Biophysical characterization and functional consequences of a slowly inactivating potassium current in neostriatal neurons.

PubMed

Gabel, L A; Nisenbaum, E S

1998-04-01

Neostriatal spiny projection neurons can display a pronounced delay in their transition to action potential discharge that is mediated by a slowly developing ramp depolarization. The possible contribution of a slowly inactivating A-type K+ current (IAs) to this delayed excitation was investigated by studying the biophysical and functional properties of IAs using whole cell voltage- and current-clamp recording from acutely isolated neostriatal neurons. Isolation of IAs from other voltage-gated, calcium-independent K+ currents was achieved through selective blockade of IAs with low concentrations (10 microM) of the benzazepine derivative, 6-chloro-7,8-dihydroxy-3-allyl- 1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepine (APB; SKF82958) and subsequent current subtraction. Examination of the voltage dependence of activation showed that IAs began to flow at approximately -60 mV in response to depolarization. The voltage dependence of inactivation revealed that approximately 50% of IAs channels were available at the normal resting potential (-80 mV) of these cells, but that only 20% of the channels were available at membrane potentials corresponding to spike threshold (about -40 mV). At these depolarized membrane potentials, the rate of activation was moderately rapid (tau approximately 60 ms), whereas the rate of inactivation was slow (tau approximately 1.5 s). The time course of removal of inactivation of IAs at -80 mV also was relatively slow (tau approximately 1.0 s). The subthreshold availability of IAs combined with its rapid activation and slow inactivation rates suggested that this current should be capable of dampening the onset of prolonged depolarizing responses, but over time its efficacy should diminish, slowly permitting the membrane to depolarize toward spike threshold. Voltage recording experiments confirmed this hypothesis by demonstrating that application of APB at a concentration (10 microM) that selectively blocks IAs substantially decreased the latency to discharge and increased the frequency of firing of neostriatal neurons. The properties of IAs suggest that it should play a critical role in placing the voltage limits on the recurring episodes of subthreshold depolarization which are characteristic of spiny neurons recorded in vivo. However, the voltage dependence and recovery kinetics of inactivation of IAs predict that its effectiveness will vary exponentially with the level and duration of hyperpolarization which precedes depolarizing episodes. Thus long periods of hyperpolarization should increase the availability of IAs and dampen succeeding depolarizations; whereas brief epochs of hyperpolarization should not sufficiently remove inactivation of IAs, thereby reducing its ability to limit subsequent depolarizing responses.

Blockade of HERG human K+ channel and IKr of guinea pig cardiomyocytes by prochlorperazine.

PubMed

Kim, Moon-Doo; Eun, Su-Yong; Jo, Su-Hyun

2006-08-21

Prochlorperazine, a drug for the symptomatic control of nausea, vomiting and psychiatric disorders, can induce prolonged QT, torsades de pointes and sudden death. We studied the effects of prochlorperazine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and also in the delayed rectifier K+ current of guinea pig cardiomyocytes. Prochlorperazine induced a concentration-dependent decrease in current amplitudes at the end of the voltage steps and tail currents of HERG. The IC50 for a prochlorperazine block of HERG current in Xenopus oocytes progressively decreased relative to the degree of depolarization, from 42.1 microM at -40 mV to 37.4 microM at 0 mV to 22.6 microM at +40 mV. The block of HERG by prochlorperazine was use-dependent, exhibiting a more rapid onset and a greater steady-state block at higher frequencies of activation, while there was partial relief of the block with reduced frequencies. In guinea pig ventricular myocytes, bath applications of 0.5 and 1 muM prochlorperazine at 36 degrees C blocked rapidly activating delayed rectifier K+ current by 38.9% and 76.5%, respectively, but did not significantly block slowly activating delayed rectifier K+ current. Our findings suggest that the arrhythmogenic side effects of prochlorperazine are caused by a blockade of HERG and the rapid component of the delayed rectifier K+ current rather than by a blockade of the slow component.

Block of HERG human K(+) channel and IKr of guinea pig cardiomyocytes by chlorpromazine.

PubMed

Lee, So-Young; Choi, Se-Young; Youm, Jae Boum; Ho, Won-Kyung; Earm, Yung E; Lee, Chin O; Jo, Su-Hyun

2004-05-01

Chlorpromazine, a commonly used antipsychotic drug, has been known to induce QT prolongation and torsades de pointes, which can cause sudden death. We studied the effects of chlorpromazine on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes and on delayed rectifier K current of guinea pig ventricular myocytes. Application of chlorpromazine showed a dose-dependent decrease in the amplitudes of steady-state currents and tail currents of HERG. The decrease became more pronounced at increasingly positive potential, suggesting that the blockade of HERG by chlorpromazine is voltage dependent. IC50 for chlorpromazine block of HERG current was progressively decreased according to depolarization: IC50 values at -30, 0, and +30 mV were 10.5, 8.8, and 4.9 microM, respectively. The block of HERG current during the voltage step increased with time starting from a level 89% of the control current. In guinea pig ventricular myocytes, bath application of 2 and 5 microM chlorpromazine at 36 degree C blocked rapidly activating delayed rectifier K current (IKr) by 31 and 83%, respectively. How-ever, the same concentrations of chlorpromazine failed to significantly block slowly activating delayed rectifier K current (IKs). Our findings suggest that the arrhythmogenic side effect of chlorpromazine is caused by blockade of HERG and rapid component of delayed rectifier K current rather than by blockade of the slow component.

Inhibition of human ether-a-go-go-related gene K+ channel and IKr of guinea pig cardiomyocytes by antipsychotic drug trifluoperazine.

PubMed

Choi, Se-Young; Koh, Young-Sang; Jo, Su-Hyun

2005-05-01

Trifluoperazine, a commonly used antipsychotic drug, has been known to induce QT prolongation and torsades de pointes, which can cause sudden death. We studied the effects of trifluoperazine on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes and on the delayed rectifier K(+) current of guinea pig cardiomyocytes. The application of trifluoperazine showed a dose-dependent decrease in current amplitudes at the end of voltage steps and tail currents of HERG. The IC(50) for a trifluoperazine block of HERG current progressively decreased according to depolarization: IC(50) values at -40, 0, and +40 mV were 21.6, 16.6, and 9.29 microM, respectively. The voltage dependence of the block could be fitted with a monoexponential function, and the fractional electrical distance was estimated to be delta = 0.65. The block of HERG by trifluoperazine was use-dependent, exhibiting more rapid onset and greater steady-state block at higher frequencies of activation; there was partial relief of the block with decreasing frequency. In guinea pig ventricular myocytes, bath applications of 0.5 and 2 microM trifluoperazine at 36 degrees C blocked the rapidly activating delayed rectifier K(+) current by 32.4 and 72.9%, respectively; however, the same concentrations of trifluoperazine failed to significantly block the slowly activating delayed rectifier K(+) current. Our findings suggest the arrhythmogenic side effect of trifluoperazine is caused by a blockade of HERG and the rapid component of the delayed rectifier K(+) current rather than by the blockade of the slow component.

Permanganate gel (PG) for groundwater remediation: compatibility, gelation, and release characteristics.

PubMed

Lee, Eung Seok; Olson, Pamela R; Gupta, Neha; Solpuker, Utku; Schwartz, Franklin W; Kim, Yongje

2014-02-01

Permanganate (MnO4(-)) is a strong oxidant that is widely used for treating chlorinated ethylenes in groundwater. This study aims to develop hyper-saline MnO4(-) solution (MnO4(-) gel; PG) that can be injected into aquifers via wells, slowly gelates over time, and slowly release MnO4(-) to flowing water. In this study, compatibility and miscibility of gels, such as chitosan, aluminosilicate, silicate, and colloidal silica gels, with MnO4(-) were tested. Of these gels, chitosan was reactive with MnO4(-). Aluminosilicates were compatible but not readily miscible with MnO4(-). Silicates and colloidal silica were both compatible and miscible with MnO4(-), and gelated with addition of KMnO4 granules. Colloidal silica has low initial viscosity (<15cP), exhibited delayed gelation characteristics with the lag times ranging from 0 to 200min. Release of MnO4(-) from the colloidal silica-based PG gel occurred in a delayed fashion, with maximum duration of 24h. These results suggested that colloidal silica can be used to create PG or delayed-gelling forms containing other oxidants which can be used for groundwater remediation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Distributed optimisation problem with communication delay and external disturbance

NASA Astrophysics Data System (ADS)

Tran, Ngoc-Tu; Xiao, Jiang-Wen; Wang, Yan-Wu; Yang, Wu

2017-12-01

This paper investigates the distributed optimisation problem for the multi-agent systems (MASs) with the simultaneous presence of external disturbance and the communication delay. To solve this problem, a two-step design scheme is introduced. In the first step, based on the internal model principle, the internal model term is constructed to compensate the disturbance asymptotically. In the second step, a distributed optimisation algorithm is designed to solve the distributed optimisation problem based on the MASs with the simultaneous presence of disturbance and communication delay. Moreover, in the proposed algorithm, each agent interacts with its neighbours through the connected topology and the delay occurs during the information exchange. By utilising Lyapunov-Krasovskii functional, the delay-dependent conditions are derived for both slowly and fast time-varying delay, respectively, to ensure the convergence of the algorithm to the optimal solution of the optimisation problem. Several numerical simulation examples are provided to illustrate the effectiveness of the theoretical results.

Slowly digestible waxy maize starch prepared by octenyl succinic anhydride esterification and heat-moisture treatment: glycemic response and mechanism.

PubMed

He, Jinhua; Liu, Jie; Zhang, Genyi

2008-01-01

The mechanism and molecular structure of the slowly digestible waxy maize starch prepared by octenyl succinic anhydride (OSA) esterification and heat-moisture treatment were investigated. The in vitro Englyst test showed a proportion of 28.3% slowly digestible starch (SDS) when waxy maize starch was esterified with 3% OSA (starch weight based, and it is named OSA-starch), and a highest SDS content of 42.8% was obtained after OSA-starch (10% moisture) was further heated at 120 degrees C for 4 h (named HOSA-starch). The in vivo glycemic response of HOSA-starch, which showed a delayed appearance of blood glucose peak and a significant reduction (32.2%) of the peak glucose concentration, further confirmed its slow digestion property. Amylopectin debranching analysis revealed HOSA-starch had the highest resistance to debranching enzymes of isoamylase and pullulanase, and a simultaneous decrease of K m and V m (enzyme kinetics) was also shown when HOSA-starch was digested by either alpha-amylase or amyloglucosidase, indicating that the slow digestion of HOSA-starch resulted from an uncompetitive inhibition of enzyme activity during digestion. Size exclusion chromatography analysis of HOSA-starch showed fragmented amylopectin molecules with more nonreducing ends that are favorable for RS conversion to SDS by the action of amyloglucosidase in the Englyst test. Further solubility analysis indicates that the water-insolubility of HOSA-starch is caused by OSA-mediated cross-linking of amylopectin and the hydrophobic interaction between OSA-modified starch molecules. The water-insolubility of HOSA-starch would decrease its enzyme accessibility, and the digestion products with attached OSA molecules might also directly act as the uncompetitive inhibitor to reduce the enzyme activity leading to a slow digestion of HOSA-starch.

Forgetting of Foreign-Language Skills: A Corpus-Based Analysis of Online Tutoring Software.

PubMed

Ridgeway, Karl; Mozer, Michael C; Bowles, Anita R

2017-05-01

We explore the nature of forgetting in a corpus of 125,000 students learning Spanish using the Rosetta Stone ® foreign-language instruction software across 48 lessons. Students are tested on a lesson after its initial study and are then retested after a variable time lag. We observe forgetting consistent with power function decay at a rate that varies across lessons but not across students. We find that lessons which are better learned initially are forgotten more slowly, a correlation which likely reflects a latent cause such as the quality or difficulty of the lesson. We obtain improved predictive accuracy of the forgetting model by augmenting it with features that encode characteristics of a student's initial study of the lesson and the activities the student engaged in between the initial and delayed tests. The augmented model can predict 23.9% of the variance in an individual's score on the delayed test. We analyze which features best explain individual performance. Copyright © 2016 Cognitive Science Society, Inc.

β1-Adrenoceptor autoantibodies affect action potential duration and delayed rectifier potassium currents in guinea pigs.

PubMed

Zhao, Yuhui; Huang, Haixia; Du, Yunhui; Li, Xiao; Lv, Tingting; Zhang, Suli; Wei, Hua; Shang, Jianyu; Liu, Ping; Liu, Huirong

2015-01-01

β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.

Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

PubMed Central

Wu, Delin; Jiang, Linqing; Wu, Hongjin; Wang, Shengqi; Zheng, Sidao; Yang, Jiyuan; Liu, Yuna; Ren, Jianxun; Chen, Xianbing

2013-01-01

Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (I K), the rapidly activating (I Kr) and slowly activating (I Ks) components of I K, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record I K (I Kr, I Ks) and the HERG K+ current. Results. GA (1, 5, and 10 μM) inhibited I K (I Kr, I Ks) and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of I K (I Kr, I Ks) and HERG K+ channel. PMID:24069049

Experience of Comamonas acidovorans keratitis with delayed onset and treatment response in immunocompromised cornea.

PubMed

Lee, Sang Mok; Kim, Mee Kum; Lee, Jae Lim; Wee, Won Ryang; Lee, Jin Hak

2008-03-01

To report 2 cases of Comamonas acidovorans keratitis in immunocompromised cornea. A complete review of the medical records of the two cases of Comamonas acidovorans keratitis. We found some similarities in clinical courses of two cases. Both of them showed development of keratitis during the management with corticosteroids, delayed onset, slow response to antibiotics, and relatively less affected corneal epithelium. Comamonas acidovorans is known as a less virulent organism. However it can cause an indolent infection that responds slowly even to adequate antibiotics therapy in immunocompromised corneas.

Management of Recurrent Delayed Neurologic Deficit After Thoracoabdominal Aortic Operation.

PubMed

Boutrous, Mina L; Afifi, Rana O; Safi, Hazim J; Estrera, Anthony L

2016-01-01

Delayed neurologic deficit (DND) is a devastating adverse event after thoracoabdominal aortic aneurysm repair. Multiple adjuncts have been devised to counteract the development of DND, most notably cerebrospinal fluid (CSF) drainage. We report a case of a 63-year-old woman in whom DND developed four times during the first 10 days after her thoracoabdominal aortic operation. This necessitated lumbar drain "weaning" to allow for a slowly rising CSF pressure and preservation of lower extremity motor function. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of guar gum on hunger and satiety after meals of differing fat content: relationship with gastric emptying.

PubMed

French, S J; Read, N W

1994-01-01

To determine whether the satiating effects of fiber are due to delaying gastric emptying or slowing absorption of meals, 3% guar gum was added to high- and low-fat soups and gastric emptying rate, hunger, and satiety were measured in eight male volunteers. Guar gum delayed the emptying of the low-fat soup but the small delays in the return of hunger and decline of fullness were significantly correlated with the gastric emptying, suggesting mediation by gastric mechanoreceptors. The high-fat soup also emptied more slowly but this had no effect on the return of hunger or the decline in fullness. The delays in the return of hunger and decline of fullness were far greater when guar gum was added to the fatty soup; these delays were not correlated with the small additional delay in gastric emptying. This is more compatible with slowed absorption and prolonged contact of nutrients with intestinal chemoreceptors.

Analysis of a dc bus system with a nonlinear constant power load and its delayed feedback control.

PubMed

Konishi, Keiji; Sugitani, Yoshiki; Hara, Naoyuki

2014-02-01

This paper tackles a destabilizing problem of a direct-current (dc) bus system with constant power loads, which can be considered a fundamental problem of dc power grid networks. The present paper clarifies scenarios of the destabilization and applies the well-known delayed-feedback control to the stabilization of the destabilized bus system on the basis of nonlinear science. Further, we propose a systematic procedure for designing the delayed feedback controller. This controller can converge the bus voltage exactly on an unstable operating point without accurate information and can track it using tiny control energy even when a system parameter, such as the power consumption of the load, is slowly varied. These features demonstrate that delayed feedback control can be considered a strong candidate for solving the destabilizing problem.

A delayed action oscillator shared by biennial, interannual, and decadal signals in the Pacific Basin

USGS Publications Warehouse

White, Warren B.; Tourre, Y.M.; Barlow, M.; Dettinger, M.

2003-01-01

Biennial, interannual, and decadal signals in the Pacific basin are observed to share patterns and evolution in covarying sea surface temperature (SST), 18??C isotherm depth (Z18), zonal surface wind (ZSW), and wind stress curl (WSC) anomalies from 1955 to 1999. Each signal has warm SST anomalies propagating slowly eastward along the equator, generating westerly ZSW anomalies in their wake. These westerly ZSW anomalies produce cyclonic WSC anomalies off the equator which pump baroclinic Rossby waves in the western/central tropical North Pacific Ocean. These Rossby waves propagate westward, taking ???6, ???12, and ???36 months to reach the western boundary near ???7??N, ???12??N, and ???18??N on biennial, interannual, and decadal period scales, respectively. There, they reflect as equatorial coupled waves, propagating slowly eastward in covarying SST, Z18, and ZSW anomalies, taking ???6, ???12, and ???24 months to reach the central/eastern equatorial ocean. These equatorial coupled waves produce a delayed-negative feedback to the warm SST anomalies there. The decrease in Rossby wave phase speed with latitude, the increase in meridional scale of equatorial SST anomalies with period scale, and the associated increase in latitude of Rossby wave forcing are consistent with the delayed action oscillator (DAO) model used to explain El Nin??o. However, this is not true of the western-boundary reflection of Rossby waves into slow equatorial coupled waves. This requires modification of the extant DAO model. We construct a modified DAO model, demonstrating how the various mechanisms and the size and sources of their delays yield the resulting frequency of each signal.

Protein kinase C epsilon mediates the inhibition of angiotensin II on the slowly activating delayed-rectifier potassium current through channel phosphorylation.

PubMed

Gou, Xiangbo; Wang, Wenying; Zou, Sihao; Qi, Yajuan; Xu, Yanfang

2018-03-01

The slowly activating delayed rectifier K + current (I Ks ) is one of the main repolarizing currents in the human heart. Evidence has shown that angiotensin II (Ang II) regulates I Ks through the protein kinase C (PKC) pathway, but the related results are controversial. This study was designed to identify PKC isoenzymes involved in the regulation of I Ks by Ang II and the underlying molecular mechanism. The whole-cell patch-clamp technique was used to record I Ks in isolated guinea pig ventricular cardiomyocytes and in human embryonic kidney (HEK) 293 cells co-transfected with human KCNQ1/KCNE1 genes and Ang II type 1 receptor genes. Ang II inhibited I Ks in a concentration-dependent manner in native cardiomyocytes. A broad PKC inhibitor Gö6983 (not inhibiting PKCε) and a selective cPKC inhibitor Gö6976 did not affect the inhibitory action of Ang II. In contrast, the inhibition was significantly attenuated by PKCε-selective peptide inhibitor εV1-2. However, direct activation of PKC by phorbol 12-myristate 13-acetate (PMA) increased the cloned human I Ks in HEK293 cells. Similarly, the cPKC peptide activator significantly enhanced the current. In contrast, the PKCε peptide activator inhibited the current. Further evidence showed that PKCε knockdown by siRNA antagonized the Ang II-induced inhibition on KCNQ1/KCNE1 current, whereas knockdown of cPKCs (PKCα and PKCβ) attenuated the potentiation of the current by PMA. Moreover, deletion of four putative phosphorylation sites in the C-terminus of KCNQ1 abolished the action of PMA. Mutation of two putative phosphorylation sites in the N-terminus of KCNQ1 and one site in KCNE1 (S102) blocked the inhibition of Ang II. Our results demonstrate that PKCε isoenzyme mediates the inhibitory action of Ang II on I Ks and by phosphorylating distinct sites in KCNQ1/KCNE1, cPKC and PKCε isoenzymes produce the contrary regulatory effects on the channel. These findings have provided new insight into the molecular mechanism underlying the modulation of the KCNQ1/KCNE1 channel. Copyright © 2018 Elsevier Ltd. All rights reserved.

Being active after a heart attack (image)

MedlinePlus

... best activity when you start exercising after a heart attack. Start slowly, and increase the amount of time ... best activity when you start exercising after a heart attack. Start slowly, and increase the amount of time ...

Mechanisms of Firing Patterns in Fast-Spiking Cortical Interneurons

PubMed Central

Golomb, David; Donner, Karnit; Shacham, Liron; Shlosberg, Dan; Amitai, Yael; Hansel, David

2007-01-01

Cortical fast-spiking (FS) interneurons display highly variable electrophysiological properties. Their spike responses to step currents occur almost immediately following the step onset or after a substantial delay, during which subthreshold oscillations are frequently observed. Their firing patterns include high-frequency tonic firing and rhythmic or irregular bursting (stuttering). What is the origin of this variability? In the present paper, we hypothesize that it emerges naturally if one assumes a continuous distribution of properties in a small set of active channels. To test this hypothesis, we construct a minimal, single-compartment conductance-based model of FS cells that includes transient Na+, delayed-rectifier K+, and slowly inactivating d-type K+ conductances. The model is analyzed using nonlinear dynamical system theory. For small Na+ window current, the neuron exhibits high-frequency tonic firing. At current threshold, the spike response is almost instantaneous for small d-current conductance, g d, and it is delayed for larger g d. As g d further increases, the neuron stutters. Noise substantially reduces the delay duration and induces subthreshold oscillations. In contrast, when the Na+ window current is large, the neuron always fires tonically. Near threshold, the firing rates are low, and the delay to firing is only weakly sensitive to noise; subthreshold oscillations are not observed. We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their g d and in the strength of their Na+ window current. We predict the existence of two types of firing patterns in FS neurons, differing in the sensitivity of the delay duration to noise, in the minimal firing rate of the tonic discharge, and in the existence of subthreshold oscillations. We report experimental results from intracellular recordings supporting this prediction. PMID:17696606

Mechanisms of firing patterns in fast-spiking cortical interneurons.

PubMed

Golomb, David; Donner, Karnit; Shacham, Liron; Shlosberg, Dan; Amitai, Yael; Hansel, David

2007-08-01

Cortical fast-spiking (FS) interneurons display highly variable electrophysiological properties. Their spike responses to step currents occur almost immediately following the step onset or after a substantial delay, during which subthreshold oscillations are frequently observed. Their firing patterns include high-frequency tonic firing and rhythmic or irregular bursting (stuttering). What is the origin of this variability? In the present paper, we hypothesize that it emerges naturally if one assumes a continuous distribution of properties in a small set of active channels. To test this hypothesis, we construct a minimal, single-compartment conductance-based model of FS cells that includes transient Na(+), delayed-rectifier K(+), and slowly inactivating d-type K(+) conductances. The model is analyzed using nonlinear dynamical system theory. For small Na(+) window current, the neuron exhibits high-frequency tonic firing. At current threshold, the spike response is almost instantaneous for small d-current conductance, gd, and it is delayed for larger gd. As gd further increases, the neuron stutters. Noise substantially reduces the delay duration and induces subthreshold oscillations. In contrast, when the Na(+) window current is large, the neuron always fires tonically. Near threshold, the firing rates are low, and the delay to firing is only weakly sensitive to noise; subthreshold oscillations are not observed. We propose that the variability in the response of cortical FS neurons is a consequence of heterogeneities in their gd and in the strength of their Na(+) window current. We predict the existence of two types of firing patterns in FS neurons, differing in the sensitivity of the delay duration to noise, in the minimal firing rate of the tonic discharge, and in the existence of subthreshold oscillations. We report experimental results from intracellular recordings supporting this prediction.

Experience of Comamonas Acidovorans Keratitis with Delayed Onset and Treatment Response in Immunocompromised Cornea

PubMed Central

Lee, Sang Mok; Lee, Jae Lim; Wee, Won Ryang; Lee, Jin Hak

2008-01-01

Purpose To report 2 cases of Comamonas Acidovorans keratitis in immunocompromised cornea. Methods A complete review of the medical records of the two cases of Comamonas acidovorans keratitis. Results We found some similarities in clinical courses of two cases. Both of them showed development of keratitis during the management with corticosteroids, delayed onset, slow response to antibiotics, and relatively less affected corneal epithelium. Conclusions Comamonas Acidovorans is known as a less virulent organism. However it can cause an indolent infection that responds slowly even to adequate antibiotics therapy in immunocompromised corneas. PMID:18323706

Child Growth, Shocks, and Food Aid in Rural Ethiopia. World Bank Policy Research Working Paper.

ERIC Educational Resources Information Center

Yamano, Takashi; Alderman, Harold; Christiaensen, Luc

Children that grow slowly experience poorer psychomotor development and tend to have delayed school enrollment and lower scores on cognitive tests. Rural households in developing countries often are unable to protect their consumption against temporary income shocks, such as droughts. Such income shocks have been shown to have negative effects on…

MCT8 deficiency: extrapyramidal symptoms and delayed myelination as prominent features.

PubMed

Tonduti, Davide; Vanderver, Adeline; Berardinelli, Angela; Schmidt, Johanna L; Collins, Christin D; Novara, Francesca; Genni, Antonia Di; Mita, Alda; Triulzi, Fabio; Brunstrom-Hernandez, Janice E; Zuffardi, Orsetta; Balottin, Umberto; Orcesi, Simona

2013-06-01

Monocarboxylate transporter 8 (MCT8) deficiency is an X-linked disorder resulting from an impairment of the transcellular transportation of thyroid hormones. Within the central nervous system thyroid hormone transport is normally mediated by MCT8. Patients are described as affected by a static or slowly progressive clinical picture which consists of variable degrees of mental retardation, hypotonia, spasticity, ataxia and involuntary movements, occasionally paroxysmal. The authors describe the clinical and neuroradiological picture of 3 males patients with marked delayed brain myelination and in which the clinical picture was dominated by early onset nonparoxysmal extrapyramidal symptoms. In one subject a novel mutation is described.

WAVE DELAYING STRUCTURE FOR RECTANGULAR WAVE-GUIDES

DOEpatents

Robertson-Shersby-Harvie, R.B.; Dain, J.

1956-11-13

This patent relates to wave-guides and in particular describes wave delaying structure located within a wave-guide. The disclosed wave-guide has an elongated fiat metal sheet arranged in a central plane of the guide and formed with a series of transverse inductive slots such that each face presents an inductive impedance to the guide. The sheet is thickened in the area between slots to increase the self capacity of the slots. Experimental results indicate that in a wave-guide loaded in accordance with the invention the guided wavelength changes more slowly as the air wavelength is changed than the guided wavelength does in wave-guides loaded by means of corrugations.

Ginseng gintonin activates the human cardiac delayed rectifier K+ channel: involvement of Ca2+/calmodulin binding sites.

PubMed

Choi, Sun-Hye; Lee, Byung-Hwan; Kim, Hyeon-Joong; Jung, Seok-Won; Kim, Hyun-Sook; Shin, Ho-Chul; Lee, Jun-Hee; Kim, Hyoung-Chun; Rhim, Hyewhon; Hwang, Sung-Hee; Ha, Tal Soo; Kim, Hyun-Ji; Cho, Hana; Nah, Seung-Yeol

2014-09-01

Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca(2+)]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K(+) (I(Ks)) channel is a cardiac K(+) channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I(Ks) channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I(Ks) channel activity by expressing human I(Ks) channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the I(Ks) channel was 0.05 ± 0.01 μg/ml. Gintonin-mediated activation of the I(Ks) channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the I(Ks) channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca(2+)]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I(Ks) channel. However, gintonin had no effect on hERG K(+) channel activity. These results show that gintonin-mediated enhancement of I(Ks) channel currents is achieved through binding of the [Ca(2+)]i/CaM complex to the C terminus of KCNQ1 subunit.

A Reduced Antigen Load In Vivo, Rather Than Weak Inflammation, Causes a Substantial Delay in CD8+ T Cell Priming against Mycobacterium bovis (Bacillus Calmette-Guérin)1

PubMed Central

Russell, Marsha S.; Iskandar, Monica; Mykytczuk, Oksana L.; Nash, John H. E.; Krishnan, Lakshmi; Sad, Subash

2014-01-01

Regardless of the dose of Ag, Ag presentation occurs rapidly within the first few days which results in rapid expansion of the CD8+ T cell response that peaks at day 7. However, we have previously shown that this rapid priming of CD8+ T cells is absent during infection of mice with Mycobacterium bovis (bacillus Calmette-Guérin (BCG)). In this study, we have evaluated the mechanisms responsible for the delayed CD8+ T cell priming. Because BCG replicates poorly and survives within phagosomes we considered whether 1) generation of reduced amounts of Ag or 2) weaker activation by pathogen-associated molecular patterns (PAMPs) during BCG infection is responsible for the delay in CD8+ T cell priming. Using rOVA-expressing bacteria, our results indicate that infection of mice with BCG-OVA generates greatly reduced levels of OVA, which are 70-fold lower in comparison to the levels generated during infection of mice with Listeria monocytogenes-expressing OVA. Furthermore, increasing the dose of OVA, but not PAMP signaling during BCG-OVA infection resulted in rapid Ag presentation and consequent expansion of the CD8+ T cell response, indicating that the generation of reduced Ag levels, not lack of PAMP-associated inflammation, was responsible for delayed priming of CD8+ T cells. There was a strong correlation between the relative timing of Ag presentation and the increase in the level of OVA in vivo. Taken together, these results reveal that some slowly replicating pathogens, such as mycobacteria, may facilitate their chronicity by generating reduced Ag levels which causes a substantial delay in the development of acquired immune responses. PMID:17579040

Action potentials in primary osteoblasts and in the MG-63 osteoblast-like cell line.

PubMed

Pangalos, Maria; Bintig, Willem; Schlingmann, Barbara; Feyerabend, Frank; Witte, Frank; Begandt, Daniela; Heisterkamp, Alexander; Ngezahayo, Anaclet

2011-06-01

Whole-cell patch-clamp analysis revealed a resting membrane potential of -60 mV in primary osteoblasts and in the MG-63 osteoblast-like cells. Depolarization-induced action potentials were characterized by duration of 60 ms, a minimal peak-to-peak distance of 180 ms, a threshold value of -20 mV and a repolarization between the spikes to -45 mV. Expressed channels were characterized by application of voltage pulses between -150 mV and 90 mV in 10 mV steps, from a holding potential of -40 mV. Voltages below -60 mV induced an inward current. Depolarizing voltages above -30 mV evoked two currents: (a) a fast activated and inactivated inward current at voltages between -30 and 30 mV, and (b) a delayed-activated outward current that was induced by voltages above -30 mV. Electrophysiological and pharmacological parameters indicated that hyperpolarization activated strongly rectifying K(+) (K(ir)) channels, whereas depolarization activated tetrodotoxin sensitive voltage gated Na(+) (Na(v)) channels as well as delayed, slowly activated, non-inactivating, and tetraethylammonium sensitive voltage gated K(+) (K(v)) channels. In addition, RT-PCR showed expression of Na(v)1.3, Na(v)1.4, Na(v)1.5, Na(v)1.6, Na(v)1.7, and K(ir)2.1, K(ir)2.3, and K(ir)2.4 as well as K(v)2.1. We conclude that osteoblasts express channels that allow firing of action potentials.

Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds.

PubMed

Solchaga, Luis A; Temenoff, Johnna S; Gao, Jizong; Mikos, Antonios G; Caplan, Arnold I; Goldberg, Victor M

2005-04-01

The natural repair of osteochondral defects can be enhanced with biocompatible, biodegradable materials that support the repair process. It is our hypothesis that hyaluronan-based scaffolds are superior to synthetic scaffolds because they provide biological cues. We tested this thesis by comparing two hyaluronan-based scaffolds [auto cross-linked polysaccharide polymer (ACP) and HYAFF-11] to polyester-based scaffolds [poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA)] with similar pore size, porosity and degradation times. Fifty-four rabbits received bilateral osteochondral defects. One defect received a hyaluronan-based scaffold and the contralateral defect received the corresponding polyester-based scaffold. Rabbits were euthanized 4, 12 and 20 weeks after surgery and the condyles dissected and processed for histology. Only ACP-treated defects presented bone at the base of the defect at 4 weeks. At 12 weeks, only defects treated with rapidly dissolving implants (ACP and PLGA) presented bone reconstitution consistently, while bone was present in only one third of those treated with slowly dissolving scaffolds (HYAFF-11 and PLLA). After 20 weeks, the articular surface of PLGA-treated defects presented fibrillation more frequently than in ACP-treated defects. The surface of defects treated with slowly dissolving scaffolds presented more cracks and fissures. The degradation rate of the scaffolds is critical for the repair process. Slowly dissolving scaffolds sustain thicker cartilage at the surface but, it frequently presents cracks and discontinuities. These scaffolds also delay bone formation at the base of the defects. Hyaluronan-based scaffolds appear to allow faster cell infiltration leading to faster tissue formation. The degradation of ACP leads to rapid bone formation while the slow degradation of HYAFF-11 prolongs the presence of cartilage and delays endochondral bone formation.

