolved fluorescence, and transient absorption spectroscopies have been used to demonstrate a 1 order of magnitude reduction in the CS quantum yield via reversible protonation of an excited-state-quenching molecular switch moiety. As in the natural system, the populations of unquenched and quenched states and therefore the overall yields of CS were found to be dependent on acid concentration.« less

  16. Reversal of age-related neural timing delays with training

    PubMed Central

    Anderson, Samira; White-Schwoch, Travis; Parbery-Clark, Alexandra; Kraus, Nina

    2013-01-01

    Neural slowing is commonly noted in older adults, with consequences for sensory, motor, and cognitive domains. One of the deleterious effects of neural slowing is impairment of temporal resolution; older adults, therefore, have reduced ability to process the rapid events that characterize speech, especially in noisy environments. Although hearing aids provide increased audibility, they cannot compensate for deficits in auditory temporal processing. Auditory training may provide a strategy to address these deficits. To that end, we evaluated the effects of auditory-based cognitive training on the temporal precision of subcortical processing of speech in noise. After training, older adults exhibited faster neural timing and experienced gains in memory, speed of processing, and speech-in-noise perception, whereas a matched control group showed no changes. Training was also associated with decreased variability of brainstem response peaks, suggesting a decrease in temporal jitter in response to a speech signal. These results demonstrate that auditory-based cognitive training can partially restore age-related deficits in temporal processing in the brain; this plasticity in turn promotes better cognitive and perceptual skills. PMID:23401541

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

    Takuwa, Y.; Takuwa, N.; Rasmussen, H.

    The effects of carbachol on polyphosphoinositides and 1,2-diacylglycerol metabolism were investigated in bovine tracheal smooth muscle by measuring both lipid mass and the turnover of (/sup 3/H)inositol-labeled phosphoinositides. Carbachol induces a rapid reduction in the mass of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate and a rapid increase in the mass of 1,2-diacylglycerol and phosphatidic acid. These changes in lipid mass are sustained for at least 60 min. The level of phosphatidylinositol shows a delayed and progressive decrease during a 60-min period of carbachol stimulation. The addition of atropine reverses these responses completely. Carbachol stimulates a rapid loss in (/sup 3/H)inositol radioactivitymore » from phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate associated with production of (/sup 3/H)inositol trisphosphate. The carbachol-induced change in the mass of phosphoinositides and phosphatidic acid is not affected by removal of extracellular Ca/sup 2 +/ and does not appear to be secondary to an increase in intracellular Ca/sup 2 +/. These results indicate that carbachol causes phospholipase C-mediated polyphosphoinositide breakdown, resulting in the production of inositol trisphosphate and a sustained increase in the actual content of 1,2-diacylglycerol. These results strongly suggest that carbachol-induced contraction is mediated by the hydrolysis of polyphosphoinositides with the resulting generation of two messengers: inositol 1,4,5-trisphosphate and 1,2-diacylglycerol.« less

  18. Women in war: operational issues of menstruation and unintended pregnancy.

    PubMed

    Christopher, Leslie A; Miller, Leslie

    2007-01-01

    With rapid and frequent deployments around the world, the current high level of military operations demands combat readiness of every military member. In the U.S. Armed Forces, women represent 15% of active duty troops and 17% of reserve and Guard troops and are a critical component for mission accomplishment. The operational issues of menstruation and unintended pregnancy, unique to this population, can decrease a female member's military readiness and affect her ability to deploy. Strategies to mitigate and even eliminate these concerns include the optional use of hormonal medications to induce reversible menstrual cycle suppression. These medications, traditionally indicated for contraception, should be considered essential for female troops during training and deployment. This article, tailored specifically for military women, provides valuable information regarding the risks and benefits, as well as the various options available for menstrual cycle suppression.

  19. Gold decorated NaYF4:Yb,Er/NaYF4/silica (core/shell/shell) upconversion nanoparticles for photothermal destruction of BE(2)-C neuroblastoma cells

    NASA Astrophysics Data System (ADS)

    Qian, Li Peng; Zhou, Li Han; Too, Heng-Phon; Chow, Gan-Moog

    2011-02-01

    Gold decorated NaYF4:Yb,Er/NaYF4/silica (core/shell/shell) upconversion (UC) nanoparticles ( 70-80 nm) were synthesized using tetraethyl orthosilicate and chloroauric acid in a one-step reverse microemulsion method. Gold nanoparticles ( 6 nm) were deposited on the surface of silica shell of these core/shell/shell nanoparticles. The total upconversion emission intensity (green, red, and blue) of the core/shell/shell nanoparticles decreased by 31% after Au was deposited on the surface of silica shell. The upconverted green light was coupled with the surface plasmon of Au leading to rapid heat conversion. These UC/silica/Au nanoparticles were very efficient to destroy BE(2)-C cancer cells and showed strong potential in photothermal therapy.

  20. Specification of haematopoietic stem cell fate via modulation of mitochondrial activity

    PubMed Central

    Vannini, Nicola; Girotra, Mukul; Naveiras, Olaia; Nikitin, Gennady; Campos, Vasco; Giger, Sonja; Roch, Aline; Auwerx, Johan; Lutolf, Matthias P.

    2016-01-01

    Haematopoietic stem cells (HSCs) differ from their committed progeny by relying primarily on anaerobic glycolysis rather than mitochondrial oxidative phosphorylation for energy production. However, whether this change in the metabolic program is the cause or the consequence of the unique function of HSCs remains unknown. Here we show that enforced modulation of energy metabolism impacts HSC self-renewal. Lowering the mitochondrial activity of HSCs by chemically uncoupling the electron transport chain drives self-renewal under culture conditions that normally induce rapid differentiation. We demonstrate that this metabolic specification of HSC fate occurs through the reversible decrease of mitochondrial mass by autophagy. Our data thus reveal a causal relationship between mitochondrial metabolism and fate choice of HSCs and also provide a valuable tool to expand HSCs outside of their native bone marrow niches. PMID:27731316

  1. Direct coupling of microbore HPLC columns to MS systems

    NASA Technical Reports Server (NTRS)

    Mcnair, H. M.

    1985-01-01

    A detailed investigation using electron microscopy was conducted which examined the conditions of materials used in the construction of stable, high performance microbore liquid chromatography (LC) columns. Small details proved to be important. The effects of temperature on the elution of several homologous series used as probe compounds was examined in reverse phase systems. They showed that accessible temperature changes provide roughly half the increase in solvent strength that would be obtained going from a 100% aqueous to a 100% organic mobile phase, which is sufficient to warrant their use in many analyses requiring the use of gradients. Air circulation temperature control systems provide the easiest means of obtaining rapid, wide range changes in column temperature. However, slow heat transfer from the gas leads to thermal nonuniformity in the column and a decrease in resolution as the temperature program progresses.

  2. Efficient Green's Function Reaction Dynamics (GFRD) simulations for diffusion-limited, reversible reactions

    NASA Astrophysics Data System (ADS)

    Bashardanesh, Zahedeh; Lötstedt, Per

    2018-03-01

    In diffusion controlled reversible bimolecular reactions in three dimensions, a dissociation step is typically followed by multiple, rapid re-association steps slowing down the simulations of such systems. In order to improve the efficiency, we first derive an exact Green's function describing the rate at which an isolated pair of particles undergoing reversible bimolecular reactions and unimolecular decay separates beyond an arbitrarily chosen distance. Then the Green's function is used in an algorithm for particle-based stochastic reaction-diffusion simulations for prediction of the dynamics of biochemical networks. The accuracy and efficiency of the algorithm are evaluated using a reversible reaction and a push-pull chemical network. The computational work is independent of the rates of the re-associations.

  3. Investigation into reversion of polyurethane encapsulants

    NASA Technical Reports Server (NTRS)

    Lynch, C. R.

    1973-01-01

    The effect of high humidity (95% RH) at 60 C, 70 C, 85 C and 100 C on the solid-to-liquid reversion of polyurethane elastomers (used for potting electrical connectors and conformal coating printed circuit boards) was investigated. Hardness measurements were conducted on eleven elastomers to track reversion for a 101-day period. The primary purpose of the tests was to provide data to predict service life for the polyurethane elastomers. This was not accomplished as the hardness did not deteriorate rapidly enough at the lower test temperatures. The tests did determine that the potting and coating materials most widely used on the S-1C Program are susceptible to reversion but appear adequate for service in the S-1C environment.

  4. Reversible hemispheric hypoperfusion in two cases of SMART syndrome.

    PubMed

    Wai, Karmen; Balabanski, Anna; Chia, Nicholas; Kleinig, Timothy

    2017-09-01

    Stroke-like migraine attacks after radiation therapy (SMART) syndrome manifests as prolonged episodes of cortical dysfunction, years after cranial irradiation. We present two cases demonstrating reversible hemispheric hypoperfusion. Case 1 presented with left hemispheric symptoms following previous similar episodes. CT perfusion (CTP) demonstrated reversible hemispheric hypoperfusion; subsequent investigations were consistent with SMART syndrome. Case 2 presented following the third episode of a hemispheric syndrome with near-identical CTP abnormalities. L-arginine was administered with rapid reversal of clinical and CTP abnormalities. We conclude that SMART syndrome may demonstrate significant hypoperfusion on hyperacute CTP without subsequent infarction. Impaired cerebrovascular autoregulation probably contributes to cortical dysfunction in SMART syndrome. L-arginine warrants investigation as a potential treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Spatial and Reversal Learning in the Morris Water Maze Are Largely Resistant to Six Hours of REM Sleep Deprivation Following Training

    ERIC Educational Resources Information Center

    Walsh, Christine M.; Booth, Victoria; Poe, Gina R.

    2011-01-01

    This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair…

  6. Reverse Evolution of Armor Plates in the Threespine Stickleback

    USGS Publications Warehouse

    Kitano, J.; Bolnick, D.I.; Beauchamp, D.A.; Mazur, M.M.; Mori, S.; Nakano, T.; Peichel, C.L.

    2008-01-01

    Faced with sudden environmental changes, animals must either adapt to novel environments or go extinct. Thus, study of the mechanisms underlying rapid adaptation is crucial not??only for the understanding of natural evolutionary processes but also for the understanding of human-induced evolutionary change, which is an increasingly important problem [1-8]. In the present study, we demonstrate that the frequency of completely plated threespine stickleback fish (Gasterosteus aculeatus) has increased in an urban freshwater lake (Lake Washington, Seattle, Washington) within the last 40 years. This is a dramatic example of "reverse evolution," [9] because the general evolutionary trajectory is toward armor-plate reduction in freshwater sticklebacks [10]. On the basis of our genetic studies and simulations, we propose that the most likely cause of reverse evolution is increased selection for the completely plated morph, which we suggest could result from higher levels of trout predation after a sudden increase in water transparency during the early 1970s. Rapid evolution was facilitated by the existence of standing allelic variation in Ectodysplasin (Eda), the gene that underlies the major plate-morph locus [11]. The Lake Washington stickleback thus provides a novel example of reverse evolution, which is probably caused by a change in allele frequency at the major plate locus in response to a changing predation regime. ?? 2008 Elsevier Ltd. All rights reserved.

  7. Reverse genetics in high throughput: rapid generation of complete negative strand RNA virus cDNA clones and recombinant viruses thereof.

    PubMed

    Nolden, T; Pfaff, F; Nemitz, S; Freuling, C M; Höper, D; Müller, T; Finke, Stefan

    2016-04-05

    Reverse genetics approaches are indispensable tools for proof of concepts in virus replication and pathogenesis. For negative strand RNA viruses (NSVs) the limited number of infectious cDNA clones represents a bottleneck as clones are often generated from cell culture adapted or attenuated viruses, with limited potential for pathogenesis research. We developed a system in which cDNA copies of complete NSV genomes were directly cloned into reverse genetics vectors by linear-to-linear RedE/T recombination. Rapid cloning of multiple rabies virus (RABV) full length genomes and identification of clones identical to field virus consensus sequence confirmed the approache's reliability. Recombinant viruses were recovered from field virus cDNA clones. Similar growth kinetics of parental and recombinant viruses, preservation of field virus characters in cell type specific replication and virulence in the mouse model were confirmed. Reduced titers after reporter gene insertion indicated that the low level of field virus replication is affected by gene insertions. The flexibility of the strategy was demonstrated by cloning multiple copies of an orthobunyavirus L genome segment. This important step in reverse genetics technology development opens novel avenues for the analysis of virus variability combined with phenotypical characterization of recombinant viruses at a clonal level.

  8. Reverse Genetics Approaches for the Development of Influenza Vaccines

    PubMed Central

    Nogales, Aitor; Martínez-Sobrido, Luis

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

  9. Remagnetization of lava flows spanning the last geomagnetic reversal

    NASA Astrophysics Data System (ADS)

    Vella, Jérôme; Carlut, Julie; Valet, Jean-Pierre; Goff, Maxime Le; Soler, Vicente; Lopes, Fernando

    2017-08-01

    Large directional changes of remanent magnetization within lava flows that cooled during geomagnetic reversals have been reported in several studies. A geomagnetic scenario implies extremely rapid geomagnetic changes of several degrees per day, thus difficult to reconcile with the rate of the earth's core liquid motions. So far, no complete rock magnetic model provides a clear explanation. We revisited lava flows sandwiched between an underlying reverse and an overlying normal polarity flow marking the last reversal in three distinct volcanic sequences of the La Palma Island (Canary archipelago, Spain) that are characterized by a gradual evolution of the direction of their remanent magnetization from bottom to top. Cleaning efficiency of thermal demagnetization was not improved by very rapid heating and cooling rates as well as by continuous demagnetization using a Triaxe magnetometer. We did not observe partial self-reversals and minor changes in magnetic grain sizes are not related to the within-flow directional changes. Microscopic observations indicate poor exsolution, which suggests post-cooling thermochemical remagnetization processes. This scenario is strongly reinforced by laboratory experiments that show large resistance to thermal demagnetization when thermoremanence was acquired over a long time period. We speculate that in the present situation exsolution was reactivated during in field reheating and yielded formation of new magnetite, yet magnetic domain state rearrangements could also play a role. Initial reheating when the overlying flow took place, albeit moderate (less than 200-300 °C), was enough to produce overlying components with significantly higher unblocking temperatures.

  10. Bending patterns of chlamydomonas flagella: III. A radial spoke head deficient mutant and a central pair deficient mutant.

    PubMed

    Brokaw, C J; Luck, D J

    1985-01-01

    Flash photomicrography at frequencies up to 300 Hz and computer-assisted image analysis have been used to obtain parameters describing the flagellar bending patterns of mutants of Chlamydomonas reinhardtii. All strains contained the uni1 mutation, to facilitate photography. The radial spoke head deficient mutant pf17, and the central pair deficient mutant, pf15, in combination with suppressor mutations that restore motility without restoring the ultrastructural or biochemical deficiencies, both generate forward mode bending patterns with increased shear amplitude and decreased asymmetry relative to the "wild-type" uni1 flagella described previously. In the reverse beating mode, the suppressed pf17 mutants generate reverse bending patterns with large shear amplitudes. Reverse beating of the suppressed pf15 mutants is rare. There is a reciprocal relationship between increased shear amplitude and decreased beat frequency, so that the velocity of sliding between flagellar microtubules is not increased by an increase in shear amplitude. The suppressor mutations alone cause decreased frequency and sliding velocity in both forward and reverse mode beating, with little change in shear amplitude or symmetry.

  11. Two distinct classes of functional α7-containing nicotinic receptor on rat superior cervical ganglion neurons

    PubMed Central

    Cuevas, Javier; Roth, Adelheid L; Berg, Darwin K

    2000-01-01

    Nicotinic acetylcholine receptors (nAChRs) that bind α-bungarotoxin (αBgt) were studied on isolated rat superior cervical ganglion (SCG) neurons using whole-cell patch clamp recording techniques.Rapid application of ACh onto the soma of voltage clamped neurons evoked a slowly desensitizing current that was reversibly blocked by αBgt (50 nm). The toxin-sensitive current constituted on average about half of the peak whole-cell response evoked by ACh.Nanomolar concentrations of methyllycaconitine blocked the αBgt-sensitive component of the ACh-evoked current as did intracellular dialysis with an anti-α7 monoclonal antibody. The results indicate that the slowly reversible toxin-sensitive response elicited by ACh arises from activation of an unusual class of α7-containing receptor (α7-nAChR) similar to that reported previously for rat intracardiac ganglion neurons.A second class of functional α7-nAChR was identified on some SCG neurons by using rapid application of choline to elicit responses. In these cases a biphasic response was obtained, which included a rapidly desensitizing component that was blocked by αBgt in a pseudo-irreversible manner. The pharmacology and kinetics of the responses resembled those previously attributed to α7-nAChRs in a number of other neuronal cell types.Experiments measuring the dissociation rate of 125I-labelled αBgt from SCG neurons revealed two classes of toxin-binding site. The times for toxin dissociation were consistent with those required to reverse blockade of the two kinds of αBgt-sensitive response.These results indicate that rat SCG neurons express two types of functional α7-nAChR, differing in pharmacology, desensitization and reversibility of αBgt blockade. PMID:10856125

  12. Rapid detection of duck hepatitis A virus genotype C using reverse transcription loop-mediated isothermal amplification.

    PubMed

    Li, Chuanfeng; Chen, Zongyan; Meng, Chunchun; Liu, Guangqing

    2014-02-01

    A one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was used and optimized to develop a rapid and sensitive detection system for duck hepatitis A virus genotype C (DHAV-C) RNA. A set of four specific primers was designed against highly conserved sequences located within the 3D gene from DHAV (strain GX1201). Under optimal reaction conditions, the sensitivity of DHAV-C-specific RT-LAMP was 100-fold higher than that of reverse transcriptase-polymerase chain reaction (RT-PCR), with a detection limit of 0.3pg (6.59×10(4) copies) per reaction. No cross-reactivity was observed from the samples of other duck viruses, which is in good accordance with RT-PCR. Furthermore, a positive reaction can be visually inspected by observing turbidity or color change after the addition of SYBR green I dye. The DHAV-C-specific RT-LAMP assay was applied to the samples and compared with RT-PCR. The positive-sample ratios were 26.7% (12 of 45) by RT-LAMP and 20% (9 of 45) by RT-PCR. Therefore, the newly developed RT-LAMP assay is a rapid, specific, sensitive, and cost-effective method of DHAV-C detection. This assay has potential applications in both clinical diagnosis and field surveillance of DHAV-C infection. Copyright © 2013. Published by Elsevier B.V.

  13. Three pools of zeaxanthin in Quercus coccifera leaves during light transitions with different roles in rapidly reversible photoprotective energy dissipation and photoprotection

    PubMed Central

    Morales, Fermín

    2013-01-01

    Under excess light, the efficient PSII light-harvesting antenna is switched into a photoprotected state in which potentially harmful absorbed energy is thermally dissipated. Changes occur rapidly and reversibly, enhanced by de-epoxidation of violaxanthin (V) to zeaxanthin (Z). This process is usually measured as non-photochemical quenching (NPQ) of chlorophyll (Chl) fluorescence. Using instrumentation for instantaneous leaf freezing, NPQ, spectral reflectance, and interconversions within the xanthophyll cycle with time resolution of seconds were recorded from Quercus coccifera leaves during low light (LL) to high light (HL) transitions, followed by relaxation at LL. During the first 30 s of both the LL to HL and HL to LL transitions, no activity of the xanthophyll cycle was detected, whereas 70–75% of the NPQ was formed and relaxed, respectively, by that time, the latter being traits of a rapidly reversible photoprotective energy dissipation. Three different Z pools were identified, which play different roles in energy dissipation and photoprotection. In conclusion, ΔpH was crucial to NPQ formation and relaxation in Q. coccifera during light transitions. Only a minor fraction of Z was associated to quenching, whereas the largest Z pool was not related to thermal dissipation. The latter is proposed to participate in photoprotection acting as antioxidant. PMID:23390289

  14. Measurements of temperature profiles at the exit of small rockets.

    PubMed

    Griggs, M; Harshbarger, F C

    1966-02-01

    The sodium line reversal technique was used to determine the reversal temperature profile across the exit of small rockets. Measurements were made on one 73-kg thrust rocket, and two 23-kg thrust rockets with different injectors. The large rocket showed little variation of reversal temperature across the plume. However, the 23-kg rockets both showed a large decrease of reversal temperature from the axis to the edge of the plume. In addition, the sodium line reversal technique of temperature measurement was compared with an infrared technique developed in these laboratories.

  15. Neuron activity in rat hippocampus and motor cortex during discrimination reversal.

    PubMed

    Disterhoft, J F; Segal, M

    1978-01-01

    Chronic unit activity and gross movement were recorded from rats during two discrimination reversals in a classical appetitive conditioning situation. The anticipatory movement decreased in response to the former CS+ tone and increased to the previous CS- tone after each reversal. Hippocampus and motor cortex were differently related to these two kinds of behavioral change. Response rates of hippocampal neurons were more closely related to the increased movement response to the former CS- which now signaled food. Motor cortex neuron responses were more closely correlated with the decrease in movement responses to the former CS+ which became neutral after the reversal. It appeared that hippocampal neurons could have been involved in one cognitive aspect of the situation, motor cortex neurons in another. The data were related to current functional concepts of these brain regions.

  16. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.

    2016-01-01

    Purpose of Review: This article presents a practical and informative approach to the evaluation of a patient with a rapidly progressive dementia (RPD). Recent Findings: Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. Aside from prion diseases, the most common causes of RPD are atypical presentations of other neurodegenerative disorders, curable disorders including autoimmune encephalopathies, as well as some infections, and neoplasms. Numerous recent case reports suggest dural arterial venous fistulas sometimes cause RPDs. Summary: RPDs, in which patients typically develop dementia over weeks to months, require an alternative differential than the slowly progressive dementias that occur over a few years. Because of their rapid decline, patients with RPDs necessitate urgent evaluation and often require an extensive workup, typically with multiple tests being sent or performed concurrently. Jakob-Creutzfeldt disease, perhaps the prototypical RPD, is often the first diagnosis many neurologists consider when treating a patient with rapid cognitive decline. Many conditions other than prion disease, however, including numerous reversible or curable conditions, can present as an RPD. This chapter discusses some of the major etiologies for RPDs and offers an algorithm for diagnosis. PMID:27042906

  17. Fasting: The History, Pathophysiology and Complications

    PubMed Central

    Kerndt, Peter R.; Naughton, James L.; Driscoll, Charles E.; Loxterkamp, David A.

    1982-01-01

    An appreciation of the physiology of fasting is essential to the understanding of therapeutic dietary interventions and the effect of food deprivation in various diseases. The practice of prolonged fasting for political or religious purposes is increasing, and a physician is likely to encounter such circumstances. Early in fasting weight loss is rapid, averaging 0.9 kg per day during the first week and slowing to 0.3 kg per day by the third week; early rapid weight loss is primarily due to negative sodium balance. Metabolically, early fasting is characterized by a high rate of gluconeogenesis with amino acids as the primary substrates. As fasting continues, progressive ketosis develops due to the mobilization and oxidation of fatty acids. As ketone levels rise they replace glucose as the primary energy source in the central nervous system, thereby decreasing the need for gluconeogenesis and sparing protein catabolism. Several hormonal changes occur during fasting, including a fall in insulin and T3 levels and a rise in glucagon and reverse T3 levels. Most studies of fasting have used obese persons and results may not always apply to lean persons. Medical complications seen in fasting include gout and urate nephrolithiasis, postural hypotension and cardiac arrhythmias. ImagesFigure 4. PMID:6758355

  18. Interaction of colistin and colistin methanesulfonate with liposomes: colloidal aspects and implications for formulation.

    PubMed

    Wallace, Stephanie J; Li, Jian; Nation, Roger L; Prankerd, Richard J; Boyd, Ben J

    2012-09-01

    Interaction of colistin and colistin methanesulfonate (CMS) with liposomes has been studied with the view to understanding the limitations to the use of liposomes as a more effective delivery system for pulmonary inhalation of this important class of antibiotic. Thus, in this study, liposomes containing colistin or CMS were prepared and characterized with respect to colloidal behavior and drug encapsulation and release. Association of anionic CMS with liposomes induced negative charge on the particles. However, degradation of the CMS to form cationic colistin over time was directly correlated with charge reversal and particle aggregation. The rate of degradation of CMS was significantly more rapid when associated with the liposome bilayer than when compared with the same concentration in aqueous solution. Colistin liposomes carried positive charge and were stable. Encapsulation efficiency for colistin was approximately 50%, decreasing with increasing concentration of colistin. Colistin was rapidly released from liposomes on dilution. Although the studies indicate limited utility of colistin or CMS liposomes for long duration controlled-release applications, colistin liposomes were highly stable and may present a potential opportunity for coformulation of colistin with a second antibiotic to colocalize the two drugs after pulmonary delivery. Copyright © 2012 Wiley Periodicals, Inc.

  19. Pathogen transmission at stage-structured infectious patches: Killers and vaccinators.

    PubMed

    Caraco, Thomas; Turner, Wendy C

    2018-01-07

    Spatial localization of an obligate-killing, free-living pathogen generates a landscape of patches where new infections occur. As an infectious patch ages, both pathogen exposure at the patch and the probability of lethal infection following exposure can decline. We model stage-structured infectious patches, where non-lethal exposure can naturally "vaccinate" susceptible hosts. We let the between-stage difference in pathogen transmission, and then the between-stage difference in patch virulence, increase independently of other parameters. Effects of increasing either between-stage difference (about a fixed mean) depend on the probability a patch transitions from the first to second stage, i.e., the chance that a killer patch becomes a vaccinator. For slower stage transition, greater between-stage differences decreased susceptibles, and increased both resistant-host and killer patch numbers. But our examples reveal that each effect can be reversed when between-stage transition occurs more rapidly. For sufficiently rapid stage transition, increased between-stage virulence differences can lead to pathogen extinction, and leave the host at disease-free equilibrium. The model's general significance lies in demonstrating how epidemiological variation among sites of environmentally transmitted disease can strongly govern host-parasite dynamics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. THE ELECTRICAL ACTIVATION OF PASSIVE IRON WIRES IN NITRIC ACID

    PubMed Central

    Lillie, Ralph S.

    1935-01-01

    1. The relation between the E. M. F. and the minimal duration of an activating current has been determined for passive iron wires in nitric acid under varying conditions of concentration of acid, duration of recovery period, and presence of surface-action compounds. 2. The characteristic intensity-duration curves resemble those of irritable living tissues with moderate speeds of response to stimulation (with chronaxies of the order of 10 to 30σ). 3. The intensity of the current required for activation, as well as its minimal effective duration for a given intensity, increases rapidly with increase in the concentration of HNO3. 4. The responsiveness of the iron wire to brief currents is low immediately after activation and returns progressively to the original level during the immediately following period, at first rapidly and then slowly, following a time curve resembling the corresponding curve of living tissues during the relative refractory period. 5. Surface-active compounds decrease reversibly, to a degree dependent on concentration, the responsiveness of iron wires to brief currents. 6. Conditions are described under which the iron wire is activated by the break of an already flowing constant current. PMID:19872905

  1. Interaction of Colistin and Colistin Methanesulfonate with Liposomes: Colloidal Aspects and Implications for Formulation

    PubMed Central

    WALLACE, STEPHANIE J.; LI, JIAN; NATION, ROGER L.; PRANKERD, RICHARD J.; BOYD, BEN J.

    2012-01-01

    Interaction of colistin and colistin methanesulfonate (CMS) with liposomes has been studied with the view to understanding the limitations to the use of liposomes as a more effective delivery system for pulmonary inhalation of this important class of antibiotic. Thus, in this study, liposomes containing colistin or CMS were prepared and characterized with respect to colloidal behavior and drug encapsulation and release. Association of anionic CMS with liposomes induced negative charge on the particles. However, degradation of the CMS to form cationic colistin over time was directly correlated with charge reversal and particle aggregation. The rate of degradation of CMS was significantly more rapid when associated with the liposome bilayer than when compared with the same concentration in aqueous solution. Colistin liposomes carried positive charge and were stable. Encapsulation efficiency for colistin was approximately 50%, decreasing with increasing concentration of colistin. Colistin was rapidly released from liposomes on dilution. Although the studies indicate limited utility of colistin or CMS liposomes for long duration controlled-release applications, colistin liposomes were highly stable and may present a potential opportunity for coformulation of colistin with a second antibiotic to colocalize the two drugs after pulmonary delivery. PMID:22623044

  2. Low Vision Enhancement: The Use of Figure-Ground Reversals with Visually Impaired Children.

    ERIC Educational Resources Information Center

    Gardner, Laurence R.

    1985-01-01

    The study employed the use of field reversals--printing white and yellow foregrounds on a black background--to decrease the amount of light reflected from printed materials to the eye with 18 visually impaired children (9-14 years old). The findings indicated that neither reversals in contrast nor chromaticity differences were effective measures…

  3. Viral dynamics in primary HIV-1 infection. Karolinska Institutet Primary HIV Infection Study Group.

    PubMed

    Lindbäck, S; Karlsson, A C; Mittler, J; Blaxhult, A; Carlsson, M; Briheim, G; Sönnerborg, A; Gaines, H

    2000-10-20

    To study the natural course of viremia during primary HIV infection (PHI). Eight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-1 RNA levels were measured frequently and the results were fitted to mathematical models. HIV-1 RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness. HIV-1 RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-1 RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/mL. This study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-1 infection: PHI peak levels correlate with steady-state levels and HIV-1 RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.

  4. Research on the Forward and Reverse Calculation Based on the Adaptive Zero-Velocity Interval Adjustment for the Foot-Mounted Inertial Pedestrian-Positioning System

    PubMed Central

    Wang, Qiuying; Guo, Zheng; Sun, Zhiguo; Cui, Xufei; Liu, Kaiyue

    2018-01-01

    Pedestrian-positioning technology based on the foot-mounted micro inertial measurement unit (MIMU) plays an important role in the field of indoor navigation and has received extensive attention in recent years. However, the positioning accuracy of the inertial-based pedestrian-positioning method is rapidly reduced because of the relatively low measurement accuracy of the measurement sensor. The zero-velocity update (ZUPT) is an error correction method which was proposed to solve the cumulative error because, on a regular basis, the foot is stationary during the ordinary gait; this is intended to reduce the position error growth of the system. However, the traditional ZUPT has poor performance because the time of foot touchdown is short when the pedestrians move faster, which decreases the positioning accuracy. Considering these problems, a forward and reverse calculation method based on the adaptive zero-velocity interval adjustment for the foot-mounted MIMU location method is proposed in this paper. To solve the inaccuracy of the zero-velocity interval detector during fast pedestrian movement where the contact time of the foot on the ground is short, an adaptive zero-velocity interval detection algorithm based on fuzzy logic reasoning is presented in this paper. In addition, to improve the effectiveness of the ZUPT algorithm, forward and reverse multiple solutions are presented. Finally, with the basic principles and derivation process of this method, the MTi-G710 produced by the XSENS company is used to complete the test. The experimental results verify the correctness and applicability of the proposed method. PMID:29883399

  5. Sexual patterns and protogynous sex reversal in the rusty parrotfish, Scarus ferrugineus (Scaridae): histological and physiological studies.

    PubMed

    Abdel-Aziz, El-Sayedah H; Bawazeer, Fayzah A; El-Sayed Ali, Tamer; Al-Otaibi, Mashael

    2012-08-01

    Gonadal histology confirmed that Scarus ferrugineus is a diandric protogynous fish. The process of protogynous sex reversal was investigated through histological observations on the gonads of females changing sex to male. This process was divided into three stages on the basis of changes in the structure of the germinal and somatic elements. Ovaries of functional females (stages IV-V) were filled with vitellogenic oocytes during the breeding season but contained no trace of spermatogenic tissue. During post-spawning period, the remaining vitellogenic oocytes began to degenerate and accompanied by a drop in plasma levels of estradiol-17β. At the commencement of sex change, previtellogenic oocytes began to degenerate and stromal cell aggregation was observed in the central region of the lamellae. At mid-reversal stage, steroid-producing cells (Leydig cells) developed at the border of the stromal aggregate and spermatogonial cysts appear at the periphery of lamellae. Finally, sex change to secondary males was considered complete, with the beginning of active spermatogenesis and spermiation. Plasma levels of testosterone remained low throughout the sex change, but II-KT increased rapidly parallel to the increased number of Leydig cells while the level of estradiol-17β decreased. The results indicate also that the sex-changed males had higher level of II-KT than primary males, while primary males had higher level of testosterone. Histological examination revealed that testes of primary and secondary males are almost identical in organization of the spermatogenic cysts, association of sertoli cells, and developing germ cells but differ in clustering and development of Leydig cells.

  6. Real-time quantification of antibody-short interfering RNA conjugate in serum by antigen capture reverse transcription-polymerase chain reaction.

    PubMed

    Tan, Martha; Vernes, Jean-Michel; Chan, Joyce; Cuellar, Trinna L; Asundi, Aarati; Nelson, Christopher; Yip, Victor; Shen, Ben; Vandlen, Richard; Siebel, Christian; Meng, Y Gloria

    2012-11-15

    Short interfering RNA (siRNA) has therapeutic potential. However, efficient delivery is a formidable task. To facilitate delivery of siRNA into cells, we covalently conjugated siRNA to antibodies that bind to cell surface proteins and internalize. Understanding how these antibody-siRNA conjugates function in vivo requires pharmacokinetic analysis. Thus, we developed a simple real-time antigen capture reverse transcription-polymerase chain reaction (RT-PCR) assay to detect intact antibody-siRNA conjugates. Biotinylated antigen bound to streptavidin-coated PCR tubes was used to capture antibody-siRNA conjugate. The captured antibody-siRNA conjugate was then reverse-transcribed in the same tube, avoiding a sample transfer step. This reproducible assay had a wide standard curve range of 0.029 to 480ng/ml and could detect as low as 0.58ng/ml antibody-siRNA conjugates in mouse serum. The presence of unconjugated antibody that could be generated from siRNA degradation in vivo did not affect the assay as long as the total antibody concentration in the antigen capture step did not exceed 480ng/ml. Using this assay, we observed a more rapid decrease in serum antibody-siRNA conjugate concentrations than the total antibody concentrations in mice dosed with antibody-siRNA conjugates, suggesting loss of siRNA from the antibody. This assay is useful for optimizing antibody-siRNA and likely aptamer-siRNA conjugates to improve pharmacokinetics and aid siRNA delivery. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Effect of hydrocortisone on cell morphology in C6 cells: the role of microfilaments in the inductive process. [Cytochalasin B; glycerol phosphate dehydrogenase

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

    Berliner, J.A.; Bennett, K.; de Vellis, J.

    Hydrocortisone induced cell spreading and the formation of microfilaments in C6 cells with a time course similar to that found for the induction of GPDH. Cytochalasin B caused a rapid and reversible cell rounding and microfilament breakdown. Breakdown of both sheath and network microfilaments occurred within 1 hour; after removal of cytochalasin B, reversal of morphological effects began within 30 min. High calcium was found to block reversal of the cytochalasin B induced alteration, but did not affect shape or microfilaments in non-cytochalasin B treated cells. It is concluded that since microfilament induction occurs late and the block in synthesismore » of GPDH by cytochalasin B occurs within hours after addition, microfilaments induced by hydrocortisone are probably not important in the sequence of events leading to GPDH induction. But, however, microfilaments present in uninduced cells may be important in the sequence of GPDH induction, since treatment with cytochalasin B rapidly breaks these down and also inhibits GPDH induction by hydrocortisone.« less

  8. Rapid Motion Adaptation Reveals the Temporal Dynamics of Spatiotemporal Correlation between ON and OFF Pathways

    PubMed Central

    Oluk, Can; Pavan, Andrea; Kafaligonul, Hulusi

    2016-01-01

    At the early stages of visual processing, information is processed by two major thalamic pathways encoding brightness increments (ON) and decrements (OFF). Accumulating evidence suggests that these pathways interact and merge as early as in primary visual cortex. Using regular and reverse-phi motion in a rapid adaptation paradigm, we investigated the temporal dynamics of within and across pathway mechanisms for motion processing. When the adaptation duration was short (188 ms), reverse-phi and regular motion led to similar adaptation effects, suggesting that the information from the two pathways are combined efficiently at early-stages of motion processing. However, as the adaption duration was increased to 752 ms, reverse-phi and regular motion showed distinct adaptation effects depending on the test pattern used, either engaging spatiotemporal correlation between the same or opposite contrast polarities. Overall, these findings indicate that spatiotemporal correlation within and across ON-OFF pathways for motion processing can be selectively adapted, and support those models that integrate within and across pathway mechanisms for motion processing. PMID:27667401

  9. Mechanisms of rapid sympatric speciation by sex reversal and sexual selection in cichlid fish.

    PubMed

    Lande, R; Seehausen, O; van Alphen, J J

    2001-01-01

    Mechanisms of speciation in cichlid fish were investigated by analyzing population genetic models of sexual selection on sex-determining genes associated with color polymorphisms. The models are based on a combination of laboratory experiments and field observations on the ecology, male and female mating behavior, and inheritance of sex-determination and color polymorphisms. The models explain why sex-reversal genes that change males into females tend to be X-linked and associated with novel colors, using the hypothesis of restricted recombination on the sex chromosomes, as suggested by previous theory on the evolution of recombination. The models reveal multiple pathways for rapid sympatric speciation through the origin of novel color morphs with strong assortative mating that incorporate both sex-reversal and suppressor genes. Despite the lack of geographic isolation or ecological differentiation, the new species coexists with the ancestral species either temporarily or indefinitely. These results may help to explain different patterns and rates of speciation among groups of cichlids, in particular the explosive diversification of rock-dwelling haplochromine cichlids.

  10. High temperature monotonic and cyclic deformation in a directionally solidified nickel-base superalloy

    NASA Technical Reports Server (NTRS)

    Huron, Eric S.

    1986-01-01

    Directionally solidified (DS) MAR-M246+Hf was tested in tension and fatigue, at temperatures from 20 C to 1093 C. Tests were performed on (001) oriented specimens at strain rates of 50 % and 0.5 % per minute. In tension, the yield strength was constant up to 704 C, above which the strength dropped off rapidly. A strong dependence of strength on strain rate was seen at the higher temperatures. The deformation mode was observed to change from heterogeneous to homogeneous with increasing temperature. Low Cycle Fatigue tests were done using a fully reversed waveform and total strain control. For a given plastic strain range, lives increased with increasing temperature. For a given temperature strain rate had a strong effect on life. At 704 C, decreasing strain rates decreased life, while at the higher temperatures, decreasing strain rates increased life, for a given plastic strain range. These results could be explained through considerations of the deformation modes and stress levels. At the higher temperatures, marked coarsening caused beneficial stress reductions, but oxidation limited the life. The longitudinal grain boundaries were found to influence slip behavior. The degree of secondary slip adjacent to the boundaries was found to be related to the degree of misorientation between the grains.

  11. Isocratic non-aqueous reversed-phase high-performance liquid chromatographic separation of capsanthin and capsorubin in red peppers (Capsicum annuum L.), paprika and oleoresin.

    PubMed

    Weissenberg, M; Schaeffler, I; Menagem, E; Barzilai, M; Levy, A

    1997-01-03

    A simple, rapid high-performance liquid chromatography method has been devised in order to separate and quantify the xanthophylls capsorubin and capasanthin present in red pepper (Capsicum annuum L.) fruits and preparations made from them (paprika and oleoresin). A reversed-phase isocratic non-aqueous system allows the separation of xanthophylls within a few minutes, with detection at 450 nm, using methyl red as internal standard to locate the various carotenoids and xanthophylls found in plant extracts. The selection of extraction solvents, mild saponification conditions, and chromatographic features is evaluated and discussed. The method is proposed for rapid screening of large plant populations, plant selection, as well as for paprika products and oleoresin, and also for nutrition and quality control studies.

  12. Reversible splenial lesion syndrome associated with encephalitis/encephalopathy presenting with great clinical heterogeneity.

    PubMed

    Zhu, Yuanzhao; Zheng, Junjun; Zhang, Ling; Zeng, Zhenguo; Zhu, Min; Li, Xiaobin; Lou, Xiaoliang; Wan, Hui; Hong, Daojun

    2016-04-18

    Reversible splenial lesion syndrome (RESLES) is a disorder radiologically characterized by reversible lesion in the splenium of the corpus callosum (SCC). Most of patients with RESLES associated with encephalitis/encephalopathy were identified in Japanese population, but almost no Chinese patients were diagnosed as RESLES associated with encephalitis/encephalopathy. Possible patients with reversible isolated SCC lesions were retrieved from January 2012 to July 2015 using keyword "restricted diffusion and isolated SCC lesion" in MRI report system from a large academic center. The clinical, laboratory and radiological data were summarized. A total of 15 encephalitis/encephalopathy patients (9 males and 6 females) were identified with a reversible isolated SCC lesion. Except for 13 patients with fever symptom, 8 patients also had cold symptoms before the onset of neurological symptoms. The neurological symptoms included headache, vertigo, seizure, disturbance of consciousness, and delirious behavior. Thirteen patients completely recovered within 1 month, but 2 patients who were subjected to mechanical ventilation had persistent neurological deficits. The initial MRI features showed isolated ovoid or extending SCC lesions with homogeneous hyperintense on diffusion weighted imaging (DWI) and decreased apparent diffusion coefficient (ADC) values. The follow-up MRI revealed that isolated SCC lesions with diffuse restriction disappeared at 10 to 32 days after the initial MRI study. Fractional anisotropy map revealed the decreased value of SCC lesion in a severe case with poor prognosis. RESLES associated with encephalitis/encephalopathy is a reversible syndrome with an excellent prognosis in most patients, while a few patients required ventilator supporting at the early stage might have severe neurological sequelae. Reversible signal changes on DWI and ADC are identified in all patients, but fractional anisotropy values can be decreased in severe patient with neurological sequelae.

  13. Contact mechanics of reverse engineered distal humeral hemiarthroplasty implants.

    PubMed

    Willing, Ryan; King, Graham J W; Johnson, James A

    2015-11-26

    Erosion of articular cartilage is a concern following distal humeral hemiarthroplasty, because native cartilage surfaces are placed in contact with stiff metallic implant components, which causes decreases in contact area and increases in contact stresses. Recently, reverse engineered implants have been proposed which are intended to promote more natural contact mechanics by reproducing the native bone or cartilage shape. In this study, finite element modeling is used in order to calculate changes in cartilage contact areas and stresses following distal humeral hemiarthroplasty with commercially available and reverse engineered implant designs. At the ulna, decreases in contact area were -34±3% (p=0.002), -27±1% (p<0.001) and -14±2% (p=0.008) using commercially available, bone reverse engineered and cartilage reverse engineered designs, respectively. Peak contact stresses increased by 461±57% (p=0.008), 387±127% (p=0.229) and 165±16% (p=0.003). At the radius, decreases in contact area were -21±3% (p=0.013), -13±2% (p<0.006) and -6±1% (p=0.020), and peak contact stresses increased by 75±52% (p>0.999), 241±32% (p=0.010) and 61±10% (p=0.021). Between the three different implant designs, the cartilage reverse engineered design yielded the largest contact areas and lowest contact stresses, but was still unable to reproduce the contact mechanics of the native joint. These findings align with a growing body of evidence indicating that although reverse engineered hemiarthroplasty implants can provide small improvements in contact mechanics when compared with commercially available designs, further optimization of shape and material properties is required in order reproduce native joint contact mechanics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

    PubMed Central

    Koulu, M; Scheinin, M; Kaarttinen, A; Kallio, J; Pyykkö, K; Vuorinen, J; Zimmer, R H

    1989-01-01

    1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non-deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged. PMID:2469451

  15. Reverse Current in Solar Flares

    NASA Technical Reports Server (NTRS)

    Knight, J. W., III

    1978-01-01

    An idealized steady state model of a stream of energetic electrons neutralized by a reverse current in the pre-flare solar plasma was developed. These calculations indicate that, in some cases, a significant fraction of the beam energy may be dissipated by the reverse current. Joule heating by the reverse current is a more effective mechanism for heating the plasma than collisional losses from the energetic electrons because the Ohmic losses are caused by thermal electrons in the reverse current which have much shorter mean free paths than the energetic electrons. The heating due to reverse currents is calculated for two injected energetic electron fluxes. For the smaller injected flux, the temperature of the coronal plasma is raised by about a factor of two. The larger flux causes the reverse current drift velocity to exceed the critical velocity for the onset of ion cyclotron turbulence, producing anomalous resistivity and an order of magnitude increase in the temperature. The heating is so rapid that the lack of ionization equilibrium may produce a soft X-ray and EUV pulse from the corona.

  16. Rapid and Sensitive Detection of Norovirus Genomes in Oysters by a Two-Step Isothermal Amplification Assay System Combining Nucleic Acid Sequence-Based Amplification and Reverse Transcription-Loop-Mediated Isothermal Amplification Assays▿

    PubMed Central

    Fukuda, Shinji; Sasaki, Yukie; Seno, Masato

    2008-01-01

    We developed a two-step isothermal amplification assay system, which achieved the detection of norovirus (NoV) genomes in oysters with a sensitivity similar to that of reverse transcription-seminested PCR. The time taken for the amplification of NoV genomes from RNA extracts was shortened to about 3 h. PMID:18456857

  17. The Role of eIF4E Activity in Breast Cancer

    DTIC Science & Technology

    2010-08-01

    ORF, open reading frame; qPCR, quantitative PCR; RACE, rapid amplification of cDNA ends; RT, reverse transcriptase ; uORF, upstream ORF; UTR...were also performed using template lacking RT ( reverse transcriptase ): products were either undetectable or greatly reduced (>30000-fold less product...have previously shown that a 5’UTR expressed from the human AXIN2 gene contains a sixty nucleotide sequence that is predicted to form a stable stem

  18. Reversible differentiation of human monoblastic leukemia U937 cells by ML-9, an inhibitor of myosin light chain kinase.

    PubMed

    Yamamoto-Yamaguchi, Y; Makishima, M; Kanatani, Y; Kasukabe, T; Honma, Y

    1996-05-01

    Human monoblastic leukemia U937 cells are induced to differentiate into monocytes and macrophages by various agents. We have shown that 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9), an inhibitor of myosin light chain kinase, induces differentiation of monocytoid leukemia cell lines U937 and THP-1 but not of myeloblastic leukemic ML-1 cell or erythroleukemia K562 cells. In the present study, we further analyzed the effect of ML-9 in comparison with that of 1 alpha, 25-dihydroxyvitamin D3 (VD3) a typical inducer of monocytic differentiation. ML-9 induced nitroblue tetrazolium (NBT)-reducing activity of U937 cell more rapidly than VD3: This differentiation marker was induced significantly after incubation with ML-9 and VD3 for 4 hours and 1 day, respectively. ML-9 also induced alpha-naphthyl acetate esterase (ANAE) activity, another monocytic differentiation marker, more rapidly than VD3. The maximum levels of these markers induced by ML-9 were comparable to those induced by VD3, but after removal of ML-9 from the medium by washing the cells, the expressions of theses markers decreased within 4 hours and reached basal levels in 1 day, indicating that ML-9's induction of expression of differentiation-associated phenotypes was reversible. The growth inhibition of U937 cells by ML-9 was also reversible. Similar effects were observed in another line of human monoblastic cells, THP-1. ML-9 had little or no effect on the morphology of U937 cells but increased the expression of monocyte-macrophage lineage-associated surface antigen, CD14, to some extent. Irreversible terminal differentiation induced by VD3 is associated with down regulation of the expression of c-myc and upregulation of the expression of c-fos and c-jun, but ML-9 did not affect the expression of these oncogenes appreciably. ML-9-induced differentiation was also reversible when the cells were cultured with cultured with ML-9 plus an anti-cancer drug such as 1-beta-D-arabino-furanosylcytosine or daunomycin. it became irreversible, however, upon simultaneous treatment with dexamethasone and transforming growth factor-beta 1 (TGF-beta 1), which did not induce differentiation of U937 cells but caused growth arrest of the cells in the G0/G1 phase of the cell cycle. These results suggest that ML-9 should be useful for studying the mechanisms of monocytic differentiation.

  19. An experimental study of Au removal from solution by non-metabolizing bacterial cells and their exudates

    NASA Astrophysics Data System (ADS)

    Kenney, Janice P. L.; Song, Zhen; Bunker, Bruce A.; Fein, Jeremy B.

    2012-06-01

    In this study, we examine the initial interactions between aqueous Au(III)-hydroxide-chloride aqueous complexes and bacteria by measuring the effects of non-metabolizing cells on the speciation and distribution of Au. We conducted batch Au(III) removal experiments, measuring the kinetics and pH dependence of Au removal, and tracking valence state transformations and binding environments using XANES spectroscopy. These experiments were conducted using non-metabolizing cells of Bacillus subtilis or Pseudomonas putida suspended in a 5 ppm Au(III)-(hydroxide)-chloride starting solution of 0.1 M NaClO4 to buffer ionic strength. Both bacterial species removed greater than 85% of the Au from solution after 2 h of exposure time below approximately pH 5. Above pH 5, the extent of Au removed from solution decreased with increasing pH, with less than approximately 10% removal of Au from solution above pH 7.5. Kinetics experiments indicated that the Au removal with both bacterial species was rapid at pH 3, and slowed with increasing pH. Reversibility experiments demonstrated that (1) once the Au was removed from solution, adjusting 35 the pH alone did not remobilize the Au into solution and (2) the presence of cysteine in solution in the reversibility experiments caused Au to desorb, suggesting that the Au was not internalized within the bacterial cells. Our results suggest that Au removal occurs as a two-step pH-dependent adsorption reduction process. The speciation of the aqueous Au and the bacterial surface appears to control the rate of Au removal from solution. Under low pH conditions, the cell walls are only weakly negatively charged and aqueous Au complexes adsorb readily and rapidly. With increasing pH, the cell wall becomes more negatively charged, slowing adsorption significantly. The XANES data demonstrate that the reduction of Au(III) by bacterial exudates is slower and less extensive than the reduction observed in the bacteria-bearing systems, and we conclude that Au reduction occurs most rapidly and extensively upon interaction with cell wall functional groups.

  20. Reverse engineering systems models of regulation: discovery, prediction and mechanisms.

    PubMed

    Ashworth, Justin; Wurtmann, Elisabeth J; Baliga, Nitin S

    2012-08-01

    Biological systems can now be understood in comprehensive and quantitative detail using systems biology approaches. Putative genome-scale models can be built rapidly based upon biological inventories and strategic system-wide molecular measurements. Current models combine statistical associations, causative abstractions, and known molecular mechanisms to explain and predict quantitative and complex phenotypes. This top-down 'reverse engineering' approach generates useful organism-scale models despite noise and incompleteness in data and knowledge. Here we review and discuss the reverse engineering of biological systems using top-down data-driven approaches, in order to improve discovery, hypothesis generation, and the inference of biological properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Water deficit modulates gene expression in growing zones of soybean seedlings. Analysis of differentially expressed cDNAs, a new beta-tubulin gene, and expression of genes encoding cell wall proteins.

    PubMed

    Creelman, R A; Mullet, J E

    1991-10-01

    Transfer of soybean seedlings to low-water-potential vermiculite (psi w = -0.3 MPa) results in a reversible decrease in hypocotyl growth and modulation of several polysomal mRNAs (Plant Physiol 92: 205-214). We report here the isolation of two cDNA clones (pGE16 and pGE95) which correspond to genes whose mRNA levels are increased, and one cDNA clone (pGE23) which corresponds to a gene whose mRNA level is decreased in the hypocotyl zone of cell elongation by water deficit. In well-watered seedlings mRNAs hybridizing to pGE16 and pGE95 are most abundant in mature regions of the seedling, but in water-deficient seedlings mRNA levels are reduced in mature regions and enhanced in elongating regions. RNA corresponding to soybean proline-rich protein 1 (sbPRP1) shows a similar tissue distribution and response to water deficit. In contrast, in well-watered seedlings, the gene corresponding to pGE23 was highly expressed in the hypocotyl and root growing zones. Transfer of seedlings to low-water-potential vermiculite caused a rapid decrease in mRNA hybridizing to pGE23. Sequence analysis revealed that pGE23 has high homology with beta-tubulin. Water deficit also reduced the level of mRNA hybridizing to JCW1, an auxin-modulated gene, although with different kinetics. Furthermore, mRNA encoding actin, glycine-rich proteins (GRPs), and hydroxyproline-rich glycoproteins (HRGPs) were down-regulated in the hypocotyl zone of elongation of seedlings exposed to water deficit. No effect of water deficit was observed on the expression of chalcone synthase. Decreased expression of beta-tubulin, actin, JCW1, HRGP and GRP and increased expression of sbPRP1, pGE95 and pGE16 in the hypocotyl zone of cell elongation could participate in the reversible growth inhibition observed in water-deficient soybean seedlings.

  2. A hydrogen fuel cell for rapid, enzyme-catalysed organic synthesis with continuous monitoring.

    PubMed

    Wan, Lei; Megarity, Clare F; Siritanaratkul, Bhavin; Armstrong, Fraser A

    2018-01-23

    A one-pot fuel cell for specific, enzyme-catalysed organic synthesis, with continuous monitoring of rate and reaction progress, combines an electrode catalysing rapid, reversible and diffusion-controlled interconversion of NADP + and NADPH with a Pt electrode catalysing 2H + /H 2 interconversion. This Communication demonstrates its performance and characteristics using the reductive amination of 2-oxoglutarate as a test system.

  3. High pressure rotating reverse osmosis for long term space missions

    NASA Astrophysics Data System (ADS)

    Christensen Pederson, Cynthia Lynn

    Rotating reverse osmosis, which uses reverse osmosis to purify water and rotating filtration to improve the efficacy of filtration, has great potential for wastewater recycling on a long term space mission. Previous investigations of a proof-of-concept device indicated that the most efficient method to improve rotating reverse osmosis performance is to increase the operational pressure. Thus, a second generation device and fluid circuit were designed, fabricated, and tested to permit high pressure operation for long time periods. The design overcame several obstacles including membrane attachment, rotating seal design, and fluid and pressure management. A theoretical model of rotating reverse osmosis was modified to properly account for the flow conditions in the new design. Tests lasting a week were conducted with a variety of model wastewaters. Significant fouling and a decrease in flux were observed after three days of testing regardless of the operational parameters. A semi-empirical model, the fouling potential, was added to the theoretical model to account for the fouling. This allowed the simulation of 48 hour cleaning cycles that significantly increased the flux of the device. Experimental investigation of the rotational speed and concentrate flow rate indicated that an increase in either parameter decreased the fouling slightly. A week long test of a wastewater ersatz with a biocide did not exhibit a decrease in flux around day three that otherwise occurred. Therefore, biofouling was identified as the primary mechanism of fouling. Rotating reverse osmosis was compared with conventional spiral wound reverse osmosis and displayed increased rejection under dead end filtration conditions. The rotating device exhibited similar rejection and increased flux compared to a tubular reverse osmosis device previously used in a NASA wastewater recovery system. The integration of the rotating device into a NASA water recovery management system was evaluated. Lastly, a theoretical model of rotating hemofiltration was developed that demonstrated that the device is not clinically feasible given the permeability of available hemofiltration membranes.

  4. Rapid Reversion from Monomer to Dimer Regenerates the Ultraviolet-B Photoreceptor UV RESISTANCE LOCUS8 in Intact Arabidopsis Plants1[W][OA

    PubMed Central

    Heilmann, Monika; Jenkins, Gareth I.

    2013-01-01

    Arabidopsis (Arabidopsis thaliana) UV RESISTANCE LOCUS8 (UVR8) is a photoreceptor that specifically mediates photomorphogenic responses to ultraviolet (UV)-B in plants. UV-B photoreception induces the conversion of the UVR8 dimer into a monomer that interacts with the CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) protein to regulate gene expression. However, it is not known how the dimeric photoreceptor is regenerated in plants. Here, we show, by using inhibitors of protein synthesis and degradation via the proteasome, that the UVR8 dimer is not regenerated by rapid de novo synthesis following destruction of the monomer. Rather, regeneration occurs by reversion from the monomer to the dimer. However, regeneration of dimeric UVR8 in darkness following UV-B exposure occurs much more rapidly in vivo than in vitro with illuminated plant extracts or purified UVR8, indicating that rapid regeneration requires intact cells. Rapid dimer regeneration in vivo requires protein synthesis, the presence of a carboxyl-terminal 27-amino acid region of UVR8, and the presence of COP1, which is known to interact with the carboxyl-terminal region. However, none of these factors can account fully for the difference in regeneration kinetics in vivo and in vitro, indicating that additional proteins or processes are involved in UVR8 dimer regeneration in vivo. PMID:23129206

  5. Effects of nuclear radiation on a high-reliability silicon power diode. 4: Analysis of reverse bias characteristics

    NASA Technical Reports Server (NTRS)

    Been, J. F.

    1973-01-01

    The effects of nuclear radiation on the reverse bias electrical characteristics of one hundred silicon power diodes were investigated. On a percentage basis, the changes in reverse currents were large but, due to very low initial values, this electrical characteristic was not the limiting factor in use of these diodes. These changes were interpreted in terms of decreasing minority carrier lifetimes as related to generation-recombination currents. The magnitudes of reverse voltage breakdown were unaffected by irradiation.

  6. Sulfanegen sodium treatment in a rabbit model of sub-lethal cyanide toxicity

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

    Brenner, Matthew, E-mail: mbrenner@uci.ed; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA 92868; Kim, Jae G.

    2010-11-01

    The aim of this study is to investigate the ability of intramuscular and intravenous sulfanegen sodium treatment to reverse cyanide effects in a rabbit model as a potential treatment for mass casualty resulting from cyanide exposure. Cyanide poisoning is a serious chemical threat from accidental or intentional exposures. Current cyanide exposure treatments, including direct binding agents, methemoglobin donors, and sulfur donors, have several limitations. Non-rhodanese mediated sulfur transferase pathways, including 3-mercaptopyruvate sulfurtransferase (3-MPST) catalyze the transfer of sulfur from 3-MP to cyanide, forming pyruvate and less toxic thiocyanate. We developed a water-soluble 3-MP prodrug, 3-mercaptopyruvatedithiane (sulfanegen sodium), with the potentialmore » to provide a continuous supply of substrate for CN detoxification. In addition to developing a mass casualty cyanide reversal agent, methods are needed to rapidly and reliably diagnose and monitor cyanide poisoning and reversal. We use non-invasive technology, diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS) to monitor physiologic changes associated with cyanide exposure and reversal. A total of 35 animals were studied. Sulfanegen sodium was shown to reverse the effects of cyanide exposure on oxyhemoglobin and deoxyhemoglobin rapidly, significantly faster than control animals when administered by intravenous or intramuscular routes. RBC cyanide levels also returned to normal faster following both intramuscular and intravenous sulfanegen sodium treatment than controls. These studies demonstrate the clinical potential for the novel approach of supplying substrate for non-rhodanese mediated sulfur transferase pathways for cyanide detoxification. DOS and CWNIRS demonstrated their usefulness in optimizing the dose of sulfanegen sodium treatment.« less

  7. Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats.

    PubMed

    Calik, Michael W; Carley, David W

    2017-09-01

    There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors located on vagal afferents; an effect blocked by cannabinoid type 1 (CB1) and/or type 2 (CB2) receptor antagonists. Here, using a natural model of central sleep apnea, we examine the effects of dronabinol, alone and in combination with selective antagonists in conscious rats chronically instrumented to stage sleep and measure cessation of breathing. Adult male Sprague-Dawley rats were anesthetized and implanted with bilateral stainless steel screws into the skull for electroencephalogram recording and bilateral wire electrodes into the nuchal muscles for electromyogram recording. Each animal was recorded by polysomnography on multiple occasions separated by at least 3 days. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections: vehicle; vehicle and CB1 antagonist (AM 251); vehicle and CB2 antagonist (AM 630); vehicle and CB1/CB2 antagonist; dronabinol; dronabinol and CB1 antagonist; dronabinol and CB2 antagonist; and dronabinol and CB1/CB2 antagonist. Dronabinol decreased the percent time spent in rapid eye movement (REM) sleep. CB receptor antagonists did not reverse this effect. Dronabinol also decreased apneas during sleep, and this apnea suppression was reversed by CB1 or CB1/CB2 receptor antagonism. Dronabinol's effects on apneas were dependent on CB1 receptor activation, while dronabinol's effects on REM sleep were CB receptor-independent. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  8. [Effect of inducible nitric oxide on intracellular homeostasis of hepatocytes].

    PubMed

    Tang, Xi-Feng; Zhou, Dong-Yao; Kang, Ge-Fei

    2002-02-01

    To investigate the effects of inducible nitric oxide (NO) and exogenous NO on the intracellular homeostasis of the hepatocytes. Endogenous NO was induced by combined action of lipopolysaccharide (LPS) and cytokines in cultured rat hepatocytes, and exogenous NO was supplied by sodium nitroprusside (SNP) to stimulate the hepatocytes. The changes in intracellular malondialdehyde (MDA), reduced glutathione(GSH) and free calcium ([Ca2+]i) were observed. substantial increase by 7.97 times in intracellular MDA level and a decrease by 57.9% in GSH occurred in the hepatocytes after the cells had been incubated with LPS and cytokines for 24 h, which were reversed by 43.5% and 98.4% respectively by treatment with N(G)-monomethyl-L-arginine (NMMA), a competitive nitric oxide synthase (NOS) inhibitor. Verapamil significantly reduced both endogenous NO production and oxidative stress, while the effect of A23187 was not conspicuous. Incubation with chlorpromazine and Vitamine E (VitE), however, did not result in decreased release of NO by LPS- and cytokines-induced hepatocytes. After SNP exposure of the hepatocytes, the oxidative status was reversibly enhanced in a time-dependent manner. Short exposure to SNP led to a concentration-dependent inhibition of the rapid and transient increase in free calcium induced by K(+) depolarization and hepatopoietin-coupled calcium mobilization. Inducible NO may initiate and play a key role in the latter stages of metabolic and functional stress responses of hepatocytes against endotoxin and cytokines, when the reduction occurs in the capacity of NO to independently mediate lipid peroxidation and counteract oxidation. The inhibitory effect of NO on [Ca2+]i mobilization may be an important autoregulatory mechanism by means of negative feedback on protein kinase C-associated NOS induction.

  9. Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous l-arginine

    PubMed Central

    Jin, Yi; Chen, Bernadette; Calvert, Thomas J.; Chicoine, Louis G.; Liu, Yusen

    2013-01-01

    Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (Ca) in right ventricular work, a decrease in Ca would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from l-arginine (l-Arg). However, little is known of the effect of l-Arg on vascular compliance (Cv) in the lung. We hypothesized that exposure to CH would decrease Ca and that this effect would be reversed by exogenous l-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter (R0). Hypoxia resulted in the expected increase in arterial resistance (Ra) as well as a decrease in both Ca and Cv. l-Arg had little effect on Ra, Ca, or Cv in isolated lungs from normoxic animals. l-Arg decreased Ra in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R0, and l-Arg reversed this increase in R0. l-Arg increased exhaled NO, and inhibition of l-Arg uptake attenuated the l-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in Ca was reversed by l-Arg, suggesting that l-Arg may improve CH-induced right ventricular dysfunction. PMID:23103497

  10. An anion channel in Arabidopsis hypocotyls activated by blue light

    NASA Technical Reports Server (NTRS)

    Cho, M. H.; Spalding, E. P.; Evans, M. L. (Principal Investigator)

    1996-01-01

    A rapid, transient depolarization of the plasma membrane in seedling stems is one of the earliest effects of blue light detected in plants. It appears to play a role in transducing blue light into inhibition of hypocotyl (stem) elongation, and perhaps other responses. The possibility that activation of a Cl- conductance is part of the depolarization mechanism was raised previously and addressed here. By patch clamping hypocotyl cells isolated from dark-grown (etiolated) Arabidopsis seedlings, blue light was found to activate an anion channel residing at the plasma membrane. An anion-channel blocker commonly known as NPPB 15-nitro-2-(3-phenylpropylamino)-benzoic acid] potently and reversibly blocked this anion channel. NPPB also blocked the blue-light-induced depolarization in vivo and decreased the inhibitory effect of blue light on hypocotyl elongation. These results indicate that activation of this anion channel plays a role in transducing blue light into growth inhibition.

  11. Salt gland distribution in limonium bicolor at the individual level

    NASA Astrophysics Data System (ADS)

    Leng, B. Y.; Yuan, F.; Dong, X. X.; Wang, B. S.

    2018-02-01

    Limonium bicolor is a typical exo-recretohalophyte with multi-cellular salt glands. A differential interference contrast (DIC) microscope were applied to investigate the pattern of salt gland distribution in L. bicolor at the individual level. For a single mature leaf, more salt glands are distributed in the leaf central and apical regions than leaf base. For the leaves in different developmental stages, firstly, the density of salt glands linearly decreased at the beginning of leaf expansion and kept a relatively constant value in the later periods, which was mainly due to the rapid expansion of epidermal cells. Secondly, the total number of glands per leaf showed a reversed trend compared to the density of salt glands. These results suggested that the salt gland density was adapted to the leaf age and area as more and more salt accumulated in the saline soils.

  12. Lung cancer: is the increasing incidence due to radioactive polonium in cigarettes

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

    Marmorstein, J.

    This paper presents clinical, experimental, and epidemiologic evidence to help explain the rapidly increasing incidence of primary lung cancer, with recently observed reversal in leading cell type from squamous cell to adenocarcinoma. It postulates that this may be due to changes in modern cigarettes, with or without filters, which allow inhalation of increased amounts of radioactive lead and polonium and decreased amounts of benzopyrene. This hypothesis is based upon measurements of increased concentrations of radioactive polonium in the lungs of cigarette smokers, in modern tobaccos grown since 1950, and in high-phosphate fertilizers used for tobacco farming in industrialized countries. Criticalmore » support for this thesis is based upon experimental animal studies in which lung cancers that resemble adenocarcinomas are induced with as little as 15 rads of radioactive polonium, equal to one fifth the dosage inhaled by cigarette smokers who average two packs a day during a 25-year period.« less

  13. Gyre-driven decay of the Earth's magnetic dipole

    PubMed Central

    Finlay, Christopher C.; Aubert, Julien; Gillet, Nicolas

    2016-01-01

    Direct observations indicate that the magnitude of the Earth's magnetic axial dipole has decreased over the past 175 years; it is now 9% weaker than it was in 1840. Here we show how the rate of dipole decay may be controlled by a planetary-scale gyre in the liquid metal outer core. The gyre's meridional limbs on average transport normal polarity magnetic flux equatorward and reverse polarity flux poleward. Asymmetry in the geomagnetic field, due to the South Atlantic Anomaly, is essential to the proposed mechanism. We find that meridional flux advection accounts for the majority of the dipole decay since 1840, especially during times of rapid decline, with magnetic diffusion making an almost steady contribution generally of smaller magnitude. Based on the morphology of the present field, and the persistent nature of the gyre, the current episode of dipole decay looks set to continue, at least for the next few decades. PMID:26814368

  14. Gyre-driven decay of the Earth's magnetic dipole.

    PubMed

    Finlay, Christopher C; Aubert, Julien; Gillet, Nicolas

    2016-01-27

    Direct observations indicate that the magnitude of the Earth's magnetic axial dipole has decreased over the past 175 years; it is now 9% weaker than it was in 1840. Here we show how the rate of dipole decay may be controlled by a planetary-scale gyre in the liquid metal outer core. The gyre's meridional limbs on average transport normal polarity magnetic flux equatorward and reverse polarity flux poleward. Asymmetry in the geomagnetic field, due to the South Atlantic Anomaly, is essential to the proposed mechanism. We find that meridional flux advection accounts for the majority of the dipole decay since 1840, especially during times of rapid decline, with magnetic diffusion making an almost steady contribution generally of smaller magnitude. Based on the morphology of the present field, and the persistent nature of the gyre, the current episode of dipole decay looks set to continue, at least for the next few decades.

  15. Electrically tunable whispering gallery mode microresonator based on a grapefruit-microstructured optical fiber infiltrated with nematic liquid crystals.

    PubMed

    Yang, Chengkun; Zhang, Hao; Liu, Bo; Lin, Shiwei; Li, Yuetao; Liu, Haifeng

    2017-08-01

    An electrically tunable whispering gallery mode (WGM) microresonator based on an HF-etched microstructured optical fiber (MOF) infiltrated with nematic liquid crystals (NLCs) is proposed and experimentally demonstrated. Experimental results indicate that as the peak-to-peak voltage of the applied AC electric field increases from 160 to 220 V, WGM resonance peaks gradually move toward a shorter wavelength region by 0.527 nm with a wavelength sensitivity up to 0.01  nm/V for a TM1691 mode, and the Q-factor for each WGM resonance peak rapidly decreases with the increment of applied electric voltage. The proposed electrically controlled WGM tuning scheme shows a linear resonance wavelength shift with good spectral reversibility, which makes it a promising candidate to serve as an integrated functional photonic device in practical use and in related fundamental scientific studies.

  16. Oxygen Tuned Local Structure and Phase-Change Performance of Germanium Telluride.

    PubMed

    Zhou, Xilin; Du, Yonghua; Behera, Jitendra K; Wu, Liangcai; Song, Zhitang; Simpson, Robert E

    2016-08-10

    The effect of oxygen on the local structure of Ge atoms in GeTe-O materials has been investigated. Oxygen leads to a significant modification to the vibrational modes of Ge octahedra, which results from a decrease in its coordination. We find that a defective octahedral Ge network is the crucial fingerprint for rapid and reversible structural transitions in GeTe-based phase change materials. The appearance of oxide Raman modes confirms phase separation into GeO and TeO at high level O doping. Counterintuitively, despite the increase in crystallization temperature of oxygen doped GeTe-O phase change materials, when GeTe-O materials are used in electrical phase change memory cells, the electrical switching energy is lower than the pure GeTe material. This switching energy reduction is ascribed to the smaller change in volume, and therefore smaller enthalpy change, for the oxygen doped GeTe materials.

  17. Temporal processing and adaptation in the songbird auditory forebrain.

    PubMed

    Nagel, Katherine I; Doupe, Allison J

    2006-09-21

    Songbird auditory neurons must encode the dynamics of natural sounds at many volumes. We investigated how neural coding depends on the distribution of stimulus intensities. Using reverse-correlation, we modeled responses to amplitude-modulated sounds as the output of a linear filter and a nonlinear gain function, then asked how filters and nonlinearities depend on the stimulus mean and variance. Filter shape depended strongly on mean amplitude (volume): at low mean, most neurons integrated sound over many milliseconds, while at high mean, neurons responded more to local changes in amplitude. Increasing the variance (contrast) of amplitude modulations had less effect on filter shape but decreased the gain of firing in most cells. Both filter and gain changes occurred rapidly after a change in statistics, suggesting that they represent nonlinearities in processing. These changes may permit neurons to signal effectively over a wider dynamic range and are reminiscent of findings in other sensory systems.

  18. Oxygen sensing and signaling.

    PubMed

    van Dongen, Joost T; Licausi, Francesco

    2015-01-01

    Oxygen is an indispensable substrate for many biochemical reactions in plants, including energy metabolism (respiration). Despite its importance, plants lack an active transport mechanism to distribute oxygen to all cells. Therefore, steep oxygen gradients occur within most plant tissues, which can be exacerbated by environmental perturbations that further reduce oxygen availability. Plants possess various responses to cope with spatial and temporal variations in oxygen availability, many of which involve metabolic adaptations to deal with energy crises induced by low oxygen. Responses are induced gradually when oxygen concentrations decrease and are rapidly reversed upon reoxygenation. A direct effect of the oxygen level can be observed in the stability, and thus activity, of various transcription factors that control the expression of hypoxia-induced genes. Additional signaling pathways are activated by the impact of oxygen deficiency on mitochondrial and chloroplast functioning. Here, we describe the molecular components of the oxygen-sensing pathway.

  19. The Role of elF4E Activity in Breast Cancer

    DTIC Science & Technology

    2011-08-01

    protein; ORF, open reading frame; qPCR, quantitative PCR; RACE, rapid amplification of cDNA ends; RT, reverse transcriptase ; uORF, upstream ORF; UTR...Reactions were also performed using template lacking RT ( reverse transcriptase ): products were either undetectable or greatly reduced (>30000-fold less...that a 5’UTR expressed from the human AXIN2 gene contains a sixty nucleotide sequence that is predicted to form a stable stem-loop structure6. This

  20. Indigenous lactobacilli strains of food and human sources reverse enteropathogenic E. coli O26:H11-induced damage in intestinal epithelial cell lines: effect on redistribution of tight junction proteins.

    PubMed

    Jariwala, Ruchi; Mandal, Hemanti; Bagchi, Tamishraha

    2017-09-01

    The aim of the study was to investigate the neutralizing effect of lactobacilli isolated from indigenous food and human sources on enteropathogenic Escherichia coli (EPEC) O26 : H11-induced epithelial barrier dysfunction in vitro. This was assessed by transepithelial electrical resistance (TEER) and permeability assays using intestinal cell lines, HT-29 and Caco-2. Furthermore, the expression and distribution of tight junction (TJ) proteins were analysed by qRT-PCR and immunofluorescence assay, respectively. The nine strains used in the study were from different species viz. Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus salivarius and Lactobacillus plantarum. All strains were able to reverse the decrease in TEER and corresponding increase in permeability across E. coli-infected monolayers. Maximum reversal was observed after 18 h [up to 93.8±2.0 % by L. rhamnosus GG followed by L. fermentum IIs11.2 (92.6±2.2 %) and L. plantarum GRI-2 (91.9±0.9 %)] of lactobacilli exposure following EPEC O26 : H11 infection. All strains were able to redistribute the TJ proteins to the cell periphery either partially or completely. Moreover, L. helveticus FA-7 was also able to significantly increase the mRNA expression of ZO-1 and claudin-1 (2.5-fold and 3.0-fold, respectively; P<0.05). The rapid reversal observed by these strains could be mostly because of the redistribution rather than increased mRNA expression of TJ proteins. In conclusion, L. helveticus FA-7, L. fermentum FA-1 and L. plantarum GRI-2 were good in all the aspects studied, and the other strains were good in some aspects. L. helveticus FA-7, L. fermentum FA-1 and L. plantarum GRI-2 can therefore be used for potential therapeutic purpose against intestinal epithelial dysfunction.

  1. Different centre of pressure patterns within the golf stroke II: group-based analysis.

    PubMed

    Ball, K A; Best, R J

    2007-05-01

    Although the golf coaching literature stresses the importance of weight transfer during the swing, research has been conflicting or lacking statistical support. A potential problem with previous studies is that no attempt was made to account for different movement strategies in the golf swing. This study evaluated the relationship between centre of pressure measures and club head velocity within two previously identified swing styles, the "Front Foot" and "Reverse" styles. Thirty-nine Front Foot golfers and 19 Reverse golfers performed swings with a driver while standing on two force plates. From the force plate data, centre of pressure displacement, velocity, range, and timing parameters were calculated. Correlation and regression analysis indicated that a larger range of centre of pressure and a more rapid centre of pressure movement in the downswing was associated with a larger club head velocity at ball contact for the Front Foot group. For the Reverse golfers, positioning the centre of pressure further from the back foot at late backswing and a more rapid centre of pressure transfer towards the back foot at ball contact was associated with a larger club head velocity at ball contact. This study has highlighted the importance of identifying different movement strategies before evaluating performance measures, as different parameters were found to be important for the Front Foot and Reverse styles.

  2. Estimation of apparent rate coefficients for radionuclides interacting with marine sediments from Novaya Zemlya.

    PubMed

    Børretzen, P; Salbu, B

    2000-10-30

    To assess the impact of radionuclides entering the marine environment from dumped nuclear waste, information on the physico-chemical forms of radionuclides and their mobility in seawater-sediment systems is essential. Due to interactions with sediment components, sediments may act as a sink, reducing the mobility of radionuclides in seawater. Due to remobilisation, however, contaminated sediments may also act as a potential source of radionuclides to the water phase. In the present work, time-dependent interactions of low molecular mass (LMM, i.e. species < 10 kDa) radionuclides with sediments from the Stepovogo Fjord, Novaya Zemlya and their influence on the distribution coefficients (Kd values) have been studied in tracer experiments using 109Cd2+ and 60Co2+ as gamma tracers. Sorption of the LMM tracers occurred rapidly and the estimated equilibrium Kd(eq)-values for 109Cd and 60Co were 500 and 20000 ml/g, respectively. Remobilisation of 109Cd and 60Co from contaminated sediment fractions as a function of contact time was studied using sequential extraction procedures. Due to redistribution, the reversibly bound fraction of the gamma tracers decreased with time, while the irreversibly (or slowly reversibly) associated fraction of the gamma tracers increased. Two different three-compartment models, one consecutive and one parallel, were applied to describe the time-dependent interaction of the LMM tracers with operationally defined reversible and irreversible (or slowly reversible) sediment fractions. The interactions between these fractions were described using first order differential equations. By fitting the models to the experimental data, apparent rate constants were obtained using numerical optimisation software. The model optimisations showed that the interactions of LMM 60Co were well described by the consecutive model, while the parallel model was more suitable to describe the interactions of LMM 109Cd with the sediments, when the squared sum of residuals were compared. The rate of sorption of the irreversibly (or slowly reversibly) associated fraction was greater than the rate of desorption of the reversibly bound fractions (i.e. k3 > k2) for both radionuclides. Thus, the Novaya Zemlya sediment are supposed to act as a sink for the radionuclides under oxic conditions, and transport to the water phase should mainly be attributed to resuspended particles.

  3. Reversible and non-reversible changes in nanostructured Si in humid atmosphere

    NASA Astrophysics Data System (ADS)

    Zhigalov, V.; Pyatilova, O.; Timoshenkov, S.; Gavrilov, S.

    2014-12-01

    Atmosphere water influence in the nanostructured silicon (NSS) was investigated by IR-spectroscopy and electron work function measurement. Long-term non-reversible dynamics of IR-spectra was found as a result of 100% humidity influence on the nanostructured silicon. It was indicated that air humidity affects on the work function. Dynamics of the electron work function consists of reversible and non-reversible components. Reversible component appears as strong anti-correlation between work function and humidity. Work function change of NSS is about 0.4 eV while the humidity changes between 0% and 100%. Reversible component can be explained by physical sorption of water molecules on the surface. Non-reversible component manifests as long-term decreasing trend of work function in humid atmosphere. Transition curve during abruptly humidity changes alters its shape. Non-reversible component can be explained by chemisorption of water.

  4. Switching times of nanoscale FePt: Finite size effects on the linear reversal mechanism

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

    Ellis, M. O. A.; Chantrell, R. W.

    2015-04-20

    The linear reversal mechanism in FePt grains ranging from 2.316 nm to 5.404 nm has been simulated using atomistic spin dynamics, parametrized from ab-initio calculations. The Curie temperature and the critical temperature (T{sup *}), at which the linear reversal mechanism occurs, are observed to decrease with system size whilst the temperature window T{sup *}

  5. JP-8 jet fuel exposure rapidly induces high levels of IL-10 and PGE2 secretion and is correlated with loss of immune function.

    PubMed

    Harris, David T; Sakiestewa, Debbie; Titone, Dominic; Witten, Mark

    2007-05-01

    The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has demonstrated that JP-8 exposure is immunosuppressive. In the present study, the potential mechanisms for the effects of JP-8 exposure on the immune system were investigated. Exposure of mice to JP-8 for 1 h/day resulted in immediate secretion of two immunosuppressive agents; namely, interleukin-10 (IL-10) and prostaglandin E2 (PGE2). JP-8 exposure rapidly induced a persistently high level of serum IL-10 and PGE2 at an exposure concentration of 1000 mg/m3. IL-10 levels peaked at 2 h post-JP-8 exposure and then stabilized at significantly elevated serum levels, while PGE2 levels peaked after 2-3 days of exposure and then stabilized. Elevated IL-10 and PGE2 levels may at least partially explain the effects of JP-8 exposure on immune function. Elevated IL-10 and PGE2 levels, however, cannot explain all of the effects due to JP-8 exposure (e.g., decreased organ weights and decreased viable immune cells), as treatment with a PGE2 inhibitor did not completely reverse the immunosuppressive effects of jet fuel exposure. Thus, low concentration JP-8 jet fuel exposures have significant effects on the immune system, which can be partially explained by the secretion of immunosuppressive modulators, which are cumulative over time.

  6. A change in competitive context reverses sexual selection on male size.

    PubMed

    Kasumovic, M M; Andrade, M C B

    2009-02-01

    In studies of sexual selection, larger size is often argued to increase male fitness, and relatively smaller males are explained by genetic and/or environmental variation. We demonstrate that a size-development life-history trade-off could underlie the maintenance of a broad, unimodal distribution of size in male redback spiders (Latrodectus hasselti). Larger males are superior in direct competition, but redback males mature rapidly at small size in the presence of females. In field enclosures, we simulated two competitive contexts favouring development of divergent male sizes. Relatively smaller males lost when competing directly, but had 10 times higher fitness than relatively larger males when given the temporal advantage of rapid development. Linear selection gradients confirmed the reversal of selection on size, showing that it is critical to consider life-history decisions underlying the development of traits related to fitness.

  7. Cross-subtype Detection of HIV-1 Using Reverse Transcription and Recombinase Polymerase Amplification

    PubMed Central

    Lillis, Lorraine; Lehman, Dara A.; Siverson, Joshua B.; Weis, Julie; Cantera, Jason; Parker, Mathew; Piepenburg, Olaf; Overbaugh, Julie; Boyle, David S.

    2016-01-01

    A low complexity diagnostic test that rapidly and reliably detects HIV infection in infants at the point of care could facilitate early treatment, improving outcomes. However, many infant HIV diagnostics can only be performed in laboratory settings. Recombinase polymerase amplification (RPA) is an isothermal amplification technology that can rapidly amplify proviral DNA from multiple subtypes of HIV-1 in under twenty minutes without complex equipment. In this study we added reverse transcription (RT) to RPA to allow detection of both HIV-1 RNA and DNA. We show that this RT-RPA HIV-1 assay has a limit of detection of 10 to 30 copies of an exact sequence matched DNA or RNA, respectively. In addition, at 100 copies of RNA or DNA, the assay detected 171 of 175 (97.7 %) sequence variants that represent all the major subtypes and recombinant forms of HIV-1 Groups M and O. This data suggests that the application of RT-RPA for the combined detection of HIV-1 viral RNA and proviral DNA may prove a highly sensitive tool for rapid and accurate diagnosis of infant HIV. PMID:26821087

  8. Differential effects of peroxynitrite on contractile protein properties in fast- and slow-twitch skeletal muscle fibers of rat.

    PubMed

    Dutka, T L; Mollica, J P; Lamb, G D

    2011-03-01

    Oxidative modification of contractile proteins is thought to be a key factor in muscle weakness observed in many pathophysiological conditions. In particular, peroxynitrite (ONOO(-)), a potent short-lived oxidant, is a likely candidate responsible for this contractile dysfunction. In this study ONOO(-) or 3-morpholinosydnonimine (Sin-1, a ONOO(-) donor) was applied to rat skinned muscle fibers to characterize the effects on contractile properties. Both ONOO(-) and Sin-1 exposure markedly reduced maximum force in slow-twitch fibers but had much less effect in fast-twitch fibers. The rate of isometric force development was also reduced without change in the number of active cross bridges. Sin-1 exposure caused a disproportionately large decrease in Ca(2+) sensitivity, evidently due to coproduction of superoxide, as it was prevented by Tempol, a superoxide dismutase mimetic. The decline in maximum force with Sin-1 and ONOO(-) treatments could be partially reversed by DTT, provided it was applied before the fiber was activated. Reversal by DTT indicates that the decrease in maximum force was due at least in part to oxidation of cysteine residues. Ascorbate caused similar reversal, further suggesting that the cysteine residues had undergone S-nitrosylation. The reduction in Ca(2+) sensitivity, however, was not reversed by either DTT or ascorbate. Western blot analysis showed cross-linking of myosin heavy chain (MHC) I, appearing as larger protein complexes after ONOO(-) exposure. The findings suggest that ONOO(-) initially decreases maximum force primarily by oxidation of cysteine residues on the myosin heads, and that the accompanying decrease in Ca(2+) sensitivity is likely due to other, less reversible actions of hydroxyl or related radicals.

  9. Performance of the Directigen EZ Flu A+B rapid influenza diagnostic test to detect pandemic influenza A/H1N1 2009.

    PubMed

    Boyanton, Bobby L; Almradi, Amro; Mehta, Tejal; Robinson-Dunn, Barbara

    2014-04-01

    The Directigen EZ Flu A+B rapid influenza diagnostic test, as compared to real-time reverse transcriptase polymerase chain reaction, demonstrated suboptimal performance to detect pandemic influenza A/H1N1 2009. Age- and viral load-stratified test sensitivity ranged from 33.3 to 84.6% and 0 to 100%, respectively. © 2013.

  10. Development of a reverse transcription loop-mediated isothermal amplification assay for the detection of vesicular stomatitis New Jersey virus: use of rapid molecular assay to differentiate between vesicular disease viruses

    USDA-ARS?s Scientific Manuscript database

    Vesicular stomatitis (VS) is endemic in Central America and northern regions of South America. Sporadic outbreaks of VS can occur in cattle and pigs where the clinical presentation can be similar to foot-and-mouth disease (FMD). There is therefore a pressing need for rapid, sensitive and specific d...

  11. Reverse strand-displacement amplification strategy for rapid detection of p53 gene.

    PubMed

    Wang, Lisha; Han, Ying; Xiao, Shuai; Lv, Sha; Wang, Cong; Zhang, Nan; Wang, Zhengyong; Tang, Yongqiong; Li, Hongbo; Lyu, Jianxin; Xu, Huo; Shen, Zhifa

    2018-09-01

    The development of rapid approaches to detect prognostic markers is significant in reducing the morbidity and mortality of cancer. In this paper, we describe a rapid and specific biosensing platform for target DNA (p53 gene as a model) detection based on reverse strand displacement amplification (R-SDA). When the p53 gene is added, multifuctional molecular beacon (MMB) is unfolded via the hybridization with p53 gene. With the assist of Klenow fragment (KF) and Nt.BbvCI (the nicking endonuclease), p53 gene recycling could be initiated and considerable amount of complementary sequences for the MMBs (Nicked fragments, NFs) could be formed, generating enhanced fluorescence signal. Using this amplification strategy, the proposed biosensor displays the detection limit of 1 nM and a wide linear range from 1 to 100 nM, even if only one type of probe is involved. Notably, remarkable detection specificity for single-base mismatched target p53 gene is achieved. Moreover, the described biosensor also exhibited the stability in real biological samples (human serum). The rapid detection strategy can be performed less than 30 min without harsh reaction conditions or expensive nanoparticles. This biosensor shows great potential for application in clinic assay, especially, for early cancer diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Magnetic reversal frequency in the Lower Cambrian Niutitang Formation, Hunan Province, South China

    NASA Astrophysics Data System (ADS)

    Duan, Zongqi; Liu, Qingsong; Ren, Shoumai; Li, Lihui; Deng, Xiaolong; Liu, Jianxing

    2018-05-01

    The reversal frequency of the paleomagnetic field bears great information of evolution of the Earth's deep interior. However, there are still debates on the frequency pattern during the older periods of the Phanerozoic. This study investigated the Niutitang Formation (Lower Cambrian) of the Ciye 1 Hole from south China. Rock magnetic results indicate that the dominant magnetic carrier is magnetite. Characteristic remanence magnetizations have been successfully isolated for the weakly-magnetized shale rocks through stepwise alternated field demagnetization using the 2 G Enterprises Rapid System Magnetometer with a low-noise thin-walled quartz-glass sample holder. Constrained by radiometric ages, our paleomagnetic results indicated frequent polarity reversals during the period of ˜524-514 Ma, which backs up the speculation about the episode of the Ediacaran-Cambrian (˜550-500 Ma) with a character of reversal hyperactivity.

  13. Carbachol regulation of rabbit ileal brush border Na+–H+ exchanger 3 (NHE3) occurs through changes in NHE3 trafficking and complex formation and is Src dependent

    PubMed Central

    Li, Xuhang; Zhang, Huiping; Cheong, Alice; Yueping Chen, Sharon Leu; Elowsky, Christian G; Donowitz, Mark

    2004-01-01

    The epithelial brush border membrane (BBM) Na+–H+ exchanger 3 (NHE3) is the major transport protein responsible for ileal electroneutral Na+ absorption. We have previously shown that ileal BBM NHE3 activity is rapidly inhibited by carbachol, an agonist that mimics cholinergic activation in digestion. In this study, we investigated the mechanisms involved in this NHE3 inhibition. Carbachol decreased the amount of ileal Na+ absorptive cell BBM NHE3 within 10 min of exposure. Based on OptiPrep gradient centrifugation, carbachol increased the amount of NHE3 in early endosomes and decreased the amount of NHE3 in BBM, consistent with effects on NHE3 trafficking. The decrease in BBM NHE3 occurred in the detergent-soluble BBM fraction with no change in the amount of NHE3 in the BBM detergent-resistant membranes. The size of BBM NHE3 complexes increased in carbachol-exposed ileum, as studied with sucrose gradient centrifugation. The NHE3 complex size increased in the total BBM, but did not change in the detergent-soluble fraction. This suggests that carbachol treatment enhanced the association of proteins with NHE3 complexes specifically in the detergent-resistant fraction of ileal BBM. NHERF2, α-actinin-4 and protein kinase C were among those NHE3-associated proteins because they were more efficiently coimmunoprecipitated from total BBM after carbachol treatment. Moreover, Src was involved in the carbachol-mediated inhibition since: (1) c-Src was rapidly activated in the detergent-resistant membranes by carbachol; and (2) carbachol inhibition of ileal Na+ absorption was completely abolished by the Src family inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2). Moreover, the carbachol-induced increase in the size of NHE3-containing complexes was reversed by PP2. These data demonstrate that regulation of NHE3 activity by carbachol can be achieved at several interrelated levels: (1) the subcellular level, at which NHE3 is rapidly endocytosed from BBM to endocytic vesicles upon treatment with carbachol; (2) multiple BBM pools, in which carbachol selectively decreases the amount of NHE3 in the BBM detergent-soluble fraction but not the detergent-resistant membrane; and (3) the molecular level, at which NHE3 complex-associated proteins can be changed upon carbachol treatment, with carbachol leading to larger BBM NHE3 complexes and increased co-IP of NHERF2 with α-actinin-4 and activated PKC. The study further describes NHE3 presence simultaneously in multiple dynamic BBM pools in which NHE3 distribution and associated proteins are altered as part of carbachol-induced and Src-mediated rapid signal transduction, which decreases the amount of BBM NHE3 and thus inhibits NHE3 activity. PMID:14978207

  14. Posterior reversible encephalopathy with late postpartum eclampsia and short-term memory loss: a case report.

    PubMed

    Gimovsky, Martin L; Guzman, Guillermo M; Koscica, Karen L; Nazir, Munir A; Ross, Diane E

    2010-01-01

    Late postpartum eclampsia is more frequently recognized than past reports indicate. This report describes the association of a reversible encephalopathy in a woman with late postpartum eclampsia. A woman with lupus nephritis presented 7 days postpartum with eclampsia. Postseizure findings included dramatic short-term memory loss. Although a computed tomography scan was negative, subsequent magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) demonstrated vascular changes associated with a reversible encephalopathy. Conservative treatment with analeptic and antihypertensive therapy allowed a rapid resolution of all symptomatology. In women with eclampsia and unusual neurologic findings, an MRI/MRA may be useful even in the presence of a negative computed tomography scan.

  15. Computer-aided dental prostheses construction using reverse engineering.

    PubMed

    Solaberrieta, E; Minguez, R; Barrenetxea, L; Sierra, E; Etxaniz, O

    2014-01-01

    The implementation of computer-aided design/computer-aided manufacturing (CAD/CAM) systems with virtual articulators, which take into account the kinematics, constitutes a breakthrough in the construction of customised dental prostheses. This paper presents a multidisciplinary protocol involving CAM techniques to produce dental prostheses. This protocol includes a step-by-step procedure using innovative reverse engineering technologies to transform completely virtual design processes into customised prostheses. A special emphasis is placed on a novel method that permits a virtual location of the models. The complete workflow includes the optical scanning of the patient, the use of reverse engineering software and, if necessary, the use of rapid prototyping to produce CAD temporary prostheses.

  16. Average output polarization dataset for signifying the temperature influence for QCA designed reversible logic circuits.

    PubMed

    Abdullah-Al-Shafi, Md; Bahar, Ali Newaz; Bhuiyan, Mohammad Maksudur Rahman; Shamim, S M; Ahmed, Kawser

    2018-08-01

    Quantum-dot cellular automata (QCA) as nanotechnology is a pledging contestant that has incredible prospective to substitute complementary metal-oxide-semiconductor (CMOS) because of its superior structures such as intensely high device thickness, minimal power depletion with rapid operation momentum. In this study, the dataset of average output polarization (AOP) for fundamental reversible logic circuits is organized as presented in (Abdullah-Al-Shafi and Bahar, 2017; Bahar et al., 2016; Abdullah-Al-Shafi et al., 2015; Abdullah-Al-Shafi, 2016) [1-4]. QCADesigner version 2.0.3 has been utilized to survey the AOP of reversible circuits at separate temperature point in Kelvin (K) unit.

  17. Highly Viscoelastic Reverse Wormlike Micellar Systems from a Mixture of Lecithin, Polyglycerol Fatty Acid Monoesters, and an Oil.