Laser-induced periodic surface structures on 6H-SiC single crystals using temporally delayed femtosecond laser double-pulse trains

NASA Astrophysics Data System (ADS)

Song, Juan; Tao, Wenjun; Song, Hui; Gong, Min; Ma, Guohong; Dai, Ye; Zhao, Quanzhong; Qiu, Jianrong

2016-04-01

In this paper, a time-delay-adjustable double-pulse train with 800-nm wavelength, 200-fs pulse duration and a repetition rate of 1 kHz, produced by a collinear two-beam optical system like a Mach-Zehnder interferometer, was employed for irradiation of 6H-SiC crystal. The dependence of the induced structures on time delay of double-pulse train for parallel-polarization configuration was studied. The results show that as the time delay of collinear parallel-polarization dual-pulse train increased, the induced near-subwavelength ripples (NSWRs) turn from irregular rippled pattern to regularly periodic pattern and have their grooves much deepened. The characteristics timescale for this transition is about 6.24 ps. Besides, the areas of NSWR were found to decay exponentially for time delay from 0 to 1.24 ps and then slowly increase for time delay from 1.24 to 14.24 ps. Analysis shows that multiphoton ionization effect, grating-assisted surface plasmon coupling effect, and timely intervene of second pulse in a certain physical stage experienced by 6H-SiC excited upon first pulse irradiation may contribute to the transition of morphology details.

Phasic and tonic fluctuations in brain, muscle, and skin temperatures during motivated drinking behavior in rats: physiological correlates of motivation and reward.

PubMed

Smirnov, Michael S; Kiyatkin, Eugene A

2010-01-15

Since brain metabolism is accompanied by heat production, measurement of brain temperature offers a method for assessing global alterations in metabolic neural activity. This approach, high-resolution (5-s bin) temperature recording from the nucleus accumbens (NAcc), temporal muscle, and facial skin, was used to study motivated drinking behavior in rats. Experienced animals were presented with a cup containing 5-ml of Coca-Cola(R) (Coke) beverage that resulted, within certain latencies, in initiation of a continuous chain of licking until all liquid was fully consumed. While cup presentation induced rapid, gradual NAcc temperature increase peaking at the start of drinking, temperatures slowly decreased during Coke consumption, but phasically increased again in the post-consumption period when rats were hyperactive, showing multiple interactions with an empty cup. Muscle temperatures followed a similar pattern, but the changes were weaker and delayed compared to those in the brain. Skin temperature rapidly dropped after cup presentation, steadily maintained at low levels during consumption, and slowly restored during the post-consumption period. Substitution of the expected Coke with either sugar-free Diet Coke(R) or water resulted in numerous drinking attempts but ultimately no consumption. During these tests, locomotor activation was much greater and more prolonged, brain and muscle temperatures increased monophasically, and their elevation was significantly greater than that with regular Coke tests. Food deprivation decreased drinking latencies, did not change the pattern of temperature fluctuations during Coke consumption, but temperature elevations were greater than in controls. Our data suggest sustained neural activation triggered by appetitive stimuli and associated with activational (seeking) aspects of appetitive motivated behavior. This seeking-related activation is rapidly ceased following consumption, suggesting this change as a neural correlate of reward. In contrast, inability to obtain an expected reward maintains neural activation and seeking behavior, resulting in larger deviations in physiological parameters. Published by Elsevier B.V.

Phasic and tonic fluctuations in brain, muscle and skin temperatures during motivated drinking behavior in rats: physiological correlates of motivation and reward

PubMed Central

Smirnov, Michael S.; Kiyatkin, Eugene A.

2009-01-01

Since brain metabolism is accompanied by heat production, measurement of brain temperature offers a method for assessing global alterations in metabolic neural activity. This approach, high-resolution (5-s bin) temperature recording from the nucleus accumbens (NAcc), temporal muscle, and facial skin, was used to study motivated drinking behavior in rats. Experienced animals were presented with a cup containing 5-ml of Coca-Cola® (Coke) beverage that resulted, within certain latencies, in initiation of a continuous chain of licking until all liquid was fully consumed. While cup presentation induced rapid, gradual NAcc temperature increase peaking at the start of drinking, temperatures slowly decreased during Coke consumption, but phasically increased again in the post-consumption period when rats were hyperactive, showing multiple interactions with an empty cup. Muscle temperatures followed a similar pattern, but the changes were weaker and delayed compared to those in the brain. Skin temperature rapidly dropped after cup presentation, steadily maintained at low levels during consumption, and slowly restored during the post-consumption period. Substitution of the expected Coke with either sugar-free Diet Coke® or water resulted in numerous drinking attempts but ultimately no consumption. During these tests, locomotor activation was much greater and more prolonged, brain and muscle temperatures increased monophasically, and their elevation was significantly greater than that with regular Coke tests. Food deprivation decreased drinking latencies, did not change the pattern of temperature fluctuations during Coke consumption, but temperature elevations were greater than in controls. Our data suggest sustained neural activation triggered by appetitive stimuli and associated with activational (seeking) aspects of appetitive motivated behavior. This seeking-related activation is rapidly ceased following consumption, suggesting this change as a neural correlate of reward. In contrast, inability to obtain an expected reward maintains neural activation and seeking behavior, resulting in larger deviations in physiological parameters. PMID:19932691

Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine.

PubMed

Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

2006-06-01

Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K(+) currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC(50) for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 microM at -40 mV, 28.3 microM at 0 mV and 22.9 microM at +40 mV), whereas the IC(50) for the clozapine-induced blockade of HERG currents in HEK293 cells at 36 degrees C was 2.5 microM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36 degrees C, treatment with 1 and 5 microM clozapine blocked the rapidly activating delayed rectifier K(+) current (I(Kr)) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K(+) current (I(Ks)). Our findings collectively suggest that blockade of HERG currents and I(Kr), but not I(Ks), may contribute to the arrhythmogenic side effects of clozapine.

Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine

PubMed Central

Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

2006-01-01

Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K+ currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC50 for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 μM at −40 mV, 28.3 μM at 0 mV and 22.9 μM at +40 mV), whereas the IC50 for the clozapine-induced blockade of HERG currents in HEK293 cells at 36°C was 2.5 μM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36°C, treatment with 1 and 5 μM clozapine blocked the rapidly activating delayed rectifier K+ current (IKr) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K+ current (IKs). Our findings collectively suggest that blockade of HERG currents and IKr, but not IKs, may contribute to the arrhythmogenic side effects of clozapine. PMID:16633353

Thermal adaptation of the crucian carp (Carassius carassius) cardiac delayed rectifier current, IKs, by homomeric assembly of Kv7.1 subunits without MinK.

PubMed

Hassinen, Minna; Laulaja, Salla; Paajanen, Vesa; Haverinen, Jaakko; Vornanen, Matti

2011-07-01

Ectothermic vertebrates experience acute and chronic temperature changes which affect cardiac excitability and may threaten electrical stability of the heart. Nevertheless, ectothermic hearts function over wide range of temperatures without cardiac arrhythmias, probably due to special molecular adaptations. We examine function and molecular basis of the slow delayed rectifier K(+) current (I(Ks)) in cardiac myocytes of a eurythermic fish (Carassius carassius L.). I(Ks) is an important repolarizing current that prevents excessive prolongation of cardiac action potential, but it is extremely slowly activating when expressed in typical molecular composition of the endothermic animals. Comparison of the I(Ks) of the crucian carp atrial myocytes with the currents produced by homomeric K(v)7.1 and heteromeric K(v)7.1/MinK channels in Chinese hamster ovary cells indicates that activation kinetics and pharmacological properties of the I(Ks) are similar to those of the homomeric K(v)7.1 channels. Consistently with electrophysiological properties and homomeric K(v)7.1 channel composition, atrial transcript expression of the MinK subunit is only 1.6-1.9% of the expression level of the K(v)7.1 subunit. Since activation kinetics of the homomeric K(v)7.1 channels is much faster than activation of the heteromeric K(v)7.1/MinK channels, the homomeric K(v)7.1 composition of the crucian carp cardiac I(Ks) is thermally adaptive: the slow delayed rectifier channels can open despite low body temperatures and curtail the duration of cardiac action potential in ectothermic crucian carp. We suggest that the homomeric K(v)7.1 channel assembly is an evolutionary thermal adaptation of ectothermic hearts and the heteromeric K(v)7.1/MinK channels evolved later to adapt I(Ks) to high body temperature of endotherms.

Learning problems, delayed development, and puberty

PubMed Central

Wright, Beverly A.; Zecker, Steven G.

2004-01-01

Language-based learning disorders such as dyslexia affect millions of people, but there is little agreement as to their cause. New evidence from behavioral measures of the ability to hear tones in the presence of background noise indicates that the brains of affected individuals develop more slowly than those of their unaffected counterparts. In addition, it seems that brain changes occurring at ≈10 years of age, presumably associated with puberty, may prematurely halt this slower-than-normal development when improvements would normally continue into adolescence. The combination of these ideas can account for a wide range of previous results, suggesting that delayed brain development, and its interaction with puberty, may be key factors contributing to learning problems. PMID:15210987

WAVE DELAYING STRUCTURE FOR RECTANGULAR WAVE-GUIDES

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

Robertson-Shersby-Harvie, R.B.; Dain, J.

1956-11-13

This patent relates to wave-guides and in particular describes wave delaying structure located within a wave-guide. The disclosed wave-guide has an elongated fiat metal sheet arranged in a central plane of the guide and formed with a series of transverse inductive slots such that each face presents an inductive impedance to the guide. The sheet is thickened in the area between slots to increase the self capacity of the slots. Experimental results indicate that in a wave-guide loaded in accordance with the invention the guided wavelength changes more slowly as the air wavelength is changed than the guided wavelength doesmore » in wave-guides loaded by means of corrugations.« less

Slowly digestible starch diets alter proximal glucosidase activity and glucose absorption

USDA-ARS?s Scientific Manuscript database

Sucrase-isomaltase (Si) and maltase-glucoamylase (Mgam) are mucosal glucosidases required for digestion of starch to glucose. Ablation of maltase-Mgam reduces in vivo starch digestion. We tested whether slowly digestible starch diets induce changes in glucosidase activities. Rice starch was encaps...

Shallow processing of ambiguous pronouns: evidence for delay.

PubMed

Stewart, Andrew J; Holler, Judith; Kidd, Evan

2007-12-01

Two self-paced reading-time experiments examined how ambiguous pronouns are interpreted under conditions that encourage shallow processing. In Experiment 1 we show that sentences containing ambiguous pronouns are processed at the same speed as those containing unambiguous pronouns under shallow processing, but more slowly under deep processing. We outline three possible models to account for the shallow processing of ambiguous pronouns. Two involve an initial commitment followed by possible revision, and the other involves a delay in interpretation. In Experiment 2 we provide evidence that supports the delayed model of ambiguous pronoun resolution under shallow processing. We found no evidence to support a processing system that makes an initial commitment to an interpretation of the pronoun when it is encountered. We extend the account of pronoun resolution proposed by Rigalleau, Caplan, and Baudiffier (2004) to include the treatment of ambiguous pronouns under shallow processing.

The procrastinators want it now: Behavioral and event-related potential evidence of the procrastination of intertemporal choices.

PubMed

Wu, Haiyan; Gui, Danyang; Lin, Wenzheng; Gu, Ruolei; Zhu, Xiangru; Liu, Xun

2016-08-01

Much past research has focused on the correlation between procrastination and personality traits (e.g., impulsivity). According to the temporal motivation theory, procrastinators are impulsive and sensitive to delays in time. However, there is still a lack of direct evidence of the tendency of procrastinators to prefer immediate over future rewards. To investigate this question, we recorded event-related potentials (ERPs) in the brain while participants performed an intertemporal choice task involving both time delay and reward processing. The participants were assigned to a high procrastination group and a low procrastination group according to their scores on self-report measures. We found that high procrastination participants preferred immediate rewards compared to future ones whereas low procrastination participants did not. High procrastinators also exhibited a larger and delayed P2 component, indicating delay time processing and abnormal reward processing. No significant effect associated with procrastination was found on the P300 component. Taken together, these findings suggest that high procrastinators are more impulsive and encode the information of delay time more slowly but with a higher level of motivation-driven attention. The current study substantiates higher impulsivity in procrastination and verifies that a difference exists in the sensitivity to time delay between high and low procrastinators. Copyright © 2016 Elsevier Inc. All rights reserved.

Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats.

PubMed

Lindquist, Derick H; Sokoloff, Greta; Milner, Eric; Steinmetz, Joseph E

2013-09-01

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink-conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4-9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 ms) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 ms) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus. Published by Elsevier Inc.

Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats

PubMed Central

Lindquist, Derick H.; Sokoloff, Greta; Milner, Eric; Steinmetz, Joseph E.

2013-01-01

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4–9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 msec) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 msec) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus. PMID:23871534

Spontaneously emerging direction selectivity maps in visual cortex through STDP.

PubMed

Wenisch, Oliver G; Noll, Joachim; Hemmen, J Leo van

2005-10-01

It is still an open question as to whether, and how, direction-selective neuronal responses in primary visual cortex are generated by feedforward thalamocortical or recurrent intracortical connections, or a combination of both. Here we present an investigation that concentrates on and, only for the sake of simplicity, restricts itself to intracortical circuits, in particular, with respect to the developmental aspects of direction selectivity through spike-timing-dependent synaptic plasticity. We show that directional responses can emerge in a recurrent network model of visual cortex with spiking neurons that integrate inputs mainly from a particular direction, thus giving rise to an asymmetrically shaped receptive field. A moving stimulus that enters the receptive field from this (preferred) direction will activate a neuron most strongly because of the increased number and/or strength of inputs from this direction and since delayed isotropic inhibition will neither overlap with, nor cancel excitation, as would be the case for other stimulus directions. It is demonstrated how direction-selective responses result from spatial asymmetries in the distribution of synaptic contacts or weights of inputs delivered to a neuron by slowly conducting intracortical axonal delay lines. By means of spike-timing-dependent synaptic plasticity with an asymmetric learning window this kind of coupling asymmetry develops naturally in a recurrent network of stochastically spiking neurons in a scenario where the neurons are activated by unidirectionally moving bar stimuli and even when only intrinsic spontaneous activity drives the learning process. We also present simulation results to show the ability of this model to produce direction preference maps similar to experimental findings.

Relation of Field-Aligned Currents Measured by the Network of Iridium® Spacecraft to Solar Wind and Substorms

NASA Astrophysics Data System (ADS)

McPherron, R. L.; Anderson, B. J.; Chu, Xiangning

2018-03-01

The strength of field-aligned currents coupling the magnetosphere to the ionosphere was obtained by the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) using the network of Iridium® spacecraft. The distribution of current was integrated giving total current in and out of the ionosphere on the dayside and nightside of the Earth in both hemispheres. The onset of auroral zone negative bays and midlatitude positive bays corresponds to an increase in nightside upward current. The total outward current tends toward saturation with increasing solar wind driver strength. The optimum solar wind coupling function for AL index predicts 73% of the variance in nightside upward current. The dayside and nightside predictors of upward current rise to a peak at 30-45 min and decay slowly over 2.5 hr. Nightside response is delayed relative to dayside.

[Oral controlled release dosage forms].

PubMed

Mehuys, Els; Vervaet, Chris

2010-06-01

Several technologies to control drug release from oral dosage forms have been developed. Drug release can be regulated in several ways: sustained release, whereby the drug is released slowly over a prolonged period of time, postponed release, whereby drug release is delayed until passage from the stomach into the intestine (via enteric coating), and targeted release, whereby the drug is targeted to a specific location of the gastrointestinal tract. This article reviews the various oral controlled release dosage forms on the market.

Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes

PubMed Central

1991-01-01

Depolarization-activated outward K+ currents in isolated adult rat ventricular myocytes were characterized using the whole-cell variation of the patch-clamp recording technique. During brief depolarizations to potentials positive to -40 mV, Ca(2+)-independent outward K+ currents in these cells rise to a transient peak, followed by a slower decay to an apparent plateau. The analyses completed here reveal that the observed outward current waveforms result from the activation of two kinetically distinct voltage-dependent K+ currents: one that activates and inactivates rapidly, and one that activates and inactivates slowly, on membrane depolarization. These currents are referred to here as Ito (transient outward) and IK (delayed rectifier), respectively, because their properties are similar (although not identical) to these K+ current types in other cells. Although the voltage dependences of Ito and IK activation are similar, Ito activates approximately 10-fold and inactivates approximately 30-fold more rapidly than IK at all test potentials. In the composite current waveforms measured during brief depolarizations, therefore, the peak current predominantly reflects Ito, whereas IK is the primary determinant of the plateau. There are also marked differences in the voltage dependences of steady-state inactivation of these two K+ currents: IK undergoes steady-state inactivation at all potentials positive to -120 mV, and is 50% inactivated at -69 mV; Ito, in contrast, is insensitive to steady-state inactivation at membrane potentials negative to -50 mV. In addition, Ito recovers from steady-state inactivation faster than IK: at -90 mV, for example, approximately 70% recovery from the inactivation produced at -20 mV is observed within 20 ms for Ito; IK recovers approximately 25-fold more slowly. The pharmacological properties of Ito and IK are also distinct: 4-aminopyridine preferentially attenuates Ito, and tetraethylammonium suppresses predominantly IK. The voltage- and time- dependent properties of these currents are interpreted here in terms of a model in which Ito underlies the initial, rapid repolarization phase of the action potential (AP), and IK is responsible for the slower phase of AP repolarization back to the resting membrane potential, in adult rat ventricular myocytes. PMID:1865177

The calcitonin gene-related peptide receptor antagonist MK-8825 decreases spinal trigeminal activity during nitroglycerin infusion.

PubMed

Feistel, Stephan; Albrecht, Stephanie; Messlinger, Karl

2013-11-20

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin. In isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours). After infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity. CGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches.

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

PubMed Central

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-01-01

Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action. PMID:23610573

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction.

PubMed

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-03-01

To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (I to), the rapidly activated omponent of delayed rectifier potassium current (I Kr), the slowly activated component of delayed rectifier potassium current (I Ks), and the L-type calcium current (I CaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca(2+) current are likely the underlying mechanism of action.

Cowpea ribonuclease: properties and effect of NaCl-salinity on its activation during seed germination and seedling establishment.

PubMed

Gomes-Filho, Enéas; Lima, Carmen Rogélia Farias Machado; Costa, José Hélio; da Silva, Ana Cláudia Marinho; da Guia Silva Lima, Maria; de Lacerda, Claudivan Feitosa; Prisco, José Tarquinio

2008-01-01

Pitiúba cowpea [Vigna unguiculata (L.) Walp] seeds were germinated in distilled water (control treatment) or in 100 mM NaCl solution (salt treatment), and RNase was purified from different parts of the seedlings. Seedling growth was reduced by the NaCl treatment. RNase activity was low in cotyledons of quiescent seeds, but the enzyme was activated during germination and seedling establishment. Salinity reduced cotyledon RNase activity, and this effect appeared to be due to a delay in its activation. The RNases from roots, stems, and leaves were immunologically identical to that found in cotyledons. Partially purified RNase fractions from the different parts of the seedling showed some activity with DNA as substrate. However, this DNA hydrolyzing activity was much lower than that of RNA hydrolyzing activity. The DNA hydrolyzing activity was strongly inhibited by Cu(2+), Hg(2+), and Zn(2+) ions, stimulated by MgCl(2), and slowly inhibited by EDTA. This activity from the most purified fraction was inhibited by increasing concentrations of RNA in the reaction medium. It is suggested that the major biological role of this cotyledon RNase would be to hydrolyze seed storage RNA during germination and seedling establishment, and it was discussed that it might have a protective role against abiotic stress during later part of seedling establishment.

Re-equilibration after quenches in athermal martensites: Conversion delays for vapor-to-liquid domain-wall phases

NASA Astrophysics Data System (ADS)

Shankaraiah, N.; Murthy, K. P. N.; Lookman, T.; Shenoy, S. R.

2015-06-01

Entropy barriers and aging states appear in martensitic structural-transition models, slowly re-equilibrating after temperature quenches, under Monte Carlo dynamics. Concepts from protein folding and aging harmonic oscillators turn out to be useful in understanding these nonequilibrium evolutions. We show how the athermal, nonactivated delay time for seeded parent-phase austenite to convert to product-phase martensite arises from an identified entropy barrier in Fourier space. In an aging state of low Monte Carlo acceptances, the strain structure factor makes constant-energy searches for rare pathways to enter a Brillouin zone "golf hole" enclosing negative-energy states, and to suddenly release entropically trapped stresses. In this context, a stress-dependent effective temperature can be defined, that re-equilibrates to the quenched bath temperature.

Rapid wall relaxation in elongating tissues. [Glycine max (L. ); Pisum sativum L

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

Matyssek, R.; Maruyama, S.; Boyer, J.S.

1988-01-01

Reported differences in the relaxation of cell walls in enlarging stem tissues of soybean (Glycine max (L.) Merr.) and pea (Pisum sativum L.) cause measurements of the yield threshold turgor, an important growth parameter, to be in doubt. Using the pressure probe and guillotine psychrometer, the authors investigated wall relaxation in these species by excising the elongating tissue in air to remove the water supply. The authors found that the rapid kinetics usually exhibited by soybean could be delayed and made similar to the slow kinetics previously reported for pea if slowly growing or mature tissue was left attached tomore » the rapidly growing tissue when relaxation was initiated. The greater the amount of attached tissue, the slower the relaxation, suggesting that slowly growing tissue acted as a water source. Consistent with this concept was a lower water potential in the rapidly elongating tissue than in the slowly growing tissue. If this tissue was removed from pea, relaxation became as rapid as usually exhibited by soybean. It is concluded that the true relaxation of cell walls to the yield threshold requires only a few minutes and that the yield threshold in the intact plant before excision. Under these conditions, the yield threshold was close to the turgor in the intact plant regardless of the species.« less

Periodic or chaotic bursting dynamics via delayed pitchfork bifurcation in a slow-varying controlled system

NASA Astrophysics Data System (ADS)

Yu, Yue; Zhang, Zhengdi; Han, Xiujing

2018-03-01

In this work, we aim to demonstrate the novel routes to periodic and chaotic bursting, i.e., the different bursting dynamics via delayed pitchfork bifurcations around stable attractors, in the classical controlled Lü system. First, by computing the corresponding characteristic polynomial, we determine where some critical values about bifurcation behaviors appear in the Lü system. Moreover, the transition mechanism among different stable attractors has been introduced including homoclinic-type connections or chaotic attractors. Secondly, taking advantage of the above analytical results, we carry out a study of the mechanism for bursting dynamics in the Lü system with slowly periodic variation of certain control parameter. A distinct delayed supercritical pitchfork bifurcation behavior can be discussed when the control item passes through bifurcation points periodically. This delayed dynamical behavior may terminate at different parameter areas, which leads to different spiking modes around different stable attractors (equilibriums, limit cycles, or chaotic attractors). In particular, the chaotic attractor may appear by Shilnikov connections or chaos boundary crisis, which leads to the occurrence of impressive chaotic bursting oscillations. Our findings enrich the study of bursting dynamics and deepen the understanding of some similar sorts of delayed bursting phenomena. Finally, some numerical simulations are included to illustrate the validity of our study.

Reducing the Deficit: Spending and Revenue Options. A Report to the Senate and House Committees on the Budget. Part 2

DTIC Science & Technology

1987-01-01

Loan Program 132 NDD-03 Reduce Funding for Research Supported by the National Institutes of Health 134 NDD-04 Reduce Subsidies Provided by the...faster pace under Strategy II but more slowly than under the Administra- tion’s plan. Both strategies would slow production and research and...develop- ment of many programs, but Strategy I probably would result in the cancel- lation or delay of a greater number of procurement and research

Augmenting Comprehension of Speech in Noise with a Facial Avatar and Its Effect on Performance

DTIC Science & Technology

2010-12-01

develop some aspects of speech more slowly than sighted children. In addition to “bleeping” or blanking the sound of censored words, network...the speech. Movie files were exported at a resolution of 600 by 800 pixels at 30 frames per second and were four seconds in length. It should be...noted that the speech, and synchronized facial movements, began one second after each movie file started. This delay was designed to ensure that the

Elderly Onset of Weakness in Facioscapulohumeral Muscular Dystrophy

PubMed Central

Fee, Dominic B.

2012-01-01

A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing. PMID:23024867

Elderly onset of weakness in facioscapulohumeral muscular dystrophy.

PubMed

Fee, Dominic B

2012-01-01

A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing.

In vitro batch fecal fermentation comparison of gas and short-chain fatty acid production using "slowly fermentable" dietary fibers.

PubMed

Kaur, Amandeep; Rose, Devin J; Rumpagaporn, Pinthip; Patterson, John A; Hamaker, Bruce R

2011-01-01

Sustained colonic fermentation supplies beneficial fermentative by-products to the distal colon, which is particularly prone to intestinal ailments. Blunted/delayed initial fermentation may also lead to less bloating. Previously, we reported that starch-entrapped alginate-based microspheres act as a slowly fermenting dietary fiber. This material was used in the present study to provide a benchmark to compare to other "slowly fermentable" fibers. Dietary fibers with previous reports of slow fermentation, namely, long-chain inulin, psyllium, alkali-soluble corn bran arabinoxylan, and long-chain β-glucan, as well as starch-entrapped microspheres were subjected to in vitro upper gastrointestinal digestion and human fecal fermentation and measured over 48 h for pH, gas, and short-chain fatty acids (SCFA). The resistant fraction of cooked and cooled potato starch was used as another form of fermentable starch and fructooligosaccharides (FOS) served as a fast fermenting control. Corn bran arabinoxylan and long-chain β-glucan initially appeared slower fermenting with comparatively low gas and SCFA production, but later fermented rapidly with little remaining in the final half of the fermentation period. Long-chain inulin and psyllium had slow and moderate, but incomplete, fermentation. The resistant fraction of cooked and cooled potato starch fermented rapidly and appeared similar to FOS. In conclusion, compared to the benchmark slowly fermentable starch-entrapped microspheres, a number of the purported slowly fermentable fibers fermented fairly rapidly overall and, of this group, only the starch-entrapped microspheres appreciably fermented in the second half of the fermentation period. Consumption of dietary fibers, particularly commercial prebiotics, leads to uncomfortable feelings of bloating and flatulence due to their rapid degradation in our large intestine. This article employs claimed potential slowly fermenting fibers and compares their fermentation rates with a benchmark slow fermenting fiber that we fabricated in an in vitro simulation of the human digestive system. Results show a variety of fermentation profiles only some of which have slow and extended rate of fermentation. © 2011 Institute of Food Technologists®

Bepridil differentially inhibits two delayed rectifier K+ currents, IKr and IKs, in guinea-pig ventricular myocytes

PubMed Central

Wang, Jin-Cheng; Kiyosue, Tatsuto; Kiriyama, Kuninori; Arita, Makoto

1999-01-01

We investigated the effects of bepridil on the two components of the delayed rectifier K+ current, i.e., the rapidly activating (IKr) and the slowly activating (IKs) currents using tight-seal whole-cell patch-clamp techniques in guinea-pig ventricular myocytes, under blockade of L-type Ca2+ current with nitrendipine (5 μM) or D600 (1 μM).Bepridil decreased IKs under blockade of IKr with E4031 (5 μM), in a concentration-dependent manner. The concentration-dependent inhibition of IKs by bepridil was fitted by a curve, assuming one-to-one interactions between the channel and the drug molecule. The concentration of half-maximal inhibition (IC50) was found to be 6.2 μM.The effect of bepridil on IKr was assessed using an envelope-of-tails test. In the control condition, a ratio of the tail current to the time-dependent current measured during depolarization was large (>1) at shorter pulses (<200 ms), and it decreased to a steady state value of ∼0.4 with increases in the pulse duration. Bepridil at a concentration of 2 μM did not decrease this ratio at shorter pulses.In a short-pulse (duration=50 ms) experiment that largely activates IKr, the drug was found to block IKr in a cooperative manner (Hill coefficient=3.03) and the IC50 was 13.2 μM.These results suggest that bepridil at a clinical therapeutic concentration (∼2 μM) selectively blocks IKs but does not inhibit IKr. This may relate to the characteristic frequency-dependent effects of bepridil on the action potential duration (APD), e.g., the non-reverse use-dependent prolongation of APD. PMID:10588929

The optical and radiation field signatures produced by lightning return strokes

NASA Technical Reports Server (NTRS)

Guo, C.; Krider, E. P.

1982-01-01

Typical examples of the signals that are produced by first and subsequent return strokes in cloud-to-ground lightning on a microsecond time scale are presented. Statistics on the structure of the waveforms and the radiance of the channels are given. The relationship between the light signals and the associated electric field signatures is discussed. It is shown that the initial light signal from a return stroke tends to be linear for about 15 microsec and then rises more slowly to a peak that is delayed by approximately 60 microsec from the electric field peak. It is thought that the transition between the fast linear portion and the slower rise may be due to the return stroke entering the cloud base. A small percentage of the records suggest that two different branches of the same stepped leader can initiate separate return strokes. The light pulses from cloud discharges tend to be smaller and to vary more slowly than those from return strokes.

The calcitonin gene-related peptide receptor antagonist MK-8825 decreases spinal trigeminal activity during nitroglycerin infusion

PubMed Central

2013-01-01

Background Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin. Methods In isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours). Results After infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity. Conclusions CGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches. PMID:24256609

Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells.

PubMed

Yuan, X J; Wang, J; Juhaszova, M; Golovina, V A; Rubin, L J

1998-04-01

K(+)-channel activity-mediated alteration of the membrane potential and cytoplasmic free Ca2+ concentration ([Ca2+]cyt) is a pivotal mechanism in controlling pulmonary vasomotor tone. By using combined approaches of patch clamp, imaging fluorescent microscopy, and molecular biology, we examined the electrophysiological properties of K+ channels and the role of different K+ currents in regulating [Ca2+]cyt and explored the molecular identification of voltage-gated K+ (KV)- and Ca(2+)-activated K+ (KCa)-channel genes expressed in pulmonary arterial smooth muscle cells (PASMC). Two kinetically distinct KV currents [IK(V)], a rapidly inactivating (A-type) and a noninactivating delayed rectifier, as well as a slowly activated KCa current [IK(Ca)] were identified. IK(V) was reversibly inhibited by 4-aminopyridine (5 mM), whereas IK(Ca) was significantly inhibited by charybdotoxin (10-20 nM). K+ channels are composed of pore-forming alpha-subunits and auxiliary beta-subunits. Five KV-channel alpha-subunit genes from the Shaker subfamily (KV1.1, KV1.2, KV1.4, KV1.5, and KV1.6), a KV-channel alpha-subunit gene from the Shab subfamily (KV2.1), a KV-channel modulatory alpha-subunit (KV9.3), and a KCa-channel alpha-subunit gene (rSlo), as well as three KV-channel beta-subunit genes (KV beta 1.1, KV beta 2, and KV beta 3) are expressed in PASMC. The data suggest that 1) native K+ channels in PASMC are encoded by multiple genes; 2) the delayed rectifier IK(V) may be generated by the KV1.1, KV1.2, KV1.5, KV1.6, KV2.1, and/or KV2.1/KV9.3 channels; 3) the A-type IK(V) may be generated by the KV1.4 channel and/or the delayed rectifier KV channels (KV1 subfamily) associated with beta-subunits; and 4) the IK(Ca) may be generated by the rSlo gene product. The function of the KV channels plays an important role in the regulation of membrane potential and [Ca2+]cyt in PASMC.