    PubMed

    Hashizaki, Kaname; Imai, Miko; Yako, Shuhei; Tsusaka, Hitomi; Sakanishi, Yuichi; Saito, Yoshihiro; Fujii, Makiko

    2017-09-01

    We report new lecithin reverse wormlike micelles with high viscoelasticity formed using lecithin/polyglycerol fatty acid monoester (PGLFA)/oil systems. In this study, the influence of the amphiphilicity (i.e., hydrophile-lipophile balance, HLB) of PGLFA on the phase behavior and rheological properties of reverse wormlike micelles was investigated in detail. PGLFAs with degrees of polymerization of polyglycerol varying between 6-40 and constituent fatty acids with chains between 6-18 carbon atoms long were used. Partial phase diagrams of the lecithin/PGLFA/n-decane systems indicated that the appropriate PGLFA could change the lecithin/oil solution into a highly viscoelastic solution comprising reverse wormlike micelles. Rheological measurements showed that all systems that formed reverse wormlike micelles exhibited an unusual phenomenon called "shear-thickening". Furthermore, reverse wormlike micelles grew as the PGLFA concentration increased and the zero-shear viscosity (η 0 ) of the solution rapidly increased. Our results indicate that the magnitude of the maximum η 0 depends on the degree of polymerization of the constituent polyglycerol in the PGLFA, while the size of the reverse micellar region and the highly viscous region in the phase diagram depends on the HLB value of the PGLFA.

  18. Preparation of Invert Sugar Syrup,

    DTIC Science & Technology

    after addn. of citric acid, in the 3rd kettle, the inverted syrup is cooled rapidly to 10 degrees. If such a cooling step is omitted, reversion will set in and also formation of hydroxymethyl furfural . (Author)

  19. Biogeochemistry: Deep ocean iron balance

    NASA Astrophysics Data System (ADS)

    Homoky, William B.

    2017-02-01

    Dissolved iron is mysteriously pervasive in deep ocean hydrothermal plumes. An analysis of gas, metals and particles from a 4,000 km plume transect suggests that dissolved iron is maintained by rapid and reversible exchanges with sinking particles.

  20. Stabilization of Reversed Replication Forks by Telomerase Drives Telomere Catastrophe.

    PubMed

    Margalef, Pol; Kotsantis, Panagiotis; Borel, Valerie; Bellelli, Roberto; Panier, Stephanie; Boulton, Simon J

    2018-01-25

    Telomere maintenance critically depends on the distinct activities of telomerase, which adds telomeric repeats to solve the end replication problem, and RTEL1, which dismantles DNA secondary structures at telomeres to facilitate replisome progression. Here, we establish that reversed replication forks are a pathological substrate for telomerase and the source of telomere catastrophe in Rtel1 -/- cells. Inhibiting telomerase recruitment to telomeres, but not its activity, or blocking replication fork reversal through PARP1 inhibition or depleting UBC13 or ZRANB3 prevents the rapid accumulation of dysfunctional telomeres in RTEL1-deficient cells. In this context, we establish that telomerase binding to reversed replication forks inhibits telomere replication, which can be mimicked by preventing replication fork restart through depletion of RECQ1 or PARG. Our results lead us to propose that telomerase inappropriately binds to and inhibits restart of reversed replication forks within telomeres, which compromises replication and leads to critically short telomeres. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Solid-phase synthesis of protein-polymers on reversible immobilization supports.

    PubMed

    Murata, Hironobu; Carmali, Sheiliza; Baker, Stefanie L; Matyjaszewski, Krzysztof; Russell, Alan J

    2018-02-27

    Facile automated biomacromolecule synthesis is at the heart of blending synthetic and biologic worlds. Full access to abiotic/biotic synthetic diversity first occurred when chemistry was developed to grow nucleic acids and peptides from reversibly immobilized precursors. Protein-polymer conjugates, however, have always been synthesized in solution in multi-step, multi-day processes that couple innovative chemistry with challenging purification. Here we report the generation of protein-polymer hybrids synthesized by protein-ATRP on reversible immobilization supports (PARIS). We utilized modified agarose beads to covalently and reversibly couple to proteins in amino-specific reactions. We then modified reversibly immobilized proteins with protein-reactive ATRP initiators and, after ATRP, we released and analyzed the protein polymers. The activity and stability of PARIS-synthesized and solution-synthesized conjugates demonstrated that PARIS was an effective, rapid, and simple method to generate protein-polymer conjugates. Automation of PARIS significantly reduced synthesis/purification timelines, thereby opening a path to changing how to generate protein-polymer conjugates.

  2. Product-to-parent reversion processes: Stream-hyporheic spiraling increases ecosystem exposure and environmental persistence

    NASA Astrophysics Data System (ADS)

    Ward, A. S.; Cwiertny, D. M.; Kolodziej, E. P.

    2014-12-01

    The product-to-parent reversion of metabolites of trenbolone acetate (TBA), a steroidal growth promoter used widely in beef cattle production, was recently observed to occur in environmental waters. The rapid forward reaction is by direct photolysis (i.e., photohydration), with the much slower reversion reaction occurring via dehydration in the dark. The objective of this study is to quantify the potential effect of this newly discovered reversible process on TBA metabolite concentrations and total bioactivity exposure in fluvial systems. Here, we demonstrate increased persistence of TBA metabolites in the stream and hyporheic zone due to the reversion process, increasing chronic and acute exposure to these endocrine-active compounds along a stream. The perpetually dark hyporheic zone is a key location for reversion in the system, ultimately providing a source of the parent compound to the stream and increasing mean in-stream concentration of 17α-trenbolone (17α-TBOH) by 40% of the input concentration under representative fluvial conditions. As such, regulatory frameworks for compounds undergoing product-to-parent reversion will require new approaches for assessing total exposure to bioactive compounds. Further, we demonstrate generalized cases for prediction of exposure for species with product-to-parent reversion in stream-hyporheic systems.

  3. Effects of co-administration of clenbuterol and testosterone propionate on skeletal muscle in paraplegic mice.

    PubMed

    Ung, Roth-Visal; Rouleau, Pascal; Guertin, Pierre A

    2010-06-01

    Spinal cord injury (SCI) is generally associated with a rapid and significant decrease in muscle mass and corresponding changes in skeletal muscle properties. Although beta(2)-adrenergic and androgen receptor agonists are anabolic substances clearly shown to prevent or reverse muscle wasting in some pathological conditions, their effects in SCI patients remain largely unknown. Here we studied the effects of clenbuterol and testosterone propionate administered separately or in combination on skeletal muscle properties and adipose tissue in adult CD1 mice spinal-cord-transected (Tx) at the low-thoracic level (i.e., induced complete paraplegia). Administered shortly post-Tx, these substances were found to differentially reduce loss in body weight, muscle mass, and muscle fiber cross-sectional area (CSA) values. Although all three treatments induced significant effects, testosterone-treated animals were generally less protected against Tx-related changes. However, none of the treatments prevented fat tissue loss or muscle fiber type conversion and functional loss generally found in Tx animals. These results provide evidence suggesting that clenbuterol alone or combined with testosterone may constitute better clinically-relevant treatments than testosterone alone to decrease muscle atrophy (mass and fiber CSA) in SCI subjects.

  4. Modeling agricultural commodity prices and volatility in response to anticipated climate change

    NASA Astrophysics Data System (ADS)

    Lobell, D. B.; Tran, N.; Welch, J.; Roberts, M.; Schlenker, W.

    2012-12-01

    Food prices have shown a positive trend in the past decade, with episodes of rapid increases in 2008 and 2011. These increases pose a threat to food security in many regions of the world, where the poor are generally net consumers of food, and are also thought to increase risks of social and political unrest. The role of global warming in these price reversals have been debated, but little quantitative work has been done. A particular challenge in modeling these effects is that they require understanding links between climate and food supply, as well as between food supply and prices. Here we combine the anticipated effects of climate change on yield levels and volatility with an empirical competitive storage model to examine how expected climate change might affect prices and social welfare in the international food commodity market. We show that price level and volatility do increase over time in response to decreasing yield, and increasing yield variability. Land supply and storage demand both increase, but production and consumption continue to fall leading to a decrease in consumer surplus, and a corresponding though smaller increase in producer surplus.

  5. Synthesis and Photophysical Characterization of an Artificial Photosynthetic Reaction Center Exhibiting Acid-Responsive Regulation of Charge Separation

    NASA Astrophysics Data System (ADS)

    Pahk, Ian

    Non-photochemical quenching (NPQ) is a photoprotective regulatory mechanism essential to the robustness of the photosynthetic apparatus of green plants. Energy flow within the low-light adapted reaction centers is dynamically optimized to match the continuously fluctuating light conditions found in nature. Activated by compartmentalized decreases in pH resulting from photosynthetic activity during periods of elevated photon flux, NPQ induces rapid thermal dissipation of excess excitation energy that would otherwise overwhelm the apparatus's ability to consume it. Consequently, the frequency of charge separation decreases and the formation of potentially deleterious, high-energy intermediates slows, thereby reducing the threat of photodamage by disallowing their accumulation. Herein is described the synthesis and photophysical analysis of a molecular triad that mimics the effects of NPQ on charge separation within the photosynthetic reaction centers. Steady-state absorption and emission, time-resolved fluorescence, and transient absorption spectroscopies were used to demonstrate reversible quenching of the first singlet excited state affecting the quantum yield of charge separation by approximately one order of magnitude. As in the natural system, the populations of unquenched and quenched states and, therefore, the overall yields of charge separation were found to be dependent upon acid concentration.

  6. Is Neurotoxicity of Metallic Nanoparticles the Cascades of Oxidative Stress?

    NASA Astrophysics Data System (ADS)

    Song, Bin; Zhang, YanLi; Liu, Jia; Feng, XiaoLi; Zhou, Ting; Shao, LongQuan

    2016-06-01

    With the rapid development of nanotechnology, metallic (metal or metal oxide) nanoparticles (NPs) are widely used in many fields such as cosmetics, the food and building industries, and bio-medical instruments. Widespread applications of metallic NP-based products increase the health risk associated with human exposures. Studies revealed that the brain, a critical organ that consumes substantial amounts of oxygen, is a primary target of metallic NPs once they are absorbed into the body. Oxidative stress (OS), apoptosis, and the inflammatory response are believed to be the main mechanisms underlying the neurotoxicity of metallic NPs. Other studies have disclosed that antioxidant pretreatment or co-treatment can reverse the neurotoxicity of metallic NPs by decreasing the level of reactive oxygen species, up-regulating the activities of antioxidant enzymes, decreasing the proportion of apoptotic cells, and suppressing the inflammatory response. These findings suggest that the neurotoxicity of metallic NPs might involve a cascade of events following NP-induced OS. However, additional research is needed to determine whether NP-induced OS plays a central role in the neurotoxicity of metallic NPs, to develop a comprehensive understanding of the correlations among neurotoxic mechanisms and to improve the bio-safety of metallic NP-based products.

  7. Monitoring spatial and temporal variations of permeability in constructed wetlands by time-lapse geophysical methods

    NASA Astrophysics Data System (ADS)

    Tapias, J. C.; Himi, M.; Lovera, R.; Blasco, R.; Folch, M.; Casas, A.

    2012-04-01

    Constructed wetlands are widely used for removing pollutants from wastewater in small communities because their simplicity and low operation costs. Nevertheless, with time the cleaning process can result in gradual clogging of the porous layer by suspended solids, bacterial film, chemical precipitates and compactation. The clogging development causes decrease of hydraulic conductivity, reduced oxygen supply and further leads to a rapid decrease of the treatment performance. As the investment involved in reversing clogging can represent a substantial fraction of the cost of a new system it is essential to assess in advance the evolution of clogging process and detect potential failures in the system. Since there is a lack of experiences for monitoring the functionality of constructed wedlands a combination of non-destructive geophysical methods have been tested in this study. With this purpose electrical resistivity tomography, induced polarisation, frequency domain EM and ground probing radar have been conducted at different horizontal subsurface flow municipal wastewater treatment wetlands of Catalonia (Spain). The obtained results have shown that the applied geophysical techniques may delineate the clogging expansion and help take the preventive measures for enlarge the lifetime of the treatment system.

  8. Context-dependent decision-making: a simple Bayesian model

    PubMed Central

    Lloyd, Kevin; Leslie, David S.

    2013-01-01

    Many phenomena in animal learning can be explained by a context-learning process whereby an animal learns about different patterns of relationship between environmental variables. Differentiating between such environmental regimes or ‘contexts’ allows an animal to rapidly adapt its behaviour when context changes occur. The current work views animals as making sequential inferences about current context identity in a world assumed to be relatively stable but also capable of rapid switches to previously observed or entirely new contexts. We describe a novel decision-making model in which contexts are assumed to follow a Chinese restaurant process with inertia and full Bayesian inference is approximated by a sequential-sampling scheme in which only a single hypothesis about current context is maintained. Actions are selected via Thompson sampling, allowing uncertainty in parameters to drive exploration in a straightforward manner. The model is tested on simple two-alternative choice problems with switching reinforcement schedules and the results compared with rat behavioural data from a number of T-maze studies. The model successfully replicates a number of important behavioural effects: spontaneous recovery, the effect of partial reinforcement on extinction and reversal, the overtraining reversal effect, and serial reversal-learning effects. PMID:23427101

  9. Context-dependent decision-making: a simple Bayesian model.

    PubMed

    Lloyd, Kevin; Leslie, David S

    2013-05-06

    Many phenomena in animal learning can be explained by a context-learning process whereby an animal learns about different patterns of relationship between environmental variables. Differentiating between such environmental regimes or 'contexts' allows an animal to rapidly adapt its behaviour when context changes occur. The current work views animals as making sequential inferences about current context identity in a world assumed to be relatively stable but also capable of rapid switches to previously observed or entirely new contexts. We describe a novel decision-making model in which contexts are assumed to follow a Chinese restaurant process with inertia and full Bayesian inference is approximated by a sequential-sampling scheme in which only a single hypothesis about current context is maintained. Actions are selected via Thompson sampling, allowing uncertainty in parameters to drive exploration in a straightforward manner. The model is tested on simple two-alternative choice problems with switching reinforcement schedules and the results compared with rat behavioural data from a number of T-maze studies. The model successfully replicates a number of important behavioural effects: spontaneous recovery, the effect of partial reinforcement on extinction and reversal, the overtraining reversal effect, and serial reversal-learning effects.

  10. Small fluorescence-activating and absorption-shifting tag for tunable protein imaging in vivo

    PubMed Central

    Plamont, Marie-Aude; Billon-Denis, Emmanuelle; Maurin, Sylvie; Gauron, Carole; Pimenta, Frederico M.; Specht, Christian G.; Shi, Jian; Quérard, Jérôme; Pan, Buyan; Rossignol, Julien; Moncoq, Karine; Morellet, Nelly; Volovitch, Michel; Lescop, Ewen; Chen, Yong; Triller, Antoine; Vriz, Sophie; Le Saux, Thomas; Jullien, Ludovic; Gautier, Arnaud

    2016-01-01

    This paper presents Yellow Fluorescence-Activating and absorption-Shifting Tag (Y-FAST), a small monomeric protein tag, half as large as the green fluorescent protein, enabling fluorescent labeling of proteins in a reversible and specific manner through the reversible binding and activation of a cell-permeant and nontoxic fluorogenic ligand (a so-called fluorogen). A unique fluorogen activation mechanism based on two spectroscopic changes, increase of fluorescence quantum yield and absorption red shift, provides high labeling selectivity. Y-FAST was engineered from the 14-kDa photoactive yellow protein by directed evolution using yeast display and fluorescence-activated cell sorting. Y-FAST is as bright as common fluorescent proteins, exhibits good photostability, and allows the efficient labeling of proteins in various organelles and hosts. Upon fluorogen binding, fluorescence appears instantaneously, allowing monitoring of rapid processes in near real time. Y-FAST distinguishes itself from other tagging systems because the fluorogen binding is highly dynamic and fully reversible, which enables rapid labeling and unlabeling of proteins by addition and withdrawal of the fluorogen, opening new exciting prospects for the development of multiplexing imaging protocols based on sequential labeling. PMID:26711992

  11. Small fluorescence-activating and absorption-shifting tag for tunable protein imaging in vivo.

    PubMed

    Plamont, Marie-Aude; Billon-Denis, Emmanuelle; Maurin, Sylvie; Gauron, Carole; Pimenta, Frederico M; Specht, Christian G; Shi, Jian; Quérard, Jérôme; Pan, Buyan; Rossignol, Julien; Moncoq, Karine; Morellet, Nelly; Volovitch, Michel; Lescop, Ewen; Chen, Yong; Triller, Antoine; Vriz, Sophie; Le Saux, Thomas; Jullien, Ludovic; Gautier, Arnaud

    2016-01-19

    This paper presents Yellow Fluorescence-Activating and absorption-Shifting Tag (Y-FAST), a small monomeric protein tag, half as large as the green fluorescent protein, enabling fluorescent labeling of proteins in a reversible and specific manner through the reversible binding and activation of a cell-permeant and nontoxic fluorogenic ligand (a so-called fluorogen). A unique fluorogen activation mechanism based on two spectroscopic changes, increase of fluorescence quantum yield and absorption red shift, provides high labeling selectivity. Y-FAST was engineered from the 14-kDa photoactive yellow protein by directed evolution using yeast display and fluorescence-activated cell sorting. Y-FAST is as bright as common fluorescent proteins, exhibits good photostability, and allows the efficient labeling of proteins in various organelles and hosts. Upon fluorogen binding, fluorescence appears instantaneously, allowing monitoring of rapid processes in near real time. Y-FAST distinguishes itself from other tagging systems because the fluorogen binding is highly dynamic and fully reversible, which enables rapid labeling and unlabeling of proteins by addition and withdrawal of the fluorogen, opening new exciting prospects for the development of multiplexing imaging protocols based on sequential labeling.

  12. A novel live cell imaging system reveals a reversible hydrostatic pressure impact on cell cycle progression.

    PubMed

    Brooker, Holly R; Gyamfi, Irene A; Wieckowska, Agnieszka; Brooks, Nicholas J; Mulvihill, Daniel P; Geeves, Michael A

    2018-06-21

    Life is dependent upon the ability of a cell to rapidly respond to changes in environment. Small perturbations in local environments change the ability of molecules to interact and hence communicate. Hydrostatic pressure provides a rapid non-invasive, fully-reversible method for modulating affinities between molecules both in vivo and in vitro We have developed a simple fluorescence imaging chamber that allows intracellular protein dynamics and molecular events to be followed at pressures up to 200 bar in living cells. Using yeast we investigate the impact of hydrostatic pressure upon cell growth and cell cycle progression. While 100 bar has no affect upon viability, it induces a delay in chromosome segregation, resulting in the accumulation of long-undivided-bent cells, consistent with disruption of the cytoskeletons. This delay is independent of stress signalling and induces synchronisation of cell-cycle progression. Equivalent affects were observed in Candida albicans , with pressure inducing a reversible cell-cycle delay and hyphal growth. We present a simple novel non-invasive fluorescence microscopy based approach to transiently impact molecular dynamics to visualise, dissect and study signalling pathways and cellular processes in living cells. © 2018. Published by The Company of Biologists Ltd.

  13. Development and validation of a rapid reversed-phase HPLC method for the determination of the non-nucleoside reverse transcriptase inhibitor dapivirine from polymeric nanoparticles.

    PubMed

    das Neves, José; Sarmento, Bruno; Amiji, Mansoor M; Bahia, Maria Fernanda

    2010-06-05

    The objective of this work was to develop and validate a rapid reversed-phase (RP) high-performance liquid chromatography (HPLC) method for the in vitro pharmaceutical characterization of dapivirine-loaded polymeric nanoparticles. Chromatographic runs were performed on a RP C18 column with a mobile phase comprising acetonitrile-0.5% (w/v) triethanolamine solution in isocratic mode (80:20, v/v) at a flow rate of 1 ml/min. Dapivirine was detected at a wavelength of 290 nm. The method was shown to be specific, linear in the range of 1-50 microg/ml (R(2)=0.9998), precise at the intra-day and inter-day levels as reflected by the relative standard deviation values (less than 0.85%), accurate (recovery rate of 100.17+/-0.35%), and robust to changes in the mobile phase and column brand. The detection and quantitation limits were 0.08 and 0.24 microg/ml, respectively. The method was successfully used to determine the loading capacity and association efficiency of dapivirine in poly(lactic-co-glycolic acid)-based nanoparticles and its in vitro release. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  14. The Role of Artificial Atmospheric CO2 Removal in Stabilizing Earth's Climate

    NASA Astrophysics Data System (ADS)

    Tokarska, Katarzyna; Zickfeld, Kirsten

    2014-05-01

    Recent research showed that global mean temperature remains approximately constant for several centuries after complete cessation of CO2 emissions, while global mean thermosteric sea level continues to rise. This implies that a net artificial removal of CO2 from the atmosphere may be necessary to decrease the atmospheric CO2 concentrations more rapidly and bring the climate system components to their previous states on human timescales. The purpose of this study is to explore the reversibility of climate responses to a range of realistic CO2 emission scenarios, which follow a gradual transition from fossil-fuel driven economy to a zero-emission energy system with implementation of negative CO2 emissions, using the University of Victoria Earth System Climate Model of intermediate complexity (UVic ESCM 2.9). The CO2 emission pathways were designed to meet constraints related to the implementation of negative emission technologies derived from the integrated assessment literature. Our simulations show that while it is possible, in principle, to revert the global mean temperature after a phase of overshoot, the thermosteric sea level rise is not reversible on human timescales for the range of emission scenarios considered. During the negative emission phase, CO2 is released form the natural (terrestrial and marine) carbon sinks, which diminishes the efficiency of negative emissions implemented. In addition, spatial changes of vegetation distribution patterns are not entirely reversible on human timescales. We suggest that while negative emissions could potentially stabilize the global mean temperature at a desired level, such technology does not supersede reductions in fossil fuel emissions, as the artificial CO2 capture at large scale has many limitations and is unable to stabilize other climate system components (e.g. sea level) at desired levels.

  15. Response of drinking-water reservoir ecosystems to decreased acidic atmospheric deposition in SE Germany: trends of chemical reversal.

    PubMed

    Ulrich, Kai-Uwe; Paul, Lothar; Meybohm, Andreas

    2006-05-01

    This study evaluates chemical trends of seven acidified reservoirs and 22 tributaries in the Erzgebirge from 1993 to 2003. About 85% of these waters showed significantly (p < 0.05) declining concentrations of protons (-69%), nitrate (-41%), sulfate (-27%), and reactive aluminum (-50% on average). This reversal is attributed to the intense reduction of industrial SO2 and NOx emissions from formerly high levels, which declined by 99% and 82% in the German-Czech border region between 1993 and 1999. The deposition rates of protons and sulfur decreased by 70-90%. Since 1993, the dry deposition of total inorganic nitrogen diminished to a minor degree, but the wet deposition remained unchanged. The surface waters reflect a substantial decrease in Al exchange processes, a release of sulfur previously stored in soils, and an uptake of nitrate by forest vegetation. The latter effect may be supported by soil protection liming which contributed to the chemical reversal in almost 20% of the study waters.

  16. The National Potential of Home Equity Conversion.

    ERIC Educational Resources Information Center

    Jacobs, Bruce

    1986-01-01

    Examined the potential effects of converting home equity into spendable income using "reverse mortgages." Analysis revealed that reverse mortgage loans could have a substantial impact on the budgets of many elderly homeowners, with impressive percentage increases in income and decreases in poverty rates. (Author/ABB)

  17. The energetic ion signature of an O-type neutral line in the geomagnetic tail

    NASA Technical Reports Server (NTRS)

    Martin, R. F., Jr.; Johnson, D. F.; Speiser, T. W.

    1991-01-01

    An energetic ion signature is presented which has the potential for remote sensing of an O-type neutral line embedded in a current sheet. A source plasma with a tailward flowing Kappa distribution yields a strongly non-Kappa distribution after interacting with the neutral line: sharp jumps, or ridges, occur in the velocity space distribution function f(nu-perpendicular, nu-parallel) associated with both increases and decreases in f. The jumps occur when orbits are reversed in the x-direction: a reversal causing initially earthward particles (low probability in the source distribution) to be observed results in a decrease in f, while a reversal causing initially tailward particles to be observed produces an increase in f. The reversals, and hence the jumps, occur at approximately constant values of perpendicular velocity in both the positive nu parallel and negative nu parallel half planes. The results were obtained using single particle simulations in a fixed magnetic field model.

  18. Reverse electron transport effects on NADH formation and metmyoglobin reduction.

    PubMed

    Belskie, K M; Van Buiten, C B; Ramanathan, R; Mancini, R A

    2015-07-01

    The objective was to determine if NADH generated via reverse electron flow in beef mitochondria can be used for electron transport-mediated reduction and metmyoglobin reductase pathways. Beef mitochondria were isolated from bovine hearts (n=5) and reacted with combinations of succinate, NAD, and mitochondrial inhibitors to measure oxygen consumption and NADH formation. Mitochondria and metmyoglobin were reacted with succinate, NAD, and mitochondrial inhibitors to measure electron transport-mediated metmyoglobin reduction and metmyoglobin reductase activity. Addition of succinate and NAD increased oxygen consumption, NADH formation, electron transport-mediated metmyoglobin reduction, and reductase activity (p<0.05). Addition of antimycin A prevented electron flow beyond complex III, therefore, decreasing oxygen consumption and electron transport-mediated metmyoglobin reduction. Addition of rotenone prevented reverse electron flow, increased oxygen consumption, increased electron transport-mediated metmyoglobin reduction, and decreased NADH formation. Succinate and NAD can generate NADH in bovine tissue postmortem via reverse electron flow and this NADH can be used by both electron transport-mediated and metmyoglobin reductase pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. 30-Year Satellite Record Reveals Accelerated Arctic Sea Ice Loss, Antarctic Sea Ice Trend Reversal

    NASA Technical Reports Server (NTRS)

    Cavalieri, Donald J.; Parkinson, C. L.; Vinnikov, K. Y.

    2003-01-01

    Arctic sea ice extent decreased by 0.30 plus or minus 0.03 x 10(exp 6) square kilometers per decade from 1972 through 2002, but decreased by 0.36 plus or minus 0.05 x 10(exp 6) square kilometers per decade from 1979 through 2002, indicating an acceleration of 20% in the rate of decrease. In contrast to the Arctic, the Antarctic sea ice extent decreased dramatically over the period 1973-1977, then gradually increased, with an overall 30-year trend of -0.15 plus or minus 0.08 x 10(exp 6) square kilometers per 10yr. The trend reversal is attributed to a large positive anomaly in Antarctic sea ice extent observed in the early 1970's.

  20. Selection Difficulty and Interitem Competition Are Independent Factors in Rapid Visual Stream Perception

    ERIC Educational Resources Information Center

    Kawahara, Jun-ichiro; Enns, James T.

    2009-01-01

    When observers try to identify successive targets in a visual stream at a rate of 100 ms per item, accuracy for the 2nd target is impaired for intertarget lags of 100-500 ms. Yet, when the same stream is presented more rapidly (e.g., 50 ms per item), this pattern reverses and a 1st-target deficit is obtained. M. C. Potter, A. Staub, and D. H.…

  1. Aldicarb

    EPA Science Inventory

    Aldicarb (CAS 116-06-3) is an N-methyl carbamate insecticide that rapidly and reversibly inhibits acetylcholinesterase. The nervous system is the most sensitive target, and there is little evidence of other forms of toxicity. Aldicarb is highly toxic to humans and wildlife. Gro...

  2. Preservation of Specific Protein Signaling States Using Heat Based Stabilizor System.

    PubMed

    Borén, Mats

    2017-01-01

    The ability to adequately measure the phosphorylation state of a protein has major biological as well as clinical relevance. Due to its variable nature, reversible protein phosphorylations are sensitive to changes in the tissue environment. Stabilizor TM T1 is a system for rapid inactivation of enzymatic activity in biological samples. Enzyme inactivation is accomplished using thermal denaturation in a rapid, homogeneous, and reproducible fashion without the need of added chemical inhibitors. Using pCREB(Ser133) as a model system, the applicability of the Stabilizor system to preserve a rapidly lost phosphorylation is shown.

  3. Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions

    PubMed Central

    2016-01-01

    ABSTRACT Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735–743, 2017, https://doi.org/10.1128/JCM.01879-16) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases. PMID:28003421

  4. Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions.

    PubMed

    Hacker, Jill K

    2017-03-01

    Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735-743, 2017, https://doi.org/10.1128/JCM.01879-16) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases. Copyright © 2017 American Society for Microbiology.

  5. Femur Model Reconstruction Based on Reverse Engineering and Rapid Prototyping

    NASA Astrophysics Data System (ADS)

    Tang, Tongming; Zhang, Zheng; Ni, Hongjun; Deng, Jiawen; Huang, Mingyu

    Precise reconstruction of 3D models is fundamental and crucial to the researches of human femur. In this paper we present our approach towards tackling this problem. The surface of a human femur was scanned using a hand-held 3D laser scanner. The data obtained, in the form of point cloud, was then processed using the reverse engineering software Geomagic and the CAD/CAM software CimatronE to reconstruct a digital 3D model. The digital model was then used by the rapid prototyping machine to build a physical model of human femur using 3D printing. The geometric characteristics of the obtained physical model matched that of the original femur. The process of "physical object - 3D data - digital 3D model - physical model" presented in this paper provides a foundation of precise modeling for the digital manufacturing, virtual assembly, stress analysis, and simulated surgery of artificial bionic femurs.

  6. Rapid Two-Step Procedure for Large-Scale Purification of Pediocin-Like Bacteriocins and Other Cationic Antimicrobial Peptides from Complex Culture Medium

    PubMed Central

    Uteng, Marianne; Hauge, Håvard Hildeng; Brondz, Ilia; Nissen-Meyer, Jon; Fimland, Gunnar

    2002-01-01

    A rapid and simple two-step procedure suitable for both small- and large-scale purification of pediocin-like bacteriocins and other cationic peptides has been developed. In the first step, the bacterial culture was applied directly on a cation-exchange column (1-ml cation exchanger per 100-ml cell culture). Bacteria and anionic compounds passed through the column, and cationic bacteriocins were subsequently eluted with 1 M NaCl. In the second step, the bacteriocin fraction was applied on a low-pressure, reverse-phase column and the bacteriocins were detected as major optical density peaks upon elution with propanol. More than 80% of the activity that was initially in the culture supernatant was recovered in both purification steps, and the final bacteriocin preparation was more than 90% pure as judged by analytical reverse-phase chromatography and capillary electrophoresis. PMID:11823243

  7. Rapid Detection of Prunus Necrotic Ringspot Virus by Reverse Transcription-cross-priming Amplification Coupled with Nucleic Acid Test Strip Cassette.

    PubMed

    Huo, Ya-Yun; Li, Gui-Fen; Qiu, Yan-Hong; Li, Wei-Min; Zhang, Yong-Jiang

    2017-11-23

    Prunus necrotic ringspot virus (PNRSV) is one of the most devastating viruses to Prunus spp. In this study, we developed a diagnostic system RT-CPA-NATSC, wherein reverse transcription-cross-priming amplification (RT-CPA) is coupled with nucleic acid test strip cassette (NATSC), a vertical flow (VF) visualization, for PNRSV detection. The RT-CPA-NATSC assay targets the encoding gene of the PNRSV coat protein with a limit of detection of 72 copies per reaction and no cross-reaction with the known Prunus pathogenic viruses and viroids, demonstrating high sensitivity and specificity. The reaction is performed on 60 °C and can be completed less than 90 min with the prepared template RNA. Field sample test confirmed the reliability of RT-CPA-NATSC, indicating the potential application of this simple and rapid detection method in routine test of PNRSV.

  8. Telling a Compelling Tale, Scientifically Speaking

    NASA Astrophysics Data System (ADS)

    Unger, M.; Hauser, R.; Backlund, P.

    2009-12-01

    We will examine three strategies for conveying science effectively to a broad audience: making science relevant, accessible, and intriguing. Through an analysis of the dissemination strategy for three research-related stories at the National Center for Atmospheric Research, we explore methods for successful communication of societally relevant science. We will discuss both time-honored and new means of conveying authentic science in a rapidly changing media landscape. This visualization from the Hayden Planetarium's Journey to the Stars shows the generation of magnetic field in the solar convection zone and its connection to a sunspot at the visible surface of the Sun. Note that the sunspot (with a size slightly larger than Earth) is enlarged for better visibility and not in proper scale relative to the Sun. (© 2009, American Museum of Natural History) New research shows that the Arctic reversed a long-term cooling trend and began warming rapidly in recent decades. The graph shows estimates of Arctic temperatures over the last 2,000 years, based on proxy records, the long-term cooling trend, and the recent warming based on actual observations. A 2000-year transient climate simulation with NCAR's Community Climate System Model shows the same overall temperature decrease as does the proxy temperature reconstruction, which gives scientists confidence that their estimates are accurate.

  9. Rapid Diagnostic Method for Detection of Mumps Virus Genome by Loop-Mediated Isothermal Amplification

    PubMed Central

    Okafuji, Takao; Yoshida, Naoko; Fujino, Motoko; Motegi, Yoshie; Ihara, Toshiaki; Ota, Yoshinori; Notomi, Tsugunori; Nakayama, Tetsuo

    2005-01-01

    Most mumps patients are clinically diagnosed without any virological examinations, but some diagnosed cases of mumps may be caused by other pathogens or secondary vaccine failure (SVF). To clarify these issues, a sensitive, specific, and rapid diagnostic method is required. We obtained 60 salivary swabs from 34 patients with natural infection during the course of the illness, 10 samples from patients with vaccine-associated parotitis, and 5 samples from patients with SVF. Total RNA was extracted and subjected to reverse transcription-PCR (RT-PCR) and loop-mediated isothermal amplification (LAMP) for genome amplification. We detected mumps virus RNA corresponding to 0.1 PFU by LAMP within 60 min after RNA extraction, with the same sensitivity as RT-nested PCR. Mumps virus was isolated in 30 of 33 samples within day 2, and mumps virus genome was amplified by LAMP in 32 of them. The quantity of virus titer was calculated by monitoring the time to reach the threshold of turbidity. The viral load decreased after day 3 and was lower in patients serologically diagnosed as having SVF with milder illness. Accuracy of LAMP for the detection of mumps virus genome was confirmed; furthermore, it is of benefit for calculating the viral load, which reflects disease pathogenesis. PMID:15814976

  10. Rheological behavior of rat mesangial cells during swelling in vitro.

    PubMed

    Craelius, W; Huang, C J; Guber, H; Palant, C E

    1997-01-01

    The response of cells to mechanical forces depends on the rheological properties of their membranes and cytoplasm. To characterize those properties, mechanical and electrical responses to swelling were measured in rat mesangial cells (MC) using electrophysiologic and video microscopic techniques. Ion transport rates during hyposmotic exposures were measured with whole-cell recording electrodes. Results showed that cell swelling varied nonlinearly with positive internal pressure, consistent with a viscoelastic cytoplasm. The extrapolated area expansivity modulus for small deformations was estimated to be 450 dyne/cm. Cell swelling, caused either by positive pipet pressure or hyposmotic exposure (40-60 mOsm Kg-1), rapidly induced an outwardly rectifying membrane conductance with an outward magnitude 4-5 times the baseline conductance of 0.9 +/- 0.5 nS (p < .01). Swelling-induced (SI) current was weakly selective for K+ over Na+, partially reversed upon return to isotonicity, and was antagonized by 0.5 mM GdCl3 (p < 0.02; n = 6). Isolated cells treated with GdCl3 rapidly lysed after hypotonic exposure, in contrast to untreated cells that exhibited regulatory volume decrease (RVD). Our results indicate that volume regulation by MC depends upon a large swelling-induced K+ efflux, and suggest that swelling in MC is a viscoelastic process, with a viscosity dependent on the degree of swelling.

  11. Plasma Membrane ATPase Activity following Reversible and Irreversible Freezing Injury 1

    PubMed Central

    Iswari, S.; Palta, Jiwan P.

    1989-01-01

    Plasma membrane ATPase has been proposed as a site of functional alteration during early stages of freezing injury. To test this, plasma membrane was purified from Solanum leaflets by a single step partitioning of microsomes in a dextran-polyethylene glycol two phase system. Addition of lysolecithin in the ATPase assay produced up to 10-fold increase in ATPase activity. ATPase activity was specific for ATP with a Km around 0.4 millimolar. Presence of the ATPase enzyme was identified by immunoblotting with oat ATPase antibodies. Using the phase partitioning method, plasma membrane was isolated from Solanum commersonii leaflets which had four different degrees of freezing damage, namely, slight (reversible), partial (partially reversible), substantial and total (irreversible). With slight (reversible) damage the plasma membrane ATPase specific activity increased 1.5- to 2-fold and its Km was decreased by about 3-fold, whereas the specific activity of cytochrome c reductase and cytochrome c oxidase in the microsomes were not different from the control. However, with substantial (lethal, irreversible) damage, there was a loss of membrane protein, decrease in plasma membrane ATPase specific activity and decrease in Km, while cytochrome c oxidase and cytochrome c reductase were unaffected. These results support the hypothesis that plasma membrane ATPase is altered by slight freeze-thaw stress. Images Figure 1 Figure 2 PMID:16666856

  12. Antidiabetic effects of pterosin A, a small-molecular-weight natural product, on diabetic mouse models.

    PubMed

    Hsu, Feng-Lin; Huang, Chun-Fa; Chen, Ya-Wen; Yen, Yuan-Peng; Wu, Cheng-Tien; Uang, Biing-Jiun; Yang, Rong-Sen; Liu, Shing-Hwa

    2013-02-01

    The therapeutic effect of pterosin A, a small-molecular-weight natural product, on diabetes was investigated. Pterosin A, administered orally for 4 weeks, effectively improved hyperglycemia and glucose intolerance in streptozotocin, high-fat diet-fed, and db/db diabetic mice. There were no adverse effects in normal or diabetic mice treated with pterosin A for 4 weeks. Pterosin A significantly reversed the increased serum insulin and insulin resistance (IR) in dexamethasone-IR mice and in db/db mice. Pterosin A significantly reversed the reduced muscle GLUT-4 translocation and the increased liver phosphoenolpyruvate carboxyl kinase (PEPCK) expression in diabetic mice. Pterosin A also significantly reversed the decreased phosphorylations of AMP-activated protein kinase (AMPK) and Akt in muscles of diabetic mice. The decreased AMPK phosphorylation and increased p38 phosphorylation in livers of db/db mice were effectively reversed by pterosin A. Pterosin A enhanced glucose uptake and AMPK phosphorylation in cultured human muscle cells. In cultured liver cells, pterosin A inhibited inducer-enhanced PEPCK expression, triggered the phosphorylations of AMPK, acetyl CoA carboxylase, and glycogen synthase kinase-3, decreased glycogen synthase phosphorylation, and increased the intracellular glycogen level. These findings indicate that pterosin A may be a potential therapeutic option for diabetes.

  13. Reversal of dopamine system dysfunction in response to high-fat diet.

    PubMed

    Carlin, Jesselea; Hill-Smith, Tiffany E; Lucki, Irwin; Reyes, Teresa M

    2013-12-01

    To test whether high-fat diet (HFD) decreases dopaminergic tone in reward regions of the brain and evaluate whether these changes reverse after removal of the HFD. Male and female mice were fed a 60% HFD for 12 weeks. An additional group was evaluated 4 weeks after removal of the HFD. These groups were compared with control fed, age-matched controls. Sucrose and saccharin preference was measured along with mRNA expression of dopamine (DA)-related genes by Real Time-quantitative PCR (RT-qPCR). DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography. DNA methylation of the dopamine transporter (DAT) promoter was measured by methylated DNA immunoprecipitation and RT-qPCR. After chronic HFD, sucrose preference was reduced, and then normalized after removal of the HFD. Decreased expression of DA genes, decreased DA content and alterations in DAT promoter methylation, was observed. Importantly, response to HFD and the persistence of changes depended on sex and brain region. These data identify diminished DA tone after early-life chronic HFD with a complex pattern of reversal and persistence that varies by both sex and brain region. Central nervous system changes that did not reverse after HFD withdrawal may contribute to the difficulty in maintaining weight-loss after diet intervention. Copyright © 2013 The Obesity Society.

  14. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

    PubMed

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-05-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal neuronal health in the brain by reversing some effects of chronic high-fat diet as well as ageing. Vagovagal neurocircuits appear to remain open to modulation and adaptation throughout life, and understanding of these mechanisms may help in development of novel interventions to alleviate environmental (e.g. dietary) ailments and also alter neuronal ageing.

  15. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones

    PubMed Central

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-01-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12–14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal neuronal health in the brain by reversing some effects of chronic high-fat diet as well as ageing. Vagovagal neurocircuits appear to remain open to modulation and adaptation throughout life, and understanding of these mechanisms may help in development of novel interventions to alleviate environmental (e.g. dietary) ailments and also alter neuronal ageing. PMID:23459752

  16. Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells.

    PubMed

    Tang, Zheng-Hai; Cao, Wen-Xiang; Wang, Zhao-Yu; Lu, Jia-Hong; Liu, Bo; Chen, Xiuping; Lu, Jin-Jian

    2017-08-01

    Chelerythrine (CHE), a natural benzo[c]phenanthridine alkaloid, shows anti-cancer effect through a number of mechanisms. Herein, the effect and mechanism of the CHE-induced autophagy, a type II programmed cell death, in non-small cell lung cancer (NSCLC) cells were studied for the first time. CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a concentration-dependent manner in NSCLC A549 and NCI-H1299 cells. In addition, CHE triggered the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II). The CHE-induced expression of LC3-II was further increased in the combination treatment with chloroquine (CQ), an autophagy inhibitor, and large amounts of red-puncta were observed in the CHE-treated A549 cells with stable expression of mRFP-EGFP-LC3, indicating that CHE induces autophagy flux. Silence of beclin 1 reversed the CHE-induced expression of LC3-II. Inhibition of autophagy remarkably reversed the CHE-induced cell viability decrease and apoptosis in NCI-H1299 cells but not in A549 cells. Furthermore, CHE triggered reactive oxygen species (ROS) generation in both cell lines. A decreased level of ROS through pretreatment with N-acetyl-L-cysteine reversed the CHE-induced cell viability decrease, apoptosis, and autophagy. Taken together, CHE induced distinctive autophagy in A549 (accompanied autophagy) and NCI-H1299 (pro-death autophagy) cells and a decreased level of ROS reversed the effect of CHE in NSCLC cells in terms of cell viability, apoptosis, and autophagy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Inhibition of CYP4A by a novel flavonoid FLA-16 prolongs survival and normalizes tumor vasculature in glioma.

    PubMed

    Wang, Chenlong; Li, Ying; Chen, Honglei; Zhang, Jie; Zhang, Jing; Qin, Tian; Duan, Chenfan; Chen, Xuewei; Liu, Yanzhuo; Zhou, Xiaoyang; Yang, Jing

    2017-08-28

    Glioblastomas rapidly become refractory to anti-VEGF therapies. We previously showed that cytochrome P450 (CYP) 4A-derived 20-hydroxyeicosatetraenoic acid (20-HETE) promotes angiogenesis. Here, we tested whether a novel flavonoid (FLA-16) prolongs survival and normalizes tumor vasculature in glioma through CYP4A inhibition. FLA-16 improved survival, reduced tumor burden, and normalized vasculature, accompanied with the decreased secretion of 20-HETE, VEGF and TGF-β in tumor-associated macrophages (TAMs) and endothelial progenitor cells (EPCs) in C6 and U87 gliomas. FLA-16 attenuated vascular abnormalization induced by co-implantation of GL261 glioma cells with CYP4A10 high macrophages or EPCs. Mechanistically, the conditional medium from TAMs and EPCs treated with FLA-16 enhanced the migration of pericyte cells, and decreased the proliferation and migration of endothelial cells, which were reversed by CYP4A overexpression or exogenous addition of 20-HETE, VEGF and TGF-β. Furthermore, FLA-16 prevented crosstalk between TAMs and EPCs during angiogenesis. These results suggest that CYP4A inhibition by FLA-16 prolongs survival and normalizes vasculature in glioma through decreasing production of TAMs and EPCs-derived VEGF and TGF-β. This may represent a potential therapeutic strategy to overcome resistance to anti-VEGF treatment by effects on vessels and immune cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Ketamine differentially restores diverse alterations of neuroligins in brain regions in a rat model of neuropathic pain-induced depression.

    PubMed

    Pan, Wei; Zhang, Guang-Fen; Li, Hui-Hui; Ji, Mu-Huo; Zhou, Zhi-Qiang; Li, Kuan-Yu; Yang, Jian-Jun

    2018-07-04

    Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities. In the present study, we found that spared nerve injury induced significant mechanical allodynia and subsequent depressive-like symptoms, along with decreased NL1 and increased NL2 in the mPFC, decreased NL1 in the ACC, and decreased NL2 in the hippocampus. In addition, brain-derived neurotrophic factor (BDNF) was reduced in these brain regions. It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC. In conclusion, NLs showed diverse changes in different brain regions in the rat model of neuropathic pain-induced depression, which could be reversed differentially by the administration of ketamine.

  19. Regulation of the endothelin-1 transmembrane signaling pathway: the potential role of agonist-induced desensitization in the coronary artery of the rapid ventricular pacing-overdrive dog model of heart failure.

    PubMed

    Calderone, A; Rouleau, J L; de Champlain, J; Bélichard, P; Stewart, D J

    1993-08-01

    This study examined the potential role of ET-1 and the contribution of protein kinase C (PKC) in the desensitization of the ET-1 transmembrane signaling pathway in the left circumflex coronary artery (CCA) of a dog model of congestive heart failure (CHF). In the CCA of the rapid ventricular pacing-overdrive dog model of CHF, elevated plasma endothelin levels were associated with a decrease in the basal accumulation of inositol phosphates and ET-1 mediated activation of phosphatidylinositol (PI) turnover (P < 0.05). To assess whether elevated plasma ET-1 levels may have contributed to the diminished ET-1 responsiveness in the heart failure dogs, ET-1 generation of inositol phosphates was measured following a one hour pretreatment of normal coronary artery rings with 0.1 nM ET-1. As compared to non-treated rings, ET-1 pretreatment resulted in a 33% decrease of ET-1 (10 nM) production of inositol phosphates. To evaluate the role of PKC in this process, normal coronary rings pretreated for a period of one hour with the phorbol ester, phorbol 12-myristate 13-acetate (PMA, 1 microM), resulted in a similar attenuation (36%) of ET-1 production of inositol phosphates. In the presence of the protein kinase C inhibitor staurosporine, both the agonist and phorbol ester induced decreases in ET-1 mediated PI turnover were reversed. Staurosporine even potentiated (75%) ET-1 induced PI turnover despite ET-1 and PMA pretreatments. These results suggest that agonist-induced desensitization of ET-1 mediated PI turnover can occur and is at least one of the possible mechanisms contributing to the desensitization of the ET-1 transmembrane signaling pathway in the pacing-overdrive model of heart failure in the dog.

  20. Preparation of SMART wound dressings based on colloidal microgels and textile fibres

    NASA Astrophysics Data System (ADS)

    Cornelius, Victoria J.; Majcen, Natasa; Snowden, Martin J.; Mitchell, John C.; Voncina, Bojana

    2007-01-01

    Wound dressings and other types of wound healing technologies are experiencing fast-paced development and rapid growth. As the population ages, demand will continue to rise for advanced dressings used to treat chronic wounds, such as pressure ulcers, venous stasis ulcers, and diabetic ulcers. Moist wound dressings, which facilitate natural wound healing in a cost-effective manner, will be increasingly important. In commercially available hydrogel / gauze wound dressings the gel swells to adsorb wound excreta and provide an efficient non adhesive particle barrier. An alternative to hydrogels are microgels. Essentially discrete colloidal gel particles, as a result of their very high surface area to volume ratio compared to bulk gels, they have a much faster response to external stimuli such as temperature or pH. In response to either an increase or decrease in solvent quality these porous networks shrink and swell reversibly. When swollen the interstitial regions within the polymer matrix are available for further chemistry; such as the incorporation of small molecules. The reversible shrinking and swelling as a function of external stimuli provides a novel drug release system. As the environmental conditions of a wound change over its lifetime, tending to increase in pH if there is an infection combining these discrete polymeric particles with a substrate such as cotton, results in a smart wound dressing.

  1. Oxaloacetate- and acetoacetate-induced calcium efflux from mitochondria occurs by reversal of the uptake pathway.

    PubMed Central

    Bardsley, M E; Brand, M D

    1982-01-01

    1. Addition of oxaloacetate or acetoacetate to isolated rat liver mitochondria results in an efflux of Ca2+. Concomitant with this efflux is an immediate oxidation of endogenous nicotinamide nucleotides, a fall in the mitochondrial membrane potential and an increase in the rate of respiration. The primary effect in this sequence may be either (a) physiologically important stimulation of a Ca2+-efflux carrier, followed by Ca2+ re-uptake, a fall in membrane potential and increased respiration, or (b) physiologically unimportant damage to mitochondrial integrity, followed by a fall in membrane potential, increased respiration and Ca2+ efflux. 2. Ruthenium Red and EGTA will restore the increased respiratory rate to one approximating to the control rate of respiration. However, addition of lanthanide, at a concentration which inhibits the uptake but not the normal efflux of Ca2+, inhibits the rate of Ca2+ efflux induced by oxaloacetate or acetoacetate. Therefore the observed efflux is occurring by a reversal of the uptake pathway (uniporter) and thus follows the fall in membrane potential. 3. From these results we conclude that the decrease in membrane potential and increase in the rate of respiration seen during oxaloacetate- or acetoacetate-induced Ca2+ efflux cannot be accounted for by rapid Ca2+ cycling, but are due to damage to mitochondrial integrity. PMID:7082307

  2. Reverse current in solar flares

    NASA Technical Reports Server (NTRS)

    Knight, J. W.; Sturrock, P. A.

    1977-01-01

    We examine the proposal that impulsive X-ray bursts are produced by high-energy electrons streaming from the corona to the chromosphere. It is known that the currents associated with these streams are so high that either the streams do not exist or their current is neutralized by a reverse current. Analysis of a simple model in which the reverse current is stable indicates that the primary electron stream leads to the development of an electric field in the ambient corona which (a) decelerates the primary beam and (b) produces a neutralizing reverse current. It appears that, in some circumstances, this electric field could prevent the primary beam from reaching the chromosphere. In any case, the electric field acts as an energy exchange mechanism, extracting kinetic energy from the primary beam and using it to heat the ambient plasma. This heating is typically so rapid that it must be expected to have important dynamical consequences.

  3. Energy density and energy flux in the focus of an optical vortex: reverse flux of light energy.

    PubMed

    Kotlyar, Victor V; Kovalev, Alexey A; Nalimov, Anton G

    2018-06-15

    Using the Richards-Wolf formulas for an arbitrary circularly polarized optical vortex with an integer topological charge m, we obtain explicit expressions for all components of the electric and magnetic field strength vectors near the focus, as well as expressions for the intensity (energy density) and for the energy flux (components of the Poynting vector) in the focal plane of an aplanatic optical system. For m=2, from the obtained expressions it follows that the energy flux near the optical axis propagates in the reversed direction, rotating along a spiral around the optical axis. On the optical axis itself, the reversed flux is maximal and decays rapidly with the distance from the axis. For m=3, in contrast, the reversed energy flux in the focal plane is minimal (zero) on the optical axis and increases (until the first ring of the light intensity) as a squared distance from the axis.

  4. Tubulin Dimer Reversible Dissociation

    PubMed Central

    Schuck, Peter; Sackett, Dan L.

    2016-01-01

    Tubulins are evolutionarily conserved proteins that reversibly polymerize and direct intracellular traffic. Of the tubulin family only αβ-tubulin forms stable dimers. We investigated the monomer-dimer equilibrium of rat brain αβ-tubulin using analytical ultracentrifugation and fluorescence anisotropy, observing tubulin in virtually fully monomeric and dimeric states. Monomeric tubulin was stable for a few hours and exchanged into preformed dimers, demonstrating reversibility of dimer dissociation. Global analysis combining sedimentation velocity and fluorescence anisotropy yielded Kd = 84 (54–123) nm. Dimer dissociation kinetics were measured by analyzing the shape of the sedimentation boundary and by the relaxation of fluorescence anisotropy following rapid dilution of labeled tubulin, yielding koff in the range 10−3–10−2 s−1. Thus, tubulin dimers reversibly dissociate with moderately fast kinetics. Monomer-monomer association is much less sensitive than dimer-dimer association to solution changes (GTP/GDP, urea, and trimethylamine oxide). PMID:26934918

  5. Leukotriene B4 catabolism: quantitation of leukotriene B4 and its omega-oxidation products by reversed-phase high-performance liquid chromatography.

    PubMed

    Shak, S

    1987-01-01

    LTB4 and its omega-oxidation products may be rapidly, sensitively, and specifically quantitated by the methods of solid-phase extraction and reversed-phase high-performance liquid chromatography (HPLC), which are described in this chapter. Although other techniques, such as radioimmunoassay or gas chromatography-mass spectrometry, may be utilized for quantitative analysis of the lipoxygenase products of arachidonic acid, only the technique of reversed-phase HPLC can quantitate as many as 10 metabolites in a single analysis, without prior derivatization. In this chapter, we also reviewed the chromatographic theory which we utilized in order to optimize reversed-phase HPLC analysis of LTB4 and its omega-oxidation products. With this information and a gradient HPLC system, it is possible for any investigator to develop a powerful assay for the potent inflammatory mediator, LTB4, or for any other lipoxygenase product of arachidonic acid.

  6. Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1

    PubMed Central

    Wu, Yuanming; Wang, Wengang; Díez-Sampedro, Ana; Richerson, George B.

    2007-01-01

    SUMMARY GABA transporters play an important but poorly understood role in neuronal inhibition. They can reverse, but this is widely thought to occur only under pathological conditions. Here we use a heterologous expression system to show that the reversal potential of GAT-1 under physiologically relevant conditions is near the normal resting potential of neurons, and that reversal can occur rapidly enough to release GABA during simulated action potentials. We then use paired recordings from cultured hippocampal neurons, and show that GABAergic transmission is not prevented by four methods widely used to block vesicular release. This nonvesicular neurotransmission was potently blocked by GAT-1 antagonists, and was enhanced as predicted by agents that increase cytosolic [GABA] or [Na+]. The results indicate that GAT-1 regulates tonic inhibition by clamping ambient [GABA] at a level high enough to activate high affinity GABAA receptors, and that transporter-mediated GABA release can contribute to phasic inhibition. PMID:18054861

  7. Sugammadex for reversal of neuromuscular blockade: a retrospective analysis of clinical outcomes and cost-effectiveness in a single center.

    PubMed

    Carron, Michele; Baratto, Fabio; Zarantonello, Francesco; Ori, Carlo

    2016-01-01

    The aim of the study is to evaluate the clinical and economic impact of introducing a rocuronium-neostigmine-sugammadex strategy into a cisatracurium-neostigmine regimen for neuromuscular block (NMB) management. We conducted a retrospective analysis of clinical outcomes and cost-effectiveness in five operating rooms at University Hospital of Padova. A clinical outcome evaluation after sugammadex administration as first-choice reversal drug in selected patients (rocuronium-sugammadex) and as rescue therapy after neostigmine reversal (rocuronium-neostigmine-sugammadex) compared to control was performed. A cost-analysis of NMB management accompanying the introduction of a rocuronium-neostigmine-sugammadex strategy into a cisatracurium-neostigmine regimen was carried out. To such purpose, two periods were compared: 2011-2012, without sugammadex available; 2013-2014, with sugammadex available. A subsequent analysis was performed to evaluate if sugammadex replacing neostigmine as first choice reversal drug is cost-effective. The introduction of a rocuronium-neostigmine-sugammadex strategy into a cisatracurium-neostigmine regimen reduced the average cost of NMB management by 36%, from €20.8/case to €13.3/case. Patients receiving sugammadex as a first-choice reversal drug (3%) exhibited significantly better train-of-four ratios at extubation (P<0.001) and were discharged to the surgical ward (P<0.001) more rapidly than controls. The cost-saving of sugammadex as first-choice reversal drug has been estimated to be €2.9/case. Patients receiving sugammadex as rescue therapy after neostigmine reversal (3.2%) showed no difference in time to discharge to the surgical ward (P=0.44) compared to controls. No unplanned intensive care unit (ICU) admissions with rocuronium-neostigmine-sugammadex strategy were observed. The potential economic benefit in avoiding postoperative residual curarization (PORC)-related ICU admission in the 2013-2014 period was estimated at an average value of €13,548 (€9,316-€23,845). Sugammadex eliminated PORC and associated morbidities. In our center, sugammadex reduced the costs of NMB management and promoted rapid turnover of patients in operating rooms, with total cost-effectiveness that counteracts the disadvantages of its high cost.

  8. Onset of a Propagating Self-Sustained Spin Reversal Front in a Magnetic System

    NASA Astrophysics Data System (ADS)

    Kent, Andrew D.

    2014-03-01

    The energy released in a magnetic material by reversing spins as they relax toward equilibrium can lead to a dynamical magnetic instability in which all the spins in a sample rapidly reverse in a run-away process known as magnetic deflagration. A well-defined front separating reversed and un-reversed spins develops that propagates at a constant speed. This process is akin to a chemical reaction in which a flammable substance ignites and the resulting exothermic reaction leads via thermal conduction to increases in the temperature of an adjacent unburned substance that ignites it. In a magnetic system the reaction is the reversal of spins that releases Zeeman energy and the magnetic anisotropy barrier is the reaction's activation energy. An interesting aspect of magnetic systems is that these key energies-the activation energy and the energy released-can be independently controlled by applied magnetic fields enabling systematic studies of these magnetic instabilities. We have studied the instability that leads to the ignition of magnetic deflagration in a thermally driven Mn12-Ac molecular magnet single crystal. Each Mn12-ac molecule is a uniaxial nanomagnet with spin 10 and energy barrier of 60 K. We use a longitudinal field (a field parallel to the easy axis) to set the energy released and a transverse field to control the activation energy. A heat pulse is applied to one end of the crystal to initiate the process. We study the crossover between slow magnetic relaxation and rapid, self-sustained magnetic deflagration as a function of these fields at low temperature (0.5 K). An array of Hall sensors adjacent to a single crystal is used to detect and measure the speed of the spin-reversal front. I will describe a simple model we developed based on a reaction-diffusion process that describes our experimental findings. I will also discuss prospects for observing spin-fronts driven by magnetic dipole interactions between molecules that can be sonic, i.e. travel near the speed of sound (~ 1000 m/s). In collaboration with P. Subedi, S. Velez, F. Macià, S. Li, M. P. Sarachik, J. Tejada, S. Mukherjee and G. Christou. Supported by NSF-DMR-1006575.

  9. Single-Reaction Multiplex Reverse Transcription PCR for Detection of Zika, Chikungunya, and Dengue Viruses

    PubMed Central

    Waggoner, Jesse J.; Gresh, Lionel; Mohamed-Hadley, Alisha; Ballesteros, Gabriela; Davila, Maria Jose Vargas; Tellez, Yolanda; Sahoo, Malaya K.; Balmaseda, Angel; Harris, Eva

    2016-01-01

    Clinical manifestations of Zika virus, chikungunya virus, and dengue virus infections can be similar. To improve virus detection, streamline molecular workflow, and decrease test costs, we developed and evaluated a multiplex real-time reverse transcription PCR for these viruses. PMID:27184629

  10. Undoing Suggestive Influence on Memory: The Reversibility of the Eyewitness Misinformation Effect

    ERIC Educational Resources Information Center

    Oeberst, Aileen; Blank, Hartmut

    2012-01-01

    Presenting inconsistent postevent information about a witnessed incident typically decreases the accuracy of memory reports concerning that event (the "misinformation effect"). Surprisingly, the "reversibility" of the effect (after an initial occurrence) has remained largely unexplored. Based on a "memory conversion" theoretical framework and…

  11. Korsakoff syndrome from retrochiasmatic suprasellar lesions: rapid reversal after relief of cerebral compression in 4 cases.

    PubMed

    Savastano, Luis E; Hollon, Todd C; Barkan, Ariel L; Sullivan, Stephen E

    2018-06-01

    Korsakoff syndrome is a chronic memory disorder caused by a severe deficiency of thiamine that is most commonly observed in alcoholics. However, some have proposed that focal structural lesions disrupting memory circuits-in particular, the mammillary bodies, the mammillothalamic tract, and the anterior thalamus-can give rise to this amnestic syndrome. Here, the authors present 4 patients with reversible Korsakoff syndromes caused by suprasellar retrochiasmatic lesions compressing the mammillary bodies and adjacent caudal hypothalamic structures. Three of the patients were found to have large pituitary macroadenomas in their workup for memory deficiency and cognitive decline with minimal visual symptoms. These tumors extended superiorly into the suprasellar region in a retrochiasmatic position and caused significant mass effect in the bilateral mammillary bodies in the base of the brain. These 3 patients had complete and rapid resolution of amnestic problems shortly after initiation of treatment, consisting of resection in 1 case of nonfunctioning pituitary adenoma or cabergoline therapy in 2 cases of prolactinoma. The fourth patient presented with bizarre and hostile behavior along with significant memory deficits and was found to have a large cystic craniopharyngioma filling the third ventricle and compressing the midline diencephalic structures. This patient underwent cyst fenestration and tumor debulking, with a rapid improvement in his mental status. The rapid and dramatic memory improvement observed in all of these cases is probably due to a reduction in the pressure imposed by the lesions on structures contiguous to the third ventricle, rather than a direct destructive effect of the tumor, and highlights the essential role of the caudal diencephalic structures-mainly the mammillary bodies-in memory function. In summary, large pituitary lesions with suprasellar retrochiasmatic extension and third ventricular craniopharyngiomas can cause severe Korsakoff-like amnestic syndromes, probably because of bilateral pressure on or damage to mammillary bodies, anterior thalamic nuclei, or their major connections. Neuropsychiatric symptoms may rapidly and completely reverse shortly after initiation of therapy via surgical decompression of tumors or pharmacological treatment of prolactinomas. Early identification of these lesions with timely treatment can lead to a favorable prognosis for this severe neuropsychiatric disorder.

  12. An in vitro recombination-based reverse genetic system for rapid mutagenesis of structural genes of the Japanese encephalitis virus.

    PubMed

    Du, Ruikun; Wang, Manli; Hu, Zhihong; Wang, Hualin; Deng, Fei

    2015-10-01

    Japanese encephalitis virus (JEV) is one of the most common pathogens of severe viral encephalitis, which is a severe threat to human health. Despite instability of the JEV genome in bacteria, many strategies have been developed to establish molecular clone systems of JEV, providing convenient tools for studying the virus life cycle and virus-host interactions. In this study, we adapted an In-Fusion enzyme-based in vitro recombination method to construct a reverse genetic system of JEV, thereby providing a rapid approach to introduce mutations into the structural genes. A truncated genome without the structural genes was constructed as the backbone, and the complementary segment containing the structural genes was recombined in vitro, which was then transfected directly into virus-permissive cells. The progeny of the infectious virus was successfully detected in the supernatant of the transfected cells, and showed an identical phenotype to its parental virus. To provide a proof-of-principle, the 12 conserved cysteine residues in the envelope (E) protein of JEV were respectively mutated using this approach, and all mutations resulted in a complete failure to generate infectious virus. However, a leucine-tophenylanine mutation at amino acid 107 of the E protein did not interfere with the production of the infectious virus. These results suggested that all 12 cysteines in the E protein are essential for the JEV life cycle. In summary, a novel reverse genetic system of JEV was established for rapidly introducing mutations into structural genes, which will serve as a useful tool for functional studies.

  13. Threshold units: A correct metric for reaction time?

    PubMed Central

    Zele, Andrew J.; Cao, Dingcai; Pokorny, Joel

    2007-01-01

    Purpose To compare reaction time (RT) to rod incremental and decremental stimuli expressed in physical contrast units or psychophysical threshold units. Methods Rod contrast detection thresholds and suprathreshold RTs were measured for Rapid-On and Rapid-Off ramp stimuli. Results Threshold sensitivity to Rapid-Off stimuli was higher than to Rapid-On stimuli. Suprathreshold RTs specified in Weber contrast for Rapid-Off stimuli were shorter than for Rapid-On stimuli. Reaction time data expressed in multiples of threshold reversed the outcomes: Reaction times for Rapid-On stimuli were shorter than those for Rapid-Off stimuli. The use of alternative contrast metrics also failed to equate RTs. Conclusions A case is made that the interpretation of RT data may be confounded when expressed in threshold units. Stimulus energy or contrast is the only metric common to the response characteristics of the cells underlying speeded responses. The use of threshold metrics for RT can confuse the interpretation of an underlying physiological process. PMID:17240416

  14. Rapid Vegetational Change in Coastal North America: The Response to Climate Since the LGM

    NASA Technical Reports Server (NTRS)

    Peteet, Dorothy; Kneller, Margaret

    1999-01-01

    The late-glacial interval provided rapid shifts in climate which are mirrored by dramatic vegetational changes in North America. Through a transect of lake and mire sites from Connecticut to Virginia on the east coast and Kodiak Island on the western coast, we trace the warming following the LGM with the response of forests and tundra. A brief cold reversal in Virginia is seen from 12,260 to 12,200. The subsequent longer and extreme Younger Dryas event is marked in the southern New England - New Jersey region by dramatic boreal and deciduous forest changes. In the southeastern US, forests also change rapidly, with hemlock forest expansion suggesting increased moisture. In Kodiak Island, the warm, moist tundra of the Bolling/Allerod is replaced by colder, windswept Empetrum-dominated tundra during the Younger Dryas. The Pleistocene/Holocene shift in vegetation is remarkably pronounced in eastern North America as well as the Alaskan coastline. Response time of vegetation to climate change appears to be on the order of decades throughout these coastal locations, probably because of the proximity of sites to important ecotonal boundaries, and the magnitude of the events. Even in Virginia's Holocene record, a cold reversal inferred from increases in spruce and fir is noted at 7500 C14 yr BP. This response of the forests to a short-lived cooling shows the sensitivity of the biosphere to a rapid climate shifts.

  15. Aminophylline and caffeine for reversal of adverse symptoms associated with regadenoson SPECT MPI.

    PubMed

    Doran, Jesse A; Sajjad, Waseem; Schneider, Marabel D; Gupta, Rohit; Mackin, Maria L; Schwartz, Ronald G

    2017-06-01

    Aminophylline shortages led us to compare intravenous (IV) aminophylline with IV and oral (PO) caffeine during routine pharmacologic stress testing with SPECT MPI. We measured presence, duration, and reversal of adverse symptoms and cardiac events following regadenoson administration in consecutive patients randomized to IV aminophylline (100 mg administered over 30-60 seconds), IV caffeine citrate (60 mg infused over 3-5 minutes), or PO caffeine as coffee or diet cola. Of 241 patients, 152 (63%) received regadenoson reversal intervention. Complete (CR), predominant (PRE), or partial (PR) reversal was observed in 99%. CR by IV aminophylline (87%), IV caffeine (87%), and PO caffeine (78%) were similar (P = NS). Time to CR (162 ± 12.6 seconds, mean ± SD) was similar in treatment arms. PO caffeine was inferior to IV aminophylline for CR + PRE. IV aminophylline and IV caffeine provide rapid, safe reversal of regadenoson-induced adverse effects during SPECT MPI. Oral caffeine appeared similarly effective for CR but not for the combined CR + PRE. Our results suggest PO caffeine may be an effective initial strategy for reversal of regadenoson, but IV aminophylline or IV caffeine should be available to optimize symptom reversal as needed.

  16. Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia.

    PubMed

    Piguet, Françoise; de Montigny, Charline; Vaucamps, Nadège; Reutenauer, Laurence; Eisenmann, Aurélie; Puccio, Hélène

    2018-05-28

    Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Here, we report a new conditional mouse model with complete frataxin deletion in parvalbumin-positive cells that recapitulate the sensory ataxia and neuropathy associated to FA, albeit with a more rapid and severe course. Interestingly, although fully dysfunctional, proprioceptive neurons can survive for many weeks without frataxin. Furthermore, we demonstrate that post-symptomatic delivery of frataxin-expressing AAV allows for rapid and complete rescue of the sensory neuropathy associated with frataxin deficiency, thus establishing the pre-clinical proof of concept for the potential of gene therapy in treating FA neuropathy. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  17. Cross-subtype detection of HIV-1 using reverse transcription and recombinase polymerase amplification.

    PubMed

    Lillis, Lorraine; Lehman, Dara A; Siverson, Joshua B; Weis, Julie; Cantera, Jason; Parker, Mathew; Piepenburg, Olaf; Overbaugh, Julie; Boyle, David S

    2016-04-01

    A low complexity diagnostic test that rapidly and reliably detects HIV infection in infants at the point of care could facilitate early treatment, improving outcomes. However, many infant HIV diagnostics can only be performed in laboratory settings. Recombinase polymerase amplification (RPA) is an isothermal amplification technology that can rapidly amplify proviral DNA from multiple subtypes of HIV-1 in under twenty minutes without complex equipment. In this study we added reverse transcription (RT) to RPA to allow detection of both HIV-1 RNA and DNA. We show that this RT-RPA HIV-1 assay has a limit of detection of 10-30 copies of an exact sequence matched DNA or RNA, respectively. In addition, at 100 copies of RNA or DNA, the assay detected 171 of 175 (97.7%) sequence variants that represent all the major subtypes and recombinant forms of HIV-1 Groups M and O. This data suggests that the application of RT-RPA for the combined detection of HIV-1 viral RNA and proviral DNA may prove a highly sensitive tool for rapid and accurate diagnosis of infant HIV. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Intra-hippocampal D-cycloserine rescues decreased social memory, spatial learning reversal, and synaptophysin levels in aged rats.

    PubMed

    Portero-Tresserra, Marta; Martí-Nicolovius, Margarita; Tarrés-Gatius, Mireia; Candalija, Ana; Guillazo-Blanch, Gemma; Vale-Martínez, Anna

    2018-05-01

    Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging. The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats. We investigated the effects of pre-training infusions of DCS (10 μg/hemisphere) in the ventral hippocampus on two hippocampal-dependent learning tasks, the social transmission of food preference (STFP), and the Morris water maze (MWM). The results revealed that infusions of DCS administered before the acquisition sessions rescued deficits in the STFP retention and MWM reversal learning in old rats. DCS also significantly increased the hippocampal levels of synaptophysin in old rats, which correlated with STFP and MWM performance in all tests. Moreover, although the levels of the GluN1 subunit correlated with the MWM acquisition and reversal, DCS did not enhance the expression of such synaptic protein. The present behavioral results support the role of DCS as a cognitive enhancer and suggest that enhancing the function of NMDARs and synaptic plasticity in the hippocampus may be related to improvement in social memory and spatial learning reversal in aged animals.

  19. Product-to-parent reversion increases ecosystem exposure to and environmental persistence of 17α-trenbolone

    NASA Astrophysics Data System (ADS)

    Ward, Adam; Cwiertny, David; Kolodziej, Edward; Brehm, Colleen

    2016-04-01

    The product-to-parent reversion of metabolites of trenbolone acetate (TBA), a steroidal growth promoter used widely in beef cattle production, was recently observed to occur in environmental waters. The rapid forward reaction is by direct photolysis (i.e., photohydration), with the much slower reversion reaction occurring via dehydration in the dark. The objective of this study is to quantify the potential effect of this newly discovered reversible process on TBA metabolite concentrations and total bioactivity exposure in fluvial systems. Here, we demonstrate increased persistence of TBA metabolites in the stream and hyporheic zone due to the reversion process, increasing chronic and acute exposure to these endocrine-active compounds along a stream. The perpetually dark hyporheic zone is a key location for reversion in the system, ultimately providing a source of the parent compound to the stream and increasing mean in-stream concentration of 17α-trenbolone (17α-TBOH) by 40% of the input concentration under representative fluvial conditions. We demonstrate generalized cases for prediction of exposure for species with product-to-parent reversion in stream-hyporheic systems. Recognizing this risk, regulatory frameworks for compounds undergoing product-to-parent reversion will require new approaches for assessing total exposure to bioactive compounds. We discuss the role of regulating "joint" or "mixture" bioactivity as an emerging paradigm for more meaningful management of micropollutants.

  20. Investigation of structural and magnetic properties of rapidly-solidified iron-silicon alloys at ambient and elevated temperatures

    DOE PAGES

    Jayaraman, T. V.; Meka, V. M.; Jiang, X.; ...

    2018-01-09

    Here we investigated the ambient temperature structural properties (thickness, width, microstructure, and lattice parameter), and the ambient and high temperature (up to 900 K) direct current (DC) magnetic properties—saturation magnetization (M S) and intrinsic coercivity (H CI)—of rapidly-solidified (melt-spun) Fe-x wt.% Si (x = 3, 5, & 8) alloys. The wheel surface speeds selected for the study were 30 m/s and 40 m/s. The ribbons produced at the lower wheel surface speed (30 m/s) were continuous having relatively uniform edges compared to the ribbons produced at the higher wheel surface speed. The thickness and the width of the melt-spun ribbonsmore » ranged between ~15 and 60 μm and 500–800 μm, respectively. The x-ray diffraction spectra of the melt-spun ribbons indicated the presence of disordered α-phase, irrespective of the composition, and the wheel surface speed. The lattice parameter decreased gradually as a function of increasing silicon content from ~0.2862 nm (Fe-3 wt.% Si) to ~0.2847 nm (Fe-8 wt.% Si). The wheel surface speed showed an insignificant effect on M S while increased silicon content resulted in a decreasing trend in M S. Elevated temperature evaluation of the magnetization (M-T curves at ~7.96 kA/m) in the case of Fe-3 & 5 wt.% Si alloy ribbons was distinctly different from that of the Fe-8 wt.% Si alloy ribbons. The curves of the as-prepared Fe-3 wt.% Si and Fe-5 wt.% Si alloy ribbons were irreversible while that of Fe-8 wt.% Si was reversible. The M S for any of the combinations of wheel surface speed and composition decreased monotonically with the increase in temperature (from 300 to 900 K). While H CI increased with the increase in temperature for all the wheel surface speed and composition combination, its nature of increase is distinct for Fe-8 wt.% Si alloy ribbons compared to Fe-3 & 5 wt.% Si alloys ribbons. Finally, it appears that rapidly-solidified Fe-3 wt.% Si and Fe-5 wt.% Si alloys ribbons are primarily comprised of the α phase (disordered phase) while the Fe-8 wt.% Si alloy ribbons are comprised primarily of disordered phase along with minor constituents of an ordered phase.« less

  1. Investigation of structural and magnetic properties of rapidly-solidified iron-silicon alloys at ambient and elevated temperatures

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

    Jayaraman, T. V.; Meka, V. M.; Jiang, X.

    Here we investigated the ambient temperature structural properties (thickness, width, microstructure, and lattice parameter), and the ambient and high temperature (up to 900 K) direct current (DC) magnetic properties—saturation magnetization (M S) and intrinsic coercivity (H CI)—of rapidly-solidified (melt-spun) Fe-x wt.% Si (x = 3, 5, & 8) alloys. The wheel surface speeds selected for the study were 30 m/s and 40 m/s. The ribbons produced at the lower wheel surface speed (30 m/s) were continuous having relatively uniform edges compared to the ribbons produced at the higher wheel surface speed. The thickness and the width of the melt-spun ribbonsmore » ranged between ~15 and 60 μm and 500–800 μm, respectively. The x-ray diffraction spectra of the melt-spun ribbons indicated the presence of disordered α-phase, irrespective of the composition, and the wheel surface speed. The lattice parameter decreased gradually as a function of increasing silicon content from ~0.2862 nm (Fe-3 wt.% Si) to ~0.2847 nm (Fe-8 wt.% Si). The wheel surface speed showed an insignificant effect on M S while increased silicon content resulted in a decreasing trend in M S. Elevated temperature evaluation of the magnetization (M-T curves at ~7.96 kA/m) in the case of Fe-3 & 5 wt.% Si alloy ribbons was distinctly different from that of the Fe-8 wt.% Si alloy ribbons. The curves of the as-prepared Fe-3 wt.% Si and Fe-5 wt.% Si alloy ribbons were irreversible while that of Fe-8 wt.% Si was reversible. The M S for any of the combinations of wheel surface speed and composition decreased monotonically with the increase in temperature (from 300 to 900 K). While H CI increased with the increase in temperature for all the wheel surface speed and composition combination, its nature of increase is distinct for Fe-8 wt.% Si alloy ribbons compared to Fe-3 & 5 wt.% Si alloys ribbons. Finally, it appears that rapidly-solidified Fe-3 wt.% Si and Fe-5 wt.% Si alloys ribbons are primarily comprised of the α phase (disordered phase) while the Fe-8 wt.% Si alloy ribbons are comprised primarily of disordered phase along with minor constituents of an ordered phase.« less

  2. Defining space around conducting polymers: reversible protonic doping of a canopied polypyrrole.

    PubMed

    Lee, Dongwhan; Swager, Timothy M

    2003-06-11

    A canopy-shaped pyrrole derivative 2 was prepared, in which a sterically demanding pendant group is juxtaposed to the pyrrole fragment to minimize interstrand pi-pi stacking interactions in the resulting polymer. Anodic polymerization of 2 afforded highly conductive poly(2), the electronic structure of which was probed by various spectroelectrochemical techniques. A limited charge delocalization within poly(2) translates into a well-defined conductivity profile, properties important for resistivity-based sensing. Notably, the bulk conductivity was precisely modulated by a rapid and reversible deprotonation and reprotonation of the polymer backbone.

  3. Conditioned suppression of sexual behavior in stallions and reversal with diazepam.

    PubMed

    McDonnell, S M; Kenney, R M; Meckley, P E; Garcia, M C

    1985-06-01

    Sexual behavior dysfunction unaccompanied by detectable physical or endocrine abnormality is an important cause of reproductive failure among domestic stallions. Several authors have suggested that such dysfunction may be psychogenic, related to negative experience associated with intense handling and training. An experimental model of experience-related dysfunction was developed by exposing pony stallions to erection-contingent aversive conditioning. This resulted in rapid, specific suppression of sexual arousal and response similar to spontaneously occurring dysfunction. Subsequently, treatment with a CNS-active benzodiazepine derivative (diazepam) reversed these effects.

  4. Investigation of the Sensitivity, Selectivity, and Reversibility of the Chemically-Sensitive Field-Effect Transistor (CHEMFET) to Detect Nitrogen Dioxide, Dimethyl Methylphosphonate, and Boron Trifluoride

    DTIC Science & Technology

    1993-09-01

    SENSITIVE FIELD- EFFECT TRANSISTOR (CHEMFET) TO DETECT NITROGEN DIOXIDE, DIMETHYL METHYLPHOSPHONATE, AND BORON TRIFLUORIDE CHAPTER 1 1 Introduction Our rapidly...AND REVERSIBILITY OF THE CHEMICALLY-SENSITIVE FIELD- EFFECT TRANSISTOR (CHEMFET) TO DETECT NITROGEN 3 E I1• DIOXIDE, DIMETHYL METHYLPHOSPHONATE, ELECTE...AND BORON TRIFLUORIDE Neal Terence Hauschild Second Lieutenant, USAF AFIT/GE/ENG/9 3S-10 93-23815I II11l11l11 l gll I 1i 1111 11 I DEPARTMENT OF THE

  5. Inhibition of glycogen synthase kinase 3[beta] activity with lithium in vitro attenuates sepsis-induced changes in muscle protein turnover.

    PubMed

    Bertsch, Stephen; Lang, Charles H; Vary, Thomas C

    2011-03-01

    Loss of lean body mass is a characteristic feature of the septic response, and the mechanisms responsible for this decrease and means of prevention have not been fully elucidated. The present study tested the hypothesis that in vitro treatment of skeletal muscle with lithium chloride (LiCl), a glycogen synthase kinase (GSK) 3 inhibitor, would reverse both the sepsis-induced increase in muscle protein degradation and inhibition of protein synthesis. Sepsis decreased GSK-3[beta] phosphorylation and increased GSK-3[beta] activity, under basal conditions. Sepsis increased muscle protein degradation, with a concomitant increase in atrogin 1 and MuRF1 mRNA and 26S proteosome activity. Incubation of septic muscle with LiCl completely reversed the increased GSK-3[beta] activity and decreased proteolysis to basal nonseptic values, but only partially reduced proteosome activity and did not diminish atrogene expression. Lithium chloride also did not ameliorate the sepsis-induced increase in LC3-II, a marker for activated autophagy. In contrast, LiCl increased protein synthesis only in nonseptic control muscle. The inability of septic muscle to respond to LiCl was independent of its ability to reverse the sepsis-induced increase in eukaryotic initiation factor (eIF) 2B[varepsilon] phosphorylation, decreased eIF2B activity, or the reduced phosphorylation of FOXO3, but instead was more closely associated with the continued suppression of mTOR (mammalian target of rapamycin) kinase activity (e.g., reduced phosphorylation of 4E-BP1 and S6). These data suggest that in vitro lithium treatment, which inhibited GSK-3[beta] activity, (a) effectively reversed the sepsis-induced increase in proteolysis, but only in part by a reduction in the ubiquitin-proteosome pathway and not by a reduction in autophagy; and (b) was ineffective at reversing the sepsis-induced decrease in muscle protein synthesis. This lithium-resistant state seems mediated at the level of mTOR and not eIF2/eIF2B. Hence, use of GSK-3[beta] inhibitors in the treatment of sepsis may not be expected to fully correct the imbalance in muscle protein turnover.

  6. Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, induces sleep via the benzodiazepine site of GABA(A) receptor in mice.

    PubMed

    Chen, Chang-Rui; Zhou, Xu-Zhao; Luo, Yan-Jia; Huang, Zhi-Li; Urade, Yoshihiro; Qu, Wei-Min

    2012-11-01

    Magnolol (6,6',7,12-tetramethoxy-2,2'-dimethyl-1-beta-berbaman, C(18)H(18)O(2)), an active ingredient of the bark of Magnolia officinalis, has been reported to exert potent anti-epileptic effects via the GABA(A) receptor. The receptor also mediates sleep in humans and animals. The aim of this study was to determine whether magnolol could modulate sleep behaviors by recording EEG and electromyogram in mice. The results showed that magnolol administered i.p. at a dose of 5 or 25 mg/kg could significantly shorten the sleep latency, increase the amount of non-rapid eye movement (non-REM, NREM) and rapid eye movement (REM) sleep for 3 h after administration with an increase in the number of NREM and REM sleep episodes. Magnolol at doses of 5 and 25 mg/kg increased the number of bouts of wakefulness but decreased their duration. On the other hand, magnolol increased the number of state transitions from wakefulness to NREM sleep and subsequently from NREM sleep to wakefulness. Immunohistochemical study showed that magnolol increased c-Fos expression in the neurons of ventrolateral preoptic area, a sleep center in the anterior hypothalamus, and decreased c-Fos expression in the arousal tuberomammillary nucleus, which was located in the caudolateral hypothalamus. The sleep-promoting effects and changes in c-Fos induced by magnolol were reversed by flumazenil, an antagonist at the benzodiazepine site of the GABA(A) receptor. These results indicate that magnolol increased NREM and REM sleep via the GABA(A) receptor. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys.

    PubMed

    Sun, Haijun D; Malabunga, Maria; Tonra, James R; DiRenzo, Roberto; Carrick, Francine E; Zheng, Huiyuan; Berthoud, Hans-Rudolf; McGuinness, Owen P; Shen, Juqun; Bohlen, Peter; Leibel, Rudolph L; Kussie, Paul

    2007-03-01

    We generated three fully human monoclonal antibody antagonists against fibroblast growth factor receptor-1 (FGFR1) that potently block FGF signaling. We found that antibodies targeting the c-splice form of the receptor (FGFR1c) were anorexigenic when administered intraperitoneally three times weekly to mice, resulting in rapid, dose-dependent weight loss that plateaued (for doses>4 mg/kg) at 35-40% in 2 wk. Animals appeared healthy during treatment and regained their normal body weights and growth trajectories upon clearance of the antibodies from the bloodstream. Measurements of food consumption and energy expenditure indicated that the rapid weight loss was induced primarily by decreased energy intake and not by increased energy expenditure or cachexia and was accompanied by a greater reduction in fat than lean body mass. Hypophagia was not caused through malaise or illness, as indicated by absence of conditioned taste aversion, pica behavior, and decreased need-induced salt intake in rats. In support of a hypothalamic site of action, we found that, after intraperitoneal injections, anti-FGFR1c (IMC-A1), but not a control antibody, accumulated in the median eminence and adjacent mediobasal hypothalamus and that FGFR1c is enriched in the hypothalamus of mice. Furthermore, a single intracerebroventricular administration of 3 microg of IMC-A1 via the 3rd ventricle to mice caused an approximately 36% reduction in food intake and an approximately 6% weight loss within the ensuing 24 h. Our data suggest that FGF signaling through FGFR1c may play a physiological role in hypothalamic feeding circuit and that blocking it leads to hypophagia and weight loss.

  8. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: possible involvement of angiotensin-converting enzyme-2.

    PubMed

    Han, Su-Xia; He, Guang-Ming; Wang, Tao; Chen, Lei; Ning, Yun-Ye; Luo, Feng; An, Jin; Yang, Ting; Dong, Jia-Jia; Liao, Zeng-Lin; Xu, Dan; Wen, Fu-Qiang

    2010-05-15

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  9. Serum C-reactive protein in patients undergoing elective shoulder arthroplasty. Prospective study.

    PubMed

    Torrens, Carlos; Santana, Fernando; Marí, Raquel; Puig, Lluis; Alier, Albert

    2017-09-01

    The objective of the study was to determine the normalization curve of the serum C-reactive protein (CRP) in elective shoulder arthroplasty. A prospective study including 58 consecutive patients who had undergone elective shoulder arthroplasty. Forty-one patients had received a Reverse Shoulder Arthroplasty, 13 a Total Shoulder Arthroplasty and 4 a Hemiarthroplasty. Based on a pilot study, blood samples to determine CRP values were obtained at baseline (1 h before surgery), on the 1st, 2nd, 6th, 8th and 14th postoperative days. All the patients included presented no postoperative complications during inpatient stay or any re-admission during the three months after surgery. Mean CRP values showed a rapid increase on the 1st postoperative day (7-fold higher than the baseline in cuff tear arthropathy, 11-fold higher in primary osteoarthritis, 1-fold higher in acute fracture) and reached a peak on the 2nd postoperative day (14-fold higher than the baseline in cuff tear arthropathy, 24-fold higher in primary osteoarthritis and 2-fold higher in acute fracture). After the 2nd postoperative day CRP values began to slowly decrease reaching the normal range in the 14th postoperative day. Serum CRP levels after elective shoulder arthroplasty rapidly increase to reach a maximum peak after the 2nd surgery day and then slowly decrease to return to normality on the 14th day. Knowing the normalization curve of CRP can be a helpful tool to help in the diagnosis of acute infections in elective shoulder arthroplasty. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  10. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

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

    Han Suxia; He Guangming; Wang Tao

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along withmore » increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.« less

  11. Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial mechanical function after reversion of atrial arrhythmias to sinus rhythm: reversal of tachycardia-mediated atrial cardiomyopathy with fish oils.

    PubMed

    Kumar, Saurabh; Sutherland, Fiona; Wheeler, Miriam; Heck, Patrick M; Lee, Geoffrey; Teh, Andrew W; Garg, Manohar L; Morgan, John G; Sparks, Paul B

    2011-05-01

    Atrial mechanical stunning is a form of tachycardia-mediated atrial cardiomyopathy that manifests after reversion of persistent atrial arrhythmias to sinus rhythm. This study sought to examine whether chronic omega-3 polyunsaturated fatty acid supplementation with fish oils can reverse atrial mechanical stunning. Patients undergoing reversion of persistent atrial fibrillation (AF) or atrial flutter (AFL) to sinus rhythm were randomized to a control group (n = 26) or an omega-3 group (n = 23). The latter were prescribed 6 g/day of fish oil for ≥1 month prior to the procedure. Parameters of left atrial appendage function were compared immediately before and immediately after reversion. After fish oil intake for a mean of 70 days, the following were noted favoring the omega-3 group among both AF and AFL patients: (1) 2-fold higher serum omega-3 levels (P < .001), (2) less mean decrease in emptying velocity (e.g., AF: 8% vs. 32%, P = .02), (3) less mean decrease in appendage emptying fraction (e.g., AFL: 7% vs. 60%, P = .002), (4) lower incidence of new or increased spontaneous echocardiographic contrast (e.g., AF: 11% vs. 62.5%, P = .003), and (5) lower incidence of atrial mechanical stunning (e.g., AFL: 20% vs. 100%, P = .001). Omega-3 intake conferred protection against stunning in a multivariable analysis (odds ratio 0.18, P = .02). Chronic fish oil ingestion in humans attenuates atrial mechanical stunning after reversion of atrial arrhythmias to sinus rhythm. This suggests that fish oils may target or even reverse underlying cellular and/or structural remodeling that occurs in response to persistent atrial arrhythmias. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  12. When dementia progresses quickly: a practical approach to the diagnosis and management of rapidly progressive dementia.

    PubMed

    Day, Gregory S; Tang-Wai, David F

    2014-01-01

    Making a diagnosis of rapidly progressive dementia requires practical adaptation of the skills used to assess patients with chronic causes of cognitive impairment. An expedited assessment, commensurate with the accelerated pace of the disease, is required to identify the cause of symptoms amidst a myriad of possibilities. Features upon history, physical examination and cognitive assessment that support specific diagnoses are reviewed, and a stratified approach to testing is presented. The use of readily-accessible investigations is prioritized, acknowledging the implications and applications of novel diagnostic tests. The coordinated use of clinical and laboratory measures are promoted as a means of facilitating rapid evaluation, with the ultimate goal of identifying patients with potentially reversible causes of rapidly progressive dementia.

  13. Slowly switching between environments facilitates reverse evolution in small populations

    NASA Astrophysics Data System (ADS)

    Tan, Longzhi; Gore, Jeff

    2011-03-01

    The rate at which a physical process occurs usually changes the behavior of a system. In thermodynamics, the reversibility of a process generally increases when it occurs at an infinitely slow rate. In biological evolution, adaptations to a new environment may be reversed by evolution in the ancestral environment. Such fluctuating environments are ubiquitous in nature, although how the rate of switching affects reverse evolution is unknown. Here we use a computational approach to quantify evolutionary reversibility as a function of the rate of switching between two environments. For small population sizes, which travel on landscapes as random walkers, we find that both genotypic and phenotypic reverse evolution increase at slow switching rates. However, slow switching of environments decreases evolutionary reversibility for a greedy walker, corresponding to large populations (extensive clonal interference). We conclude that the impact of the switching rate for biological evolution is more complicated than other common physical processes, and that a quantitative approach may yield significant insight into reverse evolution.

  14. Zero field reversal probability in thermally assisted magnetization reversal

    NASA Astrophysics Data System (ADS)

    Prasetya, E. B.; Utari; Purnama, B.

    2017-11-01

    This paper discussed about zero field reversal probability in thermally assisted magnetization reversal (TAMR). Appearance of reversal probability in zero field investigated through micromagnetic simulation by solving stochastic Landau-Lifshitz-Gibert (LLG). The perpendicularly anisotropy magnetic dot of 50×50×20 nm3 is considered as single cell magnetic storage of magnetic random acces memory (MRAM). Thermally assisted magnetization reversal was performed by cooling writing process from near/almost Curie point to room temperature on 20 times runs for different randomly magnetized state. The results show that the probability reversal under zero magnetic field decreased with the increase of the energy barrier. The zero-field probability switching of 55% attained for energy barrier of 60 k B T and the reversal probability become zero noted at energy barrier of 2348 k B T. The higest zero-field switching probability of 55% attained for energy barrier of 60 k B T which corespond to magnetif field of 150 Oe for switching.

  15. Comparison of Monoamine Oxidase Inhibitors in Decreasing Production of the Autotoxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde in PC12 Cells

    PubMed Central

    Jinsmaa, Yunden; Sullivan, Patti; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan

    2016-01-01

    According to the catecholaldehyde hypothesis, the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) contributes to the loss of nigrostriatal dopaminergic neurons in Parkinson’s disease. Monoamine oxidase-A (MAO-A) catalyzes the conversion of intraneuronal dopamine to DOPAL and may serve as a therapeutic target. The “cheese effect”—paroxysmal hypertension evoked by tyramine-containing foodstuffs—limits clinical use of irreversible MAO-A inhibitors. Combined MAO-A/B inhibition decreases DOPAL production in rat pheochromocytoma PC12 cells, but whether reversible MAO-A inhibitors or MAO-B inhibitors decrease endogenous DOPAL production is unknown. We compared the potencies of MAO inhibitors in attenuating DOPAL production and examined possible secondary effects on dopamine storage, constitutive release, synthesis, and auto-oxidation. Catechol concentrations were measured in cells and medium after incubation with the irreversible MAO-A inhibitor clorgyline, three reversible MAO-A inhibitors, or the MAO-B inhibitors selegiline or rasagiline for 180 minutes. Reversible MAO-A inhibitors were generally ineffective, whereas clorgyline (1 nM), rasagiline (500 nM), and selegiline (500 nM) decreased DOPAL levels in the cells and medium. All three drugs also increased dopamine and norepinephrine, decreased 3,4-dihydroxyphenylalanine, and increased cysteinyl-dopamine concentrations in the medium, suggesting increased vesicular uptake and constitutive release, decreased dopamine synthesis, and increased dopamine spontaneous oxidation. In conclusion, clorgyline, rasagiline, and selegiline decrease production of endogenous DOPAL. At relatively high concentrations, the latter drugs probably lose their selectivity for MAO-B. Possibly offsetting increased formation of potentially toxic oxidation products and decreased formation of DOPAL might account for the failure of large clinical trials of MAO-B inhibitors to demonstrate slowing of neurodegeneration in Parkinson’s disease. PMID:26574516

  16. Optimized 4-bit Quantum Reversible Arithmetic Logic Unit

    NASA Astrophysics Data System (ADS)

    Ayyoub, Slimani; Achour, Benslama

    2017-08-01

    Reversible logic has received a great attention in the recent years due to its ability to reduce the power dissipation. The main purposes of designing reversible logic are to decrease quantum cost, depth of the circuits and the number of garbage outputs. The arithmetic logic unit (ALU) is an important part of central processing unit (CPU) as the execution unit. This paper presents a complete design of a new reversible arithmetic logic unit (ALU) that can be part of a programmable reversible computing device such as a quantum computer. The proposed ALU based on a reversible low power control unit and small performance parameters full adder named double Peres gates. The presented ALU can produce the largest number (28) of arithmetic and logic functions and have the smallest number of quantum cost and delay compared with existing designs.