Characterizing Impulsivity in Mania

PubMed Central

Strakowski, Stephen M.; Fleck, David E.; DelBello, Melissa P.; Adler, Caleb M.; Shear, Paula K.; McElroy, Susan L.; Keck, Paul E.; Moss, Quinton; Cerullo, Michael A.; Kotwal, Renu; Arndt, Stephan

2008-01-01

Objective To determine whether specific aspects of impulsivity (response disinhibition, inability to delay gratification, inattention) differ between healthy and bipolar manic subjects, and whether these aspects of impulsivity were associated with each other and severity of affective symptoms. Methods Performance of 70 bipolar I manic or mixed patients was compared to that of 34 healthy subjects on three tasks specifically designed to study response inhibition, ability to delay gratification, and attention; namely a stop signal task, a delayed reward task, and a continuous performance task respectively. Correlations among tasks and with symptom ratings were also performed. Results Bipolar subjects demonstrated significant deficits on all three tasks as compared to healthy subjects. Performance on the three tasks was largely independent. Task performance was not significantly associated with the severity of affective symptom ratings. However, measures of response inhibition and attention were sensitive to medication effects. Differences in the delayed reward task were independent of medication effects or symptom ratings. During the delayed reward task, although bipolar patients made their choices more slowly than healthy subjects, they were significantly more likely to choose a smaller, but more quickly obtained reward. Moreover performance on this task was not associated with performance on the other impulsivity measures. Manic patients showed more impulsive responding than mixed patients. Conclusions Bipolar I manic patients demonstrate deficits on tests of various aspects of impulsivity as compared to healthy subjects. Some of these differences between groups may be mediated by medication effects. Findings suggested that inability to delay gratification (i.e., delayed reward task) was not simply a result of the speed of decision making or inattention, but rather that it reflected differences between bipolar and healthy subjects in the valuation of reward relative to delay. PMID:19133965

Improving Accuracy in Arrhenius Models of Cell Death: Adding a Temperature-Dependent Time Delay.

PubMed

Pearce, John A

2015-12-01

The Arrhenius formulation for single-step irreversible unimolecular reactions has been used for many decades to describe the thermal damage and cell death processes. Arrhenius predictions are acceptably accurate for structural proteins, for some cell death assays, and for cell death at higher temperatures in most cell lines, above about 55 °C. However, in many cases--and particularly at hyperthermic temperatures, between about 43 and 55 °C--the particular intrinsic cell death or damage process under study exhibits a significant "shoulder" region that constant-rate Arrhenius models are unable to represent with acceptable accuracy. The primary limitation is that Arrhenius calculations always overestimate the cell death fraction, which leads to severely overoptimistic predictions of heating effectiveness in tumor treatment. Several more sophisticated mathematical model approaches have been suggested and show much-improved performance. But simpler models that have adequate accuracy would provide useful and practical alternatives to intricate biochemical analyses. Typical transient intrinsic cell death processes at hyperthermic temperatures consist of a slowly developing shoulder region followed by an essentially constant-rate region. The shoulder regions have been demonstrated to arise chiefly from complex functional protein signaling cascades that generate delays in the onset of the constant-rate region, but may involve heat shock protein activity as well. This paper shows that acceptably accurate and much-improved predictions in the simpler Arrhenius models can be obtained by adding a temperature-dependent time delay. Kinetic coefficients and the appropriate time delay are obtained from the constant-rate regions of the measured survival curves. The resulting predictions are seen to provide acceptably accurate results while not overestimating cell death. The method can be relatively easily incorporated into numerical models. Additionally, evidence is presented to support the application of compensation law behavior to the cell death processes--that is, the strong correlation between the kinetic coefficients, ln{A} and E(a), is confirmed.

The Electrophysiological Effects of Qiliqiangxin on Cardiac Ventricular Myocytes of Rats

PubMed Central

Wei, Yidong; Liu, Xiaoyu; Wei, Haidong; Hou, Lei; Che, Wenliang; The, Erlinda; Li, Gang; Jhummon, Muktanand Vikash; Wei, Wanlin

2013-01-01

Qiliqiangxin, a Chinese herb, represents the affection in Ca channel function of cardiac myocytes. It is unknown whether Qiliqiangxin has an effect on Na current and K current because the pharmacological actions of this herb's compound are very complex. We investigated the rational usage of Qiliqiangxin on cardiac ventricular myocytes of rats. Ventricular myocytes were exposed acutely to 1, 10, and 50 mg/L Qiliqiangxin, and whole cell patch-clamp technique was used to study the acute effects of Qiliqiangxin on Sodium current (I Na), outward currents delayed rectifier outward K+ current (I K), slowly activating delayed rectifier outward K+ current (I Ks), transient outward K+ current (I to), and inward rectifier K+ current (I K1). Qiliqiangxin can decrease I Na by 28.53% ± 5.98%, and its IC50 was 9.2 mg/L. 10 and 50 mg/L Qiliqiangxin decreased by 37.2% ± 6.4% and 55.9% ± 5.5% summit current density of I to. 10 and 50 mg/L Qiliqiangxin decreased I Ks by 15.51% ± 4.03% and 21.6% ± 5.6%. Qiliqiangxin represented a multifaceted pharmacological profile. The effects of Qiliqiangxin on Na and K currents of ventricular myocytes were more profitable in antiarrhythmic therapy in the clinic. We concluded that the relative efficacy of Qiliqiangxin was another choice for the existing antiarrhythmic therapy. PMID:24250713

ISO Guest Observer Data Analysis and LWS Instrument Team Activities

NASA Technical Reports Server (NTRS)

Smith, Howard

2001-01-01

The following is an interim annual report. Dr. Smith is currently on an extended TDY to the Istituto di Fisica dello Spazio Interplanetario (IFSI) at the Consilio Nazionale delle Richerche (CNR) in Rome, Italy, where he has been working on a related NASA grant in support of analysis of Infrared Space Observatory (ISO) data on star formation in Ultra Luminous Infrared Galaxies and our galaxy. Work emphasizes development of metal mesh grids for use in spacecraft, and the design and fabrication of test elements by the Naval Research Laboratory, Washington D.C. Work has progressed well, but slowly, on that program due to the departure of a key engineer. NASA has been advised of the delay, and granted a no-cost extension, whereby SAO has authorized a delay in the final report from NRL. Nevertheless NRL has continued to make progress. Two papers have been submitted to refereed journals related to this program, and a new design for mesh operating in the 20-40 micron region has been developed. Meetings continue through the summer on these items. A new technical scientist has been made a job offer and hopefully will be on board NRL shortly, although most of the present grant work is already completed. A more complete report, with copies of the submitted papers, designs, and other measures of progress, will be submitted to NASA in September when Dr. Smith returns from his current TDY.

Core Noise Diagnostics of Turbofan Engine Noise Using Correlation and Coherence Functions

NASA Technical Reports Server (NTRS)

Miles, Jeffrey H.

2009-01-01

Cross-correlation and coherence functions are used to look for periodic acoustic components in turbofan engine combustor time histories, to investigate direct and indirect combustion noise source separation based on signal propagation time delays, and to provide information on combustor acoustics. Using the cross-correlation function, time delays were identified in all cases, clearly indicating the combustor is the source of the noise. In addition, unfiltered and low-pass filtered at 400 Hz signals had a cross-correlation time delay near 90 ms, while the low-pass filtered at less than 400 Hz signals had a cross-correlation time delay longer than 90 ms. Low-pass filtering at frequencies less than 400 Hz partially removes the direct combustion noise signals. The remainder includes the indirect combustion noise signal, which travels more slowly because of the dependence on the entropy convection velocity in the combustor. Source separation of direct and indirect combustion noise is demonstrated by proper use of low-pass filters with the cross-correlation function for a range of operating conditions. The results may lead to a better idea about the acoustics in the combustor and may help develop and validate improved reduced-order physics-based methods for predicting direct and indirect combustion noise.

Ablation of silicon with bursts of femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Gaudiuso, Caterina; Kämmer, Helena; Dreisow, Felix; Ancona, Antonio; Tünnermann, Andreas; Nolte, Stefan

2016-03-01

We report on an experimental investigation of ultrafast laser ablation of silicon with bursts of pulses. The pristine 1030nm-wavelength 200-fs pulses were split into bursts of up to 16 sub-pulses with time separation ranging from 0.5ps to 4080ps. The total ablation threshold fluence was measured depending on the burst features, finding that it strongly increases with the number of sub-pulses for longer sub-pulse delays, while a slowly increasing trend is observed for shorter separation time. The ablation depth per burst follows two different trends according to the time separation between the sub-pulses, as well as the total threshold fluence. For delays shorter than 4ps it decreases with the number of pulses, while for time separations longer than 510ps, deeper craters were achieved by increasing the number of subpulses in the burst, probably due to a change of the effective penetration depth.

Delay-bandwidth product of electromagnetically induced transparency media

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

Tidstroem, Jonas; Jaenes, Peter; Andersson, L. Mauritz

2007-05-15

The limitations on the delay-bandwidth product (DBP) in an electromagnetically induced transparency medium are investigated analytically by studying the susceptibility of the system, derived through Lindblad's master equation, including dephasing. The effect of inhomogeneous broadening is treated. It is shown that the DBP for a given material is fundamentally limited by the frequency-dependent absorption, while the residual absorption limits the penetration length of a pulse. Simple expression for the optimal choice of parameters to maximize the DBP are derived. Also, the length of a device is presented as a function of DBP and control-field Rabi frequency. Supporting these results, numericalmore » calculations are carried out through the Maxwell-Bloch equations in the slowly varying envelope approximation. The results are scalable, hence they apply to the case of atoms or molecules in a gas as well as quantum dots and wells.« less

Compressed Sensing in On-Grid MIMO Radar.

PubMed

Minner, Michael F

2015-01-01

The accurate detection of targets is a significant problem in multiple-input multiple-output (MIMO) radar. Recent advances of Compressive Sensing offer a means of efficiently accomplishing this task. The sparsity constraints needed to apply the techniques of Compressive Sensing to problems in radar systems have led to discretizations of the target scene in various domains, such as azimuth, time delay, and Doppler. Building upon recent work, we investigate the feasibility of on-grid Compressive Sensing-based MIMO radar via a threefold azimuth-delay-Doppler discretization for target detection and parameter estimation. We utilize a colocated random sensor array and transmit distinct linear chirps to a small scene with few, slowly moving targets. Relying upon standard far-field and narrowband assumptions, we analyze the efficacy of various recovery algorithms in determining the parameters of the scene through numerical simulations, with particular focus on the ℓ 1-squared Nonnegative Regularization method.

Selective control of cortical axonal spikes by a slowly inactivating K+ current

PubMed Central

Shu, Yousheng; Yu, Yuguo; Yang, Jing; McCormick, David A.

2007-01-01

Neurons are flexible electrophysiological entities in which the distribution and properties of ionic channels control their behaviors. Through simultaneous somatic and axonal whole-cell recording of layer 5 pyramidal cells, we demonstrate a remarkable differential expression of slowly inactivating K+ currents. Depolarizing the axon, but not the soma, rapidly activated a low-threshold, slowly inactivating, outward current that was potently blocked by low doses of 4-aminopyridine, α-dendrotoxin, and rTityustoxin-Kα. Block of this slowly inactivating current caused a large increase in spike duration in the axon but only a small increase in the soma and could result in distal axons generating repetitive discharge in response to local current injection. Importantly, this current was also responsible for slow changes in the axonal spike duration that are observed after somatic membrane potential change. These data indicate that low-threshold, slowly inactivating K+ currents, containing Kv1.2 α subunits, play a key role in the flexible properties of intracortical axons and may contribute significantly to intracortical processing. PMID:17581873

Influence of environmental pH on G2-phase arrest caused by ionizing radiation.

PubMed

Park, Heon Joo; Lee, Sang Hwa; Chung, HyunSook; Rhee, Yun Hee; Lim, Byung Uk; Ha, Sung Whan; Griffin, Robert J; Lee, Hyung Sik; Song, Chang Won; Choi, Eun Kyung

2003-01-01

We investigated the effects of an acidic environment on the G2/M-phase arrest, apoptosis, clonogenic death, and changes in cyclin B1-CDC2 kinase activity caused by a 4-Gy irradiation in RKO.C human colorectal cancer cells in vitro. The time to reach peak G2/M-phase arrest after irradiation was delayed in pH 6.6 medium compared to that in pH 7.5 medium. Furthermore, the radiation-induced G2/M-phase arrest decayed more slowly in pH 6.6 medium than in pH 7.5 medium. Finally, there was less radiation-induced apoptosis and clonogenic cell death in pH 6.6 medium than in pH 7.5 medium. It appeared that the prolongation of G2-phase arrest after irradiation in the acidic environment allowed for greater repair of radiation-induced DNA damage, thereby decreasing the radiation-induced cell death. The prolongation of G2-phase arrest after irradiation in the acidic pH environment appeared to be related at least in part to a prolongation of the phosphorylation of CDC2, which inhibited cyclin B1-CDC2 kinase activity.

Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly Isolated Mouse Dorsal Root Ganglion Neurons.

PubMed

Sheng, Anqi; Zhang, Yan; Li, Guang; Zhang, Guangqin

2018-02-01

Voltage-gated potassium (K V ) currents, subdivided into rapidly inactivating A-type currents (I A ) and slowly inactivating delayed rectifier currents (I K ), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on K V currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I A and I K in concentration-dependent manner. The IC 50 values for block of I A and I K were 30.5 and 25.7 µM, respectively. Hon (30 µM) shifted the steady-state activation curves of I A and I K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I A and I K channels, and has no effect on the resting state and inactivated state of the I A channel. Blockade on K + channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain.

A proof of Wright's conjecture

NASA Astrophysics Data System (ADS)

van den Berg, Jan Bouwe; Jaquette, Jonathan

2018-06-01

Wright's conjecture states that the origin is the global attractor for the delay differential equation y‧ (t) = - αy (t - 1) [ 1 + y (t) ] for all α ∈ (0, π/2 ] when y (t) > - 1. This has been proven to be true for a subset of parameter values α. We extend the result to the full parameter range α ∈ (0, π/2 ], and thus prove Wright's conjecture to be true. Our approach relies on a careful investigation of the neighborhood of the Hopf bifurcation occurring at α = π/2. This analysis fills the gap left by complementary work on Wright's conjecture, which covers parameter values further away from the bifurcation point. Furthermore, we show that the branch of (slowly oscillating) periodic orbits originating from this Hopf bifurcation does not have any subsequent bifurcations (and in particular no folds) for α ∈ (π/2, π/2 + 6.830 ×10-3 ]. When combined with other results, this proves that the branch of slowly oscillating solutions that originates from the Hopf bifurcation at α = π/2 is globally parametrized by α > π/2.

Overexpression of a cotton gene that encodes a putative transcription factor of AP2/EREBP family in Arabidopsis affects growth and development of transgenic plants.

PubMed

Zhou, Ying; Xia, Hui; Li, Xiao-Jie; Hu, Rong; Chen, Yun; Li, Xue-Bao

2013-01-01

In the study, a gene encoding a putative ethylene response factor of AP2/EREBP family was isolated from cotton (Gossypium hirsutum) and designated as GhERF12. Sequence alignment showed that GhERF12 protein contains a central AP2/ERF domain (58 amino acids) with two functional conserved amino acid residues (ala14 and asp19). Transactivation assay indicated that GhERF12 displayed strong transcription activation activity in yeast cells, suggesting that this protein may be a transcriptional activator in cotton. Quantitative RT-PCR analysis showed that GhERF12 expression in cotton was induced by ACC and IAA. Overexpression of GhERF12 in Arabidopsis affected seedling growth and development. The GhERF12 transgenic plants grew slowly, and displayed a dwarf phenotype. The mean bolting time of the transgenic plants was delayed for about 10 days, compared with that of wild type. Further study revealed that some ethylene-related and auxin-related genes were dramatically up-regulated in the transgenic plants, compared with those of wild type. Collectively, we speculated that GhERF12, as a transcription factor, may be involved in regulation of plant growth and development by activating the constitutive ethylene response likely related to auxin biosynthesis and/or signaling.

Overexpression of a Cotton Gene That Encodes a Putative Transcription Factor of AP2/EREBP Family in Arabidopsis Affects Growth and Development of Transgenic Plants

PubMed Central

Li, Xiao-Jie; Hu, Rong; Chen, Yun; Li, Xue-Bao

2013-01-01

In the study, a gene encoding a putative ethylene response factor of AP2/EREBP family was isolated from cotton (Gossypium hirsutum) and designated as GhERF12. Sequence alignment showed that GhERF12 protein contains a central AP2/ERF domain (58 amino acids) with two functional conserved amino acid residues (ala14 and asp19). Transactivation assay indicated that GhERF12 displayed strong transcription activation activity in yeast cells, suggesting that this protein may be a transcriptional activator in cotton. Quantitative RT-PCR analysis showed that GhERF12 expression in cotton was induced by ACC and IAA. Overexpression of GhERF12 in Arabidopsis affected seedling growth and development. The GhERF12 transgenic plants grew slowly, and displayed a dwarf phenotype. The mean bolting time of the transgenic plants was delayed for about 10 days, compared with that of wild type. Further study revealed that some ethylene-related and auxin-related genes were dramatically up-regulated in the transgenic plants, compared with those of wild type. Collectively, we speculated that GhERF12, as a transcription factor, may be involved in regulation of plant growth and development by activating the constitutive ethylene response likely related to auxin biosynthesis and/or signaling. PMID:24194949

Immense Magnetic Response of Exciplex Light Emission due to Correlated Spin-Charge Dynamics

NASA Astrophysics Data System (ADS)

Wang, Yifei; Sahin-Tiras, Kevser; Harmon, Nicholas J.; Wohlgenannt, Markus; Flatté, Michael E.

2016-01-01

As carriers slowly move through a disordered energy landscape in organic semiconductors, tiny spatial variations in spin dynamics relieve spin blocking at transport bottlenecks or in the electron-hole recombination process that produces light. Large room-temperature magnetic-field effects (MFEs) ensue in the conductivity and luminescence. Sources of variable spin dynamics generate much larger MFEs if their spatial structure is correlated on the nanoscale with the energetic sites governing conductivity or luminescence such as in coevaporated organic blends within which the electron resides on one molecule and the hole on the other (an exciplex). Here, we show that exciplex recombination in blends exhibiting thermally activated delayed fluorescence produces MFEs in excess of 60% at room temperature. In addition, effects greater than 4000% can be achieved by tuning the device's current-voltage response curve by device conditioning. Both of these immense MFEs are the largest reported values for their device type at room temperature. Our theory traces this MFE and its unusual temperature dependence to changes in spin mixing between triplet exciplexes and light-emitting singlet exciplexes. In contrast, spin mixing of excitons is energetically suppressed, and thus spin mixing produces comparatively weaker MFEs in materials emitting light from excitons by affecting the precursor pairs. Demonstration of immense MFEs in common organic blends provides a flexible and inexpensive pathway towards magnetic functionality and field sensitivity in current organic devices without patterning the constituent materials on the nanoscale. Magnetic fields increase the power efficiency of unconditioned devices by 30% at room temperature, also showing that magnetic fields may increase the efficiency of the thermally activated delayed fluorescence process.

Immense Magnetic Response of Exciplex Light Emission due to Correlated Spin-Charge Dynamics

DOE PAGES

Wang, Yifei; Sahin-Tiras, Kevser; Harmon, Nicholas J.; ...

2016-02-05

As carriers slowly move through a disordered energy landscape in organic semiconductors, tiny spatial variations in spin dynamics relieve spin blocking at transport bottlenecks or in the electron-hole recombination process that produces light. Large room-temperature magnetic-field effects (MFEs) ensue in the conductivity and luminescence. Sources of variable spin dynamics generate much larger MFEs if their spatial structure is correlated on the nanoscale with the energetic sites governing conductivity or luminescence such as in coevaporated organic blends within which the electron resides on one molecule and the hole on the other (an exciplex). Here, we show that exciplex recombination in blendsmore » exhibiting thermally activated delayed fluorescence produces MFEs in excess of 60% at room temperature. In addition, effects greater than 4000% can be achieved by tuning the device’s current-voltage response curve by device conditioning. Both of these immense MFEs are the largest reported values for their device type at room temperature. Our theory traces this MFE and its unusual temperature dependence to changes in spin mixing between triplet exciplexes and light-emitting singlet exciplexes. In contrast, spin mixing of excitons is energetically suppressed, and thus spin mixing produces comparatively weaker MFEs in materials emitting light from excitons by affecting the precursor pairs. Demonstration of immense MFEs in common organic blends provides a flexible and inexpensive pathway towards magnetic functionality and field sensitivity in current organic devices without patterning the constituent materials on the nanoscale. In conclusion, magnetic fields increase the power efficiency of unconditioned devices by 30% at room temperature, also showing that magnetic fields may increase the efficiency of the thermally activated delayed fluorescence process.« less

The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

PubMed

Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

2015-08-01

The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

PubMed Central

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

2012-01-01

BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

PubMed

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

2012-10-01

Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

[Effect of down-regulation of IKs repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy].

PubMed

Wang, Hegui; Huang, Ting; Wang, Zheng; Ge, Nannan; Ke, Yongsheng

2018-04-28

To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).
 Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers.
 Results: Compared with cardiac cells in the control group, the interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (P<0.05); while IKs densities were significantly reduced [+60 mV: (0.36±0.03) pA/pF vs (0.58±0.05) pA/pF, P<0.01]. However, LVH exerted no significant effect on IKr densities. IKr blocker markedly prolonged the QTc interval (P<0.01) and increased the incidence of ventricular arrhythmias in guinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals.
 Conclusion: The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation 
of IKs.

[Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas].

PubMed

Wakui, A

1982-08-01

This paper provides an overview of cancer chemotherapy with special reference to the pharmacokinetics of the nitrosoureas. At physiological PH, the chloroethylnitrosoureas can be decomposed into an isocyanate and 2-chloroethyl diazene hydroxide. Therefore, it is clear that they have both alkylation and carbamoylation actions. In addition to the spontaneous chemical dissociation, the nitrosoureas can be metabolized by liver microsomal enzymes to more polar hydroxylated products, and certain nitrosoureas can be denitrosated by these enzymes to the parent urea. Since the lipid-soluble nitrosoureas and some of the water-soluble nitrosoureas such as ACNU and MCNU demonstrated to cross the blood-brain barrier, they have been used in the treatment of primary brain tumors and tumors and tumors of metastatic origin. It has been demonstrated from the results of our study and other reports that the alkylation of DNA by ACNU progresses more slowly as compared with that of other alkylating agents. This is an important finding in relation to the appearance of delayed myelosuppression of the nitrosoureas and in the design of dose schedules of these agents. The major clinical emphasis has been directed towards the more active chloroethylnitrosoureas with reduced myelosuppression, and attempts are now made for this purpose. Unfortunately, the results of phase I and II trials of the newly developed nitrosoureas suggest that these agents produce delayed and cumulative bone marrow toxicity. Antitumor activity of the nitrosoureas is frequestly observed in chronic myelocytic leukemia, malignant lymphoma, brain tumors and small cell carcinoma of the lung, and less frequently in gastrointestinal carcinoma, multiple myeloma and malignant melanoma. In order to enhance clinical effects of the nitrosoureas, further investigation of the design in therapeutic schedules on the basis of their pharmacokinetic characteristics will be needed.

Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain.

PubMed

Holmqvist, Mats H; Cao, Jie; Hernandez-Pineda, Ricardo; Jacobson, Michael D; Carroll, Karen I; Sung, M Amy; Betty, Maria; Ge, Pei; Gilbride, Kevin J; Brown, Melissa E; Jurman, Mark E; Lawson, Deborah; Silos-Santiago, Inmaculada; Xie, Yu; Covarrubias, Manuel; Rhodes, Kenneth J; Distefano, Peter S; An, W Frank

2002-01-22

The Kv4 A-type potassium currents contribute to controlling the frequency of slow repetitive firing and back-propagation of action potentials in neurons and shape the action potential in heart. Kv4 currents exhibit rapid activation and inactivation and are specifically modulated by K-channel interacting proteins (KChIPs). Here we report the discovery and functional characterization of a modular K-channel inactivation suppressor (KIS) domain located in the first 34 aa of an additional KChIP (KChIP4a). Coexpression of KChIP4a with Kv4 alpha-subunits abolishes fast inactivation of the Kv4 currents in various cell types, including cerebellar granule neurons. Kinetic analysis shows that the KIS domain delays Kv4.3 opening, but once the channel is open, it disrupts rapid inactivation and slows Kv4.3 closing. Accordingly, KChIP4a increases the open probability of single Kv4.3 channels. The net effects of KChIP4a and KChIP1-3 on Kv4 gating are quite different. When both KChIP4a and KChIP1 are present, the Kv4.3 current shows mixed inactivation profiles dependent on KChIP4a/KChIP1 ratios. The KIS domain effectively converts the A-type Kv4 current to a slowly inactivating delayed rectifier-type potassium current. This conversion is opposite to that mediated by the Kv1-specific "ball" domain of the Kv beta 1 subunit. Together, these results demonstrate that specific auxiliary subunits with distinct functions actively modulate gating of potassium channels that govern membrane excitability.

Ultrasonic inspection of studs (bolts) using dynamic predictive deconvolution and wave shaping.

PubMed

Suh, D M; Kim, W W; Chung, J G

1999-01-01

Bolt degradation has become a major issue in the nuclear industry since the 1980's. If small cracks in stud bolts are not detected early enough, they grow rapidly and cause catastrophic disasters. Their detection, despite its importance, is known to be a very difficult problem due to the complicated structures of the stud bolts. This paper presents a method of detecting and sizing a small crack in the root between two adjacent crests in threads. The key idea is from the fact that the mode-converted Rayleigh wave travels slowly down the face of the crack and turns from the intersection of the crack and the root of thread to the transducer. Thus, when a crack exists, a small delayed pulse due to the Rayleigh wave is detected between large regularly spaced pulses from the thread. The delay time is the same as the propagation delay time of the slow Rayleigh wave and is proportional to the site of the crack. To efficiently detect the slow Rayleigh wave, three methods based on digital signal processing are proposed: wave shaping, dynamic predictive deconvolution, and dynamic predictive deconvolution combined with wave shaping.

Failure of tooth eruption in two patients with cerebral palsy and bruxism-a 10-year follow-up: a case report.

PubMed

Staufer, Kirsten; Hamadeh, Sinan; Gesch, Dietmar

2009-01-01

The aim of this paper was to analyze delayed tooth eruption in two children with cerebral palsy who had severe bruxism and to determine whether treatment could influence tooth eruption and alignment. Extraction of primary teeth was carried out and orthodontic treatment was considered due to severe tooth wear of primary teeth, lack of space, and development of a class III malocclusion. Analysis was based on clinical examination, photographs, radiographs, and dental casts. In both patients, early mixed dentition was delayed for more than 5 years. Calcification and root development of posterior permanent teeth corresponded with the chronological age. Root resorption of the severely abraded primary teeth and eruption of their successors were delayed or failed. Eruption of permanent teeth occurred slowly after primary teeth were extracted. Orthodontic treatment succeeded in one patient, achieving a normal overjet in combination with a successful orofacial therapy. The disturbed exfoliation of abraded primary teeth and failure of tooth eruption of the posterior teeth could be linked to the systemic pathology and to bruxism. At age 20, eruption of the canines and premolars remained questionable.

The actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

NASA Astrophysics Data System (ADS)

Westendorf, Christian; Negrete, Jose, Jr.; Bae, Albert; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

2013-03-01

We report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. The averaged F-actin response of many cells to a short-time pulse of cAMP is reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. We systematically exposed a large number of cells to periodic pulse trains. The results indicate a resonance peak at periodic inputs of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the actin regulatory network. To quantitatively test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and Aip1. These served as markers of the F-actin disassembly process and thus allow us to estimate the delay time. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed experimentally. Financial support by the Max-Planck Society and the DFG (SFB 937).

Diversity of pubertal testosterone changes in boys with constitutional delay in growth and/or adolescence.

PubMed

Kulin, H E; Finkelstein, J W; D'Arcangelo, M R; Susman, E J; Chinchilli, V; Kunselman, S; Schwab, J; Demers, L; Lookingbill, G

1997-01-01

In a group of 22 boys with constitutional delay in growth and/or adolescence, intermittent testosterone enanthate treatment was employed in a randomized clinical trial at multiple doses ranging from 25-100 mg every two weeks for three month periods extending over 15-21 months. Twelve of the patients displayed a prompt increase in endogenous testosterone levels during the study period, reaching levels in the adult male range (> 250 ng/dl). The remaining 10 boys showed sluggish changes in endogenous testosterone during the investigation, ranging from 35-177 ng/dl. The bone ages and testicular sizes of the two groups at study initiation did not differ though urine LH was significantly less at study entry in the slowly maturing group. The data reveal a great diversity in the pace and pattern of endogenous testosterone changes in the study population. The results also suggest that exogenous sex steroid treatment of such patients does not speed up the central nervous system processes controlling the onset and progression of puberty. Boys with delayed puberty should be followed until endogenous testosterone levels reach the adult male range in order to rule out mild gonadotropin deficits.

Pathogenetic mechanisms of amyloid A amyloidosis

PubMed Central

Simons, J. Paul; Al-Shawi, Raya; Ellmerich, Stephan; Speck, Ivana; Aslam, Samrina; Hutchinson, Winston L.; Mangione, Palma P.; Disterer, Petra; Gilbertson, Janet A.; Hunt, Toby; Millar, David J.; Minogue, Shane; Bodin, Karl; Pepys, Mark B.; Hawkins, Philip N.

2013-01-01

Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflammation before presenting, most commonly with renal involvement. Using dose-dependent, doxycycline-inducible transgenic expression of SAA in mice, we show that AA amyloid deposition can occur independently of inflammation and that the time before amyloid deposition is determined by the circulating SAA concentration. High level SAA expression induced amyloidosis in all mice after a short, slightly variable delay. SAA was rapidly incorporated into amyloid, acutely reducing circulating SAA concentrations by up to 90%. Prolonged modest SAA overexpression occasionally produced amyloidosis after long delays and primed most mice for explosive amyloidosis when SAA production subsequently increased. Endogenous priming and bulk amyloid deposition are thus separable events, each sensitive to plasma SAA concentration. Amyloid deposits slowly regressed with restoration of normal SAA production after doxycycline withdrawal. Reinduction of SAA overproduction revealed that, following amyloid regression, all mice were primed, especially for rapid glomerular amyloid deposition leading to renal failure, closely resembling the rapid onset of renal failure in clinical AA amyloidosis following acute exacerbation of inflammation. Clinical AA amyloidosis rarely involves the heart, but amyloidotic SAA transgenic mice consistently had minor cardiac amyloid deposits, enabling us to extend to the heart the demonstrable efficacy of our unique antibody therapy for elimination of visceral amyloid. PMID:23959890

Installation Restoration of Frankford Arsenal, Pennsylvania, Concept Plan

DTIC Science & Technology

1977-09-01

combined with 650 ml of tetrazine slurry. To this mix was added other components (e.g., antimony sulfide , powdered aluminum, PETN, barium nitrate and a...such materials as barium nitrate, magnesium and aluminum powders, potassium perchlorate, iron oxide, red phosphorus, strontium peroxide, strontium...soluble in acetone and nethyl acetate. Chemical Activity: Decomposed slowly by boiling 2.5% aqueous caustic;0 decomposed slowly by sodium sulfide

Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice.

PubMed

Xie, Kan; Neff, Frauke; Markert, Astrid; Rozman, Jan; Aguilar-Pimentel, Juan Antonio; Amarie, Oana Veronica; Becker, Lore; Brommage, Robert; Garrett, Lillian; Henzel, Kristin S; Hölter, Sabine M; Janik, Dirk; Lehmann, Isabelle; Moreth, Kristin; Pearson, Brandon L; Racz, Ildiko; Rathkolb, Birgit; Ryan, Devon P; Schröder, Susanne; Treise, Irina; Bekeredjian, Raffi; Busch, Dirk H; Graw, Jochen; Ehninger, Gerhard; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Sandholzer, Michael; Schmidt-Weber, Carsten; Weiergräber, Marco; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Gailus-Durner, Valerie; Fuchs, Helmut; Hrabě de Angelis, Martin; Ehninger, Dan

2017-07-24

Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues in aged animals fed with a lifelong every-other-day feeding or ad libitum access to food diet to determine whether molecular, cellular, physiological and histopathological aging features develop more slowly in every-other-day feeding mice than in controls. We also analyze the effects of every-other-day feeding on young mice on shorter-term every-other-day feeding or ad libitum to account for possible aging-independent restriction effects. Our large-scale analysis reveals overall only limited evidence for a retardation of the aging rate in every-other-day feeding mice. The data indicate that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice.Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

Kinetics of the formation of chromosome aberrations in X-irradiated human lymphocytes: analysis by premature chromosome condensation with delayed fusion.