  17. Thioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring eNOS function

    PubMed Central

    Hilgers, Rob H. P.; Kundumani-Sridharan, Venkatesh; Subramani, Jaganathan; Chen, Leon C.; Cuello, Luis G.; Rusch, Nancy J.; Das, Kumuda C.

    2017-01-01

    The incidence of high blood pressure with advancing age is notably high, and it is an independent prognostic factor for the onset or progression of a variety of cardiovascular disorders. Although age-related hypertension is an established phenomenon, current treatments are only palliative but not curative. Thus, there is a critical need for a curative therapy against age-related hypertension, which could greatly decrease the incidence of cardiovascular disorders. We show that overexpression of human thioredoxin (TRX), a redox protein, in mice prevents age-related hypertension. Further, injection of recombinant human TRX (rhTRX) for three consecutive days reversed hypertension in aged wild-type mice, and this effect lasted for at least 20 days. Arteries of wild-type mice injected with rhTRX or mice with TRX overexpression exhibited decreased arterial stiffness, greater endothelium-dependent relaxation, increased nitric oxide production, and decreased superoxide anion (O2•−) generation compared to either saline-injected aged wild-type mice or mice with TRX deficiency. Our study demonstrates a potential translational role of rhTRX in reversing age-related hypertension with long-lasting efficacy. PMID:28179506

  18. Resistance of Gerbil Auditory Function to Reversible Decrease in Cochlear Blood Flow.

    PubMed

    El Afia, Fahd; Giraudet, Fabrice; Gilain, Laurent; Mom, Thierry; Avan, Paul

    2017-01-01

    The objective was to design in gerbils a model of reversible decrease in cochlear blood flow (CBF) and analyze its influence on cochlear function. In Mongolian gerbils injected with ferromagnetic microbeads, a magnet placed near the porus acusticus allowed CBF to be manipulated. The cochlear microphonic potential (CM) from the basal cochlea was monitored by a round-window electrode. In 13 of the 20 successfully injected gerbils, stable CBF reduction was obtained for 11.5 min on average. The CM was affected only when CBF fell to less than 60% of its baseline, yet remained >40% of its initial level in about 2/3 of such cases. After CBF restoration, CM recovery was fast and usually complete. Reduced CM came with a 35- to 45-dB threshold elevation of neural responses determined by compound action potentials. This method allowing reversible changes of CBF confirms the robustness of cochlear function to decreased CBF. It can be used to study whether a hypovascularized cochlea is abnormally sensitive to stress. © 2017 S. Karger AG, Basel.

  19. Influence of capsaicin infusion on secondary peristalsis in patients with gastroesophageal reflux disease

    PubMed Central

    Yi, Chih-Hsun; Lei, Wei-Yi; Hung, Jui-Sheng; Liu, Tso-Tsai; Chen, Chien-Lin; Pace, Fabio

    2016-01-01

    AIM To determine whether capsaicin infusion could influence heartburn perception and secondary peristalsis in patients with gastroesophageal reflux disease (GERD). METHODS Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air in 10 patients with GERD. In a first protocol, saline and capsaicin-containing red pepper sauce infusions were randomly performed, whereas 2 consecutive sessions of capsaicin-containing red pepper sauce infusions were performed in a second protocol. Tested solutions including 5 mL of red pepper sauce diluted with 15 mL of saline and 20 mL of 0.9% saline were infused into the mid-esophagus via the manometric catheter at a rate of 10 mL/min with a randomized and double-blind fashion. During each study protocol, perception of heartburn, threshold volumes and peristaltic parameters for secondary peristalsis were analyzed and compared between different stimuli. RESULTS Infusion of capsaicin significantly increased heartburn perception in patients with GERD (P < 0.001), whereas repeated capsaicin infusion significantly reduced heartburn perception (P = 0.003). Acute capsaicin infusion decreased threshold volume of secondary peristalsis (P = 0.001) and increased its frequency (P = 0.01) during rapid air injection. The prevalence of GERD patients with successive secondary peristalsis during slow air injection significantly increased after capsaicin infusion (P = 0.001). Repeated capsaicin infusion increased threshold volume of secondary peristalsis (P = 0.002) and reduced the frequency of secondary peristalsis (P = 0.02) during rapid air injection. CONCLUSION Acute esophageal exposure to capsaicin enhances heartburn sensation and promotes secondary peristalsis in gastroesophageal reflux disease, but repetitive capsaicin infusion reverses these effects. PMID:28018112

  20. Large-scale coupling dynamics of instructed reversal learning.

    PubMed

    Mohr, Holger; Wolfensteller, Uta; Ruge, Hannes

    2018-02-15

    The ability to rapidly learn from others by instruction is an important characteristic of human cognition. A recent study found that the rapid transfer from initial instructions to fluid behavior is supported by changes of functional connectivity between and within several large-scale brain networks, and particularly by the coupling of the dorsal attention network (DAN) with the cingulo-opercular network (CON). In the present study, we extended this approach to investigate how these brain networks interact when stimulus-response mappings are altered by novel instructions. We hypothesized that residual stimulus-response associations from initial practice might negatively impact the ability to implement novel instructions. Using functional imaging and large-scale connectivity analysis, we found that functional coupling between the CON and DAN was generally at a higher level during initial than reversal learning. Examining the learning-related connectivity dynamics between the CON and DAN in more detail by means of multivariate patterns analyses, we identified a specific subset of connections which showed a particularly high increase in connectivity during initial learning compared to reversal learning. This finding suggests that the CON-DAN connections can be separated into two functionally dissociable yet spatially intertwined subsystems supporting different aspects of short-term task automatization. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Dabigatran and kidney disease: a bad combination.

    PubMed

    Knauf, Felix; Chaknos, C Michael; Berns, Jeffrey S; Perazella, Mark A

    2013-09-01

    Dabigatran is an oral direct thrombin inhibitor widely used to prevent and treat various thromboembolic complications. An advantage of this agent over other anticoagulants is that routine laboratory monitoring and related dose adjustments are considered unnecessary. A major disadvantage is the absence of a reliable means of reversing its anticoagulant effect. After U.S. Food and Drug Administration approval, recently emerged data suggest a higher bleeding risk with dabigatran, especially in the elderly. Clinicians are thus faced with caring for patients with serious bleeding events without readily available tests to measure drug levels or the anticoagulant effects of dabigatran and without effective antidotes to rapidly reverse the anticoagulant effect. On the basis of dabigatran's pharmacokinetic profile, hemodialysis and continuous renal replacement therapy have been used to remove dabigatran with the hope, still unproven, that this would rapidly reverse the anticoagulant effect and reduce bleeding in patients with normal and those with reduced kidney function. However, the best clinical approach to the patient with serious bleeding is not known, and the risks of placing a hemodialysis catheter in an anticoagulated patient can be substantial. This article reviews this issue, addressing clinical indications, drug pharmacokinetics, clinical and laboratory monitoring tests, and dialytic and nondialytic approaches to reduce bleeding in dabigatran-treated patients.

  2. 2-Deoxy-D-glucose, not mercaptoacetate, induces a reversible reduction of body temperature in male desert hamsters (Phodopus roborovskii).

    PubMed

    Chi, Qing-Sheng; Li, Xiu-Juan; Wang, De-Hua

    2018-01-01

    The initiation of torpor is supposed to be related to the availability of metabolic fuels. Studies on metabolic fuel inhibition of glucose by using 2-deoxy-D-glucose (2DG) or fatty acid by mercaptoacetate (MA) in heterothermic mammals produced mixed outcomes. To examine the roles of availability of glucose and fatty acid in the initiation of torpor in desert hamsters (Phodopus roborovskii), we intraperitoneally administrated 2DG and MA to summer-acclimated male hamsters while body temperature (T b ), metabolic rate (MR) and respiratory quotient (RQ) were simultaneously recorded to monitor their thermoregulatory response. 2DG induced a reversible reduction of T b in desert hamsters both at ambient temperature (T a ) of 23°C and 5°C. At T a of 23°C, T b , MR and RQ decreased in a dose-dependent manner with a large T b -T a differential (> 6.5°C) and a lowest T b of 28.0°C which were comparable to those in fasted hamsters. At T a of 5°C, 2DG-treated hamsters also decreased T b to the same level as at T a 23°C, but MR was significantly higher than that at T a of 23°C at each dose, suggesting doses of 2DG directly affected the hypothalamic T b set-point. Different from fasted hamsters which maintain normothermic at T a of 5°C, 2DG-treated hamsters showed a substantial reduction of T b at T a 5°C, indic a ting an overwhelming effect on the thermoregulatory system regardless of T a . Furthermore, the rapid decrease of T b and outstretched body posture in 2DG-treated hamsters suggest that the effects of 2DG were not simply mimicking the torpor pathways but that other mechanisms are involved. Interestingly, MA failed to induce a torpor-like state in male desert hamsters. Our results suggest that availability of glucose rather than fatty acid plays an important role for initiation of torpor in desert hamsters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Effective thiafentanil immobilization and physiological responses of free-ranging moose (Alces alces) in northern Sweden.

    PubMed

    Barros, Daniela Sb; Evans, Alina L; Arnemo, Jon M; Stenbacka, Fredrik; Ericsson, Göran

    2018-03-31

    To evaluate clinical and physiological responses in moose to thiafentanil administration for immobilization. Cross-sectional clinical study. Eleven (six males and five females) free-ranging adult moose (Alces alces). Each moose was darted from a helicopter with 7.5 mg thiafentanil during March 2014 in northern Sweden. Physiological evaluation included vital signs and blood gases. Arterial blood was collected after induction and again after 10 minutes of intranasal oxygen administration and analyzed immediately with an i-STAT analyzer. A total of 10 mg naltrexone per milligram of thiafentanil was administered to all animals for reversal. Data were analyzed using descriptive statistics. All moose were sufficiently immobilized with a single dart injection. Induction occurred within 3 minutes in 10 of 11 moose. One individual became recumbent while crossing a river and naltrexone was immediately administered. Animals maintained sternal recumbency with their head raised and vital signs were stable. Nine of 10 moose were hypoxemic before oxygen administration, with seven becoming markedly hypoxemic [partial pressure of arterial oxygen (PaO 2 ) between 40 and 59 mmHg (5.3-7.9 kPa)]. The PaO 2 increased significantly between samples, but six moose remained hypoxemic despite therapy. Hypercapnia was seen in all moose, with eight having marked hypercapnia [partial pressure of arterial carbon dioxide (PaCO 2 ) > 60 mmHg (>8.0 kPa)]. All moose were acidemic, with nine showing marked acidemia (pH < 7.20). The pH increased significantly with time and lactate decreased. Recoveries were rapid and uneventful, and all moose were living 6 months after capture. Thiafentanil provided rapid and sufficient immobilization of moose and its effects were rapidly reversed with naltrexone. As with other opioids, moose showed hypoxemia and varying degrees of respiratory and metabolic acidosis. Arterial oxygenation of moose improved following intranasal oxygen, but hypoxemia was not fully resolved despite therapy. Thiafentanil (7.5 mg per adult) is effective for immobilization of free-ranging moose. Supplemental oxygen may be of benefit when using this regimen; however, further investigation is required to confirm these results. Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  4. Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization

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

    Song, Changhoon; Hong, Beom-Ju; Bok, Seoyeon

    Purpose: To investigate the serial changes of tumor hypoxia in response to single high-dose irradiation by various clinical and preclinical methods to propose an optimal fractionation schedule for stereotactic ablative radiation therapy. Methods and Materials: Syngeneic Lewis lung carcinomas were grown either orthotopically or subcutaneously in C57BL/6 mice and irradiated with a single dose of 15 Gy to mimic stereotactic ablative radiation therapy used in the clinic. Serial [{sup 18}F]-misonidazole (F-MISO) positron emission tomography (PET) imaging, pimonidazole fluorescence-activated cell sorting analyses, hypoxia-responsive element-driven bioluminescence, and Hoechst 33342 perfusion were performed before irradiation (day −1), at 6 hours (day 0), and 2 (daymore » 2) and 6 (day 6) days after irradiation for both subcutaneous and orthotopic lung tumors. For F-MISO, the tumor/brain ratio was analyzed. Results: Hypoxic signals were too low to quantitate for orthotopic tumors using F-MISO PET or hypoxia-responsive element-driven bioluminescence imaging. In subcutaneous tumors, the maximum tumor/brain ratio was 2.87 ± 0.483 at day −1, 1.67 ± 0.116 at day 0, 2.92 ± 0.334 at day 2, and 2.13 ± 0.385 at day 6, indicating that tumor hypoxia was decreased immediately after irradiation and had returned to the pretreatment levels at day 2, followed by a slight decrease by day 6 after radiation. Pimonidazole analysis also revealed similar patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 co-immunostaining, we found a rapid and transient vascular collapse, which might have resulted in poor intratumor perfusion of F-MISO PET tracer or pimonidazole delivered at day 0, leading to decreased hypoxic signals at day 0 by PET or pimonidazole analyses. Conclusions: We found tumor hypoxia levels decreased immediately after delivery of a single dose of 15 Gy and had returned to the pretreatment levels 2 days after irradiation and had decreased slightly by day 6. Our results indicate that single high-dose irradiation can produce a rapid, but reversible, vascular collapse in tumors.« less

  5. Effect of 10% sodium ascorbate on the calcium: Phosphorus ratio of enamel bleached with 35% hydrogen peroxide: an in vitro quantitative energy-dispersive X-ray analysis.

    PubMed

    Poorni, Saravanan; Kumar, R Anil; Shankar, P; Indira, Rajamani; Ramachandran, S

    2010-10-01

    The study assessed quantitatively the calcium and phosphorous loss from the enamel surface following bleaching with 35% hydrogen peroxide and reversal with 10% sodium ascorbate using energy-dispersive X-ray analysis (EDAX). Eight non-carious, freshly extracted human permanent maxillary central incisors without any visible defects were used. Each specimen was bleached with 35% hydrogen peroxide activated by light and reversed with sodium ascorbate antioxidant gel. The calcium and phosphorous content in weight percent of sound, bleached and reversed enamel was acquired using EDAX. The Ca/P ratio was calculated from the obtained data. One-way ANOVA followed by Post Hoc Tukey test was used for comparing the Ca/P ratio of sound, bleached and reversed enamel. All the samples subjected to bleaching using 35% hydrogen peroxide showed a statistically significant decrease in the Ca/P ratio as compared with samples in which no bleaching procedure was performed (P-value < 0.01). The striking finding was that there was a significant increase in the Ca/P ratio on application of sodium ascorbate antioxidant gel when compared with the bleached enamel (P-value < 0.01). The authors concluded that 35% hydrogen peroxide causes a significant decrease in the Ca/P ratio. This decrease in the Ca/P ratio can be restored by the application of 10% sodium ascorbate antioxidant gel.

  6. NMDA receptor agonists reverse impaired psychomotor and cognitive functions associated with hippocampal Hbegf-deficiency in mice.

    PubMed

    Sasaki, Keita; Omotuyi, Olaposi Idowu; Ueda, Mutsumi; Shinohara, Kazuyuki; Ueda, Hiroshi

    2015-12-04

    Structural and functional changes of the hippocampus are correlated with psychiatric disorders and cognitive dysfunctions. Genetic deletion of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is predominantly expressed in cortex and hippocampus, also causes similar psychiatric and cognitive dysfunctions, accompanying down-regulated NMDA receptor signaling. However, little is known of such dysfunctions in hippocampus-specific Hbegf cKO mice. We successfully developed hippocampus-specific cKO mice by crossbreeding floxed Hbegf and Gng7-Cre knock-in mice, as Gng7 promoter-driven Cre is highly expressed in hippocampal neurons as well as striatal medium spiny neurons. In mice lacking hippocampus Hbegf gene, there was a decreased neurogenesis in the subgranular zone (SGZ) of the dentate gyrus as well as down-regulation of PSD-95/NMDA-receptor-NR1/NR2B subunits and related NMDA receptor signaling. Psychiatric, social-behavioral and cognitive abnormalities were also observed in hippocampal cKO mice. Interestingly, D-cycloserine and nefiracetam, positive allosteric modulators (PAMs) of NMDA receptor reversed the apparent reduction in NMDA receptor signaling and most behavioral abnormalities. Furthermore, decreased SGZ neurogenesis in hippocampal cKO mice was reversed by nefiracetam. The present study demonstrates that PAMs of NMDA receptor have pharmacotherapeutic potentials to reverse down-regulated NMDA receptor signaling, neuro-socio-cognitive abnormalities and decreased neurogenesis in hippocampal cKO mice.

  7. A rapid method for establishment of a reverse genetics system for canine parvovirus.

    PubMed

    Yu, Yongle; Su, Jun; Wang, Jigui; Xi, Ji; Mao, Yaping; Hou, Qiang; Zhang, Xiaomei; Liu, Weiquan

    2017-12-01

    Canine parvovirus (CPV) is an important and highly prevalent pathogen of dogs that causes acute hemorrhagic enteritis disease. Here, we describe a rapid method for the construction and characterization of a full-length infectious clone (rCPV) of CPV. Feline kidney (F81) cells were transfected with rCPV incorporating an engineered EcoR I site that served as a genetic marker. The rescued virus was indistinguishable from that of wild-type virus in its biological properties.

  8. Novel mechanism of transcriptional regulation of cell matrix protein through CREB

    PubMed Central

    Habib, Samy L; Mohan, Sumathy; Liang, Sitai; Li, Baojie; Yadav, Mukesh

    2015-01-01

    The transcription mechanism(s) of renal cell matrix accumulation in diabetes does not explored. Phosphorylation of the transcription factor cAMP-responsive element binding protein (CREB) significantly increased in cells treated with high glucose (HG) compared to cell grown in normal glucose (NG). Cells pretreated with rapamycin before exposure to HG showed significant decrease phosphorylation of CREB, increase in AMPK activity and decrease protein/mRNA and promoter activity of fibronectin. In addition, cells transfected with siRNA against CREB showed significant increase in AMPK activity, decrease in protein/mRNA and promoter activity of fibronectin. Cells treated with HG showed nuclear localization of p-CREB while pretreated cells with rapamycin reversed HG effect. Moreover, gel shift analysis shows increase binding of CREB to fibronectin promoter in cells treated with HG while cells pretreated with rapamycin reversed the effect of HG. Furthermore, db/db mice treated with rapamycin showed significant increase in AMPK activity, decrease in expression of p-CREB and protein/mRNA of fibronectin. Strong staining of fibronectin and p-CREB was detected in kidney cortex of db/db mice while treated mice with rapamycin reversed hyperglycemia effect. In summary, our data provide a novel mechanism of transcriptional regulation of fibronectin through CREB that may be used as therapeutic approach to prevent diabetes complications. PMID:26115221

  9. Upper airway resistance syndrome. Central electroencephalographic power and changes in breathing effort.

    PubMed

    Black, J E; Guilleminault, C; Colrain, I M; Carrillo, O

    2000-08-01

    Upper airway resistance syndrome (UARS) is defined by excessive daytime sleepiness and tiredness, and is associated with increased breathing effort. Its polygraphic features involve progressive increases in esophageal pressure (Pes), terminated by arousal (AR) as defined by the American Sleep Disorders Association (ASDA). With the arousal there is an abrupt decrease in Pes, called Pes reversal. However, Pes reversal can be seen without the presence of an AR. We performed spectral analysis on electroencephalographic data from a central lead for both AR and nonarousal (N-AR) events obtained from 15 UARS patients (eight men and seven women). Delta band activity was increased before and surrounding Pes reversal regardless of the presence or absence of AR. In the period after Pes reversal, alpha, sigma, and beta activity showed a greater increase in AR events than in N-AR events. The Pes measures were identical leading up to the point of reversal, but showed a longer-lasting and significantly greater decrease in respiratory effort after an AR. The data indicate that substantial electroencephalographic changes can be identified in association with Pes events, even when ARs cannot be detected according to standard criteria; however, visually identifiable electroencephalographic arousals clearly have a greater impact on ongoing inspiratory effort.

  10. Influence of Continental Geometry on the Onset and Spatial Distribution of Monsoonal Precipitation

    NASA Astrophysics Data System (ADS)

    Hui, K. L.; Bordoni, S.

    2017-12-01

    Recent studies have shown that the rapid onset of the monsoon is due to a switch between a dynamical regime where the tropical circulation strength is controlled by eddy momentum fluxes, to a monsoon regime where the strength is more directly controlled by energetic constraints, which causes the monsoonal cross-equatorial cell to grow rapidly in strength and extent. While it is now widely accepted that land-sea contrast is not necessary to generate monsoons, the spatial distribution of land can still affect important features of monsoons. This study focuses on the influence of continental geometry on the monsoonal precipitation. We use an idealized aquaplanet model with a slab ocean, where land and ocean differ only by the mixed-layer depth of the slab ocean, which is two orders of magnitude smaller over land than over ocean. The model is run with different zonally symmetric configurations of Northern Hemispheric land that extends poleward from southern boundaries at various latitudes. Simulations with a continent extending to tropical latitudes are able to reproduce the monsoonal precipitation distribution and rapid onset well. For continents with more poleward southern boundaries and weaker hemispheric asymmetry, the main precipitation zone remains over the ocean, moving gradually into the summer hemisphere. A local maximum in precipitation forms over the continent even when the continent does not extend into the deeper tropics, but this is primarily associated with local recycling from the saturated surface rather than moisture flux convergence by a deep and broad monsoonal circulation. Further analysis shows that a decrease in hemispheric asymmetry prevents the establishment of a reversed meridional gradient in lower-level moist static energy and, with it, a poleward displaced convergence zone. This suggests that in order to have the rapid onset of monsoonal precipitation, tropical regions of low thermal inertia may be necessary to facilitate the transition of the tropical circulation to a dynamical regime that restricts the degree to which eddy momentum fluxes influence the circulation strength and allows the cell the grow rapidly in strength and poleward extent. These results provide some useful insights for developing theories to better understand the mechanisms of rapid onset of monsoon systems worldwide.

  11. Current-induced alternating reversed dual-echo-steady-state for joint estimation of tissue relaxation and electrical properties.

    PubMed

    Lee, Hyunyeol; Sohn, Chul-Ho; Park, Jaeseok

    2017-07-01

    To develop a current-induced, alternating reversed dual-echo-steady-state-based magnetic resonance electrical impedance tomography for joint estimation of tissue relaxation and electrical properties. The proposed method reverses the readout gradient configuration of conventional, in which steady-state-free-precession (SSFP)-ECHO is produced earlier than SSFP-free-induction-decay (FID) while alternating current pulses are applied in between the two SSFPs to secure high sensitivity of SSFP-FID to injection current. Additionally, alternating reversed dual-echo-steady-state signals are modulated by employing variable flip angles over two orthogonal injections of current pulses. Ratiometric signal models are analytically constructed, from which T 1 , T 2 , and current-induced B z are jointly estimated by solving a nonlinear inverse problem for conductivity reconstruction. Numerical simulations and experimental studies are performed to investigate the feasibility of the proposed method in estimating relaxation parameters and conductivity. The proposed method, if compared with conventional magnetic resonance electrical impedance tomography, enables rapid data acquisition and simultaneous estimation of T 1 , T 2 , and current-induced B z , yielding a comparable level of signal-to-noise ratio in the parameter estimates while retaining a relative conductivity contrast. We successfully demonstrated the feasibility of the proposed method in jointly estimating tissue relaxation parameters as well as conductivity distributions. It can be a promising, rapid imaging strategy for quantitative conductivity estimation. Magn Reson Med 78:107-120, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  12. Microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse-transcription polymerase chain reaction for the rapid detection of Enterovirus 71 and Coxsackievirus A16 in throat swab specimens.

    PubMed

    Jia, Ruan; Chengjun, Sun; Heng, Chen; Chen, Zhou; Yuanqian, Li; Yongxin, Li

    2015-07-01

    Enterovirus 71 and Coxsackievirus A16 are the main pathogens causing hand-foot-mouth disease. In this paper, microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse transcript-polymerase chain reaction has been developed for the detection of Enterovirus 71 and Coxsackievirus A16 in throat swab specimens. The specific reverse transcription-polymerase chain reaction amplicons labeled with SYBR Orange were separated by microchip capillary electrophoresis and detected by laser induced fluorescence detector within 7 min. The intraday and interday relative standard deviation of migration time for DNA Marker was in the range of 1.36-2.94 and 2.78-3.96%, respectively. The detection limits were as low as 2.06 × 10(3) copies/mL for Enterovirus 71 and 5 × 10(3) copies/mL for Coxsackievirus A16. No cross-reactivity was observed with rotavirus, astrovirus, norovirus, and adenovirus, which showed good specificity of the method. This assay was validated using 100 throat swab specimens that were detected by real-time reverse-transcript polymerase chain reaction in parallel and the two methods produced the same results. This study provided a rapid, sensitive and specific method for the detection of Enterovirus 71 and Coxsackievirus A16, which make a contribution to significant time and cost saving for the identification and treatment of patients. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Implicit time-marching solution of the Navier-Stokes equations for thrust reversing and thrust vectoring nozzle flows

    NASA Technical Reports Server (NTRS)

    Imlay, S. T.

    1986-01-01

    An implicit finite volume method is investigated for the solution of the compressible Navier-Stokes equations for flows within thrust reversing and thrust vectoring nozzles. Thrust reversing nozzles typically have sharp corners, and the rapid expansion and large turning angles near these corners are shown to cause unacceptable time step restrictions when conventional approximate factorization methods are used. In this investigation these limitations are overcome by using second-order upwind differencing and line Gauss-Siedel relaxation. This method is implemented with a zonal mesh so that flows through complex nozzle geometries may be efficiently calculated. Results are presented for five nozzle configurations including two with time varying geometries. Three cases are compared with available experimental data and the results are generally acceptable.

  14. Chiral cavity ring down polarimetry: Chirality and magnetometry measurements using signal reversals.

    PubMed

    Bougas, Lykourgos; Sofikitis, Dimitris; Katsoprinakis, Georgios E; Spiliotis, Alexandros K; Tzallas, Paraskevas; Loppinet, Benoit; Rakitzis, T Peter

    2015-09-14

    We present the theory and experimental details for chiral-cavity-ring-down polarimetry and magnetometry, based on ring cavities supporting counterpropagating laser beams. The optical-rotation symmetry is broken by the presence of both chiral and Faraday birefringence, giving rise to signal reversals which allow rapid background subtractions. We present the measurement of the specific rotation at 800 nm of vapors of α-pinene, 2-butanol, and α-phellandrene, the measurement of optical rotation of sucrose solutions in a flow cell, the measurement of the Verdet constant of fused silica, and measurements and theoretical treatment of evanescent-wave optical rotation at a prism surface. Therefore, these signal-enhancing and signal-reversing methods open the way for ultrasensitive polarimetry measurements in gases, liquids and solids, and at surfaces.

  15. Terminal area automatic navigation, guidance, and control 1: Automatic rollout, turnoff, and taxis

    NASA Technical Reports Server (NTRS)

    Pines, S.

    1981-01-01

    A study developed for the TCV B-737, designed to apply existing navigation aids plus magnetic leader cable signals and develop breaking and reverse thrust guidance laws to provide for rapid automated rollout, turnoff, and taxi to reduce runway occupation time for a wide variety of landing conditions for conventional commercial-type aircraft, is described. Closed loop guidance laws for braking and reverse thrust are derived for rollout, turnoff, and taxi, as functions of the landing speed, the desired taxi speed and the distance to go. Brake limitations for wet runway conditions and reverse thrust limitations are taken into account to provide decision rules to avoid tire skid and to choose an alternate turnoff point, farther down the runway, to accommodate extreme landing conditions.

  16. MULTIPLE DIFFERENTIAL ROTARY MECHANICAL DRIVE

    DOEpatents

    Smits, R.G.

    1964-01-28

    This patent relates to a mechanism suitable for such applications as driving two spaced-apart spools which carry a roll film strip under conditions where the film movement must be rapidly started, stopped, and reversed while maintaining a constant tension on the film. The basic drive is provided by a variable speed, reversible rnotor coupled to both spools through a first differential mechanism and driving both spools in the same direction. A second motor, providing a constant torque, is connected to the two spools through a second differential mechanism and is coupled to impart torque to one spool in a first direction anid to the other spool in the reverse direction thus applying a constant tension to the film passing over the two spools irrespective of the speed or direction of rotation thereof. (AEC)

  17. Retinol esterification in bovine retinal pigment epithelium: reversibility of lecithin:retinol acyltransferase.

    PubMed Central

    Saari, J C; Bredberg, D L; Farrell, D F

    1993-01-01

    Esterification of all-trans-retinol is a key reaction of the vertebrate visual cycle, since it produces an insoluble, relatively non-toxic, form of the vitamin for storage and supplies substrate for the isomerization reaction. CoA-dependent and -independent pathways have been described for retinol esterification in retinal pigment epithelium (RPE). The CoA-independent reaction, catalysed by lecithin:retinol acyltransferase (LRAT) was examined in more detail in this study. Addition of retinol to RPE microsomes results in a burst of retinyl ester synthesis, followed by a rapid apparent cessation of the reaction. However, [3H]retinol, added when retinyl ester synthesis has apparently ceased, is rapidly incorporated into retinyl ester without a net increase in the amount of ester. The specific radioactivities of [3H]retinol and [3H]retinyl ester reach the same value. [14C]Palmitate from palmitoyl-CoA is incorporated into preexisting retinyl ester in the absence of net ester synthesis, too. These exchange reactions suggest that the reaction has reached equilibrium at the plateau of the progress curve and that only the accumulation of retinyl ester, and not its synthesis, has stopped during this phase of the reaction. Studies with geometrical isomers of retinol revealed that the rate of exchange of all-trans-retinol with all-trans-retinyl esters was about 6 times more rapid than exchange of 11-cis-retinol with 11-cis-retinyl ester. This is the first demonstration of the reversibility of LRAT and the first example of stereospecificity of retinyl ester synthesis in the visual system. Reversal of the LRAT reaction could contribute to the mobilization of 11-cis-retinol from 11-cis-retinyl ester pools. Images Figure 3 PMID:8489497

  18. Rapid and sensitive detection of Zika virus by reverse transcription loop-mediated isothermal amplification.

    PubMed

    Wang, Xuan; Yin, Fenggui; Bi, Yuhai; Cheng, Gong; Li, Jing; Hou, Lidan; Li, Yunlong; Yang, Baozhi; Liu, Wenjun; Yang, Limin

    2016-12-01

    Zika virus (ZIKV) is an arbovirus that recently emerged and has expanded worldwide, causing a global threat and raising international concerns. Current molecular diagnostics, e.g., real-time PCR and reverse transcription PCR (RT-PCR), are time consuming, expensive, and can only be deployed in a laboratory instead of for field diagnostics. This study aimed to develop a one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) platform showing sensitivity, specificity, and more convenience than previous methods, being easily distributed and implemented. Specific primers were designed and screened to target the entire ZIKV genome. The analytical sensitivity and specificity of the assay were evaluated and compared with traditional PCR and quantitative real-time PCR. Three different simulated clinical sample quick preparation protocols were evaluated to establish a rapid and straightforward treatment procedure for clinical specimens in open field detection. The RT-LAMP assay for detection of ZIKV demonstrated superior specificity and sensitivity compared to traditional PCR at the optimum reaction temperature. For the ZIKV RNA standard, the limit of detection was 20 copies/test. For the simulated ZIKV clinical samples, the limit of detection was 0.02 pfu/test, which was one order of magnitude higher than RT-PCR and similar to real-time PCR. The detection limit of simulated ZIKV specimens prepared using a protease quick processing method was consistent with that of samples prepared using commercial nucleic acid extraction kits, indicating that our ZIKV detection method could be used in point-of-care testing. The RT-LAMP assay had excellent sensitivity and specificity for detecting ZIKV and can be deployed together with a rapid specimen processing method, offering the possibility for ZIKV diagnosis outside of the laboratory. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. A slow-releasing form of prostacyclin agonist (ONO1301SR) enhances endogenous secretion of multiple cardiotherapeutic cytokines and improves cardiac function in a rapid-pacing-induced model of canine heart failure.

    PubMed

    Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Shiozaki, Motoko; Kawaguchi, Naomasa; Matsuura, Nariaki; Nakatani, Satoshi; Sakai, Yoshiki; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

    2013-08-01

    Cardiac functional deterioration in dilated cardiomyopathy (DCM) is known to be reversed by intramyocardial up-regulation of multiple cardioprotective factors, whereas a prostacyclin analog, ONO1301, has been shown to paracrinally activate interstitial cells to release a variety of protective factors. We here hypothesized that intramyocardial delivery of a slow-releasing form of ONO1301 (ONO1301SR) might activate regional myocardium to up-regulate cardiotherapeutic factors, leading to regional and global functional recovery in DCM. ONO1301 elevated messenger RNA and protein level of hepatocyte growth factor, vascular endothelial growth factor, and stromal-derived factor-1 of normal human dermal fibroblasts in a dose-dependent manner in vitro. Intramyocardial delivery of ONO1301SR, which is ONO1301 mixed with polylactic and glycolic acid polymer (PLGA), but not that of PLGA only, yielded significant global functional recovery in a canine rapid pacing-induced DCM model, assessed by echocardiography and cardiac catheterization (n = 5 each). Importantly, speckle-tracking echocardiography unveiled significant regional functional recovery in the ONO1301-delivered territory, consistent to significantly increased vascular density, reduced interstitial collagen accumulation, attenuated myocyte hypertrophy, and reversed mitochondrial structure in the corresponding area. Intramyocardial delivery of ONO1301SR, which is a PLGA-coated slow-releasing form of ONO1301, up-regulated multiple cardiotherapeutic factors in the injected territory, leading to region-specific reverse left ventricular remodeling and consequently a global functional recovery in a rapid-pacing-induced canine DCM model, warranting a further preclinical study to optimize this novel drug-delivery system to treat DCM. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  20. Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes.

    PubMed

    Wang, Huan; Wang, Hong-Fei; Wang, Chen; Chen, Yu-Fang; Ma, Rong; Xiang, Ji-Zhou; Du, Xin-Ling; Tang, Qiang

    2016-10-15

    In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K(+) current (Ikur) in human atrial myocytes were examined by using the whole-cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 μΜ with a Hill coefficient of 0.89. The current was maximally diminished about 71.36% at a concentration of 300μM hesperetin. Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5, while negative shifted the steady-state inactivation curve. Hesperetin also accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents. Block of Kv1.5 currents by hesperetin was in a frequency dependent manner. However, inclusion of 30μM hesperetin in pipette solution produced no effect on Kv1.5 channel current, while the current were remarkable and reversibly inhibited by extracellular application of 30μM hesperetin. We also found that hesperetin potently and reversibly inhibited the ultra-repaid delayed K(+) current (Ikur) in human atrial myocytes, which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells. In conclusion, hesperetin is a potent inhibitor of Ikur (which is encoded by Kv1.5), with blockade probably due to blocking of both open state and inactivated state channels from outside of the cell. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Reverse transport of children from a tertiary pediatric hospital.

    PubMed

    McPherson, Mona L; Jefferson, Larry S; Smith, E O'Brian; Sitler, Garry C; Graf, Jeanine M

    2007-01-01

    The purpose of this study was to determine the epidemiology and resources used and to study the potential savings of pediatric reverse transport patients. A case control study was performed with patients undergoing a reverse or outbound transport from a large, pediatric hospital. Twenty-five children undergoing reverse transport were compared with matched controls. Lengths of stay and costs were compared between the reverse transport and matched control patients. Fifty-two percent of the reverse transport patients returned home, whereas 32% went home for end-of-life care and 16% went to other facilities. The average reverse transport was more than 400 miles and cost $6,064. The reverse transport of these patients did not save pediatric intensive care unit (PICU) days but did result in a shorter hospital stay compared with the matched controls (10 vs. 19 days, P = .03). Decreased utilization of bed days came from less use of intermediate care unit resources. Pediatric patients undergo reverse transports for a variety of reasons, often for end-of-life care. The ability to reverse transport pediatric patients may not save PICU bed days but may offer pediatric tertiary care hospitals a means to provide more intermediate care bed availability.

  2. Polar Aprotic Modifiers for Chromatographic Separation and Back-Exchange Reduction for Protein Hydrogen/Deuterium Exchange Monitored by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Valeja, Santosh G.; Emmett, Mark R.; Marshall, Alan G.

    2012-04-01

    Hydrogen/deuterium exchange monitored by mass spectrometry is an important non-perturbing tool to study protein structure and protein-protein interactions. However, water in the reversed-phase liquid chromatography mobile phase leads to back-exchange of D for H during chromatographic separation of proteolytic peptides following H/D exchange, resulting in incorrect identification of fast-exchanging hydrogens as unexchanged hydrogens. Previously, fast high-performance liquid chromatography (HPLC) and supercritical fluid chromatography have been shown to decrease back-exchange. Here, we show that replacement of up to 40% of the water in the LC mobile phase by the modifiers, dimethylformamide (DMF) and N-methylpyrrolidone (NMP) (i.e., polar organic modifiers that lack rapid exchanging hydrogens), significantly reduces back-exchange. On-line LC micro-ESI FT-ICR MS resolves overlapped proteolytic peptide isotopic distributions, allowing for quantitative determination of the extent of back-exchange. The DMF modified solvent composition also improves chromatographic separation while reducing back-exchange relative to conventional solvent.

  3. Defect-Mediated Molecular Interaction and Charge Transfer in Graphene Mesh-Glucose Sensors.

    PubMed

    Kwon, Sun Sang; Shin, Jae Hyeok; Choi, Jonghyun; Nam, SungWoo; Park, Won Il

    2017-04-26

    We report the role of defects in enzymatic graphene field-effect transistor sensors by introducing engineered defects in graphene channels. Compared with conventional graphene sensors (Gr sensors), graphene mesh sensors (GM sensors), with an array of circular holes, initially exhibited a higher irreversible response to glucose, involving strong chemisorption to edge defects. However, after immobilization of glucose oxidase, the irreversibility of the responses was substantially diminished, without any reduction in the sensitivity of the GM sensors (i.e., -0.53 mV/mM for the GM sensor vs -0.37 mV/mM for Gr sensor). Furthermore, multiple cycle operation led to rapid sensing and improved the reversibility of GM sensors. In addition, control tests with sensors containing a linker showed that sensitivity was increased in Gr sensors but decreased in GM sensors. Our findings indicate that edge defects can be used to replace linkers for immobilization of glucose oxidase and improve charge transfer across glucose oxidase-graphene interfaces.

  4. Alternative Polyadenylation Regulates CELF1/CUGBP1 Target Transcripts Following T Cell Activation

    PubMed Central

    Beisang, Daniel; Reilly, Cavan; Bohjanen, Paul R.

    2014-01-01

    Alternative polyadenylation (APA) is an evolutionarily conserved mechanism for regulating gene expression. Transcript 3′ end shortening through changes in polyadenylation site usage occurs following T cell activation, but the consequences of APA on gene expression are poorly understood. We previously showed that GU-rich elements (GREs) found in the 3′ untranslated regions of select transcripts mediate rapid mRNA decay by recruiting the protein CELF1/CUGBP1. Using a global RNA sequencing approach, we found that a network of CELF1 target transcripts involved in cell division underwent preferential 3′ end shortening via APA following T cell activation, resulting in decreased inclusion of CELF1 binding sites and increased transcript expression. We present a model whereby CELF1 regulates APA site selection following T cell activation through reversible binding to nearby GRE sequences. These findings provide insight into the role of APA in controlling cellular proliferation during biological processes such as development, oncogenesis and T cell activation PMID:25123787

  5. Enhancing Cation Diffusion and Suppressing Anion Diffusion via Lewis-Acidic Polymer Electrolytes.

    PubMed

    Savoie, Brett M; Webb, Michael A; Miller, Thomas F

    2017-02-02

    Solid polymer electrolytes (SPEs) have the potential to increase both the energy density and stability of lithium-based batteries, but low Li + conductivity remains a barrier to technological viability. SPEs are designed to maximize Li + diffusivity relative to the anion while maintaining sufficient salt solubility. It is thus remarkable that poly(ethylene oxide) (PEO), the most widely used SPE, exhibits Li + diffusivity that is an order of magnitude smaller than that of typical counterions at moderate salt concentrations. We show that Lewis-basic polymers like PEO favor slow cation and rapid anion diffusion, while this relationship can be reversed in Lewis-acidic polymers. Using molecular dynamics, polyboranes are identified that achieve up to 10-fold increases in Li + diffusivities and significant decreases in anion diffusivities, relative to PEO in the dilute-ion regime. These results illustrate a general principle for increasing Li + diffusivity and transference number with chemistries that exhibit weaker cation and stronger anion coordination.

  6. Buckligami: Actuation of soft structures through mechanical instabilities

    NASA Astrophysics Data System (ADS)

    Lazarus, Arnaud; Reis, Pedro

    2013-03-01

    We present a novel mechanism for actuating soft structures, that is triggered through buckling. Our elastomeric samples are rapid-prototyped using digital fabrication and comprise of a cylindrical shell patterned with an array of voids, each of which is covered by a thin membrane. Decreasing the internal pressure of the structure induces local buckling of the ligaments of the pattern, resulting in controllable folding of the global structure. Using rigid inclusions to plug the voids in specific geometric arrangements allows us to excite a variety of different fundamental motions of the cylindrical shell, including flexure and twist. We refer to this new mechanism of buckling-induced folding as ``buckligami.'' Given that geometry, elasticity and buckling are the underlying ingredients of this local folding mechanism, the global actuation is scalable, reversible and repeatable. Characterization and rationalization of our experiments provide crucial fundamental understanding to aid the design of new scale-independent actuators, with potential implications in the field of soft robotics.

  7. Photo-responsive surface topology in chiral nematic media

    NASA Astrophysics Data System (ADS)

    Liu, Danqing; Bastiaansen, Cees W. M.; Toonder, Jaap. M. J.; Broer, Dirk J.

    2012-03-01

    We report on the design and fabrication of 'smart surfaces' that exhibit dynamic changes in their surface topology in response to exposure to light. The principle is based on anisotropic geometric changes of a liquid crystal network upon a change of the molecular order parameter. The photomechanical property of the coating is induced by incorporating an azobenzene moiety into the liquid crystal network. The responsive surface topology consists of regions with two different types of molecular order: planar chiral-nematic areas and homeotropic. Under flood exposure with 365 nm light the surfaces deform from flat to one with a surface relief. The height of the relief structures is of the order of 1 um corresponding to strain difference of around 20%. Furthermore, we demonstrate surface reliefs can form either convex or concave structures upon exposure to UV light corresponding to the decrease or increase molecular order parameter, respectively, related to the isomeric state of the azobenzene crosslinker. The reversible deformation to the initial flat state occurs rapidly after removing the light source.

  8. Phasic Stimulation of Midbrain Dopamine Neuron Activity Reduces Salt Consumption

    PubMed Central

    Sandhu, Eleanor C.; Fernando, Anushka B. P.; Tossell, Kyoko; Kokkinou, Michelle; Glegola, Justyna; Howes, Oliver D.

    2018-01-01

    Abstract Salt intake is an essential dietary requirement, but excessive consumption is implicated in hypertension and associated conditions. Little is known about the neural circuit mechanisms that control motivation to consume salt, although the midbrain dopamine system, which plays a key role in other reward-related behaviors, has been implicated. We, therefore, examined the effects on salt consumption of either optogenetic excitation or chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons in male mice. Strikingly, optogenetic excitation of dopamine neurons decreased salt intake in a rapid and reversible manner, despite a strong salt appetite. Importantly, optogenetic excitation was not aversive, did not induce hyperactivity, and did not alter salt concentration preferences in a need-free state. In addition, we found that chemogenetic inhibition of dopamine neurons had no effect on salt intake. Lastly, optogenetic excitation of dopamine neurons reduced consumption of sucrose following an overnight fast, suggesting a more general role of VTA dopamine neuron excitation in organizing motivated behaviors. PMID:29766048

  9. The effect on the patient flow in a local health care after implementing reverse triage in a primary care emergency department: a longitudinal follow-up study.

    PubMed

    Kauppila, Timo; Seppänen, Katri; Mattila, Juho; Kaartinen, Johanna

    2017-06-01

    Reverse triage means that patients who are not considered to be in need of medical services are not placed on the doctor's list in an emergency department (ED) but are sent, after face-to-face evaluation by a triage nurse, to a more appropriate health care unit. It is not known how an abrupt application of such reverse triage in a combined primary care ED alters the demand for doctors' services in collaborative parts of the health care system. An observational study. Register-based retrospective quasi-experimental longitudinal follow-up study based on a before-after setting in a Finnish city. Patients who consulted different doctors in a local health care unit. Numbers of monthly visits to different doctor groups in public and private primary care, and numbers of monthly referrals to secondary care ED from different sources of primary care were recorded before and after abrupt implementation of the reverse triage. The beginning of reverse triage decreased the number of patient visits to a primary ED doctor without increasing mortality. Simultaneously, there was an increase in doctor visits in the adjacent secondary care ED and local private sector. The number of patients who came to secondary care ED without a referral or with a referral from the private sector increased. The data suggested that the reverse triage causes redistribution of the use of doctors' services rather than a true decrease in the use of these services.

  10. Effect of load transients on SOFC operation—current reversal on loss of load

    NASA Astrophysics Data System (ADS)

    Gemmen, Randall S.; Johnson, Christopher D.

    The dynamics of solid oxide fuel cell (SOFC) operation have been considered previously, but mainly through the use of one-dimensional codes applied to co-flow fuel cell systems. In this paper several geometries are considered, including cross-flow, co-flow, and counter-flow. The details of the model are provided, and the model is compared with some initial experimental data. For parameters typical of SOFC operation, a variety of transient cases are investigated, including representative load increase and decrease and system shutdown. Of particular note for large load decrease conditions (e.g., shutdown) is the occurrence of reverse current over significant portions of the cell, starting from the moment of load loss up to the point where equilibrated conditions again provide positive current. Consideration is given as to when such reverse current conditions might most significantly impact the reliability of the cell.

  11. Two-cell embryos are more sensitive than blastocysts to AMPK-dependent suppression of anabolism and stemness by commonly used fertility drugs, a diet supplement, and stress.