PubMed

Greinert, R; Detzler, E; Volkmer, B; Harder, D

1995-11-01

Human lymphocytes irradiated with graded doses of up to 5 Gy of 150 kV X rays were fused with mitotic CHO cells after delay times ranging from 0 to 14 h after irradiation. The yields of dicentrics seen under PCC conditions, using C-banding for centromere detection, and of excess acentric fragments observed in the PCC experiment were determined by image analysis. At 4 Gy the time course of the yield of dicentrics shows an early plateau for delay times up to 2 h, then an S-shaped rise and a final plateau which is reached after a delay time of about 8 to 10 h. Whereas the dose-yield curve measured at zero delay time is strictly linear, the shape of the curve obtained for 8 h delay time is linear-quadratic. The linear yield component, alpha D, is formed entirely in the fast process manifested in the early plateau, while component beta D2 is developed slowly in the subsequent hours. Analysis of the kinetics of the rise of the S-shaped curve for yield as a function of time leads to the postulate of an "intermediate product" of pairwise DNA lesion interaction, still fragile when subjected to the stress of PCC, but gradually processed into a stable dicentric chromosome. It is concluded that the observed difference in the kinetics of the alpha and beta components explains a number of earlier results, especially the disappearance of the beta component at high LET, and opens possibilities for chemical and physical modification of the beta component during the extended formation process after irradiation observed here.

Components of gating charge movement and S4 voltage-sensor exposure during activation of hERG channels.

PubMed

Wang, Zhuren; Dou, Ying; Goodchild, Samuel J; Es-Salah-Lamoureux, Zeineb; Fedida, David

2013-04-01

The human ether-á-go-go-related gene (hERG) K(+) channel encodes the pore-forming α subunit of the rapid delayed rectifier current, IKr, and has unique activation gating kinetics, in that the α subunit of the channel activates and deactivates very slowly, which focuses the role of IKr current to a critical period during action potential repolarization in the heart. Despite its physiological importance, fundamental mechanistic properties of hERG channel activation gating remain unclear, including how voltage-sensor movement rate limits pore opening. Here, we study this directly by recording voltage-sensor domain currents in mammalian cells for the first time and measuring the rates of voltage-sensor modification by [2-(trimethylammonium)ethyl] methanethiosulfonate chloride (MTSET). Gating currents recorded from hERG channels expressed in mammalian tsA201 cells using low resistance pipettes show two charge systems, defined as Q(1) and Q(2), with V(1/2)'s of -55.7 (equivalent charge, z = 1.60) and -54.2 mV (z = 1.30), respectively, with the Q(2) charge system carrying approximately two thirds of the overall gating charge. The time constants for charge movement at 0 mV were 2.5 and 36.2 ms for Q(1) and Q(2), decreasing to 4.3 ms for Q(2) at +60 mV, an order of magnitude faster than the time constants of ionic current appearance at these potentials. The voltage and time dependence of Q2 movement closely correlated with the rate of MTSET modification of I521C in the outermost region of the S4 segment, which had a V(1/2) of -64 mV and time constants of 36 ± 8.5 ms and 11.6 ± 6.3 ms at 0 and +60 mV, respectively. Modeling of Q(1) and Q(2) charge systems showed that a minimal scheme of three transitions is sufficient to account for the experimental findings. These data point to activation steps further downstream of voltage-sensor movement that provide the major delays to pore opening in hERG channels.

Characterization and mechanisms of the pharyngeal swallow activated by stimulation of the esophagus

PubMed Central

Medda, Bidyut K.; Jadcherla, Sudarshan R.; Shaker, Reza

2016-01-01

Stimulation of the esophagus activates the pharyngeal swallow response (EPSR) in human infants and animals. The aims of this study were to characterize the stimulus and response of the EPSR and to determine the function and mechanisms generating the EPSR. Studies were conducted in 46 decerebrate cats in which pharyngeal, laryngeal, and esophageal motility was monitored using EMG, strain gauges, or manometry. The esophagus was stimulated by balloon distension or luminal fluid infusion. We found that esophageal distension increased the chance of occurrence of the EPSR, but the delay was variable. The chance of occurrence of the EPSR was related to the position, magnitude, and length of the stimulus in the esophagus. The most effective stimulus was long, strong, and situated in the cervical esophagus. Acidification of the esophagus activated pharyngeal swallows and sensitized the receptors that activate the EPSR. The EPSR was blocked by local anesthesia applied to the esophageal lumen, and electrical stimulation of the recurrent laryngeal nerve caudal to the cricoid cartilage (RLNc) activated the pharyngeal swallow response. We conclude that the EPSR is activated in a probabilistic manner. The receptors mediating the EPSR are probably mucosal slowly adapting tension receptors. The sensory neural pathway includes the RLNc and superior laryngeal nerve. We hypothesize that, because the EPSR is observed in human infants and animals, but not human adults, activation of EPSR is related to the elevated position of the larynx. In this situation, the EPSR occurs rather than secondary peristalsis to prevent supraesophageal reflux when the esophageal bolus is in the proximal esophagus. PMID:27634013

Collapse and Fragmentation Models of Tidally Interacting Molecular Cloud Cores. IV. Initial Slow Rotation and Magnetic Field Support

NASA Astrophysics Data System (ADS)

Sigalotti, Leonardo Di G.; Klapp, Jaime

2000-03-01

Fragmentation has long been advocated as the primary mechanism for explaining the observed binary frequency among pre-main-sequence stars and, more recently, for explaining the emerging evidence for binary and multiple protostellar systems. The role of magnetic fields and ambipolar diffusion is essential to understand how dense cloud cores begin dynamic collapse and eventually fragment into protostars. Here we consider new numerical models of the gravitational collapse and fragmentation of slowly rotating molecular cloud cores, including the effects of magnetic support and ambipolar diffusion. The starting point of the evolution is provided by a magnetically stable (subcritical) condensation that results from adding a magnetic field pressure, B2/8π [with the field strength given by the scaling relation B=B0(ρ/ρ0)1/2], to a reference state consisting of a thermally supercritical (α~0.36), slowly rotating (β~0.037), Gaussian cloud core of prolate shape and central density ρ0. The effects of ambipolar diffusion are approximated by allowing the reference field strength B0 to gradually decrease over a timescale of 10 free-fall times. The models also include the effects of tidal interaction due to a gravitational encounter with another protostar, and so they may apply to low-mass star formation within a cluster-forming environment. The results indicate that the magnetic forces delay the onset of dynamic collapse, and hence of fragmentation, by an amount of time that depends on the initial central mass-to-flux ratio. Compared with previous magnetic collapse calculations of rapidly rotating (β=0.12) clouds, lower initial rotation (β~0.037) is seen to result in much shorter delay periods, thus anticipating binary fragmentation. In general, the results show that the models are still susceptible to fragment into binary systems. Intermediate magnetic support (η~0.285) and low tidal forces (τ<~0.201) may lead to final triple or quadruple protostellar systems, while increasing the size of η and τ always results in final binary protostellar cores. The formed binary systems have separations of ~200-350 AU, suggesting that the recently observed peaks around ~90 AU and 215 AU for T Tauri stars may be explained by the collapse and fragmentation of initially slowly rotating magnetic cloud cores with β<~0.04.

Quantifying fluorescence enhancement for slowly diffusing single molecules in plasmonic near fields

NASA Astrophysics Data System (ADS)

Caldarola, Martín; Pradhan, Biswajit; Orrit, Michel

2018-03-01

Gold nanorods are extensively used for single-molecule fluorescence enhancement as they are easy to synthesize, bio-compatible, and provide high light confinement at their nanometer-sized tips. The current way to estimate fluorescence enhancement relies on binned time traces or on fluorescence correlation spectroscopy. We report on novel ways to extract the enhancement factor in a single-molecule enhancement experiment, avoiding the arbitrary selection of one or a few high-intensity burst(s). These new estimates for the enhancement factor make use of the whole distribution of intensity bursts or of the interphoton delay distribution, which avoids the arbitrary binning of the fluorescence intensity time traces. We present experimental results on the bi-dimensional case, experimentally achieved using a lipid bilayer to support the diffusion of fluorophores. We support our findings with histograms of fluorescence bursts and with an analytical derivation of the interphoton delay distribution of (nearly) immobilized emitters from the fluorescence intensity profile.

Characterization of slowly inactivating KV{alpha} current in rabbit pulmonary neuroepithelial bodies: effects of hypoxia and nicotine.

PubMed

Fu, Xiao Wen; Nurse, Colin; Cutz, Ernest

2007-10-01

Pulmonary neuroepithelial bodies (NEB) form innervated cell clusters that express voltage-activated currents and function as airway O(2) sensors. We investigated A-type K(+) currents in NEB cells using neonatal rabbit lung slice preparation. The whole cell K(+) current was slowly inactivating with activation threshold of approximately -30 mV. This current was blocked approximately 27% by blood-depressing substance I (BDS-I; 3 microM), a selective blocker of Kv3.4 subunit, and reduced approximately 20% by tetraethylammonium (TEA; 100 microM). The BDS-I-sensitive component had an average peak value of 189 +/- 14 pA and showed fast inactivation kinetics that could be fitted by one-component exponential function with a time constant of (tau1) 77 +/- 10 ms. This Kv slowly inactivating current was also blocked by heteropodatoxin-2 (HpTx-2; 0.2 microM), a blocker of Kv4 subunit. The HpTx-2-sensitive current had an average peak value of 234 +/- 23 pA with a time constant (tau) 82 +/- 11 ms. Hypoxia (Po(2) = 15-20 mmHg) inhibited the slowly inactivating K(+) current by approximately 47%, during voltage steps from -30 to +30 mV, and no further inhibition occurred when TEA was combined with hypoxia. Nicotine at concentrations of 50 and 100 microM suppressed the slowly inactivating K(+) current by approximately 24 and approximately 40%, respectively. This suppression was not reversed by mecamylamine suggesting a direct effect of nicotine on these K(+) channels. In situ hybridization experiments detected expression of mRNAs for Kv3.4 and Kv4.3 subunits, while double-label immunofluorescence confirmed membrane localization of respective channel proteins in NEB cells. These studies suggest that the hypoxia-sensitive current in NEB cells is carried by slowly inactivating A-type K(+) channels, which underlie their oxygen-sensitive potassium currents, and that exposure to nicotine may directly affect their function, contributing to smoking-related lung disease.

Multichannel heterodyning for wideband interferometry, correlation and signal processing

DOEpatents

Erskine, David J.

1999-01-01

A method of signal processing a high bandwidth signal by coherently subdividing it into many narrow bandwidth channels which are individually processed at lower frequencies in a parallel manner. Autocorrelation and correlations can be performed using reference frequencies which may drift slowly with time, reducing cost of device. Coordinated adjustment of channel phases alters temporal and spectral behavior of net signal process more precisely than a channel used individually. This is a method of implementing precision long coherent delays, interferometers, and filters for high bandwidth optical or microwave signals using low bandwidth electronics. High bandwidth signals can be recorded, mathematically manipulated, and synthesized.

Multichannel heterodyning for wideband interferometry, correlation and signal processing

DOEpatents

Erskine, D.J.

1999-08-24

A method is disclosed of signal processing a high bandwidth signal by coherently subdividing it into many narrow bandwidth channels which are individually processed at lower frequencies in a parallel manner. Autocorrelation and correlations can be performed using reference frequencies which may drift slowly with time, reducing cost of device. Coordinated adjustment of channel phases alters temporal and spectral behavior of net signal process more precisely than a channel used individually. This is a method of implementing precision long coherent delays, interferometers, and filters for high bandwidth optical or microwave signals using low bandwidth electronics. High bandwidth signals can be recorded, mathematically manipulated, and synthesized. 50 figs.

Cat scratch disease of the eye: a case report and literature review.

PubMed

Alaan, Kristina; Fisher, Melanie; Ellis, Brian

2014-01-01

This is the case of a middle-aged male with no other medical issues who presented with acute, unilateral visual disturbance. In lieu of specific ophthalmologic findings, his age and presentation, he was treated for presumed inflammatory process. It was only after steroids and the results of serological testing that an infectious agent was determined. He was eventually diagnosed with ocular Bartonellosis. He was treated with oral doxycycline and rifampin and slowly improved. The thesis of this case report is that a thorough history prior to rapid and somewhat presumptive treatment may have prevented unnecessary immunosuppression and delay in appropriate antimicrobial therapy.

Fast activation of dihydropyridine-sensitive calcium channels of skeletal muscle. Multiple pathways of channel gating

PubMed Central

1996-01-01

Dihydropyridine (DHP) receptors of the transverse tubule membrane play two roles in excitation-contraction coupling in skeletal muscle: (a) they function as the voltage sensor which undergoes fast transition to control release of calcium from sarcoplasmic reticulum, and (b) they provide the conducting unit of a slowly activating L-type calcium channel. To understand this dual function of the DHP receptor, we studied the effect of depolarizing conditioning pulse on the activation kinetics of the skeletal muscle DHP-sensitive calcium channels reconstituted into lipid bilayer membranes. Activation of the incorporated calcium channel was imposed by depolarizing test pulses from a holding potential of -80 mV. The gating kinetics of the channel was studied with ensemble averages of repeated episodes. Based on a first latency analysis, two distinct classes of channel openings occurred after depolarization: most had delayed latencies, distributed with a mode of 70 ms (slow gating); a small number of openings had short first latencies, < 12 ms (fast gating). A depolarizing conditioning pulse to +20 mV placed 200 ms before the test pulse (-10 mV), led to a significant increase in the activation rate of the ensemble averaged-current; the time constant of activation went from tau m = 110 ms (reference) to tau m = 45 ms after conditioning. This enhanced activation by the conditioning pulse was due to the increase in frequency of fast open events, which was a steep function of the intermediate voltage and the interval between the conditioning pulse and the test pulse. Additional analysis demonstrated that fast gating is the property of the same individual channels that normally gate slowly and that the channels adopt this property after a sojourn in the open state. The rapid secondary activation seen after depolarizing prepulses is not compatible with a linear activation model for the calcium channel, but is highly consistent with a cyclical model. A six- state cyclical model is proposed for the DHP-sensitive Ca channel, which pictures the normal pathway of activation of the calcium channel as two voltage-dependent steps in sequence, plus a voltage-independent step which is rate limiting. The model reproduced well the fast and slow gating models of the calcium channel, and the effects of conditioning pulses. It is possible that the voltage-sensitive gating transitions of the DHP receptor, which occur early in the calcium channel activation sequence, could underlie the role of the voltage sensor and yield the rapid excitation-contraction coupling in skeletal muscle, through either electrostatic or allosteric linkage to the ryanodine receptors/calcium release channels. PMID:8882865

[Clinico-psychological features of patients with favorable outcomes of slowly-progressive juvenile schizophrenia].

PubMed

Tsutsul'kovskaia, M Ia; Bil'zho, A G; Kritskaia, V P; Meleshko, T K

1986-01-01

A follow-up study of patients with favourable outcomes of juvenile slowly progressing schizophrenia at the level of clinical cure (n = 84) revealed a number of clinical characteristics in the pattern of personality changes which correlated with a high level of the patients' social and occupational adaptation. The authors also determined external factors contributing to the achievement and stabilization of the "clinical cure" status. An experimental and psychological examination of these patients revealed finer mechanisms contributing to their social adaptation. These are high motivation of activities, compliance with social norms, a high level of voluntary regulation of activity and self-regulation, as well as the ability to overcome autistic trends in situations of interpersonal activities and cooperation.

Design and evaluation of bilayered buccal film preparations for local administration of lidocaine hydrochloride.

PubMed

Preis, Maren; Woertz, Christina; Schneider, Katharina; Kukawka, Jennifer; Broscheit, Jens; Roewer, Norbert; Breitkreutz, Jörg

2014-04-01

Bilayered oromucosal film preparations (buccal films) offer a promising way to enable drug administration via the oral cavity. Adding a non-soluble or slowly eroding/dissolving backing layer to a mucoadhesive drug-loaded layer enables unidirectional drug delivery. The aim of this study was to investigate different approaches to the manufacture of bilayered films and to examine their properties by applying different characterization methods including an optimized experimental setup for the study of drug release from bilayered films. A solvent suitability study was performed screening over 15 polymers with respect to their feasibility for viscous film formation for film preparation by solvent casting method. Two methods (double-casting and pasting) were found as suitable methods for bilayered film manufacturing. Results from drug release experiments indicated that slowly eroding hypromellose backing layer films revealed the best shielding of the drug-loaded layer to enable unidirectional drug release. In summary, manufacturing of bilayered films using the described methods was feasible. Furthermore, the use of an optimized experimental setup for drug dissolution studies enabled monitoring of drug release without delays in sampling. Copyright © 2014 Elsevier B.V. All rights reserved.

Methyl bromide fumigation and delayed mortality: safe trade of live pests?

PubMed

Phillips, C B; Iline, I I; Novoselov, M; McNeill, M R; Richards, N K; van Koten, C; Stephenson, B P

Live organisms intercepted from treated commodities during phytosanitary inspections usually arouse suspicions of treatment failure, sub-standard treatment application, or post-treatment infestation. The additional possibility that some treatments could kill slowly, meaning commodities might be inspected before pests have succumbed, is seldom considered for treatments other than irradiation. We used a novel biochemical viability assay to measure delays between methyl bromide fumigation and mortality of dipteran eggs, and evaluated the correspondence between egg viability and egg morphological features. Our experimental conditions simulated shipping of rock melons from Australia to New Zealand by sea and air. No eggs survived fumigation, but they took 3-20 days to die, whereas phytosanitary inspections of rock melons occur within 2-7 days. Delays were not influenced by methyl bromide concentration, but were significantly lengthened by cooler storage temperatures. Methyl bromide's preservative effects delayed degradation of egg morphology, so the biochemical assay detected mortality long before morphological signs of egg death appeared. The results show that commodities subjected to effective methyl bromide treatments are at risk of being inspected before all pests have either died, or started to exhibit morphological signs of death. This could cause commodities to be unnecessarily rejected by quarantine authorities. Better methods than inspection for live pests are needed to assist authorities to gain assurance that treated commodities have been effectively disinfested. These could be developed by exploiting biochemical responses of pests and commodities to treatments.

The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin

PubMed Central

Broad, John; Sanger, Gareth J

2013-01-01

Background and Purpose The antibiotic azithromycin is a suggested alternative to erythromycin for treating patients with delayed gastric emptying. However, although hypothesized to activate motilin receptors, supportive evidence is unavailable. This was investigated using recombinant and naturally expressed motilin receptors in human stomach, comparing azithromycin with erythromycin. Experimental Approach [125I]-motilin binding and calcium flux experiments were conducted using human recombinant motilin receptors in CHO cells. Neuromuscular activities were studied using circular muscle of human gastric antrum, after electrical field stimulation (EFS) of intrinsic nerves. Key Results Azithromycin (1–100 μM) and erythromycin (3–30 μM) concentration-dependently displaced [125I]-motilin binding to the motilin receptor (52 ± 7 and 58 ± 18% displacement at 100 and 30 μM respectively). Azithromycin, erythromycin and motilin concentration-dependently caused short-lived increases in intracellular [Ca2+] in cells expressing the motilin receptor. EC50 values were, respectively, 2.9, 0.92 and 0.036 μM (n = 3 each); and maximal activities were similar. In human stomach, EFS evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. Azithromycin and erythromycin lactobionate (30–300 μM each) facilitated these contractions (apparent Emax values of 2007 ± 396 and 1924 ± 1375%, n = 3–4 each concentration, respectively). These actions were slow in onset and faded slowly. The higher concentrations also evoked short-lived muscle contraction. Contractions to a submaximally effective concentration of carbachol were unaffected by either drug. Conclusions and Implications Azithromcyin activates human recombinant motilin receptors in therapeutically relevant concentrations, similar to erythromycin. In humans, gastric antrum azithromycin caused long-lasting facilitation of cholinergic activity. These actions explain the gastric prokinetic activity of azithromycin. PMID:23190027

Direct negative chronotropic action of desflurane on sinoatrial node pacemaker activity in the guinea pig heart.

PubMed

Kojima, Akiko; Ito, Yuki; Kitagawa, Hirotoshi; Matsuura, Hiroshi; Nosaka, Shuichi

2014-06-01

Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct effects of desflurane on electrical activity of sinoatrial node pacemaker cells that determines the intrinsic heart rate. Whole-cell patch-clamp experiments were conducted on guinea pig sinoatrial node pacemaker cells to record spontaneous action potentials and ionic currents contributing to sinoatrial node automaticity, namely, hyperpolarization-activated cation current (If), T-type and L-type Ca currents (ICa,T and ICa,L, respectively), Na/Ca exchange current (INCX), and rapidly and slowly activating delayed rectifier K currents (IKr and IKs, respectively). Electrocardiograms were recorded from ex vivo Langendorff-perfused hearts and in vivo hearts. Desflurane at 6 and 12% decreased spontaneous firing rate of sinoatrial node action potentials by 15.9% (n = 11) and 27.6% (n = 10), respectively, which was associated with 20.4% and 42.5% reductions in diastolic depolarization rate, respectively. Desflurane inhibited If, ICa,T, ICa,L, INCX, and IKs but had little effect on IKr. The negative chronotropic action of desflurane was reasonably well reproduced in sinoatrial node computer model. Desflurane reduced the heart rate in Langendorff-perfused hearts. High concentration (12%) of desflurane inhalation was associated with transient tachycardia, which was totally abolished by pretreatment with the β-adrenergic blocker propranolol. Desflurane has a direct negative chronotropic action on sinoatrial node pacemaking activity, which is mediated by its inhibitory action on multiple ionic currents. This direct inhibitory action of desflurane on sinoatrial node automaticity seems to be counteracted by sympathetic activation associated with desflurane inhalation in vivo.

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

Teicher, B.A.; Holden, S.A.; Northey, D.

The perfluorochemical emulsion Fluosol-DA plus carbogen breathing has been shown to increase the effectiveness of radiation therapy in preclinical solid tumors when the emulsion was administered by i.v. bolus injection. Much of the enhancement in tumor radiation response was lost when the emulsion was administered slowly. The authors hypothesized that an increase in tumor perfusion resulted when Fluosol-DA was administered rapidly. In the present study, the [alpha]/[beta] agonist ephedrine, the Ca[sup 2+] channel blocker flunarizine and the nitric oxide producing vasodilating drug nitroprusside have been tested. Ephedrine administration resulted in a decrease in the radiation plus Fluosol-DA [+-] carbogen antitumormore » effects in both the Lewis lung carcinoma and FSaIIC tumor systems. In contrast, flunarizine administration resulted in an increase in the efficacy of the radiation plus carbogen and the radiation plus Fluosol-DA/carbogen in both emulsion was given rapidly. Even with flunarizine administration Fluosol-DA delivered slowly was less effective than when the emulsion was given rapidly. Flunarizine with Fluosol-DA infused i.v. over 30 min followed by carbogen breathing prior to and during radiation therapy resulted in a 1.7-1.6-fold increase in response compared with 2.4-2.2-fold with Fluosol-DA administered by injection i.v. and carbogen breathing prior to and during radiation therapy using growth delay of the Lewis lung carcinoma. The effects of nitroprusside were complex. This drug had considerably more effect at 10 Gy than at higher radiation doses. These studies suggest that Fluosol-DA given by i.v. injection may increase tumor perfusion and that a drug like flunarizine may be beneficial if the Fluosol-DA is administered slowly followed by carbogen breathing and radiation therapy. 45 refs., 4 figs.« less

Direct space-time observation of pulse tunneling in an electromagnetic band gap

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

Doiron, Serge; Hache, Alain; Winful, Herbert G.

2007-08-15

We present space-time-resolved measurements of electromagnetic pulses tunneling through a coaxial electromagnetic band gap structure. The results show that during the tunneling process the field distribution inside the barrier is an exponentially decaying standing wave whose amplitude increases and decreases as it slowly follows the temporal evolution of the input pulse. At no time is a pulse maximum found inside the barrier, and hence the transmitted peak is not the incident peak that has propagated to the exit. The results support the quasistatic interpretation of tunneling dynamics and confirm that the group delay is not the traversal time of themore » input pulse peak.« less

Optical emission spectroscopy as a tool for the biodistribution investigation of cobalt-ferrite nanoparticles in mice

NASA Astrophysics Data System (ADS)

Kückelhaus, S.; Tedesco, A. C.; Oliveira, D. M.; Morais, P. C.; Boaventura, G. R.; Lacava, Z. G. M.

2005-05-01

This study reports on the biodistribution investigation of two magnetic samples both based on cobalt-ferrite nanoparticles, a magnetic fluid sample (CoMF) and a stealth magnetoliposome polyethylene glycol-monolaurate (PEG-ML). Morphology observations and iron and cobalt concentrations were evaluated after treatment of mice upon intravenous injection. Both magnetic samples had an extended distribution throughout all investigated organs. CoMF was quickly eliminated mainly by the fecal via whereas PEG-ML was retained longer in the circulation and slowly eliminated. These differences are probably due to the presence of polyethylene glycol on the PEG-ML surface, recognized to be responsible for the internalization delay of nanoparticles.

Effect of background colour on growth and adhesion strength of Ulva sporelings.

PubMed

Finlay, John A; Fletcher, Benjamin R; Callow, Maureen E; Callow, James A

2008-01-01

This study examined the effects of a range of black, grey and white substrata on the growth and attachment strength of Ulva sporelings on glass and polydimethylsiloxane (Silastic-T2) surfaces. The rate of development of sporelings was strongly influenced by the colour of the substratum on which they grew. On black backgrounds, sporelings grew slowly and germination was delayed. Laboratory screening methods for antifouling and fouling-release coatings that rely on the growth of Ulva sporelings can be compromised if samples are of different colours. Hydrodynamic removal of sporelings from coatings may also be affected by substratum colour, since smaller plants generate lower hydrodynamic forces making them more difficult to remove.

Should soil testing services measure soil biological activity

USDA-ARS?s Scientific Manuscript database

Health of agricultural soils depends largely on conservation management to promote soil organic C accumulation. Total soil organic C changes slowly, but active fractions are more dynamic. A key indicator of healthy soil is potential biological activity, which could be measured rapidly with soil te...

Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

PubMed Central

Liu, Pin W.

2014-01-01

Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

Early and late components of EEG delay activity correlate differently with scene working memory performance

PubMed Central

Ng, Kenneth; Reichert, Chelsea P.

2017-01-01

Sustained and elevated activity during the working memory delay period has long been considered the primary neural correlate for maintaining information over short time intervals. This idea has recently been reinterpreted in light of findings generated from multiple neural recording modalities and levels of analysis. To further investigate the sustained or transient nature of activity, the temporal-spectral evolution (TSE) of delay period activity was examined in humans with high density EEG during performance of a Sternberg working memory paradigm with a relatively long six second delay and with novel scenes as stimuli. Multiple analyses were conducted using different trial window durations and different baseline periods for TSE computation. Sensor level analyses revealed transient rather than sustained activity during delay periods. Specifically, the consistent finding among the analyses was that high amplitude activity encompassing the theta range was found early in the first three seconds of the delay period. These increases in activity early in the delay period correlated positively with subsequent ability to distinguish new from old probe scenes. Source level signal estimation implicated a right parietal region of transient early delay activity that correlated positively with working memory ability. This pattern of results adds to recent evidence that transient rather than sustained delay period activity supports visual working memory performance. The findings are discussed in relation to synchronous and desynchronous intra- and inter-regional neural transmission, and choosing an optimal baseline for expressing temporal-spectral delay activity change. PMID:29016657

Supply chain risk management of newspaper industry: A quantitative study

NASA Astrophysics Data System (ADS)

Sartika, Viny; Hisjam, Muh.; Sutopo, Wahyudi

2018-02-01

The newspaper industry has several distinctive features that make it stands out from other industries. The strict delivery deadline and zero inventory led to a very short time frame for production and distribution. On the other hand, there is pressure from the newsroom to encourage the start of production as slowly as possible in order to enter the news, while there is pressure from production and distribution to start production as early as possible. Supply chain risk management is needed in determining the best strategy for dealing with possible risks in the newspaper industry. In a case study of a newspaper in Surakarta, quantitative approaches are made to the newspaper supply chain risk management by calculating the expected cost of risk based on the magnitude of the impact and the probability of a risk event. From the calculation results obtained that the five risks with the highest value are newspaper delays to the end customer, broken plate, miss print, down machine, and delayed delivery of newspaper content. Then analyzed appropriate mitigation strategies to cope with such risk events.

MRS evidence of adequate O2 supply in human skeletal muscle at the onset of exercise

PubMed Central

Richardson, Russell S.; Wary, Claire; Wray, D. Walter; Hoff, Jan; Rossiter, Harry; Layec, Gwenael; Carlier, Pierre G.

2015-01-01

Purpose At exercise onset, intramuscular oxidative energy production responds relatively slowly in comparison to the change in ATP demand. To determine if the slow kinetics of oxidative ATP production is due to inadequate O2 supply or metabolic inertia we studied the kinetics of intramyocellular deoxygenation (deoxy-myoglobin, Mb) and metabolism (phosphocreatine, PCr), using proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) in 6 healthy subjects (33 ± 5 yrs). Methods Specifically, utilizing dynamic plantar flexion exercise, rest to exercise and recovery was assessed at both 60% of maximum work rate (WRmax) (moderate intensity) and 80% of WRmax (heavy intensity). Results At exercise onset [PCr] fell without delay and with a similar time constant (τ) at both exercise intensities (~33 s). In contrast, the increase in deoxy-Mb was delayed at exercise onset by 5–7 s, after which it increased with kinetics (moderate τ = 37 ± 9 s, and heavy τ = 29 ± 6 s) that were not different from τPCr (p > 0.05). At cessation, deoxy-Mb recovered without a time delay and more rapidly (τ ~20 s) than PCr (τ ~33 s) (p < 0.05). Conclusion using a unique combination of in vivo MRS techniques with high time-resolution, this study revealed a delay in intramuscular de-oxygenation at the onset of exercise, and rapid re-oxygenation kinetics upon cessation. Together these data imply that intramuscular substrate-enzyme interactions, and not O2 availability, determine the exercise onset kinetics of oxidative metabolism in healthy human skeletal muscle. PMID:25830362

Lessons learned about spaceflight and cell biology experiments

NASA Technical Reports Server (NTRS)

Hughes-Fulford, Millie

2004-01-01

Conducting cell biology experiments in microgravity can be among the most technically challenging events in a biologist's life. Conflicting events of spaceflight include waiting to get manifested, delays in manifest schedules, training astronauts to not shake your cultures and to add reagents slowly, as shaking or quick injection can activate signaling cascades and give you erroneous results. It is important to select good hardware that is reliable. Possible conflicting environments in flight include g-force and vibration of launch, exposure of cells to microgravity for extended periods until hardware is turned on, changes in cabin gases and cosmic radiation. One should have an on-board 1-g control centrifuge in order to eliminate environmental differences. Other obstacles include getting your funding in a timely manner (it is not uncommon for two to three years to pass between notification of grant approval for funding and actually getting funded). That said, it is important to note that microgravity research is worthwhile since all terrestrial life evolved in a gravity field and secrets of biological function may only be answered by removing the constant of gravity. Finally, spaceflight experiments are rewarding and worth your effort and patience.

Intrinsic Astrocyte Heterogeneity Influences Tumor Growth in Glioma Mouse Models.

PubMed

Irvin, David M; McNeill, Robert S; Bash, Ryan E; Miller, C Ryan

2017-01-01

The influence of cellular origin on glioma pathogenesis remains elusive. We previously showed that mutations inactivating Rb and Pten and activating Kras transform astrocytes and induce tumorigenesis throughout the adult mouse brain. However, it remained unclear whether astrocyte subpopulations were susceptible to these mutations. We therefore used genetic lineage tracing and fate mapping in adult conditional, inducible genetically engineered mice to monitor transformation of glial fibrillary acidic protein (GFAP) and glutamate aspartate transporter (GLAST) astrocytes and immunofluorescence to monitor cellular composition of the tumor microenvironment over time. Because considerable regional heterogeneity exists among astrocytes, we also examined the influence of brain region on tumor growth. GFAP astrocyte transformation induced uniformly rapid, regionally independent tumor growth, but transformation of GLAST astrocytes induced slowly growing tumors with significant regional bias. Transformed GLAST astrocytes had reduced proliferative response in culture and in vivo and malignant progression was delayed in these tumors. Recruited glial cells, including proliferating astrocytes, oligodendrocyte progenitors and microglia, were the majority of GLAST, but not GFAP astrocyte-derived tumors and their abundance dynamically changed over time. These results suggest that intrinsic astrocyte heterogeneity, and perhaps regional brain microenvironment, significantly contributes to glioma pathogenesis. © 2016 International Society of Neuropathology.

Accelerated long-term forgetting in children with temporal lobe epilepsy.

PubMed

Gascoigne, Michael B; Smith, Mary Lou; Barton, Belinda; Webster, Richard; Gill, Deepak; Lah, Suncica

2014-07-01

Adults with temporal lobe epilepsy (TLE) have been found to have accelerated long-term forgetting, but this phenomenon has not yet been investigated in children. Although deficits in recall of materials after short (20- to 30-minute) delays have been shown to slowly emerge from childhood to adolescence in patients with TLE, it is unknown whether such a trend will also be found in recall of materials after long delays. This study examined the presence of accelerated long-term forgetting in children with TLE and how it relates to chronological age. Twenty-three children with TLE and 58 healthy controls of similar age, sex distribution and socioeconomic status completed a battery of neuropsychological tests, including standardised tests of story recall and design location, as well as two experimental tests requiring the learning of words and design locations to a criterion, both of which assessed recall after short (30-min) and long (7-day) delays. Word recall at the 7-day delay (relative to the 30-min recall) was significantly poorer in the TLE group, compared to the control group. The TLE group also exhibited worse 30-min recall performance on a standardised test of story recall. Individual patient analyses revealed dissociation between performance on the experimental and standardised verbal memory tests; children who were impaired on the experimental test (7-day delay) were not impaired on the standardised test (30-min delay). Compared to controls, patients with a left-hemisphere seizure focus recalled fewer words at short and long delays while patients with an abnormal hippocampus recalled fewer words at the long delay. No between-group differences were found with respect to the design location task. Age negatively correlated with the recall of words after short- and long-term delays within the TLE group, where older age was associated with worse memory. This association was not present in the control group. To our knowledge, this is the first study to show evidence of accelerated long-term forgetting in children with TLE, which could not be explained by poor performance on standardised memory tests. Additionally, these results suggest that the developmental trajectory of long-term memory in children with TLE is similar to that of short-term memory: deficits emerge gradually, therefore older children are more likely to present with long-term memory deficits. Copyright © 2014 Elsevier Ltd. All rights reserved.

Feeding ecology and development of juvenile black ducks in Maine

USGS Publications Warehouse

Reinecke, Kenneth J.

1979-01-01

Data from 41 juvenile Black Ducks (Anas rubripes) collected in the Penobscot River valley of Maine from June through August 1974-76 were used to estimate the proportion of aquatic invertebrates in the prefledging diet and the allometric growth rates of the tarsi, flight muscles, and alimentary system. The proportion of aquatic invertebrates in the diet of downy and partially feathered juveniles averaged 88 and 91% of dry weight, but decreased to 43% for fully feathered young. The most important invertebrate food organisms for juvenile Black Ducks were asellid isopods, molluscs, nymphs of Ephemeroptera and Odonata, and larvae of Coleoptera, Trichoptera, and Diptera. A high proportion of invertebrates was consumed during the period of fastest absolute and relative growth. Estimation of allometric growth rates with the power formula (Y = a·$X_{b}$) showed that (1) the legs were relatively large at hatching and developed slowly; (2) the flight muscles, which were relatively small at hatching, grew slowly until the 4-week period preceding fledging, when they increased as the 4.75 power of body weight; and (3) growth of the liver and gizzard was approximately proportional to body weight. The data support Ricklefs' thesis that delayed functional maturity of the wings permits an increase in the overall growth rate of waterfowl.

Calcium currents in a fast-twitch skeletal muscle of the rat.

PubMed

Donaldson, P L; Beam, K G

1983-10-01

Slow ionic currents were measured in the rat omohyoid muscle with the three-microelectrode voltage-clamp technique. Sodium and delayed rectifier potassium currents were blocked pharmacologically. Under these conditions, depolarizing test pulses elicited an early outward current, followed by a transient slow inward current, followed in turn by a late outward current. The early outward current appeared to be a residual delayed rectifier current. The slow inward current was identified as a calcium current on the basis that (a) its magnitude depended on extracellular calcium concentration, (b) it was blocked by the addition of the divalent cations cadmium or nickel, and reduced in magnitude by the addition of manganese or cobalt, and (c) barium was able to replace calcium as an inward current carrier. The threshold potential for inward calcium current was around -20 mV in 10mM extracellular calcium and about -35 mV in 2 mM calcium. Currents were net inward over part of their time course for potentials up to at least +30 mV. At temperatures of 20-26 degrees C, the peak inward current (at approximately 0 mV) was 139 +/- 14 microA/cm2 (mean +/- SD), increasing to 226 +/- 28 microA/cm2 at temperatures of 27-37 degrees C. The late outward current exhibited considerable fiber-to-fiber variability. In some fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it appeared to be the sum of both leak and a slowly activated outward current. The rate of activation of inward calcium current was strongly temperature dependent. For example, in a representative fiber, the time-to-peak inward current for a +10-mV test pulse decreased from approximately 250 ms at 20 degrees C to 100 ms at 30 degrees C. At 37 degrees C, the time-to-peak current was typically approximately 25 ms. The earliest phase of activation was difficult to quantify because the ionic current was partially obscured by nonlinear charge movement. Nonetheless, at physiological temperatures, the rate of calcium channel activation in rat skeletal muscle is about five times faster than activation of calcium channels in frog muscle. This pathway may be an important source of calcium entry in mammalian muscle.

On-resonance Variable Delay Multi Pulse Scheme for Imaging of Fast-exchanging Protons and semi-solid Macromolecules

PubMed Central

Xu, Jiadi; Chan, Kannie W.Y.; Xu, Xiang; Yadav, Nibhay; Liu, Guanshu; van Zijl, Peter C. M.

2016-01-01

Purpose To develop an on-resonance variable delay multi-pulse (VDMP) scheme to image magnetization transfer contrast (MTC) as well as the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above about 1 kHz. Methods A train of high power binomial pulses was applied at the water resonance. The inter-pulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions due to their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T2 components in MTC and separated out using a variable mixing time. Results Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA) and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method showing strong gray/white matter contrast for the slowly transferring MTC protons while the TFP map was more uniform across the brain but somewhat higher in gray matter. Conclusions The new method provides a simple way of imaging fast-exchanging protons, as well as MTC components with a slow transfer rate. PMID:26900759

Delayed Rapid Response Team Activation Is Associated With Increased Hospital Mortality, Morbidity, and Length of Stay in a Tertiary Care Institution.

PubMed

Barwise, Amelia; Thongprayoon, Charat; Gajic, Ognjen; Jensen, Jeffrey; Herasevich, Vitaly; Pickering, Brian W

2016-01-01

To identify whether delays in rapid response team activation contributed to worse patient outcomes (mortality and morbidity). Retrospective observational cohort study including all rapid response team activations in 2012. Tertiary academic medical center. All those 18 years old or older who had a rapid response team call activated. Vital sign data were abstracted from individual patient electronic medical records for the 24 hours before the rapid response team activation took place. Patients were considered to have a delayed rapid response team activation if more than 1 hour passed between the first appearance in the record of an abnormal vital sign meeting rapid response team criteria and the activation of an rapid response team. None. A total of 1,725 patients were included in the analysis. Data were compared between those who had a delayed rapid response team activation and those who did not. Fifty seven percent patients met the definition of delayed rapid response team activation. Patients in high-frequency physiologic monitored environments were more likely to experience delay than their floor counterparts. In the no-delay group, the most common reasons for rapid response team activation were tachycardia/bradycardia at 29% (217/748), respiratory distress/low SpO2 at 28% (213/748), and altered level of consciousness at 23% (170/748) compared with respiratory distress/low SpO2 at 43% (423/977), tachycardia/bradycardia at 33% (327/977), and hypotension at 27% (261/977) in the delayed group. The group with no delay had a higher proportion of rapid response team calls between 8:00 and 16:00, whereas those with delay had a higher proportion of calls between midnight and 08:00. The delayed group had higher hospital mortality (15% vs 8%; adjusted odds ratio, 1.6; p = 0.005); 30-day mortality (20% vs 13%; adjusted odds ratio, 1.4; p = 0.02); and hospital length of stay (7 vs 6 d; relative prolongation, 1.10; p = 0.02) compared with the no-delay group. Delays in rapid response team activation occur frequently and are independently associated with worse patient mortality and morbidity outcomes.

Mnemonic neuronal activity in somatosensory cortex.

PubMed Central

Zhou, Y D; Fuster, J M

1996-01-01

Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory. PMID:8927629

Irreparable Radial Nerve Palsy Due to Delayed Diagnostic Management of a Giant Lipoma at the Proximal Forearm Resulting in a Triple Tendon Transfer Procedure: Case report and Brief Review of Literature

PubMed Central

Schmidt, Ingo

2017-01-01

Background: Non-traumatic radial nerve palsy (RNP) caused by local tumors is a rare and uncommon entity. Methods: A 62-year-old female presented with a left non-traumatic RNP, initially starting with weakness only. It was caused by a benign giant lipoma at the proximal forearm that was misdiagnosed over a period of 2 years. The slowly growth of the tumor led to an irreparable overstretching-related partial nerve disruption. For functional recovery of the patient, a triple tendon transfer procedure had to be performed. Results: Four months after surgery, the patient was completely able to perform her activities of daily living again. At the 10-months follow-up, strength of wrist extension, thumb's extension and abduction, and long fingers II-V extension had all improved to grade 4 in Medical Research Council scale (0-5). In order to restore motion, the patient reported that she would undergo the same triple tendon transfer procedure a second time where necessary. Due to the initially misdiagnosed tumor, there was an overall delayed duration of time for functional recovery of the patient. Conclusion: The triple tendon transfer procedure offers a useful and reliable method to restore functionality for patients sustaining irreparable RNP. However, it must be noted critically with our patient that this procedure probably would have been avoided. Initially, there was weakness only by entrapment of the radial nerve. RNP caused by local tumors are uncommon but known from the literature, and so it should be considered generally in differential diagnosis of non-traumatic RNP. PMID:28979592

Non-target organism effects tests on Vip3A and their application to the ecological risk assessment for cultivation of MIR162 maize.

PubMed

Raybould, Alan; Vlachos, Demetra

2011-06-01

Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) provide economic, environmental and health benefits by maintaining or increasing crop yields with fewer applications of insecticide. To sustain these benefits, it is important to delay the evolution of insect resistance to the proteins, and to ensure that the proteins do not harm non-target organisms, particularly those that may control secondary pests that would otherwise flourish because of reduced insecticide applications. Vip3A is a Bt vegetative insecticidal protein that is active against lepidopterous pests. It has a different mode of action from other proteins for control of Lepidoptera in current Bt crops, and when combined with these proteins, it should help to delay the evolution of pest resistance to Bt crops. This paper presents data on the effects of Vip3A on non-target organisms, and an ecological risk assessment of MIR162 maize, which expresses Vip3Aa20. Laboratory studies indicate few adverse effects of Vip3A to non-target organisms: 11 of 12 species tested showed no adverse effects when exposed to high concentrations of Vip3A relative to estimated exposures resulting from cultivation of MIR162 maize. Daphnia magna exposed to Vip3Aa20 were unaffected in terms of survival or fecundity, but grew slightly more slowly than unexposed controls. The data indicate that cultivation of MIR162 maize poses negligible risk to non-target organisms, and that crops producing Vip3A are unlikely to adversely affect biological control organisms such that benefits from reduced insecticide applications are lost.

Inhibitory effects of sevoflurane on pacemaking activity of sinoatrial node cells in guinea-pig heart

PubMed Central

Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi

2012-01-01

BACKGROUND AND PURPOSE The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms. EXPERIMENTAL APPROACH Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (If), T-type and L-type Ca2+ currents (ICa,T and ICa,L, respectively), and slowly activating delayed rectifier K+ current (IKs), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation. KEY RESULTS In isolated SA node cells, sevoflurane (0.12–0.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased If, ICa,T, ICa,L and IKs by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs. CONCLUSIONS AND IMPLICATIONS Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on If, ICa,T and ICa,L. These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings. PMID:22356456

Probing the molecular mechanism of action of the HIV-1 reverse transcriptase inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) using pre-steady-state kinetics.

PubMed

Muftuoglu, Yagmur; Sohl, Christal D; Mislak, Andrea C; Mitsuya, Hiroaki; Sarafianos, Stefan G; Anderson, Karen S

2014-06-01

The novel antiretroviral 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a potent nucleoside HIV-1 reverse transcriptase (RT) inhibitor (NRTI). Unlike other FDA-approved NRTIs, EFdA contains a 3'-hydroxyl. Pre-steady-state kinetics showed RT preferred incorporating EFdA-TP over native dATP. Moreover, RT slowly inserted nucleotides past an EFdA-terminated primer, resulting in delayed chain termination with unaffected fidelity. This is distinct from KP1212, another 3'-hydroxyl-containing RT inhibitor considered to promote viral lethal mutagenesis. New mechanistic features of RT inhibition by EFdA are revealed. Copyright © 2014 Elsevier B.V. All rights reserved.

Probing the molecular mechanism of action of the HIV-1 reverse transcriptase inhibitor 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) using pre-steady-state kinetics

PubMed Central

Muftuoglu, Yagmur; Sohl, Christal D.; Mislak, Andrea C.; Mitsuya, Hiroaki; Sarafianos, Stefan G.; Anderson, Karen S.

2014-01-01

The novel antiretroviral 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) is a potent nucleoside HIV-1 reverse transcriptase (RT) inhibitor (NRTI). Unlike other FDA-approved NRTIs, EFdA contains a 3′-hydroxyl. Pre-steady-state kinetics showed RT preferred incorporating EFdA-TP over native dATP. Moreover, RT slowly inserted nucleotides past an EFdA-terminated primer, resulting in delayed chain termination with unaffected fidelity. This is distinct from KP1212, another 3′-hydroxyl-containing RT inhibitor considered to promote viral lethal mutagenesis. New mechanistic features of RT inhibition by EFdA are revealed. PMID:24632447

Time and decision making: differential contribution of the posterior insular cortex and the striatum during a delay discounting task.

PubMed

Wittmann, Marc; Leland, David S; Paulus, Martin P

2007-06-01

Delay discounting refers to the fact that an immediate reward is valued more than the same reward if it occurs some time in the future. To examine the neural substrates underlying this process, we studied 13 healthy volunteers who repeatedly had to decide between an immediate and parametrically varied delayed hypothetical reward using a delay discounting task during event-related functional magnetic resonance imaging. Subject's preference judgments resulted in different discounting slopes for shorter (<1 year) and for longer (> or =1 year) delays. Neural activation associated with the shorter delays relative to the longer delays was associated with increased activation in the head of the left caudate nucleus and putamen. When individuals selected the delayed relative to the immediate reward, a strong activation was found in bilateral posterior insular cortex. Several brain areas including the left caudate nucleus showed a correlation between the behaviorally determined discounting and brain activation for the contrast of intervals with delays <1 and > or =1 year. These results suggest that (1) the posterior insula, which is a critical component of the decision-making neural network, is involved in delaying gratification and (2) the degree of neural activation in the striatum, which plays a fundamental role in reward prediction and in time estimation, may code for the time delay.

A Comparison of the Effects of Brief Rules, a Timer, and Preferred Toys on Self-Control

ERIC Educational Resources Information Center

Newquist, Matthew H.; Dozier, Claudia L.; Neidert, Pamela L.

2012-01-01

Some children make impulsive choices (i.e., choose a small but immediate reinforcer over a large but delayed reinforcer). Previous research has shown that delay fading, providing an alternative activity during the delay, teaching participants to repeat a rule during the delay, combining delay fading with an alternative activity, and combining…

Factors associated with delay in trauma team activation and impact on patient outcomes.

PubMed

Connolly, Rory; Woo, Michael Y; Lampron, Jacinthe; Perry, Jeffrey J

2017-09-05

Trauma code activation is initiated by emergency physicians using physiological and anatomical criteria, mechanism of injury, and patient demographic factors. Our objective was to identify factors associated with delayed trauma team activation. We assessed consecutive cases from a regional trauma database from January 2008 to March 2014. We defined a delay in trauma code activation as a time greater than 30 minutes from the time of arrival. We conducted univariate analysis for factors potentially influencing trauma team activation, and we subsequently used multiple logistic regression analysis models for delayed activation in relation to mortality, length of stay, and time to operative management. Patients totalling 846 were included for our analysis; 4.1% (35/846) of trauma codes were activated after 30 minutes. Mean age was 40.8 years in the early group versus 49.2 in the delayed group (p=0.01). Patients were over age 70 years in 7.6% in the early activation group versus 17.1% in the delayed group (p=0.04). There was no significant difference in sex, type of injury, injury severity, or time from injury between the two groups. There was no significant difference in mortality, median length of stay, or median time to operative management. Delayed activation is linked with increasing age with no clear link to increased mortality. Given the severe injuries in the delayed cohort that required activation of the trauma team, further emphasis on the older trauma patient and interventions to recognize this vulnerable population should be made.

Neural correlates of sample-coding and reward-coding in the delay activity of neurons in the entopallium and nidopallium caudolaterale of pigeons (Columba livia).

PubMed

Johnston, Melissa; Anderson, Catrona; Colombo, Michael

2017-01-15

We recorded neuronal activity from the nidopallium caudolaterale, the avian equivalent of mammalian prefrontal cortex, and the entopallium, the avian equivalent of the mammalian visual cortex, in four birds trained on a differential outcomes delayed matching-to-sample procedure in which one sample stimulus was followed by reward and the other was not. Despite similar incidence of reward-specific and reward-unspecific delay cell types across the two areas, overall entopallium delay activity occurred following both rewarded and non-rewarded stimuli, whereas nidopallium caudolaterale delay activity tended to occur following the rewarded stimulus but not the non-rewarded stimulus. These findings are consistent with the view that delay activity in entopallium represents a code of the sample stimulus whereas delay activity in nidopallium caudolaterale represents a code of the possibility of an upcoming reward. However, based on the types of delay cells encountered, cells in NCL also code the sample stimulus and cells in ENTO are influenced by reward. We conclude that both areas support the retention of information, but that the activity in each area is differentially modulated by factors such as reward and attentional mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Malaria epidemiology and economics: the effect of delayed immune acquisition on the cost-effectiveness of insecticide-treated bednets.

PubMed Central

Guyatt, H L; Snow, R W; Evans, D B

1999-01-01

An understanding of the epidemiology of a disease is central in evaluating the health impact and cost-effectiveness of control interventions. The epidemiology of life-threatening malaria is receiving renewed interest, with concerns that the implementation of preventive measures such as insecticide-treated bednets (ITNs) while protecting young children might in fact increase the risks of mortality and morbidity in older ages by delaying the acquisition of functional immunity. This paper aims to illustrate how a combined approach of epidemiology and economics can be used to (i) explore the long-term impact of changes in epidemiological profiles, and (ii) identify those variables that are critical in determining whether an intervention will be an efficient use of resources. The key parameters for determining effectiveness are the protective efficacy of ITNs (reduction in all-cause mortality), the malaria attributable mortality and the increased malaria-specific mortality risk due to delays in the acquisition of functional immunity. In particular, the analysis demonstrates that delayed immune acquisition is not a problem per se, but that the critical issue is whether it occurs immediately following the implementation of an ITN programme or whether it builds up slowly over time. In the 'worst case' scenario where ITNs immediately increase malaria-specific mortality due to reduced immunity, the intervention might actually cost lives. In other words, it might be better to not use ITNs. On the other hand, if reduced immunity takes two years to develop, ITNs would still fall into the category of excellent value for money compared to other health interventions, saving a year of life (YLL) at a cost of between US$25-30. These types of calculations are important in identifying the parameters which field researchers should be seeking to measure to address the important question of the net impact of delaying the acquisition of immunity through preventive control measures. PMID:10365407

Increasing Completion of Classroom Routines through the Use of Picture Activity Schedules

ERIC Educational Resources Information Center

Watson, Kamille J.; DiCarlo, Cynthia F.

2016-01-01

Teachers spend the first few days of school teaching routines to children that will help transitions in the classroom between different activities. When children have difficulty, they move more slowly and/or require teacher prompting. A picture activity schedule intervention (Breitfelder in Teach Except Child Plus 4(5):2-15, 2008; Bryan and Gast…

Dizziness and vertigo -- aftercare

MedlinePlus

... that things are jumping or moving Loss of balance, difficulty standing up Lightheadedness usually gets better by ... slowly increase your activity. If you lose your balance, you may need help walking to stay safe. ...

The Rubella virus capsid is an anti-apoptotic protein that attenuates the pore-forming ability of Bax.

PubMed

Ilkow, Carolina S; Goping, Ing Swie; Hobman, Tom C

2011-02-01

Apoptosis is an important mechanism by which virus-infected cells are eliminated from the host. Accordingly, many viruses have evolved strategies to prevent or delay apoptosis in order to provide a window of opportunity in which virus replication, assembly and egress can take place. Interfering with apoptosis may also be important for establishment and/or maintenance of persistent infections. Whereas large DNA viruses have the luxury of encoding accessory proteins whose primary function is to undermine programmed cell death pathways, it is generally thought that most RNA viruses do not encode these types of proteins. Here we report that the multifunctional capsid protein of Rubella virus is a potent inhibitor of apoptosis. The main mechanism of action was specific for Bax as capsid bound Bax and prevented Bax-induced apoptosis but did not bind Bak nor inhibit Bak-induced apoptosis. Intriguingly, interaction with capsid protein resulted in activation of Bax in the absence of apoptotic stimuli, however, release of cytochrome c from mitochondria and concomitant activation of caspase 3 did not occur. Accordingly, we propose that binding of capsid to Bax induces the formation of hetero-oligomers that are incompetent for pore formation. Importantly, data from reverse genetic studies are consistent with a scenario in which the anti-apoptotic activity of capsid protein is important for virus replication. If so, this would be among the first demonstrations showing that blocking apoptosis is important for replication of an RNA virus. Finally, it is tempting to speculate that other slowly replicating RNA viruses employ similar mechanisms to avoid killing infected cells.

Differences in the timing of cardio-respiratory development determine whether marine gastropod embryos survive or die in hypoxia.

PubMed

Rudin-Bitterli, Tabitha S; Spicer, John I; Rundle, Simon D

2016-04-01

Physiological plasticity of early developmental stages is a key way by which organisms can survive and adapt to environmental change. We investigated developmental plasticity of aspects of the cardio-respiratory physiology of encapsulated embryos of a marine gastropod, Littorina obtusata, surviving exposure to moderate hypoxia (PO2 =8 kPa) and compared the development of these survivors with that of individuals that died before hatching. Individuals surviving hypoxia exhibited a slower rate of development and altered ontogeny of cardio-respiratory structure and function compared with normoxic controls (PO2 >20 kPa). The onset and development of the larval and adult hearts were delayed in chronological time in hypoxia, but both organs appeared earlier in developmental time and cardiac activity rates were greater. The velum, a transient, 'larval' organ thought to play a role in gas exchange, was larger in hypoxia but developed more slowly (in chronological time), and velar cilia-driven, rotational activity was lower. Despite these effects of hypoxia, 38% of individuals survived to hatching. Compared with those embryos that died during development, these surviving embryos had advanced expression of adult structures, i.e. a significantly earlier occurrence and greater activity of their adult heart and larger shells. In contrast, embryos that died retained larval cardio-respiratory features (the velum and larval heart) for longer in chronological time. Surviving embryos came from eggs with significantly higher albumen provisioning than those that died, suggesting an energetic component for advanced development of adult traits. © 2016. Published by The Company of Biologists Ltd.

Maintained Physical Activity Induced Changes in Delay Discounting.

PubMed

Sofis, Michael J; Carrillo, Ale; Jarmolowicz, David P

2017-07-01

Those who discount the subjective value of delayed rewards less steeply are more likely to engage in physical activity. There is limited research, however, showing whether physical activity can change rates of delay discounting. In a two-experiment series, treatment and maintenance effects of a novel, effort-paced physical activity intervention on delay discounting were evaluated with multiple baseline designs. Using a lap-based method, participants were instructed to exercise at individualized high and low effort levels and to track their own perceived effort. The results suggest that treatment-induced changes in discounting were maintained at follow-up for 13 of 16 participants. In Experiment 2, there were statistically significant group-level improvements in physical activity and delay discounting when comparing baseline with both treatment and maintenance phases. Percentage change in delay discounting was significantly correlated with session attendance and relative pace (min/mile) improvement over the course of the 7-week treatment. Implications for future research are discussed.

Numerical simulations and linear stability analysis of a boundary layer developed on wavy surfaces

NASA Astrophysics Data System (ADS)

Siconolfi, Lorenzo; Camarri, Simone; Fransson, Jens H. M.

2015-11-01

The development of passive methods leading to a laminar to turbulent transition delay in a boundary layer (BL) is a topic of great interest both for applications and academic research. In literature it has been shown that a proper and stable spanwise velocity modulation can reduce the growth rate of Tollmien-Schlichting (TS) waves and delay transition. In this study, we investigate numerically the possibility of obtaining a stabilizing effect of the TS waves through the use of a spanwise sinusoidal modulation of a flat plate. This type of control has been already successfully investigated experimentally. An extensive set of direct numerical simulations is carried out to study the evolution of a BL flow developed on wavy surfaces with different geometric characteristics, and the results will be presented here. Moreover, since this configuration is characterized by a slowly-varying flow field in streamwise direction, a local stability analysis is applied to define the neutral stability curves for the BL flow controlled by this type of wall modifications. These results give the possibility of investigating this control strategy and understanding the effect of the free parameters on the stabilization mechanism.

Non-standard radiotherapy fractionations delay the time to malignant transformation of low-grade gliomas.

PubMed

Henares-Molina, Araceli; Benzekry, Sebastien; Lara, Pedro C; García-Rojo, Marcial; Pérez-García, Víctor M; Martínez-González, Alicia

2017-01-01

Grade II gliomas are slowly growing primary brain tumors that affect mostly young patients. Cytotoxic therapies (radiotherapy and/or chemotherapy) are used initially only for patients having a bad prognosis. These therapies are planned following the "maximum dose in minimum time" principle, i. e. the same schedule used for high-grade brain tumors in spite of their very different behavior. These tumors transform after a variable time into high-grade gliomas, which significantly decreases the patient's life expectancy. In this paper we study mathematical models describing the growth of grade II gliomas in response to radiotherapy. We find that protracted metronomic fractionations, i.e. therapeutical schedules enlarging the time interval between low-dose radiotherapy fractions, may lead to a better tumor control without an increase in toxicity. Other non-standard fractionations such as protracted or hypoprotracted schemes may also be beneficial. The potential survival improvement depends on the tumor's proliferation rate and can be even of the order of years. A conservative metronomic scheme, still being a suboptimal treatment, delays the time to malignant progression by at least one year when compared to the standard scheme.

Seed development, seed germination and seedling growth in the R50 (sym16) pea mutant are not directly linked to altered cytokinin homeostasis.

PubMed

Long, Chengli; Held, Mark; Hayward, Allison; Nisler, Jaroslav; Spíchal, Lukas; Neil Emery, R J; Moffatt, Barbara A; Guinel, Frédérique C

2012-06-01

R50 (sym16) is a pea nodulation mutant that accumulates cytokinin (CK) in its vegetative organs. Total CK content increases as the plant ages because of the low activity of the enzyme cytokinin oxidase/dehydrogenase (CKX) responsible for CK degradation. R50 exhibits a large seed with high relative water content, and its seedling establishes itself slowly. Whether these two traits are linked to abnormal CK levels was considered here. R50 was found to have a similar germination rate but a much slower epicotyl emergence than Sparkle, its wild-type (WT). At the onset of emergence, the starch grains in R50 cotyledons were larger than those of WT; furthermore, they did not degrade as fast as in WT because of low amylase activity. No differences between the pea lines were observed in the CK forms identified during seed embryogenesis. However, while CK content compared to that of WT was reduced early in R50 embryogenesis, it was elevated later on in its dry seeds where CKX activity was low, although CKX transcript abundance remained high. Transcripts of the two known PsCKX isoforms exhibited tissue- and development-specific profiles with no detectable PsCKX2 expression in cotyledons. There were more of both transcripts in R50 roots than in WT roots, but less of PsCKX2 than PsCKX1 in R50 shoots compared to WT shoots. Thus, although there is a definite CKX post-transcriptional defect in R50 dry seeds, an abnormal CK homeostasis is not the basis of the delay in R50 seedling establishment, which we linked to abnormal amylase activity early in development. Copyright © Physiologia Plantarum 2012.

Scintigraphic measurement of regional gut transit in idiopathic constipation

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

Stivland, T.; Camilleri, M.; Vassallo, M.

1991-07-01

In this study, total gut transit and regional colonic transit in patients with idiopathic constipation were measured scintigraphically. Eight patients with severe constipation were studied, none of whom had evidence of abnormal function of the pelvic floor. 99mTc-radiolabeled Amberlite resin particles with a mixed meal were used to assess gastric emptying and small bowel transit; similar particles labeled with 111In were ingested in a coated capsule that dispersed in the ileocecal region. These were used to quantify colonic transit. Five healthy volunteers were also studied. Two patients showed delayed gastric emptying and two had slow small bowel transit. Seven ofmore » the eight patients had slow colonic transit. In five, delay affected the whole colon (pancolonic inertia); in two, transit in the ascending and transverse colon was normal, but solids moved through the left colon slowly. Mean colonic transit was also measured using radiopaque markers; this technique identified the patients with slow transit, as shown by measurements of overall colonic transit by simultaneous scintigraphy. However, estimated transit through the ascending and transverse colons was considerably shorter by the radiopaque marker technique. In conclusion, idiopathic constipation is characterized by either exaggerated reservoir functions of the ascending and transverse colons and/or impairment of propulsive function in the descending colon. Particle size may influence the result of regional colonic transit tests. Transit delays in other parts of the gut suggest that, in some patients, the condition may be a more generalized motor dysfunction.« less

On-resonance variable delay multipulse scheme for imaging of fast-exchanging protons and semisolid macromolecules.

PubMed

Xu, Jiadi; Chan, Kannie W Y; Xu, Xiang; Yadav, Nirbhay; Liu, Guanshu; van Zijl, Peter C M

2017-02-01

To develop an on-resonance variable delay multipulse (VDMP) scheme to image magnetization transfer contrast (MTC) and the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above approximately 1 kHz. A train of high power binomial pulses was applied at the water resonance. The interpulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions as a result of their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T 2 components in MTC and separated out using a variable mixing time. Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA), and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method, showing strong gray/white matter contrast for the slowly transferring MTC protons, whereas the TFP map was more uniform across the brain but somewhat higher in gray matter. The new method provides a simple way of imaging fast-exchanging protons and MTC components with a slow transfer rate. Magn Reson Med 77:730-739, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Variation in the schedules of somite and neural development in frogs

PubMed Central

Sáenz-Ponce, Natalia; Mitgutsch, Christian; del Pino, Eugenia M.

2012-01-01

The timing of notochord, somite, and neural development was analyzed in the embryos of six different frog species, which have been divided into two groups, according to their developmental speed. Rapid developing species investigated were Xenopus laevis (Pipidae), Engystomops coloradorum, and Engystomops randi (Leiuperidae). The slow developers were Epipedobates machalilla and Epipedobates tricolor (Dendrobatidae) and Gastrotheca riobambae (Hemiphractidae). Blastopore closure, notochord formation, somite development, neural tube closure, and the formation of cranial neural crest cell-streams were detected by light and scanning electron microscopy and by immuno-histochemical detection of somite and neural crest marker proteins. The data were analyzed using event pairing to determine common developmental aspects and their relationship to life-history traits. In embryos of rapidly developing frogs, elongation of the notochord occurred earlier relative to the time point of blastopore closure in comparison with slowly developing species. The development of cranial neural crest cell-streams relative to somite formation is accelerated in rapidly developing frogs, and it is delayed in slowly developing frogs. The timing of neural tube closure seemed to be temporally uncoupled with somite formation. We propose that these changes are achieved through differential timing of developmental modules that begin with the elongation of the notochord during gastrulation in the rapidly developing species. The differences might be related to the necessity of developing a free-living tadpole quickly in rapid developers. PMID:23184997

Freezing Bubbles

NASA Astrophysics Data System (ADS)

Kingett, Christian; Ahmadi, Farzad; Nath, Saurabh; Boreyko, Jonathan

2017-11-01

The two-stage freezing process of a liquid droplet on a substrate is well known; however, how bubbles freeze has not yet been studied. We first deposited bubbles on a silicon substrate that was chilled at temperatures ranging from -10 °C to -40 °C, while the air was at room temperature. We observed that the freeze front moved very slowly up the bubble, and in some cases, even came to a complete halt at a critical height. This slow freezing front propagation can be explained by the low thermal conductivity of the thin soap film, and can be observed more clearly when the bubble size or the surface temperature is increased. This delayed freezing allows the frozen portion of the bubble to cool the air within the bubble while the top part is still liquid, which induces a vapor pressure mismatch that either collapses the top or causes the top to pop. In cases where the freeze front reaches the top of the bubble, a portion of the top may melt and slowly refreeze; this can happen more than just once for a single bubble. We also investigated freezing bubbles inside of a freezer where the air was held at -20 °C. In this case, the bubbles freeze quickly and the ice grows radially from nucleation sites instead of perpendicular to the surface, which provides a clear contrast with the conduction limited room temperature bubbles.