    PubMed

    Bolnick, Alan; Abdulhasan, Mohammed; Kilburn, Brian; Xie, Yufen; Howard, Mindie; Andresen, Paul; Shamir, Alexandra M; Dai, Jing; Puscheck, Elizabeth E; Secor, Eric; Rappolee, Daniel A

    2017-12-01

    This study tests whether metformin or diet supplement BR-DIM-induced AMP-activated protein kinase (AMPK) mediated effects on development are more pronounced in blastocysts or 2-cell mouse embryos. Culture mouse zygotes to two-cell embryos and test effects after 0.5-1 h AMPK agonists' (e.g., Met, BR-DIM) exposure on AMPK-dependent ACCser79P phosphorylation and/or Oct4 by immunofluorescence. Culture morulae to blastocysts and test for increased ACCser79P, decreased Oct4 and for AMPK dependence by coculture with AMPK inhibitor compound C (CC). Test whether Met or BR-DIM decrease growth rates of morulae cultured to blastocyst by counting cells. Aspirin, metformin, and hyperosmotic sorbitol increased pACC ser79P ~ 20-fold, and BR-DIM caused a ~ 30-fold increase over two-cell embryos cultured for 1 h in KSOMaa but only 3- to 6-fold increase in blastocysts. We previously showed that these stimuli decreased Oct4 40-85% in two-cell embryos that was ~ 60-90% reversible by coculture with AMPK inhibitor CC. However, Oct4 decreased only 30-50% in blastocysts, although reversibility of loss by CC was similar at both embryo stages. Met and BR-DIM previously caused a near-complete cell proliferation arrest in two-cell embryos and here Met caused lower CC-reversible growth decrease and AMPK-independent BR-DIM-induced blastocyst growth decrease. Inducing drug or diet supplements decreased anabolism, growth, and stemness have a greater impact on AMPK-dependent processes in two-cell embryos compared to blastocysts.

  12. A living cell quartz crystal microbalance biosensor for continuous monitoring of cytotoxic responses of macrophages to single-walled carbon nanotubes

    PubMed Central

    2011-01-01

    Background Numerous engineered nanomaterials (ENMs) exist and new ENMs are being developed. A challenge to nanotoxicology and environmental health and safety is evaluating toxicity of ENMs before they become widely utilized. Cellular assays remain the predominant test platform yet these methods are limited by using discrete time endpoints and reliance on organic dyes, vulnerable to interference from ENMs. Label-free, continuous, rapid response systems with biologically meaningful endpoints are needed. We have developed a device to detect and monitor in real time responses of living cells to ENMs. The device, a living cell quartz crystal microbalance biosensor (QCMB), uses macrophages adherent to a quartz crystal. The communal response of macrophages to treatments is monitored continuously as changes in crystal oscillation frequency (Δf). We report the ability of this QCMB to distinguish benign from toxic exposures and reveal unique kinetic information about cellular responses to varying doses of single-walled carbon nanotubes (SWCNTs). Results We analyzed macrophage responses to additions of Zymosan A, polystyrene beads (PBs) (benign substances) or SWCNT (3-150 μg/ml) in the QCMB over 18 hrs. In parallel, toxicity was monitored over 24/48 hrs using conventional viability assays and histological stains to detect apoptosis. In the QCMB, a stable unchanging oscillation frequency occurred when cells alone, Zymosan A alone, PBs alone or SWCNTs without cells at the highest dose alone were used. With living cells in the QCMB, when Zymosan A, PBs or SWCNTs were added, a significant decrease in frequency occurred from 1-6 hrs. For SWCNTs, this Δf was dose-dependent. From 6-18 hrs, benign substances or low dose SWCNT (3-30 μg/ml) treatments showed a reversal of the decrease of oscillation frequency, returning to or exceeding pre-treatment levels. Cell recovery was confirmed in conventional assays. The lag time to see the Δf reversal in QCMB plots was linearly SWCNT-dose dependent. Lastly, the frequency never reversed at high dose SWCNT (100-150 μg/ml), and apoptosis/necrosis was documented in conventional 24 and 48 hr-assays. Conclusion These data suggest that the new QCMB detects and provides unique information about peak, sub-lethal and toxic exposures of living cells to ENMs before they are detected using conventional cell assays. PMID:21266033

  13. Reversible RNA adenosine methylation in biological regulation

    PubMed Central

    Jia, Guifang; Fu, Ye; He, Chuan

    2012-01-01

    N6-methyladenosine (m6A) is a ubiquitous modification in messenger RNA (mRNA) and other RNAs across most eukaryotes. For many years, however, the exact functions of m6A were not clearly understood. The discovery that the fat mass and obesity associated protein (FTO) is an m6A demethylase indicates that this modification is reversible and dynamically regulated, suggesting it has regulatory roles. In addition, it has been shown that m6A affects cell fate decisions in yeast and plant development. Recent affinity-based m6A profiling in mouse and human cells further showed that this modification is a widespread mark in coding and non-coding RNA transcripts and is likely dynamically regulated throughout developmental processes. Therefore, reversible RNA methylation, analogous to reversible DNA and histone modifications, may affect gene expression and cell fate decisions by modulating multiple RNA-related cellular pathways, which potentially provides rapid responses to various cellular and environmental signals, including energy and nutrient availability in mammals. PMID:23218460

  14. Multiscale Model of Swarming Bacteria

    NASA Astrophysics Data System (ADS)

    Alber, Mark

    2011-03-01

    Many bacteria can rapidly traverse surfaces from which they are extracting nutrient for growth. They generate flat, spreading colonies, called swarms because they resemble swarms of insects. In the beginning of the talk, swarms of the M. xanthus will be described in detail. Individual M. xanthus cells are elongated; they always move in the direction of their long axis; and they are in constant motion, repeatedly touching each other. As a cell glides, the slime capsule of a cell interacts with the bare agar surface, non-oriented slime which arises from the surface contact with the slime capsule, or oriented slime trails. Remarkably, cells regularly reverse their gliding directions. In this talk a detailed cell- and behavior-based computational model of M. xanthus swarming will be used to demonstrate that reversals of gliding direction and cell bending are essential for swarming and that specific reversal frequencies result in optimal swarming rate of the whole population. This suggests that the circuit regulating reversals evolved to its current sensitivity under selection for growth achieved by swarming.

  15. Contributions of Lateral and Orbital Frontal Regions to Abstract Rule Acquisition and Reversal in Monkeys

    PubMed Central

    La Camera, Giancarlo; Bouret, Sebastien; Richmond, Barry J.

    2018-01-01

    The ability to learn and follow abstract rules relies on intact prefrontal regions including the lateral prefrontal cortex (LPFC) and the orbitofrontal cortex (OFC). Here, we investigate the specific roles of these brain regions in learning rules that depend critically on the formation of abstract concepts as opposed to simpler input-output associations. To this aim, we tested monkeys with bilateral removals of either LPFC or OFC on a rapidly learned task requiring the formation of the abstract concept of same vs. different. While monkeys with OFC removals were significantly slower than controls at both acquiring and reversing the concept-based rule, monkeys with LPFC removals were not impaired in acquiring the task, but were significantly slower at rule reversal. Neither group was impaired in the acquisition or reversal of a delayed visual cue-outcome association task without a concept-based rule. These results suggest that OFC is essential for the implementation of a concept-based rule, whereas LPFC seems essential for its modification once established. PMID:29615854

  16. Sex Ratio Bias Leads to the Evolution of Sex Role Reversal in Honey Locust Beetles.

    PubMed

    Fritzsche, Karoline; Booksmythe, Isobel; Arnqvist, Göran

    2016-09-26

    The reversal of conventional sex roles was enigmatic to Darwin, who suggested that it may evolve when sex ratios are female biased [1]. Here we present direct evidence confirming Darwin's hypothesis. We investigated mating system evolution in a sex-role-reversed beetle (Megabruchidius dorsalis) using experimental evolution under manipulated sex ratios and food regimes. In female-biased populations, where reproductive competition among females was intensified, females evolved to be more attractive and the sex roles became more reversed. Interestingly, female-specific mating behavior evolved more rapidly than male-specific mating behavior. We show that sexual selection due to reproductive competition can be strong in females and can target much the same traits as in males of species with conventional mating systems. Our study highlights two central points: the role of ecology in directing sexual selection and the role that females play in mating system evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Reverse time migration by Krylov subspace reduced order modeling

    NASA Astrophysics Data System (ADS)

    Basir, Hadi Mahdavi; Javaherian, Abdolrahim; Shomali, Zaher Hossein; Firouz-Abadi, Roohollah Dehghani; Gholamy, Shaban Ali

    2018-04-01

    Imaging is a key step in seismic data processing. To date, a myriad of advanced pre-stack depth migration approaches have been developed; however, reverse time migration (RTM) is still considered as the high-end imaging algorithm. The main limitations associated with the performance cost of reverse time migration are the intensive computation of the forward and backward simulations, time consumption, and memory allocation related to imaging condition. Based on the reduced order modeling, we proposed an algorithm, which can be adapted to all the aforementioned factors. Our proposed method benefit from Krylov subspaces method to compute certain mode shapes of the velocity model computed by as an orthogonal base of reduced order modeling. Reverse time migration by reduced order modeling is helpful concerning the highly parallel computation and strongly reduces the memory requirement of reverse time migration. The synthetic model results showed that suggested method can decrease the computational costs of reverse time migration by several orders of magnitudes, compared with reverse time migration by finite element method.

  18. Flooding of the root system in soybean: biochemical and molecular aspects of N metabolism in the nodule during stress and recovery.

    PubMed

    Souza, Sarah C R; Mazzafera, Paulo; Sodek, Ladaslav

    2016-05-01

    Nitrogen fixation of the nodule of soybean is highly sensitive to oxygen deficiency such as provoked by waterlogging of the root system. This study aimed to evaluate the effects of flooding on N metabolism in nodules of soybean. Flooding resulted in a marked decrease of asparagine (the most abundant amino acid) and a concomitant accumulation of γ-aminobutyric acid (GABA). Flooding also resulted in a strong reduction of the incorporation of (15)N2 in amino acids. Nodule amino acids labelled before flooding rapidly lost (15)N during flooding, except for GABA, which initially increased and declined slowly thereafter. Both nitrogenase activity and the expression of nifH and nifD genes were strongly decreased on flooding. Expression of the asparagine synthetase genes SAS1 and SAS2 was reduced, especially the former. Expression of genes encoding the enzyme glutamic acid decarboxylase (GAD1, GAD4, GAD5) was also strongly suppressed except for GAD2 which increased. Almost all changes observed during flooding were reversible after draining. Possible changes in asparagine and GABA metabolism that may explain the marked fluctuations of these amino acids during flooding are discussed. It is suggested that the accumulation of GABA has a storage role during flooding stress.

  19. Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

    PubMed Central

    Doñate, F; Juarez, J C; Burnett, M E; Manuia, M M; Guan, X; Shaw, D E; Smith, E L P; Timucin, C; Braunstein, M J; Batuman, O A; Mazar, A P

    2008-01-01

    Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development. PMID:18253124

  20. Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats.

    PubMed

    Schurgers, Leon J; Spronk, Henri M H; Soute, Berry A M; Schiffers, Paul M; DeMey, Jo G R; Vermeer, Cees

    2007-04-01

    Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla protein (MGP) is a potent inhibitor of AC, and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K antagonist warfarin leads to rapid calcification of the arteries. Here, we investigated whether preformed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a normal (5 microg/g) or high (100 microg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K and also in the group changed to the normal dose of VK and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake.

  1. Effect of alkali on the structure of cell envelopes of Chlamydia psittaci elementary bodies.

    PubMed Central

    Narita, T; Wyrick, P B; Manire, G P

    1976-01-01

    Suspensions of isolated cell envelopes of infectious elementary bodies (EB) of Chlamydia psittaci at alkaline pH showed a rapid, extensive decrease in absorbance, accompanied by the release of a cell envelope component in a sedimentable form. This phenomenon was observed both at 0 C and with envelopes which had been previously heated to 100 C. Monovalent and divalent cations effectively inhibited the turbidity loss, whereas ethylenediaminetetraacetate (EDTA) caused an accelerated decrease in turbidity. The turbidity loss observed after incubation of the envelopes at alkaline pH could be reversed to the level of the initial value by dialysis against distilled water containing Mg2+. Thin-section electron photomicrographs of purified EB exposed to alkaline buffer with EDTA revealed the loss of the internal contents of cells, but these cells still maintained their round shapes. The cell surface of treated EB appeared pitted in negatively stained preparations, whereas intact EB had a smooth surface. Electron microscopic studies on negatively stained preparations of the clear supernatant obtained after the treatment of the envelope with alkaline buffer containing EDTA demonstrated the presence of spherical particles, approximately 6 to 7 nm in diameter, and rodlike particles, which appeared to be made up of two or more spherical particles. Images PMID:1375

  2. CARDIORESPIRATORY EFFECTS OF DEXMEDETOMIDINE-BUTORPHANOL-MIDAZOLAM (DBM): A FULLY REVERSIBLE ANESTHETIC PROTOCOL IN CAPTIVE AND SEMI-FREE-RANGING CHEETAHS (ACINONYX JUBATUS).

    PubMed

    Woc Colburn, A Margarita; Murray, Suzan; Hayek, Lee-Ann C; Marker, Laurie; Sanchez, Carlos R

    2017-03-01

    Multiple anesthesia protocols have been used in the cheetah ( Acinonyx jubatus ). Twenty healthy, captive cheetahs were immobilized with dexmedetomidine (15.8 ± 1.9 μg/kg), butorphanol (0.22 ± 0.03 mg/kg), and midazolam (0.18 ± 0.03 mg/kg) by intramuscular injection. Induction, recumbency, and recovery times were recorded, and physiologic parameters were monitored. Anesthesia was antagonized with atipamezole (0.125 ± 0.02 mg/kg) and naltrexone (0.1 ± 0.014 mg/kg) intramuscularly. All cheetahs were safely anesthetized with this protocol. Cheetahs were laterally recumbent by 8 ± 3.5 min. Cardiorespiratory values were stable throughout the length of anesthesia. Moderate hypertension, with systolic blood pressure ranging from 178 ± 19.8 mm Hg, was initially observed but decreased over time. There was a statistical decreasing trend in temperature; SpO2; and systolic, mean, and diastolic blood pressure, but not in heart rate and end-tidal CO 2 . Recoveries were rapid, with cheetahs standing by 11.3 ± 5.7 min postreversal administration. This is the first report of a dexmedetomidine-butorphanol-midazolam anesthetic combination in cheetahs. Overall, this anesthetic protocol proved to be safe and effective.

  3. Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin.

    PubMed

    Kurowska, Elzbieta M; Manthey, John A; Casaschi, Adele; Theriault, Andre G

    2004-02-01

    The purpose of the present study was to examine the role of tangeretin, a polymethoxylated flavone from citrus fruits, on the regulation of apolipoprotein B (apoB) and lipid metabolism in the human hepatoma cell-line HepG2. The marked reduction in apoB secretion observed in cells incubated with 72.8 microM tangeretin was rapid, apoB-specific, and partly reversible. The reduction also was observed under lipid-rich conditions and found to be insensitive to proteasomal degradation of nascent apoB. We followed our study by examining lipid synthesis and mass. A 24-h exposure of cells to 72.8 microM tangeretin decreased intracellular synthesis of cholesteryl esters, free cholesterol, and TAG by 82, 45, and 64%, respectively; tangeretin also reduced the mass of cellular TAG by 37%. The tangeretin-induced suppression of TAG synthesis and mass were associated with decreased activities of DAG acyltransferase (up to -39.0 +/- 3.0% vs. control) and microsomal triglyceride transfer protein (up to -35.5 +/- 2.5% vs. control). Tangeretin was also found to activate the peroxisome proliferator-activated receptor, a transcription factor with a positive regulatory impact on FA oxidation and TAG availability (up to 36% increase vs. control). The data suggest that tangeretin modulates apoB-containing lipoprotein metabolism through multiple mechanisms.

  4. Laying-sequence-specific variation in yolk oestrogen levels, and relationship to plasma oestrogen in female zebra finches (Taeniopygia guttata)

    PubMed Central

    Williams, Tony D.; Ames, Caroline E.; Kiparissis, Yiannis; Wynne-Edwards, Katherine E.

    2005-01-01

    We investigated the relationship between plasma and yolk oestrogens in laying female zebra finches (Taeniopygia guttata) by manipulating plasma oestradiol (E2) levels, via injection of oestradiol-17β, in a sequence-specific manner to maintain chronically high plasma levels for later-developing eggs (contrasting with the endogenous pattern of decreasing plasma E2 concentrations during laying). We report systematic variation in yolk oestrogen concentrations, in relation to laying sequence, similar to that widely reported for androgenic steroids. In sham-manipulated females, yolk E2 concentrations decreased with laying sequence. However, in E2-treated females plasma E2 levels were higher during the period of rapid yolk development of later-laid eggs, compared with control females. As a consequence, we reversed the laying-sequence-specific pattern of yolk E2: in E2-treated females, yolk E2 concentrations increased with laying-sequence. In general therefore, yolk E2 levels were a direct reflection of plasma E2 levels. However, in control females there was some inter-individual variability in the endogenous pattern of plasma E2 levels through the laying cycle which could generate variation in sequence-specific patterns of yolk hormone levels even if these primarily reflect circulating steroid levels. PMID:15695208

  5. Microfluidic system for facilitated quantification of nanoparticle accumulation to cells under laminar flow

    PubMed Central

    Kusunose, Jiro; Zhang, Hua; Gagnon, M. Karen J.; Pan, Tingrui; Simon, Scott I.; Ferrara, Katherine W.

    2012-01-01

    The identification of novel, synthetic targeting ligands to endothelial receptors has led to the rapid development of targeted nanoparticles for drug, gene and imaging probe delivery. Central to development and optimization are effective models for assessing particle binding in vitro. Here, we developed a simple and cost effective method to quantitatively assess nanoparticle accumulation under physiologically-relevant laminar flow. We designed reversibly vacuum–sealed PDMS microfluidic chambers compatible with 35 mm petri dishes, which deliver uniform or gradient shear stress. These chambers have sufficient surface area for facile cell collection for particle accumulation quantitation through FACS. We tested this model by synthesizing and flowing liposomes coated with APN (KD ~ 300 µM) and VCAM-1-targeting (KD ~ 30 µM) peptides over HUVEC. Particle binding significantly increased with ligand concentration (up to 6 mol%) and decreased with excess PEG. While the accumulation of particles with the lower affinity ligand decreased with shear, accumulation of those with the higher affinity ligand was highest in a low shear environment (2.4 dyne/cm2), as compared with greater shear or the absence of shear. We describe here a robust flow chamber model that is applied to optimize the properties of 100 nm liposomes targeted to inflamed endothelium. PMID:22855121

  6. Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.

    PubMed

    Guo, Lengqiu; Guo, Zhuangli; Luo, Xiaoqing; Liang, Rui; Yang, Shui; Ren, Haigang; Wang, Guanghui; Zhen, Xuechu

    2016-12-02

    Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Secular Dynamical Anti-friction in Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Madigan, Ann-Marie; Levin, Yuri

    2012-07-01

    We identify a gravitational-dynamical process in near-Keplerian potentials of galactic nuclei that occurs when an intermediate-mass black hole (IMBH) is migrating on an eccentric orbit through the stellar cluster towards the central supermassive black hole. We find that, apart from conventional dynamical friction, the IMBH experiences an often much stronger systematic torque due to the secular (i.e., orbit-averaged) interactions with the cluster's stars. The force which results in this torque is applied, counterintuitively, in the same direction as the IMBH's precession and we refer to its action as "secular dynamical anti-friction" (SDAF). We argue that SDAF, and not the gravitational ejection of stars, is responsible for the IMBH's eccentricity increase seen in the initial stages of previous N-body simulations. Our numerical experiments, supported by qualitative arguments, demonstrate that (1) when the IMBH's precession direction is artificially reversed, the torque changes sign as well, which decreases the orbital eccentricity; (2) the rate of eccentricity growth is sensitive to the IMBH migration rate, with zero systematic eccentricity growth for an IMBH whose orbit is artificially prevented from inward migration; and (3) SDAF is the strongest when the central star cluster is rapidly rotating. This leads to eccentricity growth/decrease for the clusters rotating in the opposite/same direction relative to the IMBH's orbital motion.

  8. A role for jasmonates in the release of dormancy by cold stratification in wheat

    PubMed Central

    Xu, Qian; Truong, Thy T.; Barrero, Jose M.; Jacobsen, John V.; Hocart, Charles H.; Gubler, Frank

    2016-01-01

    Hydration at low temperatures, commonly referred to as cold stratification, is widely used for releasing dormancy and triggering germination in a wide range of species including wheat. However, the molecular mechanism that underlies its effect on germination has largely remained unknown. Our previous studies showed that methyl-jasmonate, a derivative of jasmonic acid (JA), promotes dormancy release in wheat. In this study, we found that cold-stimulated germination of dormant grains correlated with a transient increase in JA content and expression of JA biosynthesis genes in the dormant embryos after transfer to 20 oC. The induction of JA production was dependent on the extent of cold imbibition and precedes germination. Blocking JA biosynthesis with acetylsalicylic acid (ASA) inhibited the cold-stimulated germination in a dose-dependent manner. In addition, we have explored the relationship between JA and abscisic acid (ABA), a well-known dormancy promoter, in cold regulation of dormancy. We found an inverse relationship between JA and ABA content in dormant wheat embryos following stratification. ABA content decreased rapidly in response to stratification, and the decrease was reversed by addition of ASA. Our results indicate that the action of JA on cold-stratified grains is mediated by suppression of two key ABA biosynthesis genes, TaNCED1 and TaNCED2. PMID:27140440

  9. Potentiometric determination of trypsin using a polymeric membrane polycation-sensitive electrode based on current-controlled reagent delivery.

    PubMed

    Chen, Yan; Ding, Jiawang; Qin, Wei

    2012-12-01

    A potentiometric biosensor for the determination of trypsin is described based on current-controlled reagent delivery. A polymeric membrane protamine-sensitive electrode with dinonylnaphthalene sulfonate as cation exchanger is used for in situ generation of protamine. Diffusion of protamine across the polymeric membrane can be controlled precisely by applying an external current. The hydrolysis catalyzed with trypsin in sample solution decreases the concentration of free protamine released at the sample-membrane interface and facilitates the stripping of protamine out of the membrane surface via the ion-exchange process with sodium ions from the sample solution, thus decreasing the membrane potential, by which the protease can be sensed potentiometrically. The influences of anodic current amplitude, current pulse duration and protamine concentration in the inner filling solution on the membrane potential response have been studied. Under optimum conditions, the proposed protamine-sensitive electrode is useful for continuous and reversible detection of trypsin over the concentration range of 0.5-5UmL(-1) with a detection limit of 0.3UmL(-1). The proposed detection strategy provides a rapid and reagentless way for the detection of protease activities and offers great potential in the homogeneous immunoassays using proteases as labels. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Ecological Impacts of Reverse Speciation in Threespine Stickleback.

    PubMed

    Rudman, Seth M; Schluter, Dolph

    2016-02-22

    Young species are highly prone to extinction via increased gene flow after human-caused environmental changes. This mechanism of biodiversity loss, often termed reverse speciation or introgressive extinction, is of exceptional interest because the parent species are typically highly differentiated ecologically. Reverse speciation events are potentially powerful case studies for the role of evolution in driving ecological changes, as the phenotypic shifts associated with introgressive extinction can be large and they occur over particularly short timescales. Furthermore, reverse speciation can lead to novel phenotypes, which may in turn produce novel ecological effects. Here we investigate the ecological shift associated with reverse speciation in threespine stickleback fish using a field study and a replicated experiment. We find that an instance of introgressive extinction had cascading ecological consequences that altered the abundance of both aquatic prey and the pupating aquatic insects that emerged into the terrestrial ecosystem. The community and ecosystem impacts of reverse speciation were novel, and yet they were also predictable based on ecological and morphological considerations. The study suggests that knowledge about the community ecology and changes in functional morphology of a dominant species may lead to some predictive power for the ecological effects of evolutionary change. Moreover, the rapid nature and resultant ecological impacts associated with reverse speciation demonstrates the interplay between biodiversity, evolutionary change, and ecosystem function. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. ExpoCast Framework for Rapid Exposure Forecasts (ISES ExpoDat symposium presentation)

    EPA Science Inventory

    The U.S. E.P.A. ExpoCast project uses high throughput exposure models (simulation) and any easily-obtained exposure heuristics to generate forward predictions of potential exposures from chemical properties. By comparison with exposures inferred via reverse pharmacokinetic modeli...

  12. [Development of computer aided forming techniques in manufacturing scaffolds for bone tissue engineering].

    PubMed

    Wei, Xuelei; Dong, Fuhui

    2011-12-01

    To review recent advance in the research and application of computer aided forming techniques for constructing bone tissue engineering scaffolds. The literature concerning computer aided forming techniques for constructing bone tissue engineering scaffolds in recent years was reviewed extensively and summarized. Several studies over last decade have focused on computer aided forming techniques for bone scaffold construction using various scaffold materials, which is based on computer aided design (CAD) and bone scaffold rapid prototyping (RP). CAD include medical CAD, STL, and reverse design. Reverse design can fully simulate normal bone tissue and could be very useful for the CAD. RP techniques include fused deposition modeling, three dimensional printing, selected laser sintering, three dimensional bioplotting, and low-temperature deposition manufacturing. These techniques provide a new way to construct bone tissue engineering scaffolds with complex internal structures. With rapid development of molding and forming techniques, computer aided forming techniques are expected to provide ideal bone tissue engineering scaffolds.

  13. Choosing Fitness-Enhancing Innovations Can Be Detrimental under Fluctuating Environments

    PubMed Central

    Xue, Julian Z.; Costopoulos, Andre; Guichard, Frederic

    2011-01-01

    The ability to predict the consequences of one's behavior in a particular environment is a mechanism for adaptation. In the absence of any cost to this activity, we might expect agents to choose behaviors that maximize their fitness, an example of directed innovation. This is in contrast to blind mutation, where the probability of becoming a new genotype is independent of the fitness of the new genotypes. Here, we show that under environments punctuated by rapid reversals, a system with both genetic and cultural inheritance should not always maximize fitness through directed innovation. This is because populations highly accurate at selecting the fittest innovations tend to over-fit the environment during its stable phase, to the point that a rapid environmental reversal can cause extinction. A less accurate population, on the other hand, can track long term trends in environmental change, keeping closer to the time-average of the environment. We use both analytical and agent-based models to explore when this mechanism is expected to occur. PMID:22125601

  14. [A patient with high creatinine levels but no renal failure: reversed autodialysis in a patient with a ruptured bladder].

    PubMed

    Raeymaeckers, Steven; Tosi, Maurizio; Van Bael, Kobe; Brussaard, Carola; De Mey, Johan

    2016-01-01

    In case of a ruptured bladder with urine leakage into the peritoneal cavity 'reversed autodialysis' can occur, in which urea and creatinine diffuse back into the bloodstream via the peritoneum. This causes clinical signs of pseudorenal failure, with raised concentrations of creatinine and urea. The urea/creatinine ratio does not change. A 34-year-old female patient experienced increasing abdominal pain 3 days after laparoscopic myomectomy. Acute renal failure was suspected because of increased serum concentrations of creatinine and urea, but no cause could be found. There was a build-up of fluid in the abdominal cavity, which proved to be urine originating from an iatrogenic rupture of the bladder. Serum levels normalised following repair of the rupture. If serum creatinine levels rise rapidly following abdominal surgery or blunt abdominal trauma the bladder should be examined for possible perforation, particularly if the abdominal dimension increases. A ruptured bladder leading to pseudorenal failure is an indication for rapid surgical intervention.

  15. Posterior reversible encephalopathy syndrome (PRES) after bariatric surgery—a potential consequence associated with rapid withdrawal of antihypertensive medications

    PubMed Central

    Meireles, Ozanan R; Bredella, Miriam A

    2015-01-01

    A 61-year-old woman with a medical history of intracerebral haemorrhage, hypertension, hyperlipidaemia and carotid stenosis presented to the emergency department with altered mental status 3 weeks after undergoing a vertical sleeve gastrectomy for severe obesity. She presented with a hypertensive emergency and a National Institutes of Health Stroke Scale of 4. CT of the head was unrevealing. MRI showed an abnormal signal within the bilateral posterior border-zone areas, with several foci in the parietal and occipital lobes, and thalami, suggestive of posterior reversible encephalopathy syndrome (PRES). The patient was initially placed on a labetalol drip and her preoperative antihypertensive medications—amlodipine, captopril, triamterene and hydrochlorothiazide—were gradually reintroduced. She returned to her baseline and was stable on discharge. Rapid withdrawal of antihypertensive medications in the early postoperative period of bariatric surgery was the aetiology of PRES in this patient. This case report discusses postoperative care of bariatric surgery patients having hypertension. PMID:26698202

  16. In situ regeneration of bioactive coatings enabled by an evolved Staphylococcus aureus sortase A

    NASA Astrophysics Data System (ADS)

    Ham, Hyun Ok; Qu, Zheng; Haller, Carolyn A.; Dorr, Brent M.; Dai, Erbin; Kim, Wookhyun; Liu, David R.; Chaikof, Elliot L.

    2016-04-01

    Surface immobilization of bioactive molecules is a central paradigm in the design of implantable devices and biosensors with improved clinical performance capabilities. However, in vivo degradation or denaturation of surface constituents often limits the long-term performance of bioactive films. Here we demonstrate the capacity to repeatedly regenerate a covalently immobilized monomolecular thin film of bioactive molecules through a two-step stripping and recharging cycle. Reversible transpeptidation by a laboratory evolved Staphylococcus aureus sortase A (eSrtA) enabled the rapid immobilization of an anti-thrombogenic film in the presence of whole blood and permitted multiple cycles of film regeneration in vitro that preserved its biological activity. Moreover, eSrtA transpeptidation facilitated surface re-engineering of medical devices in situ after in vivo implantation through removal and restoration film constituents. These studies establish a rapid, orthogonal and reversible biochemical scheme to regenerate selective molecular constituents with the potential to extend the lifetime of bioactive films.

  17. Dual-responsive and Multi-functional Plasmonic Hydrogel Valves and Biomimetic Architectures Formed with Hydrogel and Gold Nanocolloids

    PubMed Central

    Song, Ji Eun; Cho, Eun Chul

    2016-01-01

    We present a straightforward approach with high moldability for producing dual-responsive and multi-functional plasmonic hydrogel valves and biomimetic architectures that reversibly change volumes and colors in response to temperature and ion variations. Heating of a mixture of hybrid colloids (gold nanoparticles assembled on a hydrogel colloid) and hydrogel colloids rapidly induces (within 30 min) the formation of hydrogel architectures resembling mold shapes (cylinder, fish, butterfly). The biomimetic fish and butterfly display reversible changes in volumes and colors with variations of temperature and ionic conditions in aqueous solutions. The cylindrical plasmonic valves installed in flow tubes rapidly control water flow rate in on-off manner by responding to these stimuli. They also report these changes in terms of their colors. Therefore, the approach presented here might be helpful in developing new class of biomimetic and flow control systems where liquid conditions should be visually notified (e.g., glucose or ion concentration changes). PMID:27703195

  18. Differential Regulation of Telomerase Reverse Transcriptase Promoter Activation and Protein Degradation by Histone Deacetylase Inhibition.

    PubMed

    Qing, Hua; Aono, Jun; Findeisen, Hannes M; Jones, Karrie L; Heywood, Elizabeth B; Bruemmer, Dennis

    2016-06-01

    Telomerase reverse transcriptase (TERT) maintains telomeres and is rate limiting for replicative life span. While most somatic tissues silence TERT transcription resulting in telomere shortening, cells derived from cancer or cardiovascular diseases express TERT and activate telomerase. In the present study, we demonstrate that histone deacetylase (HDAC) inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Finally, we demonstrate that HDAC inhibition decreases TERT expression during vascular remodeling in vivo. These data illustrate a differential regulation of TERT transcription and protein stability by HDAC inhibition and suggest that TERT may constitute an important target for the anti-proliferative efficacy of HDAC inhibitors. © 2015 Wiley Periodicals, Inc.

  19. Dietary glutamine supplementation partly reverses impaired macrophage function resulting from overload training in rats.

    PubMed

    Xiao, Weihua; Chen, Peijie; Dong, Jingmei; Wang, Ru; Luo, Beibei

    2015-04-01

    The aim of this study was to evaluate the effect of overload training on the function of peritoneal macrophages in rats, and to test the hypothesis that glutamine in vivo supplementation would partly reverse the eventual functional alterations induced by overload training in these cells. Forty male Wistar rats were randomly divided into 5 groups: control group (C), overload training group (E1), overload training and restore one week group (E2), glutamine-supplementation group (EG1), and glutamine-supplementation and restore 1-week group (EG2). All rats, except those placed on sedentary control were subjected to 11 weeks of overload training protocol. Blood hemoglobin, serum testosterone, and corticosterone of rats were measured. Moreover, the functions (chemotaxis, phagocytosis, cytokines synthesis, reactive oxygen species generation) of peritoneal macrophages were determined. Data showed that blood hemoglobin, serum testosterone, corticosterone and body weight in the overload training group decreased significantly as compared with the control group. Meanwhile, the chemotaxis capacity (decreased by 31%, p = .003), the phagocytosis capacity (decreased by 27%, p = .005), the reactive oxygen species (ROS) generation (decreased by 35%, p = .003) and the cytokines response capability of macrophages were inhibited by overload training. However, the hindering of phagocytosis and the cytokines response capability of macrophages induced by overload training could be ameliorated and reversed respectively, by dietary glutamine supplementation. These results suggest that overload training impairs the function of peritoneal macrophages, which is essential for the microbicidal actions of macrophages. This may represent a novel mechanism of immunodepression induced by overload training. Nonetheless, dietary glutamine supplementation could partly reverse the impaired macrophage function resulting from overload training.

  20. Phonological False Memories in Children and Adults: Evidence for a Developmental Reversal

    ERIC Educational Resources Information Center

    Swannell, Ellen R.; Dewhurst, Stephen A.

    2012-01-01

    False memories created by the Deese/Roediger-McDermott (DRM) procedure typically show a developmental reversal whereby levels of false recall increase with age. In contrast, false memories produced by phonological lists have been shown to decrease as age increases. In the current study we show that phonological false memories, like semantic false…

  1. A School-Based Application of Modified Habit Reversal for Tourette Syndrome via a Translator: A Case Study

    ERIC Educational Resources Information Center

    Gilman, Rich; Connor, Nancy; Haney, Michelle

    2005-01-01

    A school-based modified habit reversal intervention was utilized with an adolescent diagnosed with Tourette syndrome who recently immigrated from Mexico. Because the student possessed little proficiency of the English language, an interpreter was needed to help implement the procedure. The frequency of motor tics markedly decreased from baseline…

  2. Application of Reverse Transcriptase-PCR-DGGE as a rapid method for routine determination of Vibrio spp. in foods.

    PubMed

    Chahorm, Kanchana; Prakitchaiwattana, Cheunjit

    2018-01-02

    The aim of this research was to evaluate the feasibility of PCR-DGGE and Reverse Transcriptase-PCR-DGGE techniques for rapid detection of Vibrio species in foods. Primers GC567F and 680R were initially evaluated for amplifying DNA and cDNA of ten references Vibrio species by PCR method. The GC-clamp PCR amplicons were separated according to their sequences by the DGGE using 10% (w/v) polyacrylamide gel containing 45-70% urea and formamide denaturants. Two pair of Vibrio species, which could not be differentiated on the gel, was Vibrio fluvialis - Vibrio furnissii and Vibrio parahaemolyticus - Vibrio harveyi. To determine the detection limit, in the community of 10 reference strains containing the same viable population, distinct DNA bands of 3 species; Vibrio cholerae, Vibrio mimicus and Vibrio alginolyticus were consistently observed by PCR-DGGE technique. In fact, 5 species; Vibrio cholerae, Vibrio mimicus, Vibrio alginolyticus, Vibrio parahaemolyticus and Vibrio fluvialis consistently observed by Reverse Transcriptase-PCR-DGGE. In the community containing different viable population increasing from 10 2 to 10 5 CFU/mL, PCR-DGGE analysis only detected the two most prevalent species, while RT-PCR-DGGE detected the five most prevalent species. Therefore, Reverse Transcriptase-PCR-DGGE was also selected for detection of various Vibrio cell conditions, including viable cell (VC), injured cells from frozen cultures (IVC) and injured cells from frozen cultures with pre-enrichment (PIVC). It was found that cDNA band of all cell conditions gave the same migratory patterns, except that multiple cDNA bands of Plesiomonas shigelloides under IVC and PIVC conditions were found. When Reverse Transcriptase-PCR-DGGE was used for detecting Vibrio parahaemolyticus in the pathogen-spiked food samples, Vibrio parahaemolyticus could be detected in the spiked samples containing at least 10 2 CFU/g of this pathogen. The results obtained also corresponded to standard method (USFDA, 2004). In comparison with the detection of the Vibrio profiles in fourteen food samples using standard method, Reverse Transcriptase-PCR-DGGE resulted in 100%, 75% and 50% similarity in 3, 1 and 6 food samples, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Rapid diagnosis of pulmonary tuberculosis and detection of drug resistance by combined simultaneous amplification testing and reverse dot blot.

    PubMed

    Chen, Yiwen; Zhang, Lahong; Hong, Liquan; Luo, Xian; Chen, Juping; Tang, Leiming; Chen, Jiahuan; Liu, Xia; Chen, Zhaojun

    2018-06-01

    Making a correct and rapid diagnosis is essential for managing pulmonary tuberculosis (PTB), particularly multidrug-resistant tuberculosis. We aimed to evaluate the efficacy of the combination of simultaneous amplification testing (SAT) and reverse dot blot (RDB) for the rapid detection of Mycobacterium tuberculosis (MTB) and drug-resistant mutants in respiratory samples. 225 suspected PTB and 32 non-TB pulmonary disease samples were collected. All sputum samples were sent for acid-fast bacilli smear, SAT, culture and drug susceptibility testing (DST) by the BACTEC TM MGIT TM 960 system. 53 PTB samples were tested by both RDB and DNA sequencing to identify drug resistance genes and mutated sites. The SAT positive rate (64.9%) was higher than the culture positive rate (55.1%), with a coincidence rate of 83.7%. The sensitivity and specificity of SAT for diagnosing PTB were 66.7% and 100%, respectively, while those for culture were 53.9% and 84.2%, respectively. RDB has high sensitivity and specificity in identifying drug resistance genes and mutated sites. The results of RDB correlated well with those of DST and DNA sequencing, with coincidence rates of 92.5% and 98.1%, respectively. The combination of SAT and RDB is promising for rapidly detecting PTB and monitoring drug resistance in clinical laboratories. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Water dynamics in large and small reverse micelles: From two ensembles to collective behavior

    PubMed Central

    Moilanen, David E.; Fenn, Emily E.; Wong, Daryl; Fayer, Michael D.

    2009-01-01

    The dynamics of water in Aerosol-OT reverse micelles are investigated with ultrafast infrared spectroscopy of the hydroxyl stretch. In large reverse micelles, the dynamics of water are separable into two ensembles: slow interfacial water and bulklike core water. As the reverse micelle size decreases, the slowing effect of the interface and the collective nature of water reorientation begin to slow the dynamics of the core water molecules. In the smallest reverse micelles, these effects dominate and all water molecules have the same long time reorientational dynamics. To understand and characterize the transition in the water dynamics from two ensembles to collective reorientation, polarization and frequency selective infrared pump-probe experiments are conducted on the complete range of reverse micelle sizes from a diameter of 1.6–20 nm. The crossover between two ensemble and collective reorientation occurs near a reverse micelle diameter of 4 nm. Below this size, the small number of confined water molecules and structural changes in the reverse micelle interface leads to homogeneous long time reorientation. PMID:19586114

  5. Quantitative determination for cytotoxic Friedo-nor-oleanane derivatives from five morphological types of Maytenus ilicifolia (Celastraceae) by reverse-phase high-performance liquid chromatography.

    PubMed

    Buffa Filho, Waldemar; Corsino, Joaquim; Bolzani, da Silva Vanderlan; Furlan, Maysa; Pereira, Ana Maria S; França, Suzelei Castro

    2002-01-01

    Five different morphological types of Maytenus ilicifolia of the same age and harvested under the same conditions showed distinct accumulations of some friedo-nor-oleananes. A rapid, sensitive and reliable reverse-phase HPLC method (employing an external standard) was used for the determination of the cytotoxic triterpenoids, 20 alpha-hydroxymaytenin, 22 beta-hydroxymaytenin, maytenin, celastrol and pristimerin in each of the five types. Well resolved peaks with good detection response and linearity in the range 1.0-100 micrograms/mL were obtained.

  6. On the sensitivity of transtensional versus transpressional tectonic regimes to remote dynamic triggering by Coulomb failure

    USGS Publications Warehouse

    Hill, David P.

    2015-01-01

     Accumulating evidence, although still strongly spatially aliased, indicates that although remote dynamic triggering of small-to-moderate (Mw<5) earthquakes can occur in all tectonic settings, transtensional stress regimes with normal and subsidiary strike-slip faulting seem to be more susceptible to dynamic triggering than transpressional regimes with reverse and subsidiary strike-slip faulting. Analysis of the triggering potential of Love- and Rayleigh-wave dynamic stresses incident on normal, reverse, and strike-slip faults assuming Andersonian faulting theory and simple Coulomb failure supports this apparent difference for rapid-onset triggering susceptibility.

  7. Spontaneous Generation of a Sheared Plasma Rotation in a Field-Reversed θ-Pinch Discharge

    NASA Astrophysics Data System (ADS)

    Omelchenko, Y. A.; Karimabadi, H.

    2012-08-01

    By conducting two-dimensional hybrid simulations of an infinitely long field-reversed θ-pinch discharge we discover a new type of plasma rotation, which rapidly develops at the plasma edge in the ion diamagnetic direction due to the self-consistent generation of a Hall-driven radial electric field. This effect is different from the previously identified end-shorting and particle-loss mechanisms. We also demonstrate flutelike perturbations frequently inferred in experiments and show that in the absence of axial contraction effects they may quickly alter the toroidal symmetry of the plasma.

  8. Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training

    PubMed Central

    Walsh, Christine M.; Booth, Victoria; Poe, Gina R.

    2011-01-01

    This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampus-dependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation–associated impairment in initial spatial learning with four trials/day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items. PMID:21677190

  9. PageRank and rank-reversal dependence on the damping factor

    NASA Astrophysics Data System (ADS)

    Son, S.-W.; Christensen, C.; Grassberger, P.; Paczuski, M.

    2012-12-01

    PageRank (PR) is an algorithm originally developed by Google to evaluate the importance of web pages. Considering how deeply rooted Google's PR algorithm is to gathering relevant information or to the success of modern businesses, the question of rank stability and choice of the damping factor (a parameter in the algorithm) is clearly important. We investigate PR as a function of the damping factor d on a network obtained from a domain of the World Wide Web, finding that rank reversal happens frequently over a broad range of PR (and of d). We use three different correlation measures, Pearson, Spearman, and Kendall, to study rank reversal as d changes, and we show that the correlation of PR vectors drops rapidly as d changes from its frequently cited value, d0=0.85. Rank reversal is also observed by measuring the Spearman and Kendall rank correlation, which evaluate relative ranks rather than absolute PR. Rank reversal happens not only in directed networks containing rank sinks but also in a single strongly connected component, which by definition does not contain any sinks. We relate rank reversals to rank pockets and bottlenecks in the directed network structure. For the network studied, the relative rank is more stable by our measures around d=0.65 than at d=d0.

  10. Comparison of reversal with neostigmine of low-dose rocuronium vs. reversal with sugammadex of high-dose rocuronium for a short procedure.

    PubMed

    Choi, E S; Oh, A Y; Koo, B W; Hwang, J W; Han, J W; Seo, K S; Ahn, S H; Jeong, W J

    2017-10-01

    Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty-four patients undergoing elective laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg -1 with neostigmine (50 μg.kg -1 with glycopyrrolate 10 μg.kg -1 ) reversal (moderate block group) vs. rocuronium 0.90 mg.kg -1 with sugammadex (4 mg.kg -1 ) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra-operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro-surgery, the use of rocuronium 0.9 mg.kg -1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg -1 with neostigmine. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  11. Metabonomics applied in exploring the antitumour mechanism of physapubenolide on hepatocellular carcinoma cells by targeting glycolysis through the Akt-p53 pathway

    PubMed Central

    Ma, Ting; Fan, Bo-Yi; Zhang, Chao; Zhao, Hui-Jun; Han, Chao; Gao, Cai-Yun; Luo, Jian-Guang; Kong, Ling-Yi

    2016-01-01

    Metabolomics can be used to identify potential markers and discover new targets for future therapeutic interventions. Here, we developed a novel application of the metabonomics method based on gas chromatography-mass spectrometry (GC/MS) analysis and principal component analysis (PCA) for rapidly exploring the anticancer mechanism of physapubenolide (PB), a cytotoxic withanolide isolated from Physalis species. PB inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vivo, accompanied by apoptosis-related biochemical events, including the cleavage of caspase-3/7/9 and PARP. Metabolic profiling analysis revealed that PB disturbed the metabolic pattern and significantly decreased lactate production. This suggests that the suppression of glycolysis plays an important role in the anti-tumour effects induced by PB, which is further supported by the decreased expression of glycolysis-related genes and proteins. Furthermore, the increased level of p53 and decreased expression of p-Akt were observed, and the attenuated glycolysis and enhanced apoptosis were reversed in the presence of Akt cDNA or p53 siRNA. These results confirm that PB exhibits anti-cancer activities through the Akt-p53 pathway. Our study not only reports for the first time the anti-tumour mechanism of PB, but also suggests that PB is a promising therapeutic agent for use in cancer treatments and that metabolomic approaches provide a new strategy to effectively explore the molecular mechanisms of promising anticancer compounds. PMID:27416811

  12. Metabonomics applied in exploring the antitumour mechanism of physapubenolide on hepatocellular carcinoma cells by targeting glycolysis through the Akt-p53 pathway.

    PubMed

    Ma, Ting; Fan, Bo-Yi; Zhang, Chao; Zhao, Hui-Jun; Han, Chao; Gao, Cai-Yun; Luo, Jian-Guang; Kong, Ling-Yi

    2016-07-15

    Metabolomics can be used to identify potential markers and discover new targets for future therapeutic interventions. Here, we developed a novel application of the metabonomics method based on gas chromatography-mass spectrometry (GC/MS) analysis and principal component analysis (PCA) for rapidly exploring the anticancer mechanism of physapubenolide (PB), a cytotoxic withanolide isolated from Physalis species. PB inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vivo, accompanied by apoptosis-related biochemical events, including the cleavage of caspase-3/7/9 and PARP. Metabolic profiling analysis revealed that PB disturbed the metabolic pattern and significantly decreased lactate production. This suggests that the suppression of glycolysis plays an important role in the anti-tumour effects induced by PB, which is further supported by the decreased expression of glycolysis-related genes and proteins. Furthermore, the increased level of p53 and decreased expression of p-Akt were observed, and the attenuated glycolysis and enhanced apoptosis were reversed in the presence of Akt cDNA or p53 siRNA. These results confirm that PB exhibits anti-cancer activities through the Akt-p53 pathway. Our study not only reports for the first time the anti-tumour mechanism of PB, but also suggests that PB is a promising therapeutic agent for use in cancer treatments and that metabolomic approaches provide a new strategy to effectively explore the molecular mechanisms of promising anticancer compounds.