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

Dustin Popp; Zander Mausolff; Sedat Goluoglu

We are proposing to use the code, TDKENO, to model TREAT. TDKENO solves the time dependent, three dimensional Boltzmann transport equation with explicit representation of delayed neutrons. Instead of directly integrating this equation, the neutron flux is factored into two components – a rapidly varying amplitude equation and a slowly varying shape equation and each is solved separately on different time scales. The shape equation is solved using the 3D Monte Carlo transport code KENO, from Oak Ridge National Laboratory’s SCALE code package. Using the Monte Carlo method to solve the shape equation is still computationally intensive, but the operationmore » is only performed when needed. The amplitude equation is solved deterministically and frequently, so the solution gives an accurate time-dependent solution without having to repeatedly We have modified TDKENO to incorporate KENO-VI so that we may accurately represent the geometries within TREAT. This paper explains the motivation behind using generalized geometry, and provides the results of our modifications. TDKENO uses the Improved Quasi-Static method to accomplish this. In this method, the neutron flux is factored into two components. One component is a purely time-dependent and rapidly varying amplitude function, which is solved deterministically and very frequently (small time steps). The other is a slowly varying flux shape function that weakly depends on time and is only solved when needed (significantly larger time steps).« less

The response difference of mitochondria in recalcitrant Antiaris toxicaria axes and orthodox Zea mays embryos to dehydration injury.

PubMed

Song, Song-Quan; Tian, Mei-Hua; Kan, Jing; Cheng, Hong-Yan

2009-07-01

Long-term preservation of recalcitrant seeds is very difficult because the physiological basis on their desiccation sensitivity is poorly understood. Survival of Antiaris toxicaria axes rapidly decreased and that of immature maize embryos very slowly decreased with dehydration. To understand their different responses to dehydration, we examined the changes in mitochondria activity during dehydration. Although activities of cytochrome (Cyt) c oxidase and malate dehydrogenase of the A. toxicaria axis and maize embryo mitochondria decreased with dehydration, the parameters of maize embryo mitochondria were much higher than those of A. toxicaria, showing that the damage was more severe for the A. toxicaria axis mitochondria than for those of maize embryo. The state I and III respiration of the A. toxicaria axis mitochondria were higher than those of maize embryo, the former rapidly decreased, and the latter slowly decreased with dehydration. The proportion of Cyt c pathway to state III respiration for the A. toxicaria axis mitochondria was low and rapidly decreased with dehydration, and the proportion of alternative oxidase pathway was high and slightly increased with dehydration. In contrast, the proportion of Cyt c pathway for maize embryo mitochondria was high, and that of alternative oxidase pathway was low. Both pathways decreased slowly with dehydration.

MAGNETIC CYCLES IN A DYNAMO SIMULATION OF FULLY CONVECTIVE M-STAR PROXIMA CENTAURI

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

Yadav, Rakesh K.; Wolk, Scott J.; Christensen, Ulrich R.

2016-12-20

The recent discovery of an Earth-like exoplanet around Proxima Centauri has shined a spot light on slowly rotating fully convective M-stars. When such stars rotate rapidly (period ≲20 days), they are known to generate very high levels of activity that is powered by a magnetic field much stronger than the solar magnetic field. Recent theoretical efforts are beginning to understand the dynamo process that generates such strong magnetic fields. However, the observational and theoretical landscape remains relatively uncharted for fully convective M-stars that rotate slowly. Here, we present an anelastic dynamo simulation designed to mimic some of the physical characteristicsmore » of Proxima Centauri, a representative case for slowly rotating fully convective M-stars. The rotating convection spontaneously generates differential rotation in the convection zone that drives coherent magnetic cycles where the axisymmetric magnetic field repeatedly changes polarity at all latitudes as time progress. The typical length of the “activity” cycle in the simulation is about nine years, in good agreement with the recently proposed activity cycle length of about seven years for Proxima Centauri. Comparing our results with earlier work, we hypothesis that the dynamo mechanism undergoes a fundamental change in nature as fully convective stars spin down with age.« less

Tremor evidence for dynamically triggered creep events on the deep San Andreas Fault

NASA Astrophysics Data System (ADS)

Peng, Z.; Shelly, D. R.; Hill, D. P.; Aiken, C.

2010-12-01

Deep tectonic tremor has been observed along major subduction zones and the San Andreas fault (SAF) in central and southern California. It appears to reflect deep fault slip, and it is often seen to be triggered by small stresses, including passing seismic waves from large regional and teleseismic earthquakes. Here we examine tremor activity along the Parkfield-Cholame section of the SAF from mid-2001 to early 2010, scrutinizing its relationship with regional and teleseismic earthquakes. Based on similarities in the shape and timing of seismic waveforms, we conclude that triggered and ambient tremor share common sources and a common physical mechanism. Utilizing this similarity in waveforms, we detect tremor triggered by numerous large events, including previously unreported triggering from the recent 2009 Mw7.3 Honduras, 2009 Mw8.1 Samoa, and 2010 Mw8.8 Chile earthquakes at teleseismic distances, and the relatively small 2007 Mw5.4 Alum Rock and 2008 Mw5.4 Chino Hills earthquakes at regional distances. We also find multiple examples of systematic migration in triggered tremor, similar to ambient tremor migration episodes observed at other times. Because these episodes propagate much more slowly than the triggering waves, the migration likely reflects a small, triggered creep event. As with ambient tremor bursts, triggered tremor at times persists for multiple days, probably indicating a somewhat larger creep event. This activity provides a clear example of delayed dynamic triggering, with a mechanism perhaps also relevant for triggering of regular earthquakes.

Reversible geminate recombination of hydrogen-bonded water molecule pair

NASA Astrophysics Data System (ADS)

Markovitch, Omer; Agmon, Noam

2008-08-01

The (history independent) autocorrelation function for a hydrogen-bonded water molecule pair, calculated from classical molecular dynamics trajectories of liquid water, exhibits a t-3/2 asymptotic tail. Its whole time dependence agrees quantitatively with the solution for reversible diffusion-influenced geminate recombination derived by Agmon and Weiss [J. Chem. Phys. 91, 6937 (1989)]. Agreement with diffusion theory is independent of the precise definition of the bound state. Given the water self-diffusion constant, this theory enables us to determine the dissociation and bimolecular recombination rate parameters for a water dimer. (The theory is indispensable for obtaining the bimolecular rate coefficient.) Interestingly, the activation energies obtained from the temperature dependence of these rate coefficients are similar, rather than differing by the hydrogen-bond (HB) strength. This suggests that recombination requires displacing another water molecule, which meanwhile occupied the binding site. Because these activation energies are about twice the HB strength, cleavage of two HBs may be required to allow pair separation. The autocorrelation function without the HB angular restriction yields a recombination rate coefficient that is larger than that for rebinding to all four tetrahedral water sites (with angular restrictions), suggesting the additional participation of interstitial sites. Following dissociation, the probability of the pair to be unbound but within the reaction sphere rises more slowly than expected, possibly because binding to the interstitial sites delays pair separation. An extended diffusion model, which includes an additional binding site, can account for this behavior.

Adaptive optimal stochastic state feedback control of resistive wall modes in tokamaks

NASA Astrophysics Data System (ADS)

Sun, Z.; Sen, A. K.; Longman, R. W.

2006-01-01

An adaptive optimal stochastic state feedback control is developed to stabilize the resistive wall mode (RWM) instability in tokamaks. The extended least-square method with exponential forgetting factor and covariance resetting is used to identify (experimentally determine) the time-varying stochastic system model. A Kalman filter is used to estimate the system states. The estimated system states are passed on to an optimal state feedback controller to construct control inputs. The Kalman filter and the optimal state feedback controller are periodically redesigned online based on the identified system model. This adaptive controller can stabilize the time-dependent RWM in a slowly evolving tokamak discharge. This is accomplished within a time delay of roughly four times the inverse of the growth rate for the time-invariant model used.

Adaptive Optimal Stochastic State Feedback Control of Resistive Wall Modes in Tokamaks

NASA Astrophysics Data System (ADS)

Sun, Z.; Sen, A. K.; Longman, R. W.

2007-06-01

An adaptive optimal stochastic state feedback control is developed to stabilize the resistive wall mode (RWM) instability in tokamaks. The extended least square method with exponential forgetting factor and covariance resetting is used to identify the time-varying stochastic system model. A Kalman filter is used to estimate the system states. The estimated system states are passed on to an optimal state feedback controller to construct control inputs. The Kalman filter and the optimal state feedback controller are periodically redesigned online based on the identified system model. This adaptive controller can stabilize the time dependent RWM in a slowly evolving tokamak discharge. This is accomplished within a time delay of roughly four times the inverse of the growth rate for the time-invariant model used.

A COMPARISON OF THE EFFECTS OF BRIEF RULES, A TIMER, AND PREFERRED TOYS ON SELF-CONTROL

PubMed Central

Newquist, Matthew H; Dozier, Claudia L; Neidert, Pamela L

2012-01-01

Some children make impulsive choices (i.e., choose a small but immediate reinforcer over a large but delayed reinforcer). Previous research has shown that delay fading, providing an alternative activity during the delay, teaching participants to repeat a rule during the delay, combining delay fading with an alternative activity, and combining delay fading with a countdown timer are effective for increasing self-control (i.e., choosing the large but delayed reinforcer over the small but immediate reinforcer). The purpose of the current study was to compare the effects of various interventions in the absence of delay fading (i.e., providing brief rules, providing a countdown timer during the delay, or providing preferred toys during the delay) on self-control. Results suggested that providing brief rules or a countdown timer during the delay was ineffective for enhancing self-control. However, providing preferred toys during the delay effectively enhanced self-control. PMID:23060664

A comparison of the effects of brief rules, a timer, and preferred toys on self-control.

PubMed

Newquist, Matthew H; Dozier, Claudia L; Neidert, Pamela L

2012-01-01

Some children make impulsive choices (i.e., choose a small but immediate reinforcer over a large but delayed reinforcer). Previous research has shown that delay fading, providing an alternative activity during the delay, teaching participants to repeat a rule during the delay, combining delay fading with an alternative activity, and combining delay fading with a countdown timer are effective for increasing self-control (i.e., choosing the large but delayed reinforcer over the small but immediate reinforcer). The purpose of the current study was to compare the effects of various interventions in the absence of delay fading (i.e., providing brief rules, providing a countdown timer during the delay, or providing preferred toys during the delay) on self-control. Results suggested that providing brief rules or a countdown timer during the delay was ineffective for enhancing self-control. However, providing preferred toys during the delay effectively enhanced self-control.

Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

PubMed

Bugg, George J; Siddiqui, Farah; Thornton, Jim G

2013-06-23

Slow progress in the first stage of spontaneous labour is associated with an increased caesarean section rate and fetal and maternal morbidity. Oxytocin has long been advocated as a treatment for slow progress in labour but it is unclear to what extent it improves the outcomes for that labour and whether it actually reduces the caesarean section rate or maternal and fetal morbidity. This review will address the use of oxytocin and whether it improves the outcomes for women who are progressing slowly in labour compared to situations where it is not used or where its administration is delayed. To determine if the use of oxytocin for the treatment of slow progress in the first stage of spontaneous labour is associated with a reduction in the incidence of caesarean sections, or maternal and fetal morbidity compared to situations where it is not used or where its administration is delayed. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 February 2013) and bibliographies of relevant papers. Randomised controlled trials which compared oxytocin with either placebo, no treatment or delayed oxytocin in the active stage of spontaneous labour in low-risk women at term. Two authors independently assessed studies for inclusion, assessed risk of bias and extracted data. We sought additional information from trial authors. We included eight studies in the review involving a total of 1338 low-risk women in the first stage of spontaneous labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo or no treatment (three trials); 2) the early use of oxytocin versus its delayed use (five trials). There were no significant differences in the rates of caesarean section or instrumental vaginal delivery in either comparison. Early use of oxytocin resulted in an increase in uterine hyperstimulation associated with fetal heart changes. However, the early use of oxytocin versus its delayed use resulted in no significant differences in a range of neonatal and maternal outcomes. Use of early oxytocin resulted in a statistically significant reduction in the mean duration in labour of approximately two hours but did not increase the normal delivery rate. There was significant heterogeneity for this analysis and we carried out a random-effects meta-analysis; however, all of the trials are strongly in the same direction so it is reasonable to conclude that this is the true effect. We also performed a random-effects meta-analysis for the four other analyses which showed substantial heterogeneity in the review. For women making slow progress in spontaneous labour, treatment with oxytocin as compared with no treatment or delayed oxytocin treatment did not result in any discernable difference in the number of caesarean sections performed. In addition there were no detectable adverse effects for mother or baby. The use of oxytocin was associated with a reduction in the time to delivery of approximately two hours which might be important to some women. However, if the primary goal of this treatment is to reduce caesarean section rates, then doctors and midwives may have to look for alternative options.

Effects of Topical Emu Oil on Burn Wounds in the Skin of Balb/c Mice

PubMed Central

Afshar, Mohammad; Ghaderi, Reza; Zardast, Mahmoud; Delshad, Parvin

2016-01-01

The goal of this study was to determine the effect of topical Emu oil on the healing of burn wounds and hair follicle restoration in superficial II-degree burns in the skin of Balb/c mice. Thirty-two male Balb/c mice with burns on the back of the neck were divided into two groups: The Emu oil group received topical Emu oil twice daily, whereas the control was left untreated. Skin biopsies were obtained on days 4, 7, 10, and 14 of the experiment. Then the specimens were viewed with Olympus SZX research microscope. The Emu oil treated burns were found to heal more slowly and inflammation lasted longer in this group. The number of hair follicles in the margins of the wounds increased through time in the Emu oil group compared to the control group. Also, the hair follicles in the Emu oil group were in several layers and seemed to be more active and mature. Moreover, Emu oil had a positive effect on fibrogenesis and synthesis of collagen. The findings indicate that although Emu oil delays the healing process, it has a positive effect on wound healing and it increases the number of hair follicles in the margins of the wound. PMID:27069472

Protective effects of long-term lithium administration in a slowly progressive SMA mouse model.

PubMed

Biagioni, Francesca; Ferrucci, Michela; Ryskalin, Larisa; Fulceri, Federica; Lazzeri, Gloria; Calierno, Maria Teresa; Busceti, Carla L; Ruffoli, Riccardo; Fornai, Francesco

2017-12-01

In the present study we evaluated the long-term effects of lithium administration to a knock-out double transgenic mouse model (Smn-/-; SMN1A2G+/-; SMN2+/+) of Spinal Muscle Atrophy type III (SMA-III). This model is characterized by very low levels of the survival motor neuron protein, slow disease progression and motor neuron loss, which enables to detect disease-modifying effects at delayed time intervals. Lithium administration attenuates the decrease in motor activity and provides full protection from motor neuron loss occurring in SMA-III mice, throughout the disease course. In addition, lithium prevents motor neuron enlargement and motor neuron heterotopy and suppresses the occurrence of radial-like glial fibrillary acidic protein immunostaining in the ventral white matter of SMA-III mice. In SMA-III mice long-term lithium administration determines a dramatic increase of survival motor neuron protein levels in the spinal cord. These data demonstrate that long-term lithium administration during a long-lasting motor neuron disorder attenuates behavioural deficit and neuropathology. Since low level of survival motor neuron protein is bound to disease severity in SMA, the robust increase in protein level produced by lithium provides solid evidence which calls for further investigations considering lithium in the long-term treatment of spinal muscle atrophy.

Maltase Has Most Versatile α-Hydrolytic Activity Among the Mucosal α-Glucosidases of the Small Intestine.

PubMed

Lee, Byung-Hoo; Hamaker, Bruce R

2018-06-01

Complete digestion of the glycemic carbohydrates to glucose takes place through the combined action of the 4 mucosal α-glucosidases (maltase-glucoamylase and sucrase-isomaltase) in the small intestine. Maltase digests α-1,2- and α-1,3-disaccharides better than the other α-glucosidases, and has, as well, the capability to effectively hydrolyze α-1,4 and α-1,6 linkages that form the major backbone of a starch molecule. This broad hydrolytic activity on α-linkages makes it an enzyme that has the most versatile α-hydrolytic activity among the 4mucosal α-glucosidases. The slowly digestible properties of the unusual linkages from this research suggest the development of new glycemic oligosaccharides which will be hydrolyzed slowly, compared to α-1,4 linkages, for modulating the postprandial glycemic response. In addition, using mammalian mucosal α-glucosidases is a better fit to characterize carbohydrate digestion properties, compared to fungal amyloglucosidase which is currently applied in in vitro assays.

Vaginal delivery - discharge

MedlinePlus

... slowly. Get plenty of rest. You can start sexual activity around 6 weeks after delivery, if the discharge or lochia has stopped. Women who breastfeed may have a lower sex drive than normal, along with vaginal dryness and pain ...

Mycobacterium intermedium sp. nov.

PubMed

Meier, A; Kirschner, P; Schröder, K H; Wolters, J; Kroppenstedt, R M; Böttger, E C

1993-04-01

Strains of a new type of slowly growing mycobacterium were repeatedly isolated from sputum from a patient with pulmonary disease. This photochromogenic organism grew at 22, 31, 37, and 41 degrees C, possessed catalase, acid phosphatase, esterase, beta-galactosidase, and arylsulfatase activities, and hydrolyzed Tween. It did not produce nicotinic acid or have nitrate reductase, acetamidase, benzamidase, isonicotinamidase, nicotinamidase, pyrazinamidase, succinidamidase, and acid phosphatase activities. Urease activity was variable. The organism is susceptible to ethambutol and resistant to isoniazid and streptomycin. A mycolic acid analysis revealed the presence of alpha-mycolates, alpha'-mycolates, and keto-mycolates. The results of comparative 16S rRNA sequencing placed this organism at an intermediate position between the rapidly and slowly growing mycobacteria. On the basis of the pattern of enzymatic activities and metabolic properties, the results of fatty acid analyses, and the unique 16S rRNA sequence, we propose that this organism represents a new species, for which we propose the name Mycobacterium intermedium. The type strain is strain 1669/91; a culture of this strain has been deposited in the Deutsche Sammlung von Mikroorganismen und Zellkulturen as strain DSM 44049.

Threshold cascades with response heterogeneity in multiplex networks

NASA Astrophysics Data System (ADS)

Lee, Kyu-Min; Brummitt, Charles D.; Goh, K.-I.

2014-12-01

Threshold cascade models have been used to describe the spread of behavior in social networks and cascades of default in financial networks. In some cases, these networks may have multiple kinds of interactions, such as distinct types of social ties or distinct types of financial liabilities; furthermore, nodes may respond in different ways to influence from their neighbors of multiple types. To start to capture such settings in a stylized way, we generalize a threshold cascade model to a multiplex network in which nodes follow one of two response rules: some nodes activate when, in at least one layer, a large enough fraction of neighbors is active, while the other nodes activate when, in all layers, a large enough fraction of neighbors is active. Varying the fractions of nodes following either rule facilitates or inhibits cascades. Near the inhibition regime, global cascades appear discontinuously as the network density increases; however, the cascade grows more slowly over time. This behavior suggests a way in which various collective phenomena in the real world could appear abruptly yet slowly.

Delay activity of saccade-related neurons in the caudal dentate nucleus of the macaque cerebellum

PubMed Central

Sommer, Marc A.

2013-01-01

The caudal dentate nucleus (DN) in lateral cerebellum is connected with two visual/oculomotor areas of the cerebrum: the frontal eye field and lateral intraparietal cortex. Many neurons in frontal eye field and lateral intraparietal cortex produce “delay activity” between stimulus and response that correlates with processes such as motor planning. Our hypothesis was that caudal DN neurons would have prominent delay activity as well. From lesion studies, we predicted that this activity would be related to self-timing, i.e., the triggering of saccades based on the internal monitoring of time. We recorded from neurons in the caudal DN of monkeys (Macaca mulatta) that made delayed saccades with or without a self-timing requirement. Most (84%) of the caudal DN neurons had delay activity. These neurons conveyed at least three types of information. First, their activity was often correlated, trial by trial, with saccade initiation. Correlations were found more frequently in a task that required self-timing of saccades (53% of neurons) than in a task that did not (27% of neurons). Second, the delay activity was often tuned for saccade direction (in 65% of neurons). This tuning emerged continuously during a trial. Third, the time course of delay activity associated with self-timed saccades differed significantly from that associated with visually guided saccades (in 71% of neurons). A minority of neurons had sensory-related activity. None had presaccadic bursts, in contrast to DN neurons recorded more rostrally. We conclude that caudal DN neurons convey saccade-related delay activity that may contribute to the motor preparation of when and where to move. PMID:23365182

Growth in bone and body size among Asian and white girls in the Female Adolescent Maturation (FAM) study.

PubMed

Novotny, Rachel; Davis, James

2015-01-01

This study intends to identify differences in growth of Asian and White girls. Asian girls gained bone at similar rates to White girls. Physical activity was important to bone growth. Ethnic differences remained after adjusting for physical activity, demographics, and diet. Physical activity can improve bone gain. The purpose of this study is to examine differences in body size and bone growth of Asian, White, and Asian-White Mixed girls. Three prospective examinations of 99 Asian, 73 White, and 63 Mixed Asian and White girls, with a mean age of 11.0 years at enrollment were performed. Calcaneal bone mass, skeletal breadths, and body fat were measured. Physical activity, diet, and birth size were reported. The analyses examined the extent that body dimensions and bone size changed over time by demographic, diet, physical activity, body, and bone size parameters. White children were the most physically active yet had lower calcaneal ultrasound values for speed of sound (SOS). Based on regression models, bone mass, and subscapular skinfold thickness were greater in Asian girls compared to White and Asian-White Mixed girls at age 10 years. Asian-White Mixed girls had greater BMI compared to Asian or White girls. Asian girls gained body size more slowly than White girls, but changes in bone parameters did not differ significantly; Asian-White Mixed girls gained abdomen, hip, and weight more slowly than White girls. Among all girls, SOS and broadband ultrasound attenuation (BUA) increased significantly by level of physical activity before 12 years, but not after. Asian girls had more upper body (subscapular) fat at age 10 years and gained height and hip and abdomen circumferences more slowly than Asian-White and White girls. Asian girls had greater bone SOS and BUA at age 10 years but gained bone at similar rates to White girls. Physical activity was especially important to bone growth before age 12 years. However, ethnic differences remained after adjusting for physical activity, demographic, and dietary factors.

Slowly biodegradable organic compounds impact the biostability of non-chlorinated drinking water produced from surface water.

PubMed

Hijnen, W A M; Schurer, R; Bahlman, J A; Ketelaars, H A M; Italiaander, R; van der Wal, A; van der Wielen, P W J J

2018-02-01

It is possible to distribute drinking water without a disinfectant residual when the treated water is biologically stable. The objective of this study was to determine the impact of easily and slowly biodegradable compounds on the biostability of the drinking water at three full-scale production plants which use the same surface water, and on the regrowth conditions in the related distribution systems. Easily biodegradable compounds in the drinking water were determined with AOC-P17/Nox during 2012-2015. Slowly biodegradable organic compounds measured as particulate and/or high-molecular organic carbon (PHMOC), were monitored at the inlet and after the different treatment stages of the three treatments during the same period. The results show that PHMOC (300-470 μg C L -1 ) was approximately 10% of the TOC in the surface water and was removed to 50-100 μg C L -1 . The PHMOC in the water consisted of 40-60% of carbohydrates and 10% of proteins. A significant and strong positive correlation was observed for PHMOC concentrations and two recently introduced bioassay methods for slowly biodegradable compounds (AOC-A3 and biomass production potential, BPC 14 ). Moreover, these three parameters in the biological active carbon effluent (BACF) of the three plants showed a positive correlation with regrowth in the drinking water distribution system, which was assessed with Aeromonas, heterotrophic plate counts, coliforms and large invertebrates. In contrast, the AOC-P17/Nox concentrations did not correlate with these regrowth parameters. We therefore conclude that slowly biodegradable compounds in the treated water from these treatment plants seem to have a greater impact on regrowth in the distribution system than easily biodegradable compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic effects on beef tenderness in Bos indicus composite and Bos taurus cattle.

PubMed

O'Connor, S F; Tatum, J D; Wulf, D M; Green, R D; Smith, G C

1997-07-01

Bos indicus composite and Bos taurus cattle, originating from diverse production environments, were used to quantify genetic variation in marbling, 24-h calpastatin activity, and beef tenderness and to identify strategies for prevention of beef tenderness problems in Bos indicus composite cattle. Comparisons among 3/8 Bos indicus breeds (Braford, Red Brangus, Simbrah) revealed significant differences in marbling and 24-h calpastatin activity, but not in tenderness. Compared with Bos taurus cattle, 3/ 8 Bos indicus cattle had similar marbling scores but higher 24-h calpastatin activities. Also, beef from 3/8 Bos indicus composites aged more slowly from 1 to 7 d and was less tender at 4, 7, 14, 21, and 35 d postmortem than beef from Bos taurus cattle. However, beef from 3/8 Bos indicus cattle was relatively tender if it was aged for a sufficient period of time (21 d). The delayed response to aging and greater toughness of beef from 3/8 Bos indicus cattle was associated with Brahman breed effects and was not related to the Bos taurus germplasm source. Marbling was moderately heritable (.52 +/- .21) but exhibited positive genetic correlations with shear force at d 1 through 14 of aging, suggesting that, in these cattle, selection for increased marbling would have an unfavorable effect on beef tenderness. A low heritability estimate for 24-h calpastatin activity (.15 +/- .15), coupled with low genetic correlations between calpastatin activity and shear force at 7, 14, and 35 d, suggested that selection for low calpastatin activity would have little effect on aged beef tenderness. Panel tenderness and shear force at 7, 14, and 21 d were moderately heritable (.27 to .47), indicating that aged beef tenderness could be improved by direct selection (via progeny testing). Comparisons among Simbrah, Senegus x Simbrah, and Red Angus x Simmental steers showed that inclusion of a tropically adapted Bos taurus breed (Senepol) could be an effective strategy for preventing beef tenderness problems in heat-tolerant cattle.

Finite-time robust stabilization of uncertain delayed neural networks with discontinuous activations via delayed feedback control.

PubMed

Wang, Leimin; Shen, Yi; Sheng, Yin

2016-04-01

This paper is concerned with the finite-time robust stabilization of delayed neural networks (DNNs) in the presence of discontinuous activations and parameter uncertainties. By using the nonsmooth analysis and control theory, a delayed controller is designed to realize the finite-time robust stabilization of DNNs with discontinuous activations and parameter uncertainties, and the upper bound of the settling time functional for stabilization is estimated. Finally, two examples are provided to demonstrate the effectiveness of the theoretical results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fainting

MedlinePlus

... sure kids: drink plenty of fluids, especially in hot weather or during physical activity take frequent breaks and move around as much as possible when sitting or standing for long periods of time slowly breathe into a paper bag when they are anxious and breathing too ...

WATER INGESTION DURING SWIMMING ACTIVITIES IN A POOL: A PILOT STUDY

EPA Science Inventory

Chloroisocyanurates are commonly added to outdoor swimming pools to stabilize chlorine disinfectants. The chloroisocyanurates decompose slowly to release chlorine and cyanuric acid. Studies conducted to determine if the chloroisocyanurates might be toxic to swimmers showed that...

A KCNQ1 Mutation Causes a High Penetrance for Familial Atrial Fibrillation

PubMed Central

Bartos, Daniel C.; Anderson, Jeffrey B.; Bastiaenen, Rachel; Johnson, Jonathan N.; Gollob, Michael H; Tester, David J.; Burgess, Don E.; Homfray, Tessa; Behr, Elijah R.; Ackerman, Michael J.; Guicheney, Pascale; Delisle, Brian P.

2012-01-01

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is expected to grow. A genetic predisposition for AF has long been recognized, but its manifestation in these patients likely involves a combination of rare and common genetic variants. Identifying genetic variants that associate with a high penetrance for AF would represent a significant breakthrough for understanding the mechanisms that associate with disease. Method and Results Candidate gene sequencing in five unrelated families with familial AF identified the KCNQ1 missense mutation p.Arg231His (R231H). In addition to AF, several of the family members have abnormal QTc intervals, syncope, or experienced sudden cardiac arrest or death. KCNQ1 encodes the voltage-gated K+ channel that conducts the slowly activating delayed rectifier K+ current in the heart. Functional and computational analyses suggested that R231H increases KCNQ1 current (IKCNQ1) to shorten the atrial action potential (AP) duration. R231H is predicted to minimally affect ventricular excitability, but it prevented the increase in IKCNQ1 following PKA activation. The unique properties of R231H appeared to be caused by a loss in voltage-dependent gating. Conclusions The R231H variant causes a high penetrance for interfamilial early-onset AF. Our study indicates R231H likely shortens atrial refractoriness to promote a substrate for reentry. Additionally, R231H might cause abnormal ventricular repolarization by disrupting PKA activation of IKCNQ1. We conclude genetic variants, which increase IKs during the atrial AP, decrease the atrial AP duration, and/or shorten atrial refractoriness, present a high risk for interfamilial AF. PMID:23350853

Leaf Area Influence on Surface Layer in a Deciduous Forest. Part 2; Detecting Leaf Area and Surface Resistance During Transition Seasons

NASA Technical Reports Server (NTRS)

Sakai, Ricardo K.; Fitzjarrald, David R.; Moore, Kathleen E.; Sicker, John W.; Munger, Willian J.; Goulden, Michael L.; Wofsy, Steven C.

1996-01-01

Temperate deciduous forest exhibit dramatic seasonal changes in surface exchange properties following on the seasonal changes in leaf area index. The canopy resistance to water vapor transport r(sub c) decreased abruptly at leaf emergence in each year but then also continued to decrease slowly during the remaining growing season due to slowly increasing LAI. Canopy resistance and PAR-albedo (albedo from photosynthetically active radiation) began to increase about one month before leaf fall with the diminishment of CO2 gradient above the canopy as well. At this time evaporation begun to be controlled as if the canopy were leafless.

Delivery and Establishing Slow Release Carbon Source to the Hanford Vadose Zone Using Colloidal Silica Suspension Injection and Subsequent Gelation - Laboratory Study

NASA Astrophysics Data System (ADS)

Zhong, L.; Lee, M. H.; Lee, B.; Yang, S.

2016-12-01

Delivery of nutrient to and establish a slow release carbon source in the vadose zone and capillary fringe zone is essential for setting up of a long-lasting bioremediation of contaminations in those zones. Conventional solution-based injection and infiltration approaches are facing challenges to achieve the delivery and remedial goals. Aqueous silica suspensions undergo a delayed gelation process under favorite geochemical conditions. The delay in gelation provides a time window for the injection of the suspension into the subsurface; and the gelation of the amendment-silica suspension enables the amendment-laden gel to stay in the target zone and slowly release the constituents for contaminant remediation. This approach can potentially be applied to deliver bio-nutrients to the vadose zone and capillary fringe zone for enhanced bioremediation and achieve remedial goals. This research was conducted to demonstrate delayed gelation of colloidal silica suspensions when carbon sources were added and to prove the gelation occurs in sediments under vadose conditions. Sodium lactate, vegetable oil, ethanol, and molasses were tested as the examples of carbon source (or nutrient) amendments. The rheological properties of the silica suspensions during the gelation were characterized. The influence of silica, salinity, nutrient concentrations, and the type of nutrients was studied. The kinetics of nutrient release from silica-nutrient gel was quantified using molasses as the example, and the influence of suspension gelation time was evaluated. The injection behavior of the suspensions was investigated by monitoring their viscosity changes and the injection pressures when the suspensions were delivered into sediment columns.

Actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

PubMed Central

Westendorf, Christian; Negrete, Jose; Bae, Albert J.; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

2013-01-01

The rapid reorganization of the actin cytoskeleton in response to external stimuli is an essential property of many motile eukaryotic cells. Here, we report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. When averaging the actin response of many cells to a short pulse of the chemoattractant cAMP, we observed a transient accumulation of cortical actin reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. To substantiate that an oscillatory mechanism governs the actin dynamics in these cells, we systematically exposed a large number of cells to periodic pulse trains of different frequencies. Our results indicate a resonance peak at a stimulation period of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the regulatory network of the actin system. To test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and actin-interacting protein 1, as well as knockout mutants that lack Coronin and actin-interacting protein 1. These actin-binding proteins enhance the disassembly of actin filaments and thus allow us to estimate the delay time in the regulatory feedback loop. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed in our periodic stimulation experiments. PMID:23431176

Time correlation between mononucleosis and initial symptoms of MS

PubMed Central

Endriz, John; Ho, Peggy P.

2017-01-01

Objective: To determine the average age of MS onset vs the age at which Epstein-Barr infection has previously occurred and stratify this analysis by sex and the blood level of Epstein-Barr nuclear antigen 1 (EBNA1) antibody. Methods: Using infectious mononucleosis (IM) as a temporal marker in data from the Swedish epidemiologic investigation of MS, 259 adult IM/MS cases were identified and then augmented to account for “missing” childhood data so that the average age of MS onset could be determined for cases binned by age of IM (as stratified by sex and EBNA1 titer level). Results: Mean age of IM vs mean age of MS reveals a positive time correlation for all IM ages (from ∼5 to ∼30 years), with IM-to-MS delay decreasing with increased age. When bifurcated by sex or EBNA1 blood titer levels, males and high-titer subpopulations show even stronger positive time correlation, while females and low-titer populations show negative time correlation in early childhood (long IM/MS delay). The correlation becomes positive in females beyond puberty. Conclusions: IM/MS time correlation implies causality if IM is time random. Alternative confounding models seem implausible, in light of constraints imposed by time-invariant delay observed here. Childhood infection with Epstein-Barr virus (EBV) in females and/or those genetically prone to low EBNA1 blood titers will develop MS slowly. Males and/or high EBNA1-prone develop MS more rapidly following IM infection at all ages. For all, postpubescent EBV infection is critical for the initiation and rapid development of MS. PMID:28271078

Effect of immediate or delayed light activation on curing kinetics and shrinkage stress of dual-cure resin cements.

PubMed

Faria-e-Silva, Andre; Boaro, Leticia; Braga, Roberto; Piva, Evandro; Arias, Vanessa; Martins, Luis

2011-01-01

This study evaluated the effect of light activation (absence, immediate, or delayed) on conversion kinetics and polymerization stress of three commercial dual-cured resin cements (Enforce, RelyX ARC, and Panavia F). Degree of conversion (DC) was monitored for 30 minutes using real-time near–Fourier transform infrared spectroscopy. The cement was mixed, placed on the spectrometer sample holder, and light activated either immediately or after five minutes (delayed light activation). When no light activation was performed, the materials were protected from light exposure (control). DC was evaluated at five and 30 minutes postmixture. Maximum rates of polymerization (Rp(max)) were obtained from the first derivative of the DC vs time curve. Polymerization stress was monitored for 30 minutes in 1-mm-thick specimens inserted between two cylinders attached to a universal testing machine. Data were submitted to analysis of variance/Tukey tests (α=0.05). Immediate light activation promoted the highest DC at five minutes. At 30 minutes, only RelyX ARC did not present a significant difference in DC between activation modes. Enforce and Panavia F presented higher Rp(max) for immediate and delayed light-activation, respectively. RelyX ARC showed similar Rp(max) for all activation modes. The absence of light activation resulted in the lowest stress followed by delayed light activation, while immediate light activation led to the highest values. RelyX ARC showed higher stress than Enforce, while the stress of Panavia F was similar to that of the others. Delayed light activation reduced the polymerization stress of the resin cements tested without jeopardizing DC.

Induction of a G1-S checkpoint in fission yeast.

PubMed

Bøe, Cathrine A; Krohn, Marit; Rødland, Gro Elise; Capiaghi, Christoph; Maillard, Olivier; Thoma, Fritz; Boye, Erik; Grallert, Beáta

2012-06-19

Entry into S phase is carefully regulated and, in most organisms, under the control of a G(1)-S checkpoint. We have previously described a G(1)-S checkpoint in fission yeast that delays formation of the prereplicative complex at chromosomal replication origins after exposure to UV light (UVC). This checkpoint absolutely depends on the Gcn2 kinase. Here, we explore the signal for activation of the Gcn2-dependent G(1)-S checkpoint in fission yeast. If some form of DNA damage can activate the checkpoint, deficient DNA repair should affect the length of the checkpoint-induced delay. We find that the cell-cycle delay differs in repair-deficient mutants from that in wild-type cells. However, the duration of the delay depends not only on the repair capacity of the cells, but also on the nature of the repair deficiency. First, the delay is abolished in cells that are deficient in the early steps of repair. Second, the delay is prolonged in repair mutants that fail to complete repair after the incision stage. We conclude that the G(1)-S delay depends on damage to the DNA and that the activating signal derives not from the initial DNA damage, but from a repair intermediate(s). Surprisingly, we find that activation of Gcn2 does not depend on the processing of DNA damage and that activated Gcn2 alone is not sufficient to delay entry into S phase in UVC-irradiated cells. Thus, the G(1)-S delay depends on at least two different inputs.

RNA Futile Cycling in Model Persisters Derived from MazF Accumulation (Open Access)

DTIC Science & Technology

2015-11-17

they remained highly metabolically active . We further uncovered a futile cycle driven by continued transcription and MazF-mediated transcript degradation...presence of antibiotics (7), although exceptions have been noted for prod- rugs that require activation (8). Rather, they are rare phenotypic variants...arise from slowly grow- ing or nongrowing bacteria with reduced metabolic activity , where antibiotic targets are inactive and resilient to antibiotic

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

PubMed

Goldsmith, B A; Abrams, T W

1992-12-01

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

Neural activation during delay discounting is associated with 6-month change in risky sexual behavior in adolescents.

PubMed

Gardiner, Casey K; Karoly, Hollis C; Thayer, Rachel E; Gillman, Arielle S; Sabbineni, Amithrupa; Bryan, Angela D

2018-04-19

Identifying cognitive and neural mechanisms of decision making in adolescence can enhance understanding of, and interventions to reduce, risky health behaviors in adolescence. Delay discounting, or the propensity to discount the magnitude of temporally distal rewards, has been associated with diverse health risk behaviors, including risky sex. This cognitive process involves recruitment of reward and cognitive control brain regions, which develop on different trajectories in adolescence and are also implicated in real-world risky decision making. However, no extant research has examined how neural activation during delay discounting is associated with adolescents' risky sexual behavior. To determine whether a relationship exists between adolescents' risky sexual behavior and neural activation during delay discounting. Adolescent participants completed a delay discounting paradigm during functional magnetic resonance imaging (fMRI) scanning, and they reported risky sexual behavior at baseline, 3-, 6-, 9-, and 12-month follow-up time points. Latent growth curve models were employed to determine relationships between brain activation during delay discounting and change in risky sexual behavior over time. Greater activation in brain regions associated with reward and cognitive control (caudate, putamen, nucleus accumbens, anterior cingulate, insula, orbitofrontal cortex, inferior frontal gyrus, dorsolateral prefrontal cortex) during delay discounting was associated with lower mean levels of risky sexual behavior but greater growth over the period from baseline to 6 months. Neural activation during delay discounting is cross-sectionally and prospectively associated with risky sexual behavior in adolescence, highlighting a neural basis of risky decision-making as well as opportunities for early identification and intervention.

High amylose starch consumption induces obesity in Drosophila melanogaster and metformin partially prevents accumulation of storage lipids and shortens lifespan of the insects.

PubMed

Abrat, Oleksandra B; Storey, Janet M; Storey, Kenneth B; Lushchak, Volodymyr I

2018-01-01

There are very few studies that have directly analyzed the effects of dietary intake of slowly digestible starches on metabolic parameters of animals. The present study examined the effects of slowly digestible starch with high amylose content (referred also as amylose starch) either alone, or in combination with metformin on the development, lifespan, and levels of glucose and storage lipids in the fruit fly Drosophila melanogaster. Consumption of amylose starch in concentrations 0.25-10% did not affect D. melanogaster development, whereas 20% starch delayed pupation and reduced the number of larvae that reached the pupal stage. Starch levels in larval food, but not in adult food, determined levels of triacylglycerides in eight-day-old adult flies. Rearing on diet with 20% starch led to shorter lifespan and a higher content of triacylglycerides in the bodies of adult flies as compared with the same parameters in flies fed on 4% starch diet. Food supplementation with 10mM metformin partly attenuated the negative effects of high starch concentrations on larval pupation and decreased triacylglyceride levels in adult flies fed on 20% starch. Long-term consumption of diets supplemented with metformin and starch decreased lifespan of the insects, compared with the diet supplemented with starch only. The data show that in Drosophila high starch consumption may induce a fat fly phenotype and metformin may partially prevent it. Copyright © 2017. Published by Elsevier Inc.

Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein

NASA Astrophysics Data System (ADS)

Chaurasiya, Kathy R.; McCauley, Micah J.; Wang, Wei; Qualley, Dominic F.; Wu, Tiyun; Kitamura, Shingo; Geertsema, Hylkje; Chan, Denise S. B.; Hertz, Amber; Iwatani, Yasumasa; Levin, Judith G.; Musier-Forsyth, Karin; Rouzina, Ioulia; Williams, Mark C.

2014-01-01

The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalysed DNA elongation. Here, we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription.

Sculpting Silica Colloids by Etching Particles with Nonuniform Compositions

PubMed Central

2017-01-01

We present the synthesis of new shapes of colloidal silica particles by manipulating their chemical composition and subsequent etching. Segments of silica rods, prepared by the ammonia catalyzed hydrolysis and condensation of tetraethylorthosilicate (TEOS) from polyvinylpyrrolidone loaded water droplets, were grown under different conditions. Upon decreasing temperature, delaying ethanol addition, or increasing monomer concentration, the rate of dissolution of the silica segment subsequently formed decreased. A watery solution of NaOH (∼mM) selectively etched these segments. Further tuning the conditions resulted in rod–cone or cone–cone shapes. Deliberately modulating the composition along the particle’s length by delayed addition of (3-aminopropyl)-triethoxysilane (APTES) also allowed us to change the composition stepwise. The faster etching of this coupling agent in neutral conditions or HF afforded an even larger variety of particle morphologies while in addition changing the chemical functionality. A comparable step in composition was applied to silica spheres. Biamine functional groups used in a similar way as APTES caused a charge inversion during the growth, causing dumbbells and higher order aggregates to form. These particles etched more slowly at the neck, resulting in a biconcave silica ring sandwiched between two silica spheres, which could be separated by specifically etching the functionalized layer using HF. PMID:28413261

Patellofemoral Pain Syndrome

MedlinePlus

... But do this slowly, increasing the amount of time you do the sports activity a little at a time. Talk to ... 20 seconds. Do the exercise 6 to 10 times and then switch legs. Citations Management of Patellofemoral Pain Syndrome by S Dixit, M.D., ...

Bubbling in delay-coupled lasers.

PubMed

Flunkert, V; D'Huys, O; Danckaert, J; Fischer, I; Schöll, E

2009-06-01

We theoretically study chaos synchronization of two lasers which are delay coupled via an active or a passive relay. While the lasers are synchronized, their dynamics is identical to a single laser with delayed feedback for a passive relay and identical to two delay-coupled lasers for an active relay. Depending on the coupling parameters the system exhibits bubbling, i.e., noise-induced desynchronization, or on-off intermittency. We associate the desynchronization dynamics in the coherence collapse and low-frequency fluctuation regimes with the transverse instability of some of the compound cavity's antimodes. Finally, we demonstrate how, by using an active relay, bubbling can be suppressed.

New exponential synchronization criteria for time-varying delayed neural networks with discontinuous activations.

PubMed

Cai, Zuowei; Huang, Lihong; Zhang, Lingling

2015-05-01

This paper investigates the problem of exponential synchronization of time-varying delayed neural networks with discontinuous neuron activations. Under the extended Filippov differential inclusion framework, by designing discontinuous state-feedback controller and using some analytic techniques, new testable algebraic criteria are obtained to realize two different kinds of global exponential synchronization of the drive-response system. Moreover, we give the estimated rate of exponential synchronization which depends on the delays and system parameters. The obtained results extend some previous works on synchronization of delayed neural networks not only with continuous activations but also with discontinuous activations. Finally, numerical examples are provided to show the correctness of our analysis via computer simulations. Our method and theoretical results have a leading significance in the design of synchronized neural network circuits involving discontinuous factors and time-varying delays. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Computer Simulation Analysis of Conventional and Trunked Land Mobile Radio Systems at Wright Patterson Air Force Base

DTIC Science & Technology

1988-11-01

ATRIB(1) .EQ.21,CD20; ACTIVITY,ND,ATRIB(1) .EQ.22, CD22 ; ACTIVITY,MD,ATRIB(l) .EQ.23,CD23; ACTIVITY,MD,ATRIB(1).EQ.24,CD24; ACTIVITY,MD,ATRIB(1) .EQ.25...TCD; CD20 COLCT,INT(5),FLT 20 CH DELAY; ACT,, ,TCD; CD21 COLCT,INT(5),FLT 21 CH DELAY; ACT,, ,TCD; CD22 COLCT,INT(5),FLT 22 CH DELAY; ACT,, ,TCD

Ictal high frequency oscillations distinguish two types of seizure territories in humans

PubMed Central

Weiss, Shennan A.; Banks, Garrett P.; McKhann, Guy M.; Goodman, Robert R.; Emerson, Ronald G.; Trevelyan, Andrew J.

2013-01-01

High frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80–150 Hz) amplitude, phase-locked to the low-frequency (1–25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure. These repetitive high frequency oscillations were seen in recordings from subdural electrodes adjacent to the microelectrode array several seconds after seizure onset, following ictal wavefront passage. Conversely, microelectrode recordings demonstrating only low-level, heterogeneous neural firing correlated with a lack of high frequency oscillations in adjacent subdural recording sites, despite the presence of a strong low-frequency signature. Previously, we reported that this pattern indicates a failure of the seizure to invade the area, because of a feedforward inhibitory veto mechanism. Because multi-unit firing rate and high gamma amplitude are closely related, high frequency oscillations can be used as a surrogate marker to distinguish the core seizure territory from the surrounding penumbra. We developed an efficient measure to detect delayed-onset, sustained ictal high frequency oscillations based on cross-frequency coupling between high gamma amplitude and the low-frequency (1–25 Hz) ictal rhythm. When applied to the broader subdural recording, this measure consistently predicted the timing or failure of ictal invasion, and revealed a surprisingly small and slowly spreading seizure core surrounded by a far larger penumbral territory. Our findings thus establish an underlying neural mechanism for delayed-onset, sustained ictal high frequency oscillations, and provide a practical, efficient method for using them to identify the small ictal core regions. Our observations suggest that it may be possible to reduce substantially the extent of cortical resections in epilepsy surgery procedures without compromising seizure control. PMID:24176977

Where do we stand after twenty years of dynamic triggering studies? (Invited)

NASA Astrophysics Data System (ADS)

Prejean, S. G.; Hill, D. P.

2013-12-01

In the past two decades, remote dynamic triggering of earthquakes by other earthquakes has been explored in a variety of physical environments with a wide array of observation and modeling techniques. These studies have significantly refined our understanding of the state of the crust and the physical conditions controlling earthquake nucleation. Despite an ever growing database of dynamic triggering observations, significant uncertainties remain and vigorous debate in almost all aspects of the science continues. For example, although dynamic earthquake triggering can occur with peak dynamic stresses as small as 1 kPa, triggering thresholds and their dependence on local stress state, hydrological environment, and frictional properties of faults are not well understood. Some studies find a simple threshold based on the peak amplitude of shaking while others find dependencies on frequency, recharge time, and other parameters. Considerable debate remains over the range of physical processes responsible for dynamic triggering, and the wide variation in dynamic triggering responses and time scales suggests triggering by multiple physical processes. Although Coulomb shear failure with various friction laws can often explain dynamic triggering, particularly instantaneous triggering, delayed dynamic triggering may be dependent on fluid transport and other slowly evolving aseismic processes. Although our understanding of the global distribution of dynamic triggering has improved, it is far from complete due to spatially uneven monitoring. A major challenge involves establishing statistical significance of potentially triggered earthquakes, particularly if they are isolated events or time-delayed with respect to triggering stresses. Here we highlight these challenges and opportunities with existing data. We focus on environmental dependence of dynamic triggering by large remote earthquakes particularly in volcanic and geothermal systems, as these systems often have high rates of background seismicity. In many volcanic and geothermal systems, such as the Geysers in Northern California, dynamic triggering of micro-earthquakes is frequent and predictable. In contrast, most active and even erupting volcanoes in Alaska (with the exception of the Katmai Volcanic Cluster) do not experience dynamic triggering. We explore why.

Long-acting κ opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity.

PubMed

Munro, Thomas A; Berry, Loren M; Van't Veer, Ashlee; Béguin, Cécile; Carroll, F Ivy; Zhao, Zhiyang; Carlezon, William A; Cohen, Bruce M

2012-05-29

Nor-BNI, GNTI and JDTic induce κ opioid antagonism that is delayed by hours and can persist for months. Other effects are transient. It has been proposed that these drugs may be slowly absorbed or distributed, and may dissolve in cell membranes, thus slowing elimination and prolonging their effects. Recent evidence suggests, instead, that they induce prolonged desensitization of the κ opioid receptor. To evaluate these hypotheses, we measured relevant physicochemical properties of nor-BNI, GNTI and JDTic, and the timecourse of brain and plasma concentrations in mice after intraperitoneal administration (using LC-MS-MS). In each case, plasma levels were maximal within 30 min and declined by >80% within four hours, correlating well with previously reported transient effects. A strong negative correlation was observed between plasma levels and the delayed, prolonged timecourse of κ antagonism. Brain levels of nor-BNI and JDTic peaked within 30 min, but while nor-BNI was largely eliminated within hours, JDTic declined gradually over a week. Brain uptake of GNTI was too low to measure accurately, and higher doses proved lethal. None of the drugs were highly lipophilic, showing high water solubility (> 45 mM) and low distribution into octanol (log D7.4 < 2). Brain homogenate binding was within the range of many shorter-acting drugs (>7% unbound). JDTic showed P-gp-mediated efflux; nor- BNI and GNTI did not, but their low unbound brain uptake suggests efflux by another mechanism. The negative plasma concentration-effect relationship we observed is difficult to reconcile with simple competitive antagonism, but is consistent with desensitization. The very slow elimination of JDTic from brain is surprising given that it undergoes active efflux, has modest affinity for homogenate, and has a shorter duration of action than nor-BNI under these conditions. We propose that this persistence may result from entrapment in cellular compartments such as lysosomes.

Comparison of delayed versus immediate pushing during second stage of labor for nulliparous women with epidural anesthesia.

PubMed

Gillesby, Erica; Burns, Suzan; Dempsey, Amy; Kirby, Shirley; Mogensen, Kami; Naylor, Kelly; Petrella, Joann; Vanicelli, Rebecca; Whelan, Breon

2010-01-01

To determine if the use of delayed pushing after the onset of the second stage of labor decreases the time of active pushing and decreases maternal fatigue. Randomized clinical trial. Labor and delivery unit of a not-for-profit community hospital. Convenience sample of nulliparous laboring women with epidural anesthesia. Immediate or delayed pushing (2 hours) during the second stage of labor at the time of complete cervical dilatation. The length of pushing, total length of the second stage, and maternal fatigue. A total of 77 women were studied (immediate pushing group=39; delayed pushing=38). The immediate pushing group averaged 94 (± 57) minutes in active pushing, while the delayed pushing group averaged 68 (± 46) minutes, a statistically significant difference (p=.04). No significant differences were found in fatigue scores between the immediate and delayed pushing groups (p>.05). We found that by delaying the onset of active pushing for 2 hours after the beginning of the second stage of labor, the time that nulliparous women with epidural anesthesia spent in active pushing was significantly decreased by 27%. Although the delayed pushing group rested for up to 2 hours, the total time in the second stage of labor averaged only 59 minutes longer than the immediate pushing group. © 2010 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Slow Inactivation in Shaker K Channels Is Delayed by Intracellular Tetraethylammonium

PubMed Central

González-Pérez, Vivian; Neely, Alan; Tapia, Christian; González-Gutiérrez, Giovanni; Contreras, Gustavo; Orio, Patricio; Lagos, Verónica; Rojas, Guillermo; Estévez, Tania; Stack, Katherine; Naranjo, David

2008-01-01

After removal of the fast N-type inactivation gate, voltage-sensitive Shaker (Shaker IR) K channels are still able to inactivate, albeit slowly, upon sustained depolarization. The classical mechanism proposed for the slow inactivation observed in cell-free membrane patches—the so called C inactivation—is a constriction of the external mouth of the channel pore that prevents K+ ion conduction. This constriction is antagonized by the external application of the pore blocker tetraethylammonium (TEA). In contrast to C inactivation, here we show that, when recorded in whole Xenopus oocytes, slow inactivation kinetics in Shaker IR K channels is poorly dependent on external TEA but severely delayed by internal TEA. Based on the antagonism with internally or externally added TEA, we used a two-pulse protocol to show that half of the channels inactivate by way of a gate sensitive to internal TEA. Such gate had a recovery time course in the tens of milliseconds range when the interpulse voltage was −90 mV, whereas C-inactivated channels took several seconds to recover. Internal TEA also reduced gating charge conversion associated to slow inactivation, suggesting that the closing of the internal TEA-sensitive inactivation gate could be associated with a significant amount of charge exchange of this type. We interpreted our data assuming that binding of internal TEA antagonized with U-type inactivation (Klemic, K.G., G.E. Kirsch, and S.W. Jones. 2001. Biophys. J. 81:814–826). Our results are consistent with a direct steric interference of internal TEA with an internally located slow inactivation gate as a “foot in the door” mechanism, implying a significant functional overlap between the gate of the internal TEA-sensitive slow inactivation and the primary activation gate. But, because U-type inactivation is reduced by channel opening, trapping the channel in the open conformation by TEA would also yield to an allosteric delay of slow inactivation. These results provide a framework to explain why constitutively C-inactivated channels exhibit gating charge conversion, and why mutations at the internal exit of the pore, such as those associated to episodic ataxia type I in hKv1.1, cause severe changes in inactivation kinetics. PMID:19029372

High-risk long QT syndrome mutations in the Kv7.1 (KCNQ1) pore disrupt the molecular basis for rapid K(+) permeation.

PubMed

Burgess, Don E; Bartos, Daniel C; Reloj, Allison R; Campbell, Kenneth S; Johnson, Jonathan N; Tester, David J; Ackerman, Michael J; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J; Ohno, Seiko; Horie, Minoru; Delisle, Brian P

2012-11-13

Type 1 long QT syndrome (LQT1) is caused by loss-of-function mutations in the KCNQ1 gene, which encodes the K(+) channel (Kv7.1) that underlies the slowly activating delayed rectifier K(+) current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss of function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confers a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated nonfunctional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamics simulations of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K(+)-K(+) repulsive forces required for rapid K(+) permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K(+) channel selectivity filter.

FOXC2 regulates the G2/M transition of stem cell-rich breast cancer cells and sensitizes them to PLK1 inhibition

PubMed Central

Pietilä, Mika; Vijay, Geraldine V.; Soundararajan, Rama; Yu, Xian; Symmans, William F.; Sphyris, Nathalie; Mani, Sendurai A.

2016-01-01

Cancer cells with stem cell properties (CSCs) underpin the chemotherapy resistance and high therapeutic failure of triple-negative breast cancers (TNBCs). Even though CSCs are known to proliferate more slowly, they are sensitive to inhibitors of G2/M kinases such as polo-like kinase 1 (PLK1). Understanding the cell cycle regulatory mechanisms of CSCs will help target these cells more efficiently. Herein, we identify a novel role for the transcription factor FOXC2, which is mostly expressed in CSCs, in the regulation of cell cycle of CSC-enriched breast cancer cells. We demonstrate that FOXC2 expression is regulated in a cell cycle-dependent manner, with FOXC2 protein levels accumulating in G2, and rapidly decreasing during mitosis. Knockdown of FOXC2 in CSC-enriched TNBC cells delays mitotic entry without significantly affecting the overall proliferation rate of these cells. Moreover, PLK1 activity is important for FOXC2 protein stability, since PLK1 inhibition reduces FOXC2 protein levels. Indeed, FOXC2 expressing CSC-enriched TNBC cells are sensitive to PLK1 inhibition. Collectively, our findings demonstrate a novel role for FOXC2 as a regulator of the G2/M transition and elucidate the reason for the observed sensitivity of CSC-enriched breast cancer cells to PLK1 inhibitor. PMID:27064522

Ten Guidelines for Preschool Music Programs.

ERIC Educational Resources Information Center

Warner, Laverne

1999-01-01

Asserts that music is an important part of child development, but music experiences in preschool are often haphazard. Provides suggestions for developing music activities, including: using singing as program basis; choosing easy to sing music; understanding the relationship between music and creativity; slowly introducing movement experiences;…

Technology in Business Communication.

ERIC Educational Resources Information Center

Rainey, Carolyn

Technology can be incorporated as a tool in business communication courses to help students format, revise, and enhance pieces of writing. The capabilities of the microcomputer should be introduced slowly to build competencies and confidence. This paper provides instructional tips and activities for introducing technology into assignments. Steps…

Prospective associations between measures of gross and fine motor coordination in infants and objectively measured physical activity and sedentary behavior in childhood

PubMed Central

Sánchez, Guillermo F López; Williams, Genevieve; Aggio, Daniel; Vicinanza, Domenico; Stubbs, Brendon; Kerr, Catherine; Johnstone, James; Roberts, Justine; Smith, Lee

2017-01-01

Abstract One important determinant of childhood physical activity and sedentary behavior may be that of motor development in infancy. The present analyses aimed to investigate whether gross and fine motor delays in infants were associated with objective and self-reported activity in childhood. Data were from the UK Millennium Cohort Study, a prospective cohort study, involving UK children born on or around the millennium (September 2000 and January 2002). When children were 9 months old, parents reported children's fine and gross motor-coordination, and at 7 years, sports club attendance and daily TV viewing time. Children's physical activity was measured using accelerometers at 7 years. Adjusted regression models were used to examine associations between delayed motor development and accelerometry measured moderate-to-vigorous physical activity and sedentary behavior, and parent-reported sport club attendance and TV viewing time. In this sample (n = 13,021), gross motor delay in infancy was associated with less time in moderate-to-vigorous physical activity (B −5.0 95% confidence interval [CI] −6.8, −3.2) and more time sedentary (B 13.5 95% CI 9.3, 17.8) in childhood. Gross and fine motor delays during infancy were associated with a reduced risk of having high attendance at sports clubs in childhood (both relative risk [RR] 0.7, 95% CI 0.6, 0.9). Fine motor delays, but not gross delays, were also associated with an increased risk of having high TV viewing time (RR 1.3 95% CI 1.0, 1.6). Findings from the present study suggest that delays in motor development in infancy are associated with physical activity and sedentary time in childhood. PMID:29145249

Prospective associations between measures of gross and fine motor coordination in infants and objectively measured physical activity and sedentary behavior in childhood.

PubMed

Sánchez, Guillermo F López; Williams, Genevieve; Aggio, Daniel; Vicinanza, Domenico; Stubbs, Brendon; Kerr, Catherine; Johnstone, James; Roberts, Justin; Smith, Lee

2017-11-01

One important determinant of childhood physical activity and sedentary behavior may be that of motor development in infancy. The present analyses aimed to investigate whether gross and fine motor delays in infants were associated with objective and self-reported activity in childhood. Data were from the UK Millennium Cohort Study, a prospective cohort study, involving UK children born on or around the millennium (September 2000 and January 2002). When children were 9 months old, parents reported children's fine and gross motor-coordination, and at 7 years, sports club attendance and daily TV viewing time. Children's physical activity was measured using accelerometers at 7 years. Adjusted regression models were used to examine associations between delayed motor development and accelerometry measured moderate-to-vigorous physical activity and sedentary behavior, and parent-reported sport club attendance and TV viewing time. In this sample (n = 13,021), gross motor delay in infancy was associated with less time in moderate-to-vigorous physical activity (B -5.0 95% confidence interval [CI] -6.8, -3.2) and more time sedentary (B 13.5 95% CI 9.3, 17.8) in childhood. Gross and fine motor delays during infancy were associated with a reduced risk of having high attendance at sports clubs in childhood (both relative risk [RR] 0.7, 95% CI 0.6, 0.9). Fine motor delays, but not gross delays, were also associated with an increased risk of having high TV viewing time (RR 1.3 95% CI 1.0, 1.6). Findings from the present study suggest that delays in motor development in infancy are associated with physical activity and sedentary time in childhood.

The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay

PubMed Central

Strickland, Justin C.; Feinstein, Max A.; Lacy, Ryan T.; Smith, Mark A.

2016-01-01

Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-second delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures. PMID:26964905

Differential effects of dopamine and opioid receptor blockade on motivated Coca-Cola drinking behavior and associated changes in brain, skin and muscle temperatures

PubMed Central

Kiyatkin, Eugene A.

2010-01-01

Although pharmacological blockade of both dopamine (DA) and opiate receptors has an inhibiting effect on appetitive motivated behaviors, it is still unclear which physiological mechanisms affected by these treatments underlie the behavioral deficit. To clarify this issue, we examined how pharmacological blockade of either DA (SCH23390 + eticlopride at 0.2 mg/kg each) or opioid receptors (naloxone 1 mg/kg) affects motor activity and temperature fluctuations in the nucleus acumens (NAcc), temporal muscle, and facial skin associated with motivated Coca-Cola drinking behavior in rats. In drug-free conditions, presentation of a cup containing 5 ml of Coca-Cola induced locomotor activation and rapid NAcc temperature increases, which both transiently decreased during drinking, and phasically increased again after the cup was emptied. Muscle temperatures followed this pattern, but increases were weaker and more delayed than those in the NAcc. Skin temperature rapidly dropped after cup presentation, remained at low levels during consumption, and slowly restored during post-consumption behavioral activation. By itself, DA receptor blockade induced robust decrease in spontaneous locomotion, moderate increases in brain and muscle temperatures, and a relative increase in skin temperatures, suggesting metabolic activation coupled with adynamia. Following this treatment (∼180 min), motor activation to cup presentation and Coca-Cola consumption were absent, but rats showed NAcc and muscle temperature increases following cup presentation comparable to control. Therefore, DA receptor blockade does not affect significantly central and peripheral autonomic responses to appetitive stimuli, but eliminates their behavior-activating effects, thus disrupting appetitive behavior and blocking consumption. Naloxone alone slightly decreased brain and muscle temperatures and increased skin temperatures, pointing at the enhanced heat loss and possible minor inhibition of basal metabolic activity. This treatment (∼60 min) had minimal effects on the latencies of drinking, but increased its total duration, with licking interrupted by pauses and retreats. This behavioral attenuation was coupled with weaker than in control locomotor activation and diminished temperature fluctuations in each recording location. Therefore, attenuation of normal behavioral and physiological responses to appetitive stimuli appears to underlie modest inhibiting effects of opiate receptor blockade on motivated behavior and consumption. PMID:20167257

Working Memory Delay Activity Predicts Individual Differences in Cognitive Abilities

PubMed Central

Unsworth, Nash; Fukuda, Keisuke; Awh, Edward; Vogel, Edward K.

2015-01-01

A great deal of prior research has examined the relation between estimates of working memory and cognitive abilities. Yet, the neural mechanisms that account for these relations are still not very well understood. The current study explored whether individual differences in working memory delay activity would be a significant predictor of cognitive abilities. A large number of participants performed multiple measures of capacity, attention control, long-term memory, working memory span, and fluid intelligence, and latent variable analyses were used to examine the data. During two working memory change detection tasks, we acquired EEG data and examined the contra-lateral delay activity. The results demonstrated that the contralateral delay activity was significantly related to cognitive abilities, and importantly these relations were because of individual differences in both capacity and attention control. These results suggest that individual differences in working memory delay activity predict individual differences in a broad range of cognitive abilities, and this is because of both differences in the number of items that can be maintained and the ability to control access to working memory. PMID:25436671

Working memory delay activity predicts individual differences in cognitive abilities.