  13. Immobilization of mule deer with thiafentanil (A-3080) or thiafentanil plus xylazine.

    PubMed

    Wolfe, Lisa L; Lance, William R; Miller, Michael W

    2004-04-01

    We evaluated thiafentanil oxalate (A-3080) for the immobilization of mule deer (Odocoileus hemionus) under laboratory and field conditions. In a crossover experiment comparing recommended (0.1 mg/kg) and 2x recommended thiafentanil doses in captive deer, both produced rapid induction and immobilization. Mean induction was shorter (P = 0.013) for the 2x group (1.9 vs. 3 min); mean reversals for both groups were rapid (recommended = 0.9 min after naltrexone injection; 2x = 1 min) and did not differ (P = 0.29). Six free-ranging mule deer were immobilized with 7 mg thiafentanil and four with 10 mg; mean induction was 2.3 min for both groups (95% confidence interval [CI]: 7 mg, 1.2-3.4; 10 mg, 1.9-2.8), and mean reversal was <1 min for both groups. Of 165 free-ranging deer darted with various combinations of thiafentanil and xylazine, we successfully immobilized 148 (90%). Mean induction ranged from 2.1 to 4.9 min for different drug combinations. Reversals were not compared because naltrexone and yohimbine doses varied, but overall mean reversal was 1.9 min (95% CI, 1.7-2.1 min) after injection of naltrexone and yohimbine intravenously (i.v.); naltrexone:thiafentanil ratios ranging from 10:1 to 43:1 provided mean recoveries ranging from 1.5 to 2.3 min. All 25 deer fitted with radio collars were alive at 30 days postcapture. On the basis of overall reliability and effectiveness, drug volumes, and ease of handling drugged animals, we recommend using a combination of 10-12 mg thiafentanil (0.15-0.2 mg/kg) and 100 mg xylazine to immobilize mule deer; immobilization can be effectively reversed with 100 mg naltrexone or more and 15 mg yohimbine or more i.v. Where feasible, we also recommend the use of transmitter darts when immobilizing mule deer with opioids in order to maximize recovery of darted deer and to ensure that missed darts are found.

  14. The pattern of acropetal and basipetal cytoplasmic streaming velocities in Chara rhizoids and protonemata, and gravity effect on the pattern as measured by laser-Doppler-velocimetry.

    PubMed

    Ackers, D; Buchen, B; Hejnowicz, Z; Sievers, A

    2000-06-01

    The spatial pattern of acropetal and basipetal cytoplasmic streaming velocities has been studied by laser-Doppler-velocimetry (LDV) in the positively gravitropic (downward growing) rhizoids of Chara globularis Thuill. and for the first time in the negatively gravitropic (upward growing) protonemata. The LDV method proved to be precise and yielded reproducible results even when tiny differences in velocities were measured. In the apical parts of the streaming regions of both cell types, acropetal streaming was faster than basipetal streaming. Starting at the apical reversal point of streaming, the velocity increased basipetally with the distance from that point and became fairly constant close to the basal reversal point; subsequently, the velocity decreased slightly acropetally as the apical reversal point was again approached. There was no change in velocity at the basal reversal point. However, at the apical reversal point there was an abrupt decrease in velocity. The pattern of the ratio of acropetal to basipetal streaming velocity (VR) was a function of the relative distance of the site of measurement from the apical reversal point rather than a function of the absolute distance. Upon inversion of the rhizoids, the VR decreased on average by 3.8% (+/- 0.4%), indicating that the effect of gravity on the streaming velocity was merely physical and without a physiological amplification. Rhizoids that had developed on the slowly rotating horizontal axis of a clinostat, and had never experienced a constant gravity vector, were similar to normally grown rhizoids with respect to VR pattern. In protonemata, the VR pattern was not significantly different from that in rhizoids although the direction of growth was inverse. In rhizoids, oryzalin caused the polar organization of the cell to disappear and nullified the differences in streaming velocities, and cytochalasin D decreased the velocity of basipetal streaming slightly more than that of acropetal streaming. Cyclopiazonic acid, known as an inhibitor of the Ca2+-ATPase of the endoplasmic reticulum, also reduced the streaming velocities in rhizoids, but had slightly more effect on the acropetal stream. It is possible that the endogenous difference in streaming velocities in both rhizoids and protonemata is caused by differences in the cytoskeletal organization of the opposing streams and/or loading of inhibitors (like Ca2+) from the apical/subapical zone into the basipetally streaming endoplasm.

  15. High stoma prevalence and stoma reversal complications following anterior resection for rectal cancer: a population-based multicentre study.

    PubMed

    Holmgren, K; Kverneng Hultberg, D; Haapamäki, M M; Matthiessen, P; Rutegård, J; Rutegård, M

    2017-12-01

    Fashioning a defunctioning stoma is common when performing an anterior resection for rectal cancer in order to avoid and mitigate the consequences of an anastomotic leakage. We investigated the permanent stoma prevalence, factors influencing stoma outcome and complication rates following stoma reversal surgery. Patients who had undergone an anterior resection for rectal cancer between 2007 and 2013 in the northern healthcare region were identified using the Swedish Colorectal Cancer Registry and were followed until the end of 2014 regarding stoma outcome. Data were retrieved by a review of medical records. Multiple logistic regression was used to evaluate predefined risk factors for stoma permanence. Risk factors for non-reversal of a defunctioning stoma were also analysed, using Cox proportional-hazards regression. A total of 316 patients who underwent anterior resection were included, of whom 274 (87%) were defunctioned primarily. At the end of the follow-up period 24% had a permanent stoma, and 9% of patients who underwent reversal of a stoma experienced major complications requiring a return to theatre, need for intensive care or mortality. Anastomotic leakage and tumour Stage IV were significant risk factors for stoma permanence. In this series, partial mesorectal excision correlated with a stoma-free outcome. Non-reversal was considerably more prevalent among patients with leakage and Stage IV; Stage III patients at first had a decreased reversal rate, which increased after the initial year of surgery. Stoma permanence is common after anterior resection, while anastomotic leakage and advanced tumour stage decrease the chances of a stoma-free outcome. Stoma reversal surgery entails a significant risk of major complications. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

  16. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach.

    PubMed

    Bebb, R A; Anawalt, B D; Christensen, R B; Paulsen, C A; Bremner, W J; Matsumoto, A M

    1996-02-01

    Studies using high dose testosterone (T) administration in normal men as a male contraceptive have resulted in azoospermia rates of only 50-70%. Previous studies of T and progestogen combinations have shown comparable rates of azoospermia, but have been uncontrolled or used T in doses less than that associated with maximal suppression of sperm production. We conducted a randomized, placebo-controlled, single blind trial comparing 6 months of T enanthate administration (100 mg, im, weekly) with the same dose of T enanthate in conjunction with the progestogen levonorgestrel (LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n = 18 in each group). The primary end points were induction of azoospermia or severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG was much more effective in suppressing sperm production than T alone. Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe oligospermia or azoospermia developed in 94% of the T plus LNG (17 of 18) group compared to 61% of the T alone group (11 of 18; P < 0.05). T plus LNG also suppressed sperm production more rapidly than T alone. Time to azoospermia was 9.9 +/- 1.0 vs. 15.3 +/- 1.9 weeks in the T plus LNG and T alone groups, respectively (mean +/- SEM; P < 0.05). Serum high density lipoprotein cholesterol decreased 21.7 +/- 3.6% in men given T plus LNG (P < 0.05), compared to only a 1.8 +/- 3.8% decrease in men in the T alone group. Average weight gain was 5.3 +/- 0.8 kg in the T plus LNG group and 2.3 +/- 0.9 kg in the T alone group (P < 0.05). Acne and increase in hemoglobin were similar in the two groups. We conclude that combination hormonal therapy with T plus a progestogen might offer a reversible male contraceptive approach with a more rapid onset of action and more reliable induction of both azoospermia and severe oligospermia than T alone.

  17. Modeling the Origin and Possible Control of the Wealth Inequality Surge

    PubMed Central

    Berman, Yonatan; Shapira, Yoash; Ben-Jacob, Eshel

    2015-01-01

    The rapid increase of wealth inequality in the past few decades is a most disturbing social and economic issue of our time. In order to control, and even reverse that surge, its origin and underlying mechanisms should be revealed. One of the challenges in studying these mechanisms is to incorporate realistic individual dynamics in the population level in a self-consistent manner. Our theoretical approach meets the challenge by using interacting multi-agent master-equations to model the dynamics of wealth inequality. The model is solved using stochastic multi-agent iterated maps. Taking into account growth rate, return on capital, private savings and economic mobility, we were able to capture the historical dynamics of wealth inequality in the United States during the course of the 20th century. We show that the fraction of capital income in the national income and the fraction of private savings are the critical factors that govern the wealth inequality dynamics. In addition, we found that economic mobility plays a crucial role in wealth accumulation. Notably, we found that the major decrease in private savings since the 1980s could be associated primarily with the recent surge in wealth inequality and if nothing changes in this respect we predict further increase in wealth inequality in the future. However, the 2007–08 financial crisis brought an opportunity to restrain the wealth inequality surge by increasing private savings. If this trend continues, it may lead to prevention, and even reversing, of the ongoing inequality surge. PMID:26107388

  18. Modeling the Origin and Possible Control of the Wealth Inequality Surge.

    PubMed

    Berman, Yonatan; Shapira, Yoash; Ben-Jacob, Eshel

    2015-01-01

    The rapid increase of wealth inequality in the past few decades is a most disturbing social and economic issue of our time. In order to control, and even reverse that surge, its origin and underlying mechanisms should be revealed. One of the challenges in studying these mechanisms is to incorporate realistic individual dynamics in the population level in a self-consistent manner. Our theoretical approach meets the challenge by using interacting multi-agent master-equations to model the dynamics of wealth inequality. The model is solved using stochastic multi-agent iterated maps. Taking into account growth rate, return on capital, private savings and economic mobility, we were able to capture the historical dynamics of wealth inequality in the United States during the course of the 20th century. We show that the fraction of capital income in the national income and the fraction of private savings are the critical factors that govern the wealth inequality dynamics. In addition, we found that economic mobility plays a crucial role in wealth accumulation. Notably, we found that the major decrease in private savings since the 1980s could be associated primarily with the recent surge in wealth inequality and if nothing changes in this respect we predict further increase in wealth inequality in the future. However, the 2007-08 financial crisis brought an opportunity to restrain the wealth inequality surge by increasing private savings. If this trend continues, it may lead to prevention, and even reversing, of the ongoing inequality surge.

  19. Role of Plastid Protein Phosphatase TAP38 in LHCII Dephosphorylation and Thylakoid Electron Flow

    PubMed Central

    Pribil, Mathias; Pesaresi, Paolo; Hertle, Alexander; Barbato, Roberto; Leister, Dario

    2010-01-01

    Short-term changes in illumination elicit alterations in thylakoid protein phosphorylation and reorganization of the photosynthetic machinery. Phosphorylation of LHCII, the light-harvesting complex of photosystem II, facilitates its relocation to photosystem I and permits excitation energy redistribution between the photosystems (state transitions). The protein kinase STN7 is required for LHCII phosphorylation and state transitions in the flowering plant Arabidopsis thaliana. LHCII phosphorylation is reversible, but extensive efforts to identify the protein phosphatase(s) that dephosphorylate LHCII have been unsuccessful. Here, we show that the thylakoid-associated phosphatase TAP38 is required for LHCII dephosphorylation and for the transition from state 2 to state 1 in A. thaliana. In tap38 mutants, thylakoid electron flow is enhanced, resulting in more rapid growth under constant low-light regimes. TAP38 gene overexpression markedly decreases LHCII phosphorylation and inhibits state 1→2 transition, thus mimicking the stn7 phenotype. Furthermore, the recombinant TAP38 protein is able, in an in vitro assay, to directly dephosphorylate LHCII. The dependence of LHCII dephosphorylation upon TAP38 dosage, together with the in vitro TAP38-mediated dephosphorylation of LHCII, suggests that TAP38 directly acts on LHCII. Although reversible phosphorylation of LHCII and state transitions are crucial for plant fitness under natural light conditions, LHCII hyperphosphorylation associated with an arrest of photosynthesis in state 2 due to inactivation of TAP38 improves photosynthetic performance and plant growth under state 2-favoring light conditions. PMID:20126264

  20. Rapidly Progressive Hypertrophic Cardiomyopathy in an Infant with Noonan syndrome with multiple Lentigines. Palliative Treatment with a Rapamycin Analog

    PubMed Central

    Hahn, Andreas; Lauriol, Jessica; Thul, Josef; Behnke-Hall, Kachina; Logeswaran, Tushiha; Schänzer, Anne; Böğürcü, Nuray; Garvalov, Boyan K.; Zenker, Martin; Gelb, Bruce D.; von Gerlach, Susanne; Kandolf, Reinhard; Kontaridis, Maria I.; Schranz, Dietmar

    2015-01-01

    Noonan syndrome with multiple lentigines (NSML) frequently manifests with hypertrophic cardiomyopathy (HCM). Recently, it was demonstrated that mTOR inhibition reverses HCM in NSML mice. We report for the first time on the effects of treatment with a rapamycin analog in an infant with LS and a malignant form of HCM. In the boy, progressive HCM was diagnosed during the first week of life and diagnosis of NSML was established at age 20 weeks by showing a heterozygous Q510E mutation in the PTPN11 gene. Immunoblotting with antibodies against pERK, pAkt, and pS6RP in fibroblasts demonstrated reduced RAS/MAPK and enhanced Akt/mTOR pathway activities. Because of the patient’s critical condition, everolimus therapy was started at age 24 weeks and continued until heart transplantation at age 36 weeks. Prior to surgery, heart failure improved from NYHA stage IV to II and brain natriuretic peptide values decreased from 9600 to <1000 pg/ml, but no reversal of cardiac hypertrophy was observed. Examination of the explanted heart revealed severe hypertrophy and myofiber disarray with extensive perivascular fibrosis. These findings provide evidence that Akt/mTOR activity is enhanced in NSML with HCM and suggest that rapamycin treatment could be principally feasible for infantile NSML. But the preliminary experiences made in this single patient indicate that therapy should start early to prevent irreversible cardiac remodelling. PMID:25708222

  1. Compressibility and reversible amorphization of thaumasite Ca3Si(OH)6(CO3)(SO4)·12H2O pressurized in methanol-ethanol-H2O up to 5 GPa

    NASA Astrophysics Data System (ADS)

    Likhacheva, A. Yu.; Dementiev, S. N.; Goryainov, S. V.

    2017-08-01

    The elastic and structure behavior of natural thaumasite compressed in methanol-ethanol-H2O up to 5 GPa was studied by synchrotron powder diffraction with a diamond anvil cell. In the pressure range between 0.0001 and 4.5 GPa, the compression is regular and slightly anisotropic, with a more rigid ab-plane coinciding with the orientation of hydrogen bonds and S-O, C-O bonds in anion groups. The corresponding bulk moduli derived from the third-order Birch-Murnaghan EoS fit are K a = 43(2), K c = 35(2), K T = 39(2) GPa. Rietveld refinements reveal some general features of the structure evolution of thaumasite, which are consistent with the observed elastic anisotropy. The compression within the ab-plane proceeds mainly at the expense of shortening of hydrogen bonds and much lesser decrease of C-O and S-O bonds. In the range of 0.0001-3 GPa the Ca-O polyhedra contract more rapidly along the c-axis as compared to the ab-plane. At about 5 GPa, thaumasite undergoes a reversible transformation to an amorphous phase. The observed behavior differs drastically with that studied previously using helium as the pressure medium, which suggests the effect of He penetration increasing the structure stiffness. Without helium support, the thaumasite structure is preserved only up to 4.5 GPa.

  2. Rapid modulation of ultraviolet shielding in plants is influenced by solar ultraviolet radiation and linked to alterations in flavonoids.

    PubMed

    Barnes, Paul W; Tobler, Mark A; Keefover-Ring, Ken; Flint, Stephan D; Barkley, Anne E; Ryel, Ronald J; Lindroth, Richard L

    2016-01-01

    The accumulation of ultraviolet (UV)-absorbing compounds (flavonoids and related phenylpropanoids) and the resultant decrease in epidermal UV transmittance (TUV ) are primary protective mechanisms employed by plants against potentially damaging solar UV radiation and are critical components of the overall acclimation response of plants to changing solar UV environments. Whether plants can adjust this UV sunscreen protection in response to rapid changes in UV, as occurs on a diurnal basis, is largely unexplored. Here, we use a combination of approaches to demonstrate that plants can modulate their UV-screening properties within minutes to hours, and these changes are driven, in part, by UV radiation. For the cultivated species Abelmoschus esculentus, large (30-50%) and reversible changes in TUV occurred on a diurnal basis, and these adjustments were associated with changes in the concentrations of whole-leaf UV-absorbing compounds and several quercetin glycosides. Similar results were found for two other species (Vicia faba and Solanum lycopersicum), but no such changes were detected in Zea mays. These findings reveal a much more dynamic UV-protection mechanism than previously recognized, raise important questions concerning the costs and benefits of UV-protection strategies in plants and have practical implications for employing UV to enhance crop vigor and quality in controlled environments. © 2015 John Wiley & Sons Ltd.

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

    McClure, Janela; Margineantu, Daciana H.; Sweet, Ian R.

    In this report, we further characterized the effects of silibinin (SbN), derived from milk thistle extract, and Legalon-SIL (SIL), a water-soluble derivative of SbN, on T cell metabolism and HIV infection. We assessed the effects of SbN and SIL on peripheral blood mononuclear cells (PBMC) and CEM-T4 cells in terms of cellular growth, ATP content, metabolism, and HIV infection. SIL and SbN caused a rapid and reversible (upon removal) decrease in cellular ATP levels, which was associated with suppression of mitochondrial respiration and glycolysis. SbN, but not SIL inhibited glucose uptake. Exposure of T cells to SIL (but not SbNmore » or metabolic inhibitors) during virus adsorption blocked HIV infection. Thus, both SbN and SIL rapidly perturb T cell metabolism in vitro, which may account for its anti-inflammatory and anti-proliferative effects that arise with prolonged exposure of cells. However, the metabolic effects are not involved in SIL's unique ability to block HIV entry. - Highlights: • Silibinin (SbN) and Legalon-SIL (SIL) are cytoprotective mixtures of natural products. • SbN and SIL reduce T cell oxidative phosphorylation and glycolysis in vitro. • SIL but not SbN blocks entry of multiple HIV isolates into T cells in vitro. • SIL's suppression of HIV appears independent of its effects on T cell metabolism. • Metabolic effects of SIL and SbN may be relevant in inflammatory diseases.« less

  4. Azathioprine and 6-mercaptopurine (6-MP) suppress the human mixed lymphocyte reaction (MLR) by different mechanisms.

    PubMed Central

    Al-Safi, S A; Maddocks, J L

    1984-01-01

    6-MP inhibitory effects on the MLR were reversed by AIC (46%), adenine (32%), hypoxanthine (89%), adenosine (86%) and inosine (93%). AIC, adenine, hypoxanthine and inosine had no effect on azathioprine inhibition of the MLR. Adenosine at 10 microM caused 29% reversal and had no effect at 100-400 microM on azathioprine inhibition of the MLR. Reversal of 6-MP suppression of the MLR was decreased with the delay of adenosine addition. Guanine, xanthine and guanosine caused no reversal of 6-MP or azathioprine inhibitory effects on the MLR. These results show that azathioprine and 6-MP suppress the MLR by different mechanisms. PMID:6232936

  5. Reverse shoulder arthroplasty.

    PubMed

    Jarrett, Claudius D; Brown, Brandon T; Schmidt, Christopher C

    2013-07-01

    The reverse shoulder arthroplasty is considered to be one of the most significant technological advancements in shoulder reconstructive surgery over the past 30 years. It is able to successfully decrease pain and improve function for patients with rotator cuff-deficient shoulders. The glenoid is transformed into a sphere that articulates with a humeral socket. The current reverse prosthesis shifts the center of rotation more medial and distal, improving the deltoid's mechanical advantage. This design has resulted in successful improvement in both active shoulder elevation and in quality of life. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. The functional organization of the crayfish lamina ganglionaris. I. Nonspiking monopolar cells.

    PubMed

    Wang-Bennett, L T; Glantz, R M

    1987-06-01

    The light responses of the second order lamina monopolar neurons were examined in the crayfish compound eye. Single cartridge monopolar neurons (M1-M4) exhibited nonspiking hyperpolarizing light responses; for M1, M3 and M4 the transient 'on' response operated over the same intensity range as the receptor, 3.5 log units. M2 operated in a much narrower intensity range (1.5 log unit). The 'on' responses were associated with a 19% increase in conductance. The hyperpolarizing 'on' response can be reversed at 18 mV below the resting membrane potential. The half-angular sensitivity width of monopolar cells (in partially dark-adapted eyes) is 15 degrees X 8 degrees (horizontal by vertical). Off axis stimuli elicit attenuated hyperpolarizing responses associated with a diminished conductance increase or depolarizing responses associated with a net decrease in conductance. The latter result is consistent with the presynaptic inhibition of a 'back-ground' transmitter release which normally persists in the dark. Lateral inhibition is elicited from the area immediately surrounding the excitatory field, and it is associated with diminished transient responses and an accelerated decay of the response. Inhibitory stimuli decrease the conductance change associated with the hyperpolarizing response. The surround stimuli can also elicit depolarizing 'off' responses with reversal potentials positive to the membrane resting potential. It is concluded that the rapidly repolarizing monopolar cell response is modulated by both pre- and postsynaptic inhibitory mechanisms. A compartment model indicates that signal attenuation along a 500 microns length of monopolar cell axon is 22-34%. Simulation of steady-state signal transmission suggests that passive (decremental) conduction is sufficient to convey 66 to 78% of the monopolar cell signal from lamina to medulla. The current-voltage relation in current clamp is linear over the physiological operating range, and there is no evidence for rectification. Hyperpolarization of single monopolar cells (M1-M4) provides a polysynaptic excitatory signal to the medullary sustaining fibers.

  7. The influence of hydrous Mn–Zn oxides on diel cycling of Zn in an alkaline stream draining abandoned mine lands

    USGS Publications Warehouse

    Shope, Christopher L.; Xie, Ying; Gammons, Christopher H.

    2006-01-01

    Many mining-impacted streams in western Montana with pH near or above neutrality display large (up to 500%) diel cycles in dissolved Zn concentrations. The streams in question typically contain boulders coated with a thin biofilm, as well as black mineral crusts composed of hydrous Mn–Zn oxides. Laboratory mesocosm experiments simulating diel behavior in High Ore Creek (one of the Montana streams with particularly high Zn concentrations) show that the Zn cycles are not caused by 24-h changes in streamflow or hyporheic exchange, but rather to reversible in-stream processes that are driven by the solar cycle and its attendant influence on pH and water temperature (T). Laboratory experiments using natural Mn–Zn precipitates from the creek show that the mobilities of Zn and Mn increase nearly an order of magnitude for each unit decrease in pH, and decrease 2.4-fold for an increase in T from 5 to 20 °C. The response of dissolved metal concentration to small changes in either pH or T was rapid and reversible, and dissolved Zn concentrations were roughly an order of magnitude higher than Mn. These observations are best explained by sorption of Zn2+ and Mn2+ onto the secondary Mn–Zn oxide surfaces. From the T-dependence of residual metal concentrations in solution, approximate adsorption enthalpies of +50 kJ/mol (Zn) and +46 kJ/mol (Mn) were obtained, which are within the range of enthalpy values reported in the literature for sorption of divalent metal cations onto hydrous metal oxides. Using the derived pH- and T-dependencies from the experiments, good agreement is shown between predicted and observed diel Zn cycles for several historical data sets collected from High Ore Creek.

  8. HYDROSTATIC PRESSURE AND TEMPERATURE IN RELATION TO STIMULATION AND CYCLOSIS IN NITELLA FLEXILIS

    PubMed Central

    Harvey, E. Newton

    1942-01-01

    Nitella flexilis cells are not stimulated to "shock stoppage" of cyclosis by suddenly evacuating the air over the water or on sudden readmission of air, or on suddenly striking a piston in the water-filled chamber in which they are kept with a ball whose energy is 7.6 joules, provided the Nitella cell is not moved by currents against the side of the chamber. Sudden increases in hydrostatic pressure from zero to 1000 lbs. or 0 to 5000 lbs. per square inch or 5000 to 9000 lbs. per square inch usually do not stimulate to "shock stoppage" of cyclosis, but some cells are stimulated. Sudden decreases of pressure are more likely to stimulate, again with variation depending on the cell. In the absence of stimulation, the cyclosis velocity at 23°C. slows as the pressure is increased in steps of 1000 lbs. per square inch. In some cells a regular slowing is observed, in others there is little slowing until 4000 to 6000 lbs. per square inch, when a rapid slowing appears, with only 50 per cent to 30 per cent of the original velocity at 9000 lbs. per square inch. The cyclosis does not completely stop at 10000 lbs. per square inch. The pressure effect is reversible unless the cells have been kept too long at the high pressure. At low temperatures (10°C.) and at temperatures near and above (32°–38°C.) the optimum temperature for maximum cyclosis (35–36°C.) pressures of 3000 to 6000 lbs. per square inch cause only further slowing of cyclosis, with no reversal of the temperature effect, such as has been observed in pressure-temperature studies on the luminescence of luminous bacteria. Sudden increase in temperature may cause shock stoppage of cyclosis as well as sudden decrease in temperature. PMID:19873318

  9. Reverse Transcription Recombinase Polymerase Amplification Assay for the Detection of Middle East Respiratory Syndrome Coronavirus

    PubMed Central

    Abd El Wahed, Ahmed; Patel, Pranav; Heidenreich, Doris; Hufert, Frank T.; Weidmann, Manfred

    2013-01-01

    The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the eastern Mediterranean and imported cases to Europe has alerted public health authorities. Currently, detection of MERS-CoV in patient samples is done by real-time RT-PCR. Samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. A rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. In this study, we describe the development of a reverse transcription isothermal Recombinase Polymerase Amplification (RT-RPA) assay for the identification of MERS-CoV. A partial nucleocapsid gene RNA molecular standard of MERS-coronavirus was used to determine the assay sensitivity. The isothermal (42°C) MERS-CoV RT-RPA was as sensitive as real-time RT-PCR (10 RNA molecules), rapid (3-7 minutes) and mobile (using tubescanner weighing 1kg). The MERS-CoV RT-RPA showed cross-detection neither of any of the RNAs of several coronaviruses and respiratory viruses affecting humans nor of the human genome. The developed isothermal real-time RT-RPA is ideal for rapid mobile molecular MERS-CoV monitoring in acute patients and may also facilitate the search for the animal reservoir of MERS-CoV. PMID:24459611

  10. A rapid method of accurate detection and differentiation of Newcastle disease virus pathotypes by demonstrating multiple bands in degenerate primer based nested RT-PCR.

    PubMed

    Desingu, P A; Singh, S D; Dhama, K; Kumar, O R Vinodh; Singh, R; Singh, R K

    2015-02-01

    A rapid and accurate method of detection and differentiation of virulent and avirulent Newcastle disease virus (NDV) pathotypes was developed. The NDV detection was carried out for different domestic avian field isolates and pigeon paramyxo virus-1 (25 field isolates and 9 vaccine strains) by using APMV-I "fusion" (F) gene Class II specific external primer A and B (535bp), internal primer C and D (238bp) based reverses transcriptase PCR (RT-PCR). The internal degenerative reverse primer D is specific for F gene cleavage position of virulent strain of NDV. The nested RT-PCR products of avirulent strains showed two bands (535bp and 424bp) while virulent strains showed four bands (535bp, 424bp, 349bp and 238bp) on agar gel electrophoresis. This is the first report regarding development and use of degenerate primer based nested RT-PCR for accurate detection and differentiation of NDV pathotypes by demonstrating multiple PCR band patterns. Being a rapid, simple, and economical test, the developed method could serve as a valuable alternate diagnostic tool for characterizing NDV isolates and carrying out molecular epidemiological surveillance studies for this important pathogen of poultry. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) Assay Coupled with a Portable Device for Rapid Diagnosis of Ebola Virus Disease in Guinea

    PubMed Central

    Kurosaki, Yohei; Magassouba, N’Faly; Oloniniyi, Olamide K.; Cherif, Mahamoud S.; Sakabe, Saori; Takada, Ayato; Hirayama, Kenji; Yasuda, Jiro

    2016-01-01

    Given the current absence of specific drugs or vaccines for Ebola virus disease (EVD), rapid, sensitive, and reliable diagnostic methods are required to stem the transmission chain of the disease. We have developed a rapid detection assay for Zaire ebolavirus based on reverse transcription-loop-mediated isothermal amplification (RT-LAMP) and coupled with a novel portable isothermal amplification and detection platform. The RT-LAMP assay is based on primer sets that target the untranscribed trailer region or nucleoprotein coding region of the viral RNA. The test could specifically detect viral RNAs of Central and West African Ebola virus strains within 15 minutes with no cross-reactivity to other hemorrhagic fever viruses and arboviruses, which cause febrile disease. The assay was evaluated using a total of 100 clinical specimens (serum, n = 44; oral swab, n = 56) collected from suspected EVD cases in Guinea. The specificity of this diagnostic test was 100% for both primer sets, while the sensitivity was 100% and 97.9% for the trailer and nucleoprotein primer sets, respectively, compared with a reference standard RT-PCR test. These observations suggest that our diagnostic assay is useful for identifying EVD cases, especially in the field or in settings with insufficient infrastructure. PMID:26900929

  12. Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) Assay Coupled with a Portable Device for Rapid Diagnosis of Ebola Virus Disease in Guinea.

    PubMed

    Kurosaki, Yohei; Magassouba, N'Faly; Oloniniyi, Olamide K; Cherif, Mahamoud S; Sakabe, Saori; Takada, Ayato; Hirayama, Kenji; Yasuda, Jiro

    2016-02-01

    Given the current absence of specific drugs or vaccines for Ebola virus disease (EVD), rapid, sensitive, and reliable diagnostic methods are required to stem the transmission chain of the disease. We have developed a rapid detection assay for Zaire ebolavirus based on reverse transcription-loop-mediated isothermal amplification (RT-LAMP) and coupled with a novel portable isothermal amplification and detection platform. The RT-LAMP assay is based on primer sets that target the untranscribed trailer region or nucleoprotein coding region of the viral RNA. The test could specifically detect viral RNAs of Central and West African Ebola virus strains within 15 minutes with no cross-reactivity to other hemorrhagic fever viruses and arboviruses, which cause febrile disease. The assay was evaluated using a total of 100 clinical specimens (serum, n = 44; oral swab, n = 56) collected from suspected EVD cases in Guinea. The specificity of this diagnostic test was 100% for both primer sets, while the sensitivity was 100% and 97.9% for the trailer and nucleoprotein primer sets, respectively, compared with a reference standard RT-PCR test. These observations suggest that our diagnostic assay is useful for identifying EVD cases, especially in the field or in settings with insufficient infrastructure.

  13. High-speed pulsed mixing in a short distance with high-frequency switching of pumping from three inlets

    NASA Astrophysics Data System (ADS)

    Sugano, K.; Nakata, A.; Tsuchiya, T.; Tabata, O.

    2015-08-01

    In this study, we propose a mixing method using alternate pulsed flows from three inlets with flow direction control. In conventional pulsed mixing, a residual flow near the sidewalls inhibits the rapid mixing of two solutions at high switching frequency. In this study, we addressed this issue in order to perform rapid mixing in a short distance with a low Reynolds number. We fabricated a microfluidic mixing device consisting of a cross-shaped mixing channel with three inlet microchannels and three valveless micropumps. In conventional T-shaped or Y-shaped mixing channels, a residual flow is observed because of the incomplete switching of solutions. The three inlet configuration enabled us to split the residual flow at a switching frequency of pumping of up to 200 Hz, thus resulting in rapid mixing. Furthermore, by controlling the flow direction at the confluent area using the reverse flow of the micropump, the mixing speed was dramatically increased because of the complete switching of the two solutions. As a result, we achieved the mixing time of 3.6 ms and the mixing length of 20.7 µm, which were necessary to achieve a 90% mixing ratio at a high micropump switching frequency of 400 Hz and reverse flow ratio of 1/4.

  14. Development of a reverse transcription loop-mediated isothermal amplification method for the rapid detection of avian influenza virus subtype H7.

    PubMed

    Bao, Hongmei; Wang, Xiurong; Zhao, Yuhui; Sun, Xiaodong; Li, Yanbing; Xiong, Yongzhong; Chen, Hualan

    2012-01-01

    A rapid and sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of the H7 avian influenza virus (H7 AIV) isotype was developed. The minimum detection limit of the RT-LAMP assay was 0.1-0.01 PFU per reaction for H7 AIV RNA, making this assay 100-fold more sensitive than the conventional RT-PCR method. This RT-LAMP assay also has the capacity to detect both high- and low-pathogenic H7 AIV strains. Using a pool of RNAs extracted from influenza viruses corresponding to all 15 HA subtypes (in addition to other avian pathogenic viruses), the RT-LAMP system was confirmed to amplify only H7 AIV RNA. Furthermore, specific pathogen free (SPF) chickens were infected artificially with H7 AIV, throat and cloacal swabs were collected, and viral shedding was examined using viral isolation, RT-PCR and RT-LAMP. Shedding was detected following viral isolation and RT-LAMP one day after infection, whereas viral detection using RT-PCR was effective only on day 3 post-infection. These results indicate that the RT-LAMP method could facilitate epidemiological surveillance and the rapid diagnosis of the avian influenza subtype H7. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Paleomagnetic Study of a Reversal of the Earth's Magnetic Field.

    PubMed

    Dunn, J R; Fuller, M; Ito, H; Schmidt, V A

    1971-05-21

    A detailed record of a field reversal has been obtained from the natural remanent magnetization of the Tatoosh intrusion in Mount Rainier National Park, Washington. The reversal took place at 14.7 +/- 1 million years and is interpreted to be from reverse to normal. A decrease in the intensity of the field of about an order of magnitude occurs immediately before the reversal, while its orientation remains substantially unchanged. The onset of the reversal is marked by abrupt swinging of the virtual geomagnetic pole along an arc of a great circle. During the reversal the pole traces a path across the Pacific. In the last stage of the process recorded in the sections, the succession of virtual geomagnetic poles is very similar to those generated by secular variation in the recent past. Although the cooling rate of the intrusion is not sufficiently well known to permit a useful calculation of the duration of the reversal process, an estimate based on the length of the supposed secular variation cycles gives 1 to 4 x 103 years for the reversal of field direction and approximately 1 x 104 years for the time scale of the intensity changes.

  16. Rapid reversal of innate immune dysregulation in blood of patients and livers of humanized mice with HCV following DAA therapy

    PubMed Central

    Burchill, Matthew A.; Roby, Justin A.; Crochet, Nanette; Wind-Rotolo, Megan; Stone, Amy E.; Edwards, Michael G.; Dran, Rachael J.; Kriss, Michael S.; Gale, Michael

    2017-01-01

    Chronic hepatitis C virus (HCV) infection results in sustained immune activation in both the periphery and hepatic tissue. HCV infection induces innate immune signaling that is responsible for recognition of dsRNA, leading to activation of transcription factors and production of Type I and III IFNs, as well as pro-inflammatory cytokines and chemokines. Continued activation of host-immune mediated inflammation is thought to contribute to pathologic changes that result in progressive hepatic fibrosis. The current standard treatment for chronic HCV infection is directly-acting antivirals (DAAs), which have provided the unique opportunity to determine whether successful, rapid treatment-induced eradication of viral RNA normalizes the dysregulated antiviral innate immune response in patients chronically infected with HCV. Results First, in patients receiving two different combinations of DAAs, we found that DAAs induced not only rapid viral clearance, but also a re-setting of antiviral immune responses in the peripheral blood. Specifically, we see a rapid decline in the expression of genes associated with chronic IFN stimulation (IFIT3, USP18, IFIT1) as well as a rapid decline in genes associated with inflammation (IL1β, CXCL10, CXCL11) in the peripheral blood that precedes the complete removal of virus from the blood. Interestingly, this rapid reversal of innate immune activation was not seen in patients who successfully clear chronic HCV infection using IFN-based therapy. Next, using a novel humanized mouse model (Fah-/-RAG2-/-IL2rgnull—FRG), we assessed the changes that occur in the hepatic tissue following DAA treatment. DAA-mediated rapid HCV clearance resulted in blunting of the expression of proinflammatory responses while functionally restoring the RIG-I/MAVS axis in the liver of humanized mice. Conclusions Collectively, our data demonstrate that the rapid viral clearance following treatment with DAAs results in the rebalancing of innate antiviral response in both the peripheral blood and the liver as well as enhanced antiviral signaling within previously infected hepatocytes. PMID:29040318

  17. Gene regulation of atrial natriuretic peptide A, B, and C receptors in rat glomeruli.

    PubMed

    Itoh, K; Nonoguchi, H; Shiraishi, N; Tomita, K

    1999-01-01

    Atrial natriuretic peptide (ANP) has three types of receptor. We investigated the gene regulation of three types of ANP receptors (ANPR-A, B, and C) in rat glomeruli using reverse transcription coupled with competitive polymerase chain reaction (PCR). Competitive PCR revealed that ANPR-C mRNA expression was most abundant (ANPR-C > A > B) in glomeruli from control rats among mRNA expressions of three receptors, which were 20- to 15,000-fold higher than those in inner medullary collecting ducts. Two days' dehydration caused reversible decreases of ANPR-A, B, and C mRNAs by 50-80%. To determine the mechanisms of down-regulation of mRNA expression, isolated glomeruli were incubated in isotonic or hypertonic solution. Hyperosmolality induced by NaCl, mannitol or raffinose caused significant increases of ANPR-A, B, and C mRNA expression. Hypertonicity by urea showed smaller effects. ANP stimulated the expression of ANPR-A, B, and C mRNA in vitro. These results indicate that dehydration caused reversible decreases of ANPR-A, B, and C mRNA expression in glomeruli, and these decreases were not caused by increased plasma osmolality but probably by lower circulating levels of ANP.

  18. Reverse Current in Solar Flares

    NASA Technical Reports Server (NTRS)

    Knight, J. W.; Sturrock, P. A.

    1976-01-01

    The theory that impulsive X ray bursts are produced by high energy electrons streaming from the corona to the chromosphere is investigated. Currents associated with these streams are so high that either the streams do not exist or their current is neutralized by a reverse current. Analysis of a simple model indicates that the primary electron stream leads to the development of an electric field in the ambient corona which decelerates the primary beam and produces a neutralizing reverse current. It appears that, in some circumstances, this electric field could prevent the primary beam from reaching the chromosphere. In any case, the electric field acts as an energy exchange mechanism, extracting kinetic energy from the primary beam and using it to heat the ambient plasma. This heating is typically so rapid that it must be expected to have important dynamical consequences.

  19. Reversible dilatancy in entangled single-wire materials.

    PubMed

    Rodney, David; Gadot, Benjamin; Martinez, Oriol Riu; du Roscoat, Sabine Rolland; Orgéas, Laurent

    2016-01-01

    Designing structures that dilate rapidly in both tension and compression would benefit devices such as smart filters, actuators or fasteners. This property however requires an unusual Poisson ratio, or Poisson function at finite strains, which has to vary with applied strain and exceed the familiar bounds: less than 0 in tension and above 1/2 in compression. Here, by combining mechanical tests and discrete element simulations, we show that a simple three-dimensional architected material, made of a self-entangled single long coiled wire, behaves in between discrete and continuum media, with a large and reversible dilatancy in both tension and compression. This unusual behaviour arises from an interplay between the elongation of the coiled wire and rearrangements due to steric effects, which, unlike in traditional discrete media, are hysteretically reversible when the architecture is made of an elastic fibre.

  20. Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH

    PubMed Central

    Bandyopadhyay, Anupam

    2015-01-01

    Bioorthogonal reactions that are fast and reversible under physiologic conditions are in high demand for biological applications. Herein, we show that an ortho boronic acid substituent makes aryl ketones to rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 102 to 103 M−1 s−1, comparable to the fastest bioorthogonal conjugations known to date. 11B-NMR analysis reveals varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiologic conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology. PMID:26311464

  1. Security protection of DICOM medical images using dual-layer reversible watermarking with tamper detection capability.

    PubMed

    Tan, Chun Kiat; Ng, Jason Changwei; Xu, Xiaotian; Poh, Chueh Loo; Guan, Yong Liang; Sheah, Kenneth

    2011-06-01

    Teleradiology applications and universal availability of patient records using web-based technology are rapidly gaining importance. Consequently, digital medical image security has become an important issue when images and their pertinent patient information are transmitted across public networks, such as the Internet. Health mandates such as the Health Insurance Portability and Accountability Act require healthcare providers to adhere to security measures in order to protect sensitive patient information. This paper presents a fully reversible, dual-layer watermarking scheme with tamper detection capability for medical images. The scheme utilizes concepts of public-key cryptography and reversible data-hiding technique. The scheme was tested using medical images in DICOM format. The results show that the scheme is able to ensure image authenticity and integrity, and to locate tampered regions in the images.

  2. Thermally driven microfluidic pumping via reversible shape memory polymers

    NASA Astrophysics Data System (ADS)

    Robertson, J. M.; Rodriguez, R. X.; Holmes, L. R., Jr.; Mather, P. T.; Wetzel, E. D.

    2016-08-01

    The need exists for autonomous microfluidic pumping systems that utilize environmental cues to transport fluid within a network of channels for such purposes as heat distribution, self-healing, or optical reconfiguration. Here, we report on reversible thermally driven microfluidic pumping enabled by two-way shape memory polymers. After developing a suitable shape memory polymer (SMP) through variation in the crosslink density, thin and flexible microfluidic devices were constructed by lamination of plastic films with channels defined by laser-cutting of double-sided adhesive film. SMP blisters integrated into the devices provide thermally driven pumping, while opposing elastic blisters are used to generate backpressure for reversible operation. Thermal cycling of the device was found to drive reversible fluid flow: upon heating to 60 °C, the SMP rapidly contracted to fill the surface channels with a transparent fluid, and upon cooling to 8 °C the flow reversed and the channel re-filled with black ink. Combined with a metallized backing layer, this device results in refection of incident light at high temperatures and absorption of light (at the portions covered with channels) at low temperatures. We discuss power-free, autonomous applications ranging from thermal regulation of structures to thermal indication via color change.

  3. Sugammadex as a reversal agent for neuromuscular block: an evidence-based review

    PubMed Central

    Schaller, Stefan Josef; Fink, Heidrun

    2013-01-01

    Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the “gold standard” muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing. PMID:24098155

  4. Reversible colour change in Arthropoda.

    PubMed

    Umbers, Kate D L; Fabricant, Scott A; Gawryszewski, Felipe M; Seago, Ainsley E; Herberstein, Marie E

    2014-11-01

    The mechanisms and functions of reversible colour change in arthropods are highly diverse despite, or perhaps due to, the presence of an exoskeleton. Physiological colour changes, which have been recorded in 90 arthropod species, are rapid and are the result of changes in the positioning of microstructures or pigments, or in the refractive index of layers in the integument. By contrast, morphological colour changes, documented in 31 species, involve the anabolism or catabolism of components (e.g. pigments) directly related to the observable colour. In this review we highlight the diversity of mechanisms by which reversible colour change occurs and the evolutionary context and diversity of arthropod taxa in which it has been observed. Further, we discuss the functions of reversible colour change so far proposed, review the limited behavioural and ecological data, and argue that the field requires phylogenetically controlled approaches to understanding the evolution of reversible colour change. Finally, we encourage biologists to explore new model systems for colour change and to engage scientists from other disciplines; continued cross-disciplinary collaboration is the most promising approach to this nexus of biology, physics, and chemistry. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  5. Depletion of intracellular GSH and NPSH by buthionine sulfoximine and diethyl maleate: factors that influence enhancement of aerobic radiation response

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

    Varnes, M.E.; Biaglow, J.E.; Roizin-Towle, L.

    1984-08-01

    Many investigators have observed aerobic sensitization of V79, CHO and A549 (human lung carcinoma) cells upon depletion of GSH using buthionine sulfoximine (BSO). Recently the authors discovered that this aerobic sensitization can be reversed if WR-2721 or N-acetylcysteine is added to the cells just prior to irradiation. Reversal requires that the exogenous thiols be present during the time of irradiation. One possible explanation was that these thiols entered the cells and either increased the pool of cellular nonprotein thiols or reversed the thiol-depleted state by stimulation of GSH synthesis. Cells treated with BSO do not readily regenerate intracellular GSH becausemore » this agent irreversibly inhibits ..gamma..-glutamyl synthetase. They found that addition of WR-2721 or N-acetylcysteine to BSO-treated cells did not affect the rate of regeneration of intracellular GSH. Thus, reversal of the aerobic sensitization of A549 cells by BSO cannot be explained on the basis of intracellular thiol levels alone, or by rapid reversal of BSO inhibition. In addition, diethylmaleate (DEM)-treated cells are considerably different from BSO-treated cells with respect to the ability to regenerate GSH.« less

  6. When stress predicts a shrinking gene pool, trading early reproduction for longevity can increase fitness, even with lower fecundity.

    PubMed

    Ratcliff, William C; Hawthorne, Peter; Travisano, Michael; Denison, R Ford

    2009-06-25

    Stresses like dietary restriction or various toxins increase lifespan in taxa as diverse as yeast, Caenorhabditis elegans, Drosophila and rats, by triggering physiological responses that also tend to delay reproduction. Food odors can reverse the effects of dietary restriction, showing that key mechanisms respond to information, not just resources. Such environmental cues can predict population trends, not just individual prospects for survival and reproduction. When population size is increasing, each offspring produced earlier makes a larger proportional contribution to the gene pool, but the reverse is true when population size is declining. We show mathematically that natural selection can favor facultative delay in reproduction when environmental cues predict a decrease in total population size, even if lifetime fecundity decreases with delay. We also show that increased reproduction from waiting for better conditions does not increase fitness (proportional representation) when the whole population benefits similarly. We conclude that the beneficial effects of stress on longevity (hormesis) in diverse taxa are a side-effect of delaying reproduction in response to environmental cues that population size is likely to decrease. The reversal by food odors of the effects of dietary restriction can be explained as a response to information that population size is less likely to decrease, reducing the chance that delaying reproduction will increase fitness.

  7. Telomerase reverse transcriptase (TERT) - enhancer of zeste homolog 2 (EZH2) network regulates lipid metabolism and DNA damage responses in glioblastoma.

    PubMed

    Ahmad, Fahim; Patrick, Shruti; Sheikh, Touseef; Sharma, Vikas; Pathak, Pankaj; Malgulwar, Prit Benny; Kumar, Anupam; Joshi, Shanker Datt; Sarkar, Chitra; Sen, Ellora

    2017-12-01

    Elevated expression of enhancer of zeste homolog 2 (EZH2), a histone H3K27 methyltransferase, was observed in gliomas harboring telomerase reverse transcriptase (TERT) promoter mutations. Given the known involvement of TERT and EZH2 in glioma progression, the correlation between the two and subsequently its involvement in metabolic programming was investigated. Inhibition of human telomerase reverse transcriptase either pharmacologically or through genetic manipulation not only decreased EZH2 expression, but also (i) abrogated FASN levels, (ii) decreased de novo fatty acid accumulation, and (iii) increased ataxia-telangiectasia-mutated (ATM) phosphorylation levels. Conversely, diminished TERT and FASN levels upon siRNA-mediated EZH2 knockdown indicated a positive correlation between TERT and EZH2. Interestingly, ATM kinase inhibitor rescued TERT inhibition-mediated decrease in FASN and EZH2 levels. Importantly, TERT promoter mutant tumors exhibited greater microsatellite instability, heightened FASN levels and lipid accumulation. Coherent with in vitro findings, pharmacological inhibition of TERT by costunolide decreased lipid accumulation and elevated ATM expression in heterotypic xenograft glioma mouse model. By bringing TERT-EZH2 network at the forefront as driver of dysregulated metabolism, our findings highlight the non-canonical but distinct role of TERT in metabolic reprogramming and DNA damage responses in glioblastoma. © 2017 International Society for Neurochemistry.

  8. Development of a simple algorithm to guide the effective management of traumatic cardiac arrest.

    PubMed

    Lockey, David J; Lyon, Richard M; Davies, Gareth E

    2013-06-01

    Major trauma is the leading worldwide cause of death in young adults. The mortality from traumatic cardiac arrest remains high but survival with good neurological outcome from cardiopulmonary arrest following major trauma has been regularly reported. Rapid, effective intervention is required to address potential reversible causes of traumatic cardiac arrest if the victim is to survive. Current ILCOR guidelines do not contain a standard algorithm for management of traumatic cardiac arrest. We present a simple algorithm to manage the major trauma patient in actual or imminent cardiac arrest. We reviewed the published English language literature on traumatic cardiac arrest and major trauma management. A treatment algorithm was developed based on this and the experience of treatment of more than a thousand traumatic cardiac arrests by a physician - paramedic pre-hospital trauma service. The algorithm addresses the need treat potential reversible causes of traumatic cardiac arrest. This includes immediate resuscitative thoracotomy in cases of penetrating chest trauma, airway management, optimising oxygenation, correction of hypovolaemia and chest decompression to exclude tension pneumothorax. The requirement to rapidly address a number of potentially reversible pathologies in a short time period lends the management of traumatic cardiac arrest to a simple treatment algorithm. A standardised approach may prevent delay in diagnosis and treatment and improve current poor survival rates. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Automated Sanger Analysis Pipeline (ASAP): A Tool for Rapidly Analyzing Sanger Sequencing Data with Minimum User Interference.

    PubMed

    Singh, Aditya; Bhatia, Prateek

    2016-12-01

    Sanger sequencing platforms, such as applied biosystems instruments, generate chromatogram files. Generally, for 1 region of a sequence, we use both forward and reverse primers to sequence that area, in that way, we have 2 sequences that need to be aligned and a consensus generated before mutation detection studies. This work is cumbersome and takes time, especially if the gene is large with many exons. Hence, we devised a rapid automated command system to filter, build, and align consensus sequences and also optionally extract exonic regions, translate them in all frames, and perform an amino acid alignment starting from raw sequence data within a very short time. In full capabilities of Automated Mutation Analysis Pipeline (ASAP), it is able to read "*.ab1" chromatogram files through command line interface, convert it to the FASTQ format, trim the low-quality regions, reverse-complement the reverse sequence, create a consensus sequence, extract the exonic regions using a reference exonic sequence, translate the sequence in all frames, and align the nucleic acid and amino acid sequences to reference nucleic acid and amino acid sequences, respectively. All files are created and can be used for further analysis. ASAP is available as Python 3.x executable at https://github.com/aditya-88/ASAP. The version described in this paper is 0.28.

  10. Early Hypoparathyroidism Reversibility with Treatment of Riedel's Thyroiditis.

    PubMed

    Stan, Marius N; Haglind, Elizabeth G; Drake, Matthew T

    2015-09-01

    Riedel's thyroiditis (RT) is a rare, fibroinflammatory condition which induces gradual thyroid gland destruction and adjacent soft-tissue fibrous infiltration. About one- seventh of RT cases are associated with hypoparathyroidism, necessitating long-term therapy for symptomatic hypocalcemia. The reversibility of the parathyroid hormone deficit has not been fully described. A 40-year-old woman with no prior history of thyroid disease presented with a six month history of progressive thyroid enlargement complicated by worsening dysphagia and positional dyspnea. Her past medical history was remarkable only for retroperitoneal fibrosis. Physical examination revealed a large, hard, non-mobile goiter. Thyroid indices while maintained on levothyroxine were normal, but marked asymptomatic hypocalcemia with an inappropriately normal parathyroid hormone level was noted. Thyroid imaging and fine needle aspiration were consistent with RT. Isthmectomy and subsequent serial corticosteroid and tamoxifen treatment led to rapid symptom improvement. Serum calcium and parathyroid hormone levels returned to the reference range within three months. We describe a case of RT in which hypoparathyroidism resolved after treatment targeted the mechanical compression and the fibroinflammatory milieu of the patient's thyroidal disease. RT can be associated with hypoparathyroidism that is clinically silent at presentation. Mechanical decompression of the goiter and immunomodulatory therapy can reverse the fibrosclerotic process and lead to rapid recovery of parathyroid gland function, as in this patient. However, in most cases hypoparathyroidism is persistent and requires continued treatment to prevent symptomatic hypocalcemia.

  11. One-Step Reverse Transcription-Polymerase Chain Reaction for Ebola and Marburg Viruses.

    PubMed

    Park, Sun-Whan; Lee, Ye-Ji; Lee, Won-Ja; Jee, Youngmee; Choi, WooYoung

    2016-06-01

    Ebola and Marburg viruses (EBOVs and MARVs, respectively) are causative agents of severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. In 2014, there was a major Ebola outbreak in various countries in West Africa, including Guinea, Liberia, Republic of Sierra Leone, and Nigeria. EBOV and MARV are clinically difficult to diagnose and distinguish from other African epidemic diseases. Therefore, in this study, we aimed to develop a method for rapid identification of the virus to prevent the spread of infection. We established a conventional one-step reverse transcription-polymerase chain reaction (RT-PCR) assay for these pathogens based on the Superscript Reverse Transcriptase-Platinum Taq polymerase enzyme mixture. All assays were thoroughly optimized using in vitro-transcribed RNA. We designed seven primer sets of nucleocapsid protein (NP) genes based on sequences from seven filoviruses, including five EBOVs and two MARVs. To evaluate the sensitivity of the RT-PCR assay for each filovirus, 10-fold serial dilutions of synthetic viral RNA transcripts of EBOV or MARV NP genes were used to assess detection limits of viral RNA copies. The potential for these primers to cross react with other filoviruses was also examined. The results showed that the primers were specific for individual genotype detection in the examined filoviruses. The assay established in this study may facilitate rapid, reliable laboratory diagnosis in suspected cases of Ebola and Marburg hemorrhagic fevers.

  12. A Portable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of Foot-and-Mouth Disease Virus

    PubMed Central

    Abd El Wahed, Ahmed; El-Deeb, Ayman; El-Tholoth, Mohamed; Abd El Kader, Hanaa; Ahmed, Abeer; Hassan, Sayed; Hoffmann, Bernd; Haas, Bernd; Shalaby, Mohamed A.; Hufert, Frank T.; Weidmann, Manfred

    2013-01-01

    Foot-and-mouth disease (FMD) is a trans-boundary viral disease of livestock, which causes huge economic losses and constitutes a serious infectious threat for livestock farming worldwide. Early diagnosis of FMD helps to diminish its impact by adequate outbreak management. In this study, we describe the development of a real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of FMD virus (FMDV). The FMDV RT-RPA design targeted the 3D gene of FMDV and a 260 nt molecular RNA standard was used for assay validation. The RT-RPA assay was fast (4–10 minutes) and the analytical sensitivity was determined at 1436 RNA molecules detected by probit regression analysis. The FMDV RT-RPA assay detected RNA prepared from all seven FMDV serotypes but did not detect classical swine fever virus or swine vesicular disease virus. The FMDV RT-RPA assay was used in the field during the recent FMD outbreak in Egypt. In clinical samples, reverse transcription polymerase chain reaction (RT-PCR) and RT-RPA showed a diagnostic sensitivity of 100% and 98%, respectively. In conclusion, FMDV RT-RPA was quicker and much easier to handle in the field than real-time RT-PCR. Thus RT-RPA could be easily implemented to perform diagnostics at quarantine stations or farms for rapid spot-of-infection detection. PMID:23977101

  13. A portable reverse transcription recombinase polymerase amplification assay for rapid detection of foot-and-mouth disease virus.

    PubMed

    Abd El Wahed, Ahmed; El-Deeb, Ayman; El-Tholoth, Mohamed; Abd El Kader, Hanaa; Ahmed, Abeer; Hassan, Sayed; Hoffmann, Bernd; Haas, Bernd; Shalaby, Mohamed A; Hufert, Frank T; Weidmann, Manfred

    2013-01-01

    Foot-and-mouth disease (FMD) is a trans-boundary viral disease of livestock, which causes huge economic losses and constitutes a serious infectious threat for livestock farming worldwide. Early diagnosis of FMD helps to diminish its impact by adequate outbreak management. In this study, we describe the development of a real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of FMD virus (FMDV). The FMDV RT-RPA design targeted the 3D gene of FMDV and a 260 nt molecular RNA standard was used for assay validation. The RT-RPA assay was fast (4-10 minutes) and the analytical sensitivity was determined at 1436 RNA molecules detected by probit regression analysis. The FMDV RT-RPA assay detected RNA prepared from all seven FMDV serotypes but did not detect classical swine fever virus or swine vesicular disease virus. The FMDV RT-RPA assay was used in the field during the recent FMD outbreak in Egypt. In clinical samples, reverse transcription polymerase chain reaction (RT-PCR) and RT-RPA showed a diagnostic sensitivity of 100% and 98%, respectively. In conclusion, FMDV RT-RPA was quicker and much easier to handle in the field than real-time RT-PCR. Thus RT-RPA could be easily implemented to perform diagnostics at quarantine stations or farms for rapid spot-of-infection detection.

  14. Optimized ventricular restraint therapy: adjustable restraint is superior to standard restraint in an ovine model of ischemic cardiomyopathy.

    PubMed

    Lee, Lawrence S; Ghanta, Ravi K; Mokashi, Suyog A; Coelho-Filho, Otavio; Kwong, Raymond Y; Kwon, Michael; Guan, Jian; Liao, Ronglih; Chen, Frederick Y

    2013-03-01

    The effects of ventricular restraint level on left ventricular reverse remodeling are not known. We hypothesized that restraint level affects the degree of reverse remodeling and that restraint applied in an adjustable manner is superior to standard, nonadjustable restraint. This study was performed in 2 parts using a model of chronic heart failure in the sheep. In part I, restraint was applied at control (0 mm Hg, n = 3), low (1.5 mm Hg, n = 3), and high (3.0 mm Hg, n = 3) levels with an adjustable and measurable ventricular restraint (AMVR) device. Restraint level was not altered throughout the 2-month treatment period. Serial restraint level measurements and transthoracic echocardiography were performed. In part II, restraint was applied with the AMVR device set at 3.0 mm Hg (n = 6) and adjusted periodically to maintain that level. This was compared with restraint applied in a standard, nonadjustable manner using a mesh wrap (n = 6). All subjects were followed up for 2 months with serial magnetic resonance imaging. In part I, there was greater and earlier reverse remodeling in the high restraint group. In both groups, the rate of reverse remodeling peaked and then declined as the measured restraint level decreased with progression of reverse remodeling. In part II, adjustable restraint resulted in greater reverse remodeling than standard restraint. Left ventricular end diastolic volume decreased by 12.7% (P = .005) with adjustable restraint and by 5.7% (P = .032) with standard restraint. Left ventricular ejection fraction increased by 18.9% (P = .014) and 14.4% (P < .001) with adjustable and standard restraint, respectively. Restraint level affects the rate and degree of reverse remodeling and is an important determinant of therapy efficacy. Adjustable restraint is more effective than nonadjustable restraint in promoting reverse remodeling. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  15. Ketene reactions with tertiary amines.

    PubMed

    Allen, Annette D; Andraos, John; Tidwell, Thomas T; Vukovic, Sinisa

    2014-01-17

    Tertiary amines react rapidly and reversibly with arylketenes in acetonitrile forming observable zwitterions, and these undergo amine catalyzed dealkylation forming N,N-disubstituted amides. Reactions of N-methyldialkylamines show a strong preference for methyl group loss by displacement, as predicted by computational studies. Loss of ethyl groups in reactions with triethylamine also occur by displacement, but preferential loss of isopropyl groups in the phenylketene reaction with diisopropylethylamine evidently involves elimination. Quinuclidine rapidly forms long-lived zwitterions with arylketenes, providing a model for catalysis by cinchona and related alkaloids in stereoselective additions to ketenes.

  16. Deployable, Field-Sustainable, Reverse Transcription-Polymerase Chain Reaction Assays for Rapid Screening and Serotype Identification of Dengue Virus in Mosquitoes

    DTIC Science & Technology

    2007-03-01

    C, Gottig S, Schiiiing S, et ai: Rapid detection and quantiilcation of RNA of Eboia and Marburg viruses, L.assa virus, Crimean - Congo hemorrhagic fever ...the past two decades, dengue fever (DF) and the poten- tially fatal forms ofthe disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome, have...Viroi 2003; 77: i 1436-47. 5. Gubler DJ: Dengue and dengue hemorrhagic fever . Ciin Microbiol Rev 1998; 11: 480-96. 6. Fonseca BA, Fonseca SN: Dengue virus

  17. A comparison between the blocking actions of 2-(4-phenylpiperidino) cyclohexanol (AH 5183) and its N-methyl quaternary analogue (AH 5954)

    PubMed Central

    Marshall, I. G.

    1970-01-01

    1. The neuromuscular blocking activities of AH 5183 (2-(4-phenylpiperidino) cyclohexanol) and its N-methyl quaternary analogue (AH 5954) were compared in rapidly stimulated nerve-skeletal muscle preparations of the rat, chicken and cat. 2. The evidence indicated that in isolated preparations the neuromuscular block produced by both AH 5183 and AH 5954 was primarily pre-junctional in origin. That produced by AH 5954 was readily reversible either by washing the tissue or by reducing the stimulation frequency, whereas that produced by AH 5183 was difficult to reverse in these ways. 3. Low doses of AH 5954 sensitized the rat hemidiaphragm preparation to the neuromuscular blocking action of choline. The neuromuscular block produced by choline was reversible by tetraethylammonium but not by neostigmine. This suggested that the blocking action of choline is at least partly pre-junctional in nature. 4. In anaesthetized cats AH 5954 possessed a biphasic neuromuscular blocking action. The initial phase was rapid in onset, suggestive of a post-junctional action, whereas the second phase was prolonged and reversible by choline, suggestive of a prejunctional inhibitory action on the choline transport mechanism. AH 5183 produced no initial blocking action and was irreversible by choline. 5. Both AH 5183 and AH 5954 possessed local anaesthetic and α-adrenoceptor blocking actions. These actions and the neuromuscular blocking action were affected to different degrees by quaternization, suggesting that the three main actions of the two drugs are independent. 6. It was concluded that AH 5954 and AH 5183 act at different pre-junctional sites at the neuromuscular junction, AH 5954 acting extraneuronally by inhibiting choline transport and AH 5183 intraneuronally at the level of the synaptic vesicle membrane. PMID:4395087

  18. Integration of continuous-flow sampling with microchip electrophoresis using poly(dimethylsiloxane)-based valves in a reversibly sealed device.

    PubMed

    Li, Michelle W; Martin, R Scott

    2007-07-01

    Here we describe a reversibly sealed microchip device that incorporates poly(dimethylsiloxane) (PDMS)-based valves for the rapid injection of analytes from a continuously flowing stream into a channel network for analysis with microchip electrophoresis. The microchip was reversibly sealed to a PDMS-coated glass substrate and microbore tubing was used for the introduction of gas and fluids to the microchip device. Two pneumatic valves were incorporated into the design and actuated on the order of hundreds of milliseconds, allowing analyte from a continuously flowing sampling stream to be injected into an electrophoresis separation channel. The device was characterized in terms of the valve actuation time and pushback voltage. It was also found that the addition of sodium dodecyl sulfate (SDS) to the buffer system greatly increased the reproducibility of the injection scheme and enabled the analysis of amino acids derivatized with naphthalene-2,3-dicarboxaldehyde/cyanide. Results from continuous injections of a 0.39 nL fluorescein plug into the optimized system showed that the injection process was reproducible (RSD of 0.7%, n = 10). Studies also showed that the device was capable of monitoring off-chip changes in concentration with a device lag time of 90 s. Finally, the ability of the device to rapidly monitor on-chip concentration changes was demonstrated by continually sampling from an analyte plug that was derivatized upstream from the electrophoresis/continuous flow interface. A reversibly sealed device of this type will be useful for the continuous monitoring and analysis of processes that occur either off-chip (such as microdialysis sampling) or on-chip from other integrated functions.

  19. Rapid directional changes associated with a 6.5 kyr-long Blake geomagnetic excursion at the Blake-Bahama Outer Ridge

    NASA Astrophysics Data System (ADS)

    Bourne, Mark; Mac Niocaill, Conall; Thomas, Alex L.; Knudsen, Mads Faurschou; Henderson, Gideon M.

    2012-06-01

    Geomagnetic excursions are recognized as intrinsic features of the Earth's magnetic field. High-resolution records of field behaviour, captured in marine sedimentary cores, present an opportunity to determine the temporal and geometric character of the field during geomagnetic excursions and provide constraints on the mechanisms producing field variability. We present here the highest resolution record yet published of the Blake geomagnetic excursion (∼125 ka) measured in three cores from Ocean Drilling Program (ODP) Site 1062 on the Blake-Bahama Outer Ridge. The Blake excursion has a controversial structure and timing but these cores have a sufficiently high sedimentation rate (∼10 cm ka-1) to allow detailed reconstruction of the field behaviour at this site during the excursion. Palaeomagnetic measurements of the cores reveal rapid transitions (<500 yr) between the contemporary stable normal polarity and a completely reversed state of long duration which spans a stratigraphic interval of 0.7 m. We determine the duration of the reversed state during the Blake excursion using oxygen isotope stratigraphy, combined with 230Th excess measurements to assess variations in the sedimentation rates through the sections of interest. This provides an age and duration for the Blake excursion with greater accuracy and with constrained uncertainty. We date the directional excursion as falling between 129 and 122 ka with a duration for the deviation of 6.5±1.3 kyr. The long duration of this interval and the fully reversed field suggest the existence of a pseudo-stable, reversed dipole field component during the excursion and challenge the idea that excursions are always of short duration.

  20. Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles

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

    Peretz, Jackye, E-mail: peretz@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    Bisphenol A (BPA) is the backbone of polycarbonate plastic products and the epoxy resin lining of aluminum cans. Previous studies have shown that exposure to BPA decreases sex steroid hormone production in mouse antral follicles. The current study tests the hypothesis that BPA first decreases the expression levels of the steroidogenic enzyme cytochrome P450 side-chain cleavage (Cyp11a1) and steroidogenic acute regulatory protein (StAR) in mouse antral follicles, leading to a decrease in sex steroid hormone production in vitro. Further, the current study tests the hypothesis that these effects are acute and reversible after removal of BPA. Exposure to BPA (10more » μg/mL and 100 μg/mL) significantly decreased expression of Cyp11a1 and StAR beginning at 18 h and 72 h, respectively, compared to controls. Exposure to BPA (10 μg/mL and 100 μg/mL) significantly decreased progesterone levels beginning at 24 h and decreased androstenedione, testosterone, and estradiol levels at 72 h and 96 h compared to controls. Further, after removing BPA from the culture media at 20 h, expression of Cyp11a1 and progesterone levels were restored to control levels by 48 h and 72 h, respectively. Additionally, expression of StAR and levels of androstenedione, testosterone, and estradiol never decreased compared to controls. These data suggest that BPA acutely decreases expression of Cyp11a1 as early as 18 h and this reduction in Cyp11a1 may lead to a decrease in progesterone production by 24 h, followed by a decrease in androstenedione, testosterone, and estradiol production and expression of StAR at 72 h. Therefore, BPA exposure likely targets Cyp11a1 and steroidogenesis, but these effects are reversible with removal of BPA exposure. - Highlights: • BPA may target Cyp11a1 to inhibit steroidogenesis in antral follicles. • BPA may decrease the expression of Cyp11a1 prior to inhibiting steroidogenesis. • The adverse effects of BPA on steroidogenesis in antral follicles are reversible.« less

  1. The reversal effects of 3-bromopyruvate on multidrug resistance in vitro and in vivo derived from human breast MCF-7/ADR cells.

    PubMed

    Wu, Long; Xu, Jun; Yuan, Weiqi; Wu, Baojian; Wang, Hao; Liu, Guangquan; Wang, Xiaoxiong; Du, Jun; Cai, Shaohui

    2014-01-01

    P-glycoprotein mediated efflux is one of the main mechanisms for multidrug resistance in cancers, and 3-Bromopyruvate acts as a promising multidrug resistance reversal compound in our study. To test the ability of 3-Bromopyruvate to overcome P-glycoprotein-mediated multidrug resistance and to explore its mechanisms of multidrug resistance reversal in MCF-7/ADR cells, we evaluate the in vitro and in vivo modulatory activity of this compound. The in vitro and in vivo activity was determined using the MTT assay and human breast cancer xenograft models. The gene and protein expression of P-glycoprotein were determined using real-time polymerase chain reaction and the Western blotting technique, respectively. ABCB-1 bioactivity was tested by fluorescence microscopy, multi-mode microplate reader, and flow cytometry. The intracellular levels of ATP, HK-II, and ATPase activity were based on an assay kit according to the manufacturer's instructions. 3-Bromopyruvate treatment led to marked decreases in the IC50 values of selected chemotherapeutic drugs [e.g., doxorubicin (283 folds), paclitaxel (85 folds), daunorubicin (201 folds), and epirubicin (171 folds)] in MCF-7/ADR cells. 3-Bromopyruvate was found also to potentiate significantly the antitumor activity of epirubicin against MCF-7/ADR xenografts. The intracellular level of ATP decreased 44%, 46% in the presence of 12.5.25 µM 3-Bromopyruvate, whereas the accumulation of rhodamine 123 and epirubicin (two typical P-glycoprotein substrates) in cells was significantly increased. Furthermore, we found that the mRNA and the total protein level of P-glycoprotein were slightly altered by 3-Bromopyruvate. Moreover, the ATPase activity was significantly inhibited when 3-Bromopyruvate was applied. We demonstrated that 3-Bromopyruvate can reverse P-glycoprotein-mediated efflux in MCF-7/ADR cells. Multidrug resistance reversal by 3-Bromopyruvate occurred through at least three approaches, namely, a decrease in the intracellular level of ATP and HK-II bioactivity, the inhibition of ATPase activity, and the slight decrease in P-glycoprotein expression in MCF-7/ADR cells.

  2. The Reversal Effects of 3-Bromopyruvate on Multidrug Resistance In Vitro and In Vivo Derived from Human Breast MCF-7/ADR Cells

    PubMed Central

    Yuan, Weiqi; Wu, Baojian; Wang, Hao; Liu, Guangquan; Wang, Xiaoxiong; Du, Jun; Cai, Shaohui

    2014-01-01

    Purpose P-glycoprotein mediated efflux is one of the main mechanisms for multidrug resistance in cancers, and 3-Bromopyruvate acts as a promising multidrug resistance reversal compound in our study. To test the ability of 3-Bromopyruvate to overcome P-glycoprotein-mediated multidrug resistance and to explore its mechanisms of multidrug resistance reversal in MCF-7/ADR cells, we evaluate the in vitro and in vivo modulatory activity of this compound. Methods The in vitro and in vivo activity was determined using the MTT assay and human breast cancer xenograft models. The gene and protein expression of P-glycoprotein were determined using real-time polymerase chain reaction and the Western blotting technique, respectively. ABCB-1 bioactivity was tested by fluorescence microscopy, multi-mode microplate reader, and flow cytometry. The intracellular levels of ATP, HK-II, and ATPase activity were based on an assay kit according to the manufacturer’s instructions. Results 3-Bromopyruvate treatment led to marked decreases in the IC50 values of selected chemotherapeutic drugs [e.g., doxorubicin (283 folds), paclitaxel (85 folds), daunorubicin (201 folds), and epirubicin (171 folds)] in MCF-7/ADR cells. 3-Bromopyruvate was found also to potentiate significantly the antitumor activity of epirubicin against MCF-7/ADR xenografts. The intracellular level of ATP decreased 44%, 46% in the presence of 12.5.25 µM 3-Bromopyruvate, whereas the accumulation of rhodamine 123 and epirubicin (two typical P-glycoprotein substrates) in cells was significantly increased. Furthermore, we found that the mRNA and the total protein level of P-glycoprotein were slightly altered by 3-Bromopyruvate. Moreover, the ATPase activity was significantly inhibited when 3-Bromopyruvate was applied. Conclusion We demonstrated that 3-Bromopyruvate can reverse P-glycoprotein-mediated efflux in MCF-7/ADR cells. Multidrug resistance reversal by 3-Bromopyruvate occurred through at least three approaches, namely, a decrease in the intracellular level of ATP and HK-II bioactivity, the inhibition of ATPase activity, and the slight decrease in P-glycoprotein expression in MCF-7/ADR cells. PMID:25372840

  3. Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric mucosal glycoproteins, cell proliferation, antioxidants and free radicals.

    PubMed

    Mohan Kumar, M; Joshi, M C; Prabha, T; Dorababu, M; Goel, R K

    2006-04-01

    Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems.

  4. Asphaltene-laden interfaces form soft glassy layers in contraction experiments: a mechanism for coalescence blocking.

    PubMed

    Pauchard, Vincent; Rane, Jayant P; Banerjee, Sanjoy

    2014-11-04

    In previous studies, the adsorption kinetics of asphaltenes at the water-oil interface were interpreted utilizing a Langmuir equation of state (EOS) based on droplet expansion experiments.1-3 Long-term adsorption kinetics followed random sequential adsorption (RSA) theory predictions, asymptotically reaching ∼85% limiting surface coverage, which is similar to limiting random 2D close packing of disks. To extend this work beyond this slow adsorption process, we performed rapid contractions and contraction-expansions of asphaltene-laden interfaces using the pendant drop experiment to emulate a Langmuir trough. This simulates the rapid increase in interfacial asphaltene concentration that occurs during coalescence events. For the contraction of droplets aged in asphaltene solutions, deviation from the EOS consistently occurs at a surface pressure value ∼21 mN/m corresponding to a surface coverage ∼80%. At this point droplets lose the shape required for validity of the Laplace-Young equation, indicating solidlike surface behavior. On further contraction wrinkles appear, which disappear when the droplet is held at constant volume. Surface pressure also decreases down to an equilibrium value near that measured for slow adsorption experiments. This behavior appears to be due to a transition to a glassy interface on contraction past the packing limit, followed by relaxation toward equilibrium by desorption at constant volume. This hypothesis is supported by cycling experiments around the close-packed limit where the transition to and from a solidlike state appears to be both fast and reversible, with little hysteresis. Also, the soft glass rheology model of Sollich is shown to capture previously reported shear behavior during adsorption. The results suggest that the mechanism by which asphaltenes stabilize water-in-oil emulsions is by blocking coalescence due to rapid formation of a glassy interface, in turn caused by interfacial asphaltenes rapidly increasing in concentration beyond the glass transition point.

  5. Impact of human immunodeficiency virus type 1 reverse transcriptase inhibitor drug resistance mutation interactions on phenotypic susceptibility.

    PubMed

    Trivedi, Vinod; Von Lindern, Jana; Montes-Walters, Miguel; Rojo, Daniel R; Shell, Elisabeth J; Parkin, Neil; O'Brien, William A; Ferguson, Monique R

    2008-10-01

    The role specific reverse transcriptase (RT) drug resistance mutations play in influencing phenotypic susceptibility to RT inhibitors in virus strains with complex resistance interaction patterns was assessed using recombinant viruses that consisted of RT-PCR-amplified pol fragments derived from plasma HIV-1 RNA from two treatment-experienced patients. Specific modifications of key RT amino acids were performed by site-directed mutagenesis. A panel of viruses with defined genotypic resistance mutations was assessed for phenotypic drug resistance. Introduction of M184V into several different clones expressing various RT resistance mutations uniformly decreased susceptibility to abacavir, lamivudine, and didanosine, and increased susceptibility to zidovudine, stavudine, and tenofovir; replication capacity was decreased. The L74V mutation had similar but slightly different effects, contributing to decreased susceptibility to abacavir, lamivudine, and didanosine and increased susceptibility to zidovudine and tenofovir, but in contrast to M184V, L74V contributed to decreased susceptibility to stavudine. In virus strains with the nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E and G190S, the L74V mutation increased replication capacity, consistent with published observations, but replication capacity was decreased in strains without NNRTI resistance mutations. K101E and G190S together tend to decrease susceptibility to all nucleoside RT inhibitors, but the K103N mutation had little effect on nucleoside RT inhibitor susceptibility. Mutational interactions can have a substantial impact on drug resistance phenotype and replication capacity, and this has been exploited in clinical practice with the development of fixed-dose combination pills. However, we are the first to report these mutational interactions using molecularly cloned recombinant strains derived from viruses that occur naturally in HIV-infected individuals.

  6. Impact of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitor Drug Resistance Mutation Interactions on Phenotypic Susceptibility

    PubMed Central

    Trivedi, Vinod; Von Lindern, Jana; Montes-Walters, Miguel; Rojo, Daniel R.; Shell, Elisabeth J.; Parkin, Neil; O'Brien, William A.

    2008-01-01

    Abstract The role specific reverse transcriptase (RT) drug resistance mutations play in influencing phenotypic susceptibility to RT inhibitors in virus strains with complex resistance interaction patterns was assessed using recombinant viruses that consisted of RT-PCR-amplified pol fragments derived from plasma HIV-1 RNA from two treatment-experienced patients. Specific modifications of key RT amino acids were performed by site-directed mutagenesis. A panel of viruses with defined genotypic resistance mutations was assessed for phenotypic drug resistance. Introduction of M184V into several different clones expressing various RT resistance mutations uniformly decreased susceptibility to abacavir, lamivudine, and didanosine, and increased susceptibility to zidovudine, stavudine, and tenofovir; replication capacity was decreased. The L74V mutation had similar but slightly different effects, contributing to decreased susceptibility to abacavir, lamivudine, and didanosine and increased susceptibility to zidovudine and tenofovir, but in contrast to M184V, L74V contributed to decreased susceptibility to stavudine. In virus strains with the nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E and G190S, the L74V mutation increased replication capacity, consistent with published observations, but replication capacity was decreased in strains without NNRTI resistance mutations. K101E and G190S together tend to decrease susceptibility to all nucleoside RT inhibitors, but the K103N mutation had little effect on nucleoside RT inhibitor susceptibility. Mutational interactions can have a substantial impact on drug resistance phenotype and replication capacity, and this has been exploited in clinical practice with the development of fixed-dose combination pills. However, we are the first to report these mutational interactions using molecularly cloned recombinant strains derived from viruses that occur naturally in HIV-infected individuals. PMID:18844463

  7. Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice

    PubMed Central

    Li, Huihui; Choesang, Tenzin; Bao, Weili; Chen, Huiyong; Feola, Maria; Garcia-Santos, Daniel; Li, Jie; Sun, Shuming; Follenzi, Antonia; Pham, Petra; Liu, Jing; Zhang, Jinghua; Ponka, Prem; An, Xiuli; Mohandas, Narla; Fleming, Robert E.; Rivella, Stefano; Li, Guiyuan

    2017-01-01

    Iron availability for erythropoiesis and its dysregulation in β-thalassemia are incompletely understood. We previously demonstrated that exogenous apotransferrin leads to more effective erythropoiesis, decreasing erythroferrone (ERFE) and derepressing hepcidin in β-thalassemic mice. Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. We hypothesize that apotransferrin’s effect is mediated via decreased TfR1 expression and evaluate TfR1 expression in β-thalassemic mice in vivo and in vitro with and without added apotransferrin. Our findings demonstrate that β-thalassemic erythroid precursors overexpress TfR1, an effect that can be reversed by the administration of exogenous apotransferrin. In vitro experiments demonstrate that apotransferrin inhibits TfR1 expression independent of erythropoietin- and iron-related signaling, decreases TfR1 partitioning to reticulocytes during enucleation, and enhances enucleation of defective β-thalassemic erythroid precursors. These findings strongly suggest that overexpressed TfR1 may play a regulatory role contributing to iron overload and anemia in β-thalassemic mice. To evaluate further, we crossed TfR1+/− mice, themselves exhibiting iron-restricted erythropoiesis with increased hepcidin, with β-thalassemic mice. Resultant double-heterozygote mice demonstrate long-term improvement in ineffective erythropoiesis, hepcidin derepression, and increased erythroid enucleation in relation to β-thalassemic mice. Our data demonstrate for the first time that TfR1+/− haploinsufficiency reverses iron overload specifically in β-thalassemic erythroid precursors. Taken together, decreasing TfR1 expression during β-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in β-thalassemic mice. PMID:28151426

  8. Temperature driven structural-memory-effects in carbon nanotubes filled with Fe3C nano crystals

    NASA Astrophysics Data System (ADS)

    Boi, Filippo S.; Zhang, Xiaotian; Corrias, Anna

    2018-02-01

    We report the observation of novel temperature-driven structural-memory-effects in carbon nanotubes (CNTs) filled with Fe3C nano-crystals. These structural-transitions were measured by means of temperature (T) dependent x-ray diffraction (XRD) in the T-range from 298 K to 12 K. A clear reversible 2θ-shift in the 002-peak of the graphitic-CNTs-walls is found with the decrease of the temperature. As determined by Rietveld refinement, such 2θ-shift translates in a not previously reported decrease in the value of the CNT graphitic c-axis with the decrease of the temperature (from 298 K to 12 K). Also, a clear reversible 2θ-shift in the 031 and 131 diffraction-peaks of Fe3C is observed within the same T-range. Rietveld refinements confirm the existence of such memory-effect and also reveal a gradual decrease of the 010-axis of Fe3C with the decrease of the temperature. These observations imply that the observed structural-memory-effect is a characteristic of CNTs when Fe3C is the encapsulated ferromagnet. The generality of such memory-effects was further confirmed by additional measurements performed on other types of CNTs characterized by continuous Fe3C-filling. XRD measurements in the T-range from 298 K to 673 K revealed also an unusual reversible decrease of the Fe3C-peak intensities with the increase of the temperature. These observations can have important implications on the magnetic data recording applications of these nanostructures by helping in better understanding the unusual temperature-dependent magnetic instabilities of iron-based nano-crystals which have been recently reported in literature.

  9. Rapid determination of human globin chains using reversed-phase high-performance liquid chromatography.

    PubMed

    Wan, Jun-Hui; Tian, Pei-Ling; Luo, Wei-Hao; Wu, Bing-Yi; Xiong, Fu; Zhou, Wan-Jun; Wei, Xiang-Cai; Xu, Xiang-Min

    2012-07-15

    Reversed-phase high-performance liquid chromatography (RP-HPLC) of human globin chains is an important tool for detecting thalassemias and hemoglobin variants. The challenges of this method that limit its clinical application are a long analytical time and complex sample preparation. The aim of this study was to establish a simple, rapid and high-resolution RP-HPLC method for the separation of globin chains in human blood. Red blood cells from newborns and adults were diluted in deionized water and injected directly onto a micro-jupiter C18 reversed-phase column (250 mm × 4.6 mm) with UV detection at 280 nm. Under the conditions of varying pH or the HPLC gradient, the globin chains (pre-β, β, δ, α, (G)γ and (A)γ) were denatured and separated from the heme groups in 12 min with a retention time coefficient of variation (CV) ranging from 0.11 to 1.29% and a peak area CV between 0.32% and 4.86%. Significant differences (P<0.05) among three groups (normal, Hb H and β thalassemia) were found in the area ratio of α/pre-β+β applying the rapid elution procedure, while P≥0.05 was obtained between the normal and α thalassemia silent/trait group. Based on the ANOVA results, receiver operating characteristic (ROC) curve analysis of the δ/β and α/pre-β+β area ratios showed a sensitivity of 100.0%, and a specificity of 100.0% for indicating β thalassemia carriers, and a sensitivity of 96.6% and a specificity of 89.6% for the prediction of hemoglobin H (Hb H) disease. The proposed cut-off was 0.026 of δ/β for β thalassemia carriers and 0.626 of α/pre-β+β for Hb H disease. In addition, abnormal hemoglobin hemoglobin E (Hb E) and Hb Westmead (Hb WS) were successfully identified using this RP-HPLC method. Our experience in developing this RP-HPLC method for the rapid separation of human globin chains could be of use for similar work. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Reverse technology transfer; obtaining feedback from managers.

    Treesearch

    A.B. Carey; J.M. Calhoun; B. Dick; K. O' Halloran; L.S. Young; R.E. Bigley; S. Chan; C.A. Harrington; J.P. Hayes; J. Marzluff

    1999-01-01

    Forestry policy, planning, and practice have changed rapidly with implementation of ecosystem management by federal, state, tribal, and private organizations. Implementation entails new concepts, terminology, and management approaches. Yet there seems to have been little organized effort to obtain feedback from on-the-ground managers on the practicality of implementing...

  11. Project-Based Teaching-Learning Computer-Aided Engineering Tools

    ERIC Educational Resources Information Center

    Simoes, J. A.; Relvas, C.; Moreira, R.

    2004-01-01

    Computer-aided design, computer-aided manufacturing, computer-aided analysis, reverse engineering and rapid prototyping are tools that play an important key role within product design. These are areas of technical knowledge that must be part of engineering and industrial design courses' curricula. This paper describes our teaching experience of…

  12. Smart, stretchable supercapacitors.

    PubMed

    Chen, Xuli; Lin, Huijuan; Chen, Peining; Guan, Guozhen; Deng, Jue; Peng, Huisheng

    2014-07-09

    Smart supercapacitors are developed by depositing conducting polymers onto aligned carbon-nanotube sheets. These supercapacitors rapidly and reversibly demonstrate color changes in response to a variation in the level of stored energy and the chromatic transitions can be directly observed by the naked eye. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Hypothyroidism and its rapid correction alter cardiac remodeling.

    PubMed

    Hajje, Georges; Saliba, Youakim; Itani, Tarek; Moubarak, Majed; Aftimos, Georges; Farès, Nassim

    2014-01-01

    The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

  14. Hypothyroidism and Its Rapid Correction Alter Cardiac Remodeling

    PubMed Central

    Itani, Tarek; Moubarak, Majed; Aftimos, Georges; Farès, Nassim

    2014-01-01

    The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease. PMID:25333636

  15. Groundwater salinization processes and reversibility of seawater intrusion in coastal carbonate aquifers

    NASA Astrophysics Data System (ADS)

    Han, Dongmei; Post, Vincent E. A.; Song, Xianfang

    2015-12-01

    Seawater intrusion (SWI) has led to salinization of fresh groundwater reserves in coastal areas worldwide and has forced the closure of water supply wells. There is a paucity of well-documented studies that report on the reversal of SWI after the closure of a well field. This study presents data from the coastal carbonate aquifer in northeast China, where large-scale extraction has ceased since 2001 after salinization of the main well field. The physical flow and concomitant hydrogeochemical processes were investigated by analyzing water level and geochemical data, including major ion chemistry and stable water isotope data. Seasonal water table and salinity fluctuations, as well as changes of δ2H-δ18O values of groundwater between the wet and dry season, suggest local meteoric recharge with a pronounced seasonal regime. Historical monitoring testifies of the reversibility of SWI in the carbonate aquifer, as evidenced by a decrease of the Cl- concentrations in groundwater following restrictions on groundwater abstraction. This is attributed to the rapid flushing in this system where flow occurs preferentially along karst conduits, fractures and fault zones. The partially positive correlation between δ18O values and TDS concentrations of groundwater, as well as high NO3- concentrations (>39 mg/L), suggest that irrigation return flow is a significant recharge component. Therefore, the present-day elevated salinities are more likely due to agricultural activities rather than SWI. Nevertheless, seawater mixing with fresh groundwater cannot be ruled out in particular where formerly intruded seawater may still reside in immobile zones of the carbonate aquifer. The massive expansion of fish farming in seawater ponds in the coastal zone poses a new risk of salinization. Cation exchange, carbonate dissolution, and fertilizer application are the dominant processes further modifying the groundwater composition, which is investigated quantitatively using hydrogeochemical models.

  16. CER-001, a HDL-mimetic, stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice.

    PubMed

    Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Ackermann, Rose; Sy, Gavin; Bluteau, Alice; Cholez, Guy; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

    2014-01-01

    CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and phospholipids that was designed to mimic the beneficial properties of nascent pre-β HDL. In this study, we have evaluated the capacity of CER-001 to perform reverse lipid transport in single dose studies as well as to regress atherosclerosis in LDLr(-/-) mice after short-term multiple-dose infusions. CER-001 induced cholesterol efflux from macrophages and exhibited anti-inflammatory response similar to natural HDL. Studies with HUVEC demonstrated CER-001 at a concentration of 500 μg/mL completely suppressed the secretion of cytokines IL-6, IL-8, GM-CSF and MCP-1. Following infusion of CER-001 (10mg/kg) in C57Bl/6J mice, we observed a transient increase in the mobilization of unesterified cholesterol in HDL particles containing recombinant human apoA-I. Finally we show that cholesterol elimination was stimulated in CER-001 treated animals as demonstrated by the increased cholesterol concentration in liver and feces. In a familial hypercholesterolemia mouse model (LDL-receptor deficient mice), the infusion of CER-001 caused 17% and 32% reductions in plaque size, 17% and 23% reductions in lipid content after 5 and 10 doses given every 2 days, respectively. Also, there was an 80% reduction in macrophage content in the plaque following 5 doses, and decreased VCAM-1 expression by 16% and 22% in the plaque following 5 and 10 intravenous doses of CER-001, respectively. These data demonstrate that CER-001 rapidly enhances reverse lipid transport in the mouse, reducing vascular inflammation and promoting regression of diet-induced atherosclerosis in LDLr(-/-) mice upon a short-term multiple dose treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Comparison of Traditional and Reverse Syphilis Screening Algorithms in Medical Health Checkups.

    PubMed

    Nah, Eun Hee; Cho, Seon; Kim, Suyoung; Cho, Han Ik; Chai, Jong Yil

    2017-11-01

    The syphilis diagnostic algorithms applied in different countries vary significantly depending on the local syphilis epidemiology and other considerations, including the expected workload, the need for automation in the laboratory and budget factors. This study was performed to investigate the efficacy of traditional and reverse syphilis diagnostic algorithms during general health checkups. In total, 1,000 blood specimens were obtained from 908 men and 92 women during their regular health checkups. Traditional screening and reverse screening were applied to the same specimens using automatic rapid plasma regain (RPR) and Treponema pallidum latex agglutination (TPLA) tests, respectively. Specimens that were reverse algorithm (TPLA) reactive, were subjected to a second treponemal test performed by using the chemiluminescent microparticle immunoassay (CMIA). Of the 1,000 specimens tested, 68 (6.8%) were reactive by reverse screening (TPLA) compared with 11 (1.1%) by traditional screening (RPR). The traditional algorithm failed to detect 48 specimens [TPLA(+)/RPR(-)/CMIA(+)]. The median TPLA cutoff index (COI) was higher in CMIA-reactive cases than in CMIA-nonreactive cases (90.5 vs 12.5 U). The reverse screening algorithm could detect the subjects with possible latent syphilis who were not detected by the traditional algorithm. Those individuals could be provided with opportunities for evaluating syphilis during their health checkups. The COI values of the initial TPLA test may be helpful in excluding false-positive TPLA test results in the reverse algorithm. © The Korean Society for Laboratory Medicine

  18. A Reversible Logical Circuit Synthesis Algorithm Based on Decomposition of Cycle Representations of Permutations

    NASA Astrophysics Data System (ADS)

    Zhu, Wei; Li, Zhiqiang; Zhang, Gaoman; Pan, Suhan; Zhang, Wei

    2018-05-01

    A reversible function is isomorphic to a permutation and an arbitrary permutation can be represented by a series of cycles. A new synthesis algorithm for 3-qubit reversible circuits was presented. It consists of two parts, the first part used the Number of reversible function's Different Bits (NDBs) to decide whether the NOT gate should be added to decrease the Hamming distance of the input and output vectors; the second part was based on the idea of exploring properties of the cycle representation of permutations, decomposed the cycles to make the permutation closer to the identity permutation and finally turn into the identity permutation, it was realized by using totally controlled Toffoli gates with positive and negative controls.

  19. Effect of Detergent on Electrical Properties of Squid Axon Membrane

    PubMed Central

    Kishimoto, Uichiro; Adelman, William J.

    1964-01-01

    The effects of detergents on squid giant axon action and resting potentials as well as membrane conductances in the voltage clamp have been studied. Anionic detergents (sodium lauryl sulfate, 0.1 to 1.0 mM; dimethyl benzene sulfonate, 1 to 20 mM, pH 7.6) cause a temporary increase and a later decrease of action potential height and the value of the resting potential. Cationic detergent (cetyl trimethyl ammonium chloride, 6 x 10-5 M or more, pH 7.6) generally brings about immediate and irreversible decreases in the action and resting potentials. Non-ionic detergent (tween 80, 0.1 M, pH 7.6) causes a slight reversible reduction of action potential height without affecting the value of the resting potential. Both anionic and cationic detergents generally decrease the sodium and potassium conductances irreversibly. The effect of non-ionic detergent is to decrease the sodium conductance reversibly, leaving the potassium conductance almost unchanged. PMID:14158665

  20. Magnetization reversal in exchange biased Co/CoO probed with anisotropic magnetoresistance

    NASA Astrophysics Data System (ADS)

    Gredig, Thomas; Krivorotov, Ilya N.; Dahlberg, E. Dan

    2002-05-01

    The magnetization reversal in exchange coupled polycrystalline Co/CoO bilayers has been investigated as a function of CoO thickness using anisotropic magnetoresistance as a probe. The anisotropic magnetoresistance (AMR) was measured during the magnetization reversal and it was used to determine the orientation of the magnetization. For thin CoO layers large training effects were present; ergo the first hysteresis loop after field cooling was not the same as the second. The magnitude of the observed training was found to decrease with increasing CoO thickness. In the samples where substantial training was observed, the first magnetization reversal was dominated by nucleation of reversed domains. For the reversal from the antiparallel state back to the parallel direction, the AMR is consistent with a rotation process. In thicker CoO films where the training was less, the asymmetry was drastically reduced. A simple model that couples the antiferromagnetic grains to the ferromagnetic layer simulates qualitatively the observed magnetoresistance.

Top