PubMed

Unsworth, Nash; Fukuda, Keisuke; Awh, Edward; Vogel, Edward K

2015-05-01

A great deal of prior research has examined the relation between estimates of working memory and cognitive abilities. Yet, the neural mechanisms that account for these relations are still not very well understood. The current study explored whether individual differences in working memory delay activity would be a significant predictor of cognitive abilities. A large number of participants performed multiple measures of capacity, attention control, long-term memory, working memory span, and fluid intelligence, and latent variable analyses were used to examine the data. During two working memory change detection tasks, we acquired EEG data and examined the contralateral delay activity. The results demonstrated that the contralateral delay activity was significantly related to cognitive abilities, and importantly these relations were because of individual differences in both capacity and attention control. These results suggest that individual differences in working memory delay activity predict individual differences in a broad range of cognitive abilities, and this is because of both differences in the number of items that can be maintained and the ability to control access to working memory.

An electric vehicle driving behavior model in the traffic system with a wireless charging lane

NASA Astrophysics Data System (ADS)

He, Jia; Huang, Hai-Jun; Yang, Hai; Tang, Tie-Qiao

2017-09-01

In this paper, a car-following model is proposed to study each EV's (electric vehicle) motion behavior near the WCL (wireless charging lane) and a lane-changing rule is designed to describe the EV's lane-changing behavior. Then, the car-following model and lane-changing rule are used to explore each EV's micro driving behavior in a two-lane system with a WCL. Finally, the impacts of the WCL on each EV's motion behavior are investigated. The numerical results show that each EV should run slowly on the WCL if it needs charge of electricity, that the EV's lane-changing behavior has great effects on the whole system, that the delay time caused by the WCL turns more prominent when the traffic turns heavy, and that lane-changing frequently occurs near the WCL (especially at the downstream of the WCL).

Coupled resonator optical waveguide sensors: sensitivity and the role of slow light

NASA Astrophysics Data System (ADS)

Terrel, Matthew A.; Digonnet, Michel J. F.; Fan, Shanhui

2009-05-01

We compare the sensitivity of two configurations of coupled resonator optical waveguide (CROW) gyroscopes proposed by others to conventional optical gyroscopes. In both cases, we demonstrate that for equal device footprint and loss, neither of these CROW gyroscopes configurations is more sensitive than its conventional counterpart. In all cases, loss ultimately limits the maximum rotation sensitivity. The fact that light travels more slowly (i.e., with a greater group delay) in a CROW than in a fiber therefore has no effect on sensitivity. The only benefit slow light does have is that it reduces the device length requirement, or equivalently it increases the sensitivity per unit length. However, we show that this improvement is quantitatively the same as in an RFOG. These conclusions are not limited to these two CROW configurations or to rotation sensing, but applicable to any measurand that modifies the phase of the signal(s) traveling in the resonators.

Auditory agnosia associated with bilateral putaminal hemorrhage: A case report of clinical course of recovery.

PubMed

Tokida, Haruki; Kanaya, Yuhei; Shimoe, Yutaka; Imagawa, Madoka; Fukunaga, Shinya; Kuriyama, Masaru

2017-08-31

A 45-year-old right-handed man with a past history (10 years) of putaminal hemorrage presented with auditory agnosia associated with left putaminal hemorrhage. It was suspected that the auditory agnosia was due to bilateral damage in the acoustic radiations. Generalized auditory agnosia, verbal and non-verbal (music and environmental), was diagnosed by neuropsychological examinations. It improved 4 months after the onset. However, the clinical assessment of attention remained poor. The cognition for speech sounds improved slowly, but once it started to improve, the progress of improvement was rapid. Subsequently, the cognition for music sounds also improved, while the recovery of the cognition for environmental sounds remained delayed. There was a dissociation in recovery between these cognitions. He was able to return to work a year after the onset. We also reviewed the literature for cases with auditory agnosia and discuss their course of recovery in this report.

Ankle Distraction Arthroplasty: Indications, Technique, and Outcomes.

PubMed

Bernstein, Mitchell; Reidler, Jay; Fragomen, Austin; Rozbruch, S Robert

2017-02-01

Ankle distraction is an alternative to ankle arthrodesis or total ankle arthroplasty in younger patients with arthritis. Ankle distraction involves the use of external fixation to mechanically unload the ankle joint, which allows for stable, congruent range of motion in the setting of decreased mechanical loading, potentially promoting cartilage repair. Adjunct surgical procedures are frequently done to address lower-extremity malalignment, ankle equinus contractures, and impinging tibiotalar osteophytes. Patients can bear full weight during the treatment course. The distraction frame frequently uses a hinge, and patients are encouraged to do daily range-of-motion exercises. Although the initial goal of the procedure is to delay arthrodesis, many patients achieve lasting clinical benefits, obviating the need for total ankle arthroplasty or fusion. Complications associated with external fixation are common, and patients should be counseled that clinical improvements occur slowly and often are not achieved until at least 1 year after frame removal.

Update: Influenza Activity - United States, October 2-December 17, 2016.

PubMed

Shang, Mei; Blanton, Lenee; Kniss, Krista; Mustaquim, Desiree; Alabi, Noreen; Barnes, Stephen; Budd, Alicia; Davlin, Stacy L; Kramer, Natalie; Garg, Shikha; Cummings, Charisse N; Flannery, Brendan; Fry, Alicia M; Grohskopf, Lisa A; Olsen, Sonja J; Bresee, Joseph; Sessions, Wendy; Garten, Rebecca; Xu, Xiyan; Elal, Anwar Isa Abd; Gubareva, Larisa; Barnes, John; Wentworth, David E; Burns, Erin; Katz, Jacqueline; Jernigan, Daniel; Brammer, Lynnette

2016-12-30

This report summarizes U.S. influenza activity * during October 2-December 17, 2016. † Influenza activity in the United States remained low in October and has been slowly increasing since November. Influenza A viruses were identified most frequently, with influenza A (H3N2) viruses predominating. Most influenza viruses characterized during this period were genetically or antigenically similar to the reference viruses representing vaccine components recommended for production in the 2016-17 Northern Hemisphere influenza vaccines.

CK1/Doubletime activity delays transcription activation in the circadian clock

PubMed Central

O'Neil, Jenna L; Merz, Gregory E; Dusad, Kritika; Crane, Brian R; Young, Michael W

2018-01-01

In the Drosophila circadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms that regulate delayed PER degradation (and Clock reactivation) remain unclear. Here we show that phosphorylation of certain DBT target sites within a central region of PER affect PER inhibition of Clock and the stability of the PER/TIM complex. Our results indicate that phosphorylation of PER residue S589 stabilizes and activates PER inhibitory function in the presence of TIM, but promotes PER degradation in its absence. The role of DBT in regulating PER activity, stabilization and degradation ensures that these events are chronologically and biochemically linked, and contributes to the timing of an essential delay that influences the period of the circadian clock. PMID:29611807

Exploring the daily activities associated with delayed bedtime of Japanese university students.

PubMed

Asaoka, Shoichi; Komada, Yoko; Fukuda, Kazuhiko; Sugiura, Tatsuki; Inoue, Yuichi; Yamazaki, Katuo

2010-07-01

University students show delayed sleep-wake patterns, i.e., later bed- and rise-times, and this pattern is known to be associated with various malfunctions. There may be a variety of daily activities associated with their delayed sleep patterns, such as watching TV. However, it is unclear to what extent each activity possesses an impact on their sleep patterns. The purpose of this study was to determine the daily activities associated with delayed bedtime in Japanese university students who live with or without their families. Three hundred and thirty-one participants were required to record the timing and duration of their sleep and daily activities, and the data from the 275 students (160 men and 115 women; 19.01 +/- 1.66 years) who completely filled forms were used for analysis. The results of multiple regression analyses suggested that interpersonal communication late at night is one of the major factors leading to the delayed bedtime of students living away from home. Among those living with their families, indoor activities such as watching TV and using the Internet were related to their delayed bedtimes. Attending classes and having a morning meal were related to the earlier bedtimes of the students living away from home, but there were no activities associated with those of the students living with their families. These results suggest that ensuring attendance at morning classes and having appropriate mealtimes, as well as restricting the use of visual media and socializing activities at night, are necessary for preventing late bedtimes in university students.

Possible delayed respiratory depression following intrathecal injection of morphine and bupivacaine in an alpaca.

PubMed

Martínez, Miguel; Murison, Pamela J; Murrell, Jo

2014-01-01

To describe general anesthesia and successful treatment of an alpaca, which developed respiratory arrest 2 hours after intrathecal injection of morphine and bupivacaine. A 10-day-old female alpaca weighing 7.3 kg was presented to our hospital with a fractured right tibia. The cria was anesthetized to repair the fracture with a dynamic compression plate. Anesthesia was induced with IV propofol and maintained with sevoflurane in 100% oxygen. Prior to the start of surgery the alpaca received an unintended intrathecal injection of 0.6 mL of a solution of 0.5 mg morphine (0.068 mg/kg) and 1.5 mg bupivacaine (0.2 mg/kg), after an attempted lumbo-sacral epidural. The alpaca developed respiratory arrest 120 minutes after the intrathecal injection was administered. Adequate hemoglobin-oxygen saturation was maintained despite minimal intermittent manual ventilation, but marked hypercapnia developed (PaCO2 of 17.3 KPa [130 mm Hg]). Delayed respiratory depression resulting from cephalad migration of intrathecal morphine was suspected. Ventilation was supported until the end of surgery when sevoflurane was discontinued. The trachea remained intubated, 100% oxygen was supplied, and ventilation was supported at 2-4 breaths/min for the next 60 minutes, but no attempts to breathe spontaneously were detected. Intravenous naloxone (0.3 mg [0.04 mg/kg]) was administered slowly to effect until adequate spontaneous ventilation and full consciousness returned. The anesthetic recovery of the alpaca was rapid and uneventful after the opioid antagonist was given. Delayed respiratory depression is a potential complication after intrathecal administration of morphine. Careful dose-adjustment may reduce the risk, and close monitoring will result in early detection and treatment of this complication. © Veterinary Emergency and Critical Care Society 2014.

Interrelations in the Oxidative Metabolism of Free Fatty Acids, Glucose, and Glycerol in Normal and Hyperlipemic Patients A COMPARTMENTAL MODEL

PubMed Central

Malmendier, C. L.; Delcroix, C.; Berman, M.

1974-01-01

Palmitate, glucose, and glycerol oxidation to CO2 have been investigated in the fasted state in ten normal subjects and nine patients (six hyperlipoproteinemias, one xanthomatosis, and two glycogenosis) after intravenous injection of [1-14C]palmitate, [1-14C]glucose, or [1-14C]glycerol in tracer amounts. The specific activities and concentrations of plasma palmitate, glycerol, or glucose and expired CO2 were measured at various intervals after the injection for a period of 24 h. All the studies were analyzed in terms of a multicompartment model describing the structure for each of the subsystems, the transfer of carbon label between subsystems, and the oxidation to CO2. A bicarbonate subsystem was also included in the model to account for its role in shaping the CO2 curves. All the CO2 activity following a palmitate injection could be accounted for by a direct oxidative pathway from plasm FFA with the addition of a 20-min delay compartment. The same also applied to glucose, except that the delay compartment had a mean time of about 150 min. Only about a third of the injected glycerol was directly oxidized to CO2 from plasma; the delay time was about 4 min. Most of the remainder was converted to glucose. In normals about 45% of the FFA is oxidized to CO2 directly. This constitutes about 30% of the total CO2 output. In hyperlipemia the CO2 output is nearly unchanged and the contribution from FFA is nearly the same. There is a considerable increase (factor of 2), however, in FFA mobilization, most of which is probably diverted to triglyceride synthesis. The glucose and glycerol subsystems are roughly the same in normals and hyperlipemics. About 50% of glucose is oxidized by the direct pathways which accounts for about 35% of the CO2 output. Glycerol accounts for only 1.5% of the CO2 produced. Major changes occurred in the glycerol and glucose subsystems in glycogenosis. The changes are consistent with the known deficiency in glucose-6-phosphatase in this disorder. There is a considerable reduction (factor of 2 or more) in the release of glucose to plasma (gluconeogenesis) and in the conversion of glycerol to glucose. Despite the integration of the kinetics of the glucose, glycerol, and FFA subsystems over a 24-h period, 36% of the CO2 production was still unaccounted for in normals and 50% in hyperlipemics. Thus, some of the carbon must wind up in very slowly turning-over pools which supply CO2 through subsystems not covered in these studies (triglycerides, glycogen, amino acids, etc.). All the modeling was carried out with the aid of the SAAM25 computer program. PMID:4527190

Delay-slope-dependent stability results of recurrent neural networks.

PubMed

Li, Tao; Zheng, Wei Xing; Lin, Chong

2011-12-01

By using the fact that the neuron activation functions are sector bounded and nondecreasing, this brief presents a new method, named the delay-slope-dependent method, for stability analysis of a class of recurrent neural networks with time-varying delays. This method includes more information on the slope of neuron activation functions and fewer matrix variables in the constructed Lyapunov-Krasovskii functional. Then some improved delay-dependent stability criteria with less computational burden and conservatism are obtained. Numerical examples are given to illustrate the effectiveness and the benefits of the proposed method.

Synchronization and anti-synchronization of a fractional order delayed memristor-based chaotic system using active control

NASA Astrophysics Data System (ADS)

Ding, Dawei; Qian, Xin; Wang, Nian; Liang, Dong

2018-05-01

In this paper, the issue of synchronization and anti-synchronization for fractional-delayed memristor-based chaotic system is studied by using active control strategy. Firstly, some explicit conditions are proposed to guarantee the synchronization and anti-synchronization of the proposed system. Secondly, the influence of order and time delay on the synchronization (anti-synchronization) is discussed. It reveals that synchronization (anti-synchronization) is faster as the order increases or the time delay decreases. Finally, some numerical simulations are presented to verify the validity of our theoretical analysis.

An active balance board system with real-time control of stiffness and time-delay to assess mechanisms of postural stability.

PubMed

Cruise, Denise R; Chagdes, James R; Liddy, Joshua J; Rietdyk, Shirley; Haddad, Jeffrey M; Zelaznik, Howard N; Raman, Arvind

2017-07-26

Increased time-delay in the neuromuscular system caused by neurological disorders, concussions, or advancing age is an important factor contributing to balance loss (Chagdes et al., 2013, 2016a,b). We present the design and fabrication of an active balance board system that allows for a systematic study of stiffness and time-delay induced instabilities in standing posture. Although current commercial balance boards allow for variable stiffness, they do not allow for manipulation of time-delay. Having two controllable parameters can more accurately determine the cause of balance deficiencies, and allows us to induce instabilities even in healthy populations. An inverted pendulum model of human posture on such an active balance board predicts that reduced board rotational stiffness destabilizes upright posture through board tipping, and limit cycle oscillations about the upright position emerge as feedback time-delay is increased. We validate these two mechanisms of instability on the designed balance board, showing that rotational stiffness and board time-delay induced the predicted postural instabilities in healthy, young adults. Although current commercial balance boards utilize control of rotational stiffness, real-time control of both stiffness and time-delay on an active balance board is a novel and innovative manipulation to reveal balance deficiencies and potentially improve individualized balance training by targeting multiple dimensions contributing to standing balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relations among Temperament, Self-regulatory Strategies and Gender in Predicting Delay of Gratification.

PubMed

Hong, Fang; Doan, Stacey N; Lopez, Angelica; Evans, Gary W

2017-01-01

Self-regulation is associated with many positive outcomes, but there is limited information about individual difference regarding children's spontaneous use of strategies to self-regulate and the relative success of those strategies. In the current study, we examined whether temperament and gender are associated with self-regulation and explored the types of spontaneous strategies children use during Mischel's delay of gratification protocol. In addition, we investigated whether spontaneous strategy use during the task could moderate the effects of temperament on self-regulation and whether temperament would mediate the effect of gender on self-regulation. Participants were 349 9-year-olds (182 boys, M age = 9.18, SD = 1.17). Mothers reported on children's temperament and the Delay of Gratification task was used to assess self-regulation. Both temperament and child's gender were significantly associated with children's delay time. Girls were able to delay longer than boys, and children scoring high on activity level were less able to delay. Activity level also mediated the relationship between gender and delay time. Finally, we found an interaction effect between activity level and certain strategies in relation to self-regulatory behavior.

Relations among Temperament, Self-regulatory Strategies and Gender in Predicting Delay of Gratification

PubMed Central

Hong, Fang; Doan, Stacey N.; Lopez, Angelica; Evans, Gary W.

2017-01-01

Self-regulation is associated with many positive outcomes, but there is limited information about individual difference regarding children’s spontaneous use of strategies to self-regulate and the relative success of those strategies. In the current study, we examined whether temperament and gender are associated with self-regulation and explored the types of spontaneous strategies children use during Mischel’s delay of gratification protocol. In addition, we investigated whether spontaneous strategy use during the task could moderate the effects of temperament on self-regulation and whether temperament would mediate the effect of gender on self-regulation. Participants were 349 9-year-olds (182 boys, Mage = 9.18, SD = 1.17). Mothers reported on children’s temperament and the Delay of Gratification task was used to assess self-regulation. Both temperament and child’s gender were significantly associated with children’s delay time. Girls were able to delay longer than boys, and children scoring high on activity level were less able to delay. Activity level also mediated the relationship between gender and delay time. Finally, we found an interaction effect between activity level and certain strategies in relation to self-regulatory behavior. PMID:29163300

Caudate responses to reward anticipation associated with delay discounting behavior in healthy youth

PubMed Central

Benningfield, Margaret M.; Blackford, Jennifer U.; Ellsworth, Melissa E.; Samanez-Larkin, Gregory R.; Martin, Peter R.; Cowan, Ronald L.; Zald, David H.

2014-01-01

Background Choices requiring delay of gratification made during adolescence can have significant impact on life trajectory. Willingness to delay gratification can be measured using delay discounting tasks that require a choice between a smaller immediate reward and a larger delayed reward. Individual differences in the subjective value of delayed rewards are associated with risk for development of psychopathology including substance abuse. The neurobiological underpinnings related to these individual differences early in life are not fully understood. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that individual differences in delay discounting behavior in healthy youth are related to differences in responsiveness to potential reward. Method Nineteen 10 to 14 year-olds performed a monetary incentive delay task to assess neural sensitivity to potential reward and a questionnaire to measure discounting of future monetary rewards. Results Left ventromedial caudate activation during anticipation of potential reward was negatively correlated with delay discounting behavior. There were no regions where brain responses during notification of reward outcome were associated with discounting behavior. Conclusions Brain activation during anticipation of potential reward may serve as a marker for individual differences in ability or willingness to delay gratification in healthy youth. PMID:24309299

An Argument for Weakly Magnetized, Slowly Rotating Progenitors of Long Gamma-Ray Bursts

NASA Astrophysics Data System (ADS)

Moreno Méndez, Enrique

2014-01-01

Using binary evolution with Case-C mass transfer, the spins of several black holes (BHs) in X-ray binaries (XBs) have been predicted and confirmed (three cases) by observations. The rotational energy of these BHs is sufficient to power up long gamma-ray bursts (GRBs) and hypernovae (HNe) and still leave a Kerr BH behind. However, strong magnetic fields and/or dynamo effects in the interior of such stars deplete their cores from angular momentum preventing the formation of collapsars. Thus, even though binaries can produce Kerr BHs, most of their rotation is acquired from the stellar mantle, with a long delay between BH formation and spin up. Such binaries would not form GRBs. We study whether the conditions required to produce GRBs can be met by the progenitors of such BHs. Tidal-synchronization and Alfvén timescales are compared for magnetic fields of different intensities threading He stars. A search is made for a magnetic field range that allows tidal spin up all the way in to the stellar core but prevents its slow down during differential rotation phases. The energetics for producing a strong magnetic field during core collapse, which may allow for a GRB central engine, are also estimated. An observationally reasonable choice of parameters is found (B <~ 102 G threading a slowly rotating He star) that allows Fe cores to retain substantial angular momentum. Thus, the Case-C mass-transfer binary channel is capable of explaining long GRBs. However, the progenitors must have low initial spin and low internal magnetic field throughout their H-burning and He-burning phases.

Bringing "Invisible" Side Activities to Light. A Case Study of Rural Female Entrepreneurs in the Veenkolonien, the Netherlands

ERIC Educational Resources Information Center

Markantoni, Marianna; van Hoven, Bettina

2012-01-01

Over the past 20 years, rural areas in Western societies have transformed from a production to a consumption space. Much research on rural diversification and revitalization has focused on farmers and their wives. However, it is useful to examine side activities run by non-farm women which have slowly emerged in the last few years. In view of…

Macroscopic response in active nonlinear photonic crystals.

PubMed

Alagappan, Gandhi; John, Sajeev; Li, Er Ping

2013-09-15

We derive macroscopic equations of motion for the slowly varying electric field amplitude in three-dimensional active nonlinear optical nanostructures. We show that the microscopic Maxwell equations and polarization dynamics can be simplified to a macroscopic one-dimensional problem in the direction of group velocity. For a three-level active material, we derive the steady-state equations for normal mode frequency, threshold pumping, nonlinear Bloch mode amplitude, and lasing in photonic crystals. Our analytical results accurately recapture the results of exact numerical methods.

The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay.

PubMed

Strickland, Justin C; Feinstein, Max A; Lacy, Ryan T; Smith, Mark A

2016-05-01

Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-s delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of quebracho tannin extract (Schinopsis balansae Engl.) and activated charcoal on nitrogen balance, rumen microbial protein synthesis and faecal composition of growing Boer goats.

PubMed

Al-Kindi, Amal; Dickhoefer, Uta; Schlecht, Eva; Sundrum, Albert; Schiborra, Anne

2016-08-01

Under irrigated arid conditions, organic fertiliser rich in slowly decomposable nitrogen (N) and carbon (C) is needed for soil fertility maintenance. Feeding ruminants with condensed tannins will lower ruminal protein degradation, reduce urinary N excretion and might increase the faecal fraction of slowly decomposable N. Supplementation with activated charcoal (AC) might enrich manure with slowly degrading C. Therefore, we investigated the effects of feeding quebracho tannin extract (QTE) and AC on the N balance of goats, the efficiency of microbial protein synthesis in the rumen (EMPS) and the composition of faeces. The feeding trial comprised three periods; in each period, 12 male Boer goats (28 ± 3.9 kg live weight) were assigned to six treatments: a Control diet (per kg diet 500 g grass hay and 500 g concentrate) and to further five treatments the Control diet was supplemented with QTE (20 g and 40 g/kg; diets QTE2 and QTE4, respectively), with AC (15 g and 30 g/kg, diets AC1.5 and AC3.0, respectively) and a mixture of QTE (20 g/kg) plus AC (15 g/kg) (diet QTEAC). In addition to the N balance, EMPS was calculated from daily excretions of purine derivatives, and the composition of faecal N was determined. There was no effect of QTE and AC supplementation on the intake of organic matter (OM), N and fibre, but apparent total tract digestibility of OM was reduced (p = 0.035). Feeding QTE induced a shift in N excretion from urine to faeces (p ≤ 0.001) without altering N retention. Total N excretion tended to decrease with QTE treatments (p = 0.053), but EMPS was not different between treatments. Faecal C excretion was higher in QTE and AC treatments (p = 0.001) compared with the Control, while the composition of faecal N differed only in concentration of undigested dietary N (p = 0.001). The results demonstrate that QTE can be included into diets of goats up to 40 g/kg, without affecting N utilisation, but simultaneously increasing the excretion of slowly decomposable N and C fractions. Feeding AC up to 30 g/kg of the diet increases slowly degradable faecal C concentration, without negative effects on N metabolism of goats.

Noise pair velocity and range echo location system

DOEpatents

Erskine, D.J.

1999-02-16

An echo-location method for microwaves, sound and light capable of using incoherent and arbitrary waveforms of wide bandwidth to measure velocity and range (and target size) simultaneously to high resolution is disclosed. Two interferometers having very long and nearly equal delays are used in series with the target interposed. The delays can be longer than the target range of interest. The first interferometer imprints a partial coherence on an initially incoherent source which allows autocorrelation to be performed on the reflected signal to determine velocity. A coherent cross-correlation subsequent to the second interferometer with the source determines a velocity discriminated range. Dithering the second interferometer identifies portions of the cross-correlation belonging to a target apart from clutter moving at a different velocity. The velocity discrimination is insensitive to all slowly varying distortions in the signal path. Speckle in the image of target and antenna lobing due to parasitic reflections is minimal for an incoherent source. An arbitrary source which varies its spectrum dramatically and randomly from pulse to pulse creates a radar elusive to jamming. Monochromatic sources which jigger in frequency from pulse to pulse or combinations of monochromatic sources can simulate some benefits of incoherent broadband sources. Clutter which has a symmetrical velocity spectrum will self-cancel for short wavelengths, such as the apparent motion of ground surrounding target from a sidelooking airborne antenna. 46 figs.

How decoherence affects the probability of slow-roll eternal inflation

NASA Astrophysics Data System (ADS)

Boddy, Kimberly K.; Carroll, Sean M.; Pollack, Jason

2017-07-01

Slow-roll inflation can become eternal if the quantum variance of the inflaton field around its slowly rolling classical trajectory is converted into a distribution of classical spacetimes inflating at different rates, and if the variance is large enough compared to the rate of classical rolling that the probability of an increased rate of expansion is sufficiently high. Both of these criteria depend sensitively on whether and how perturbation modes of the inflaton interact and decohere. Decoherence is inevitable as a result of gravitationally sourced interactions whose strength are proportional to the slow-roll parameters. However, the weakness of these interactions means that decoherence is typically delayed until several Hubble times after modes grow beyond the Hubble scale. We present perturbative evidence that decoherence of long-wavelength inflaton modes indeed leads to an ensemble of classical spacetimes with differing cosmological evolutions. We introduce the notion of per-branch observables—expectation values with respect to the different decohered branches of the wave function—and show that the evolution of modes on individual branches varies from branch to branch. Thus, single-field slow-roll inflation fulfills the quantum-mechanical criteria required for the validity of the standard picture of eternal inflation. For a given potential, the delayed decoherence can lead to slight quantitative adjustments to the regime in which the inflaton undergoes eternal inflation.

Chitosan inactivates spoilage yeasts but enhances survival of Escherichia coli O157:H7 in apple juice.

PubMed

Kiskó, G; Sharp, R; Roller, S

2005-01-01

To develop new measures for controlling both spoilage and pathogenic micro-organisms in unpasteurized apple juice using chitosan. Micro-organisms were isolated and identified from apple juice treated or untreated with chitosan using enrichment, selective media, microscopy, substrate assimilation patterns and ribosomal DNA profiling. Chitosan (0.05-0.1%) delayed spoilage by yeasts at 25 degrees C for up to 12 days but the effect was species specific: Kloeckera apiculata and Metschnikowia pulcherrima were inactivated but Saccharomyces cerevisiae and Pichia spp. multiplied slowly. In challenge experiments at 25 degrees C, total yeast counts were 3-5 log CFU ml(-1) lower in chitosan-treated juices than in the controls for 4 days but the survival of Escherichia coli O157:H7 was extended from 1 to 2 days; at 4 degrees C, chitosan reduced the yeast counts by 2-3 log CFU ml(-1) for up to 10 days but survival of the pathogen was prolonged from 3 to 5 days. The survival of Salmonella enterica serovar Typhimurium was unaffected by chitosan at either temperature. The addition of chitosan to apple juice delayed spoilage by yeasts but enhanced the survival of E. coli O157:H7. The results suggest that the use of chitosan in the treatment of fruit juices may potentially lead to an increased risk of food poisoning from E. coli O157:H7.

Killer whales (Orcinus orca) face protracted health risks associated with lifetime exposure to PCBs.

PubMed

Hickie, Brendan E; Ross, Peter S; Macdonald, Robie W; Ford, John K B

2007-09-15

Polychlorinated biphenyl (PCB) concentrations declined rapidly in environmental compartments and most biota following implementation of regulations in the 1970s. However, the metabolic recalcitrance of PCBs may delay responses to such declines in large, long-lived species, such as the endangered and highly PCB-contaminated resident killer whales (Orcinus orca) of the Northeastern Pacific Ocean. To investigate the influence of life history on PCB-related health risks, we developed models to estimate PCB concentrations in killer whales during the period from 1930 forward to 2030, both within a lifetime (approximately 50 years) and across generations, and then evaluated these in the context of health effects thresholds established for marine mammals. Modeled PCB concentrations in killer whales responded slowly to changes in loadings to the environment as evidenced by slower accumulation and lower magnitude increases in PCB concentrations relative to prey, and a delayed decline that was particularly evident in adult males. Since PCBs attained peak levels well above the effects threshold (17 mg/kg lipid) in approximately 1969, estimated concentrations in both the northern and the more contaminated southern resident populations have declined gradually. Projections suggest that the northern resident population could largely fall below the threshold concentration by 2030 while the endangered southern residents may not do so until at least 2063. Long-lived aquatic mammals are therefore not protected from PCBs by current dietary residue guidelines.

Noise pair velocity and range echo location system

DOEpatents

Erskine, David J.

1999-01-01

An echo-location method for microwaves, sound and light capable of using incoherent and arbitrary waveforms of wide bandwidth to measure velocity and range (and target size) simultaneously to high resolution. Two interferometers having very long and nearly equal delays are used in series with the target interposed. The delays can be longer than the target range of interest. The first interferometer imprints a partial coherence on an initially incoherent source which allows autocorrelation to be performed on the reflected signal to determine velocity. A coherent cross-correlation subsequent to the second interferometer with the source determines a velocity discriminated range. Dithering the second interferometer identifies portions of the cross-correlation belonging to a target apart from clutter moving at a different velocity. The velocity discrimination is insensitive to all slowly varying distortions in the signal path. Speckle in the image of target and antenna lobing due to parasitic reflections is minimal for an incoherent source. An arbitrary source which varies its spectrum dramatically and randomly from pulse to pulse creates a radar elusive to jamming. Monochromatic sources which jigger in frequency from pulse to pulse or combinations of monochromatic sources can simulate some benefits of incoherent broadband sources. Clutter which has a symmetrical velocity spectrum will self-cancel for short wavelengths, such as the apparent motion of ground surrounding target from a sidelooking airborne antenna.

Neotectonics and seismicity of a slowly deforming segment of the Adria-Europe convergence zone - the northern Dinarides fold-and-thrust belt

NASA Astrophysics Data System (ADS)

Ustaszewski, Kamil; Herak, Marijan; Tomljenović, Bruno; Herak, Davorka; Matej, Srebrenka

2014-05-01

With GPS-derived shortening rates of c. 3-5 mm/a, the Adria-Europe convergence zone across the fold-and-thrust belt of the Dinarides (Balkan Peninsula) is a slowly deforming plate boundary by global standards. We have analysed the active tectonics and instrumental seismicity of the northernmost segment of this fold-and-thrust belt at its border to the Pannonian Basin. This area hosts a Maastrichtian collisional suture formed by closure of Mesozoic fragments of the Neotethys, overprinted by Miocene back-arc extension, which led to the exhumation of greenschist- to amphibolite-grade rocks in several core complexes. Geological, geomorphological and reflection seismic data provide evidence for a compressive or transpressive reactivation of extensional faults after about 5 Ma. The study area represents the seismically most active region of the Dinarides apart from the Adriatic Sea coast and the area around Zagreb. The strongest instrumentally recorded earthquake (27 October 1969) affected the city of Banja Luka (northern Bosnia and Herzegovina). Fault plane solutions for the main shock (ML 6.4) and its largest foreshock (ML 6.0) indicate reverse faulting along ESE-WNW-striking nodal planes and generally N-S trending pressure axes. The spatial distribution of epicentres and focal depths, analyses of the macroseismic field and fault-plane solutions for several smaller events suggest on-going shortening in the internal Dinarides. Our results therefore imply that current Adria-Europe convergence is widely distributed across c. 300 km, rendering the entire Dinarides fold-and-thrust belt a slowly deforming plate boundary.

Use of blood-pool imaging in evaluation of diffuse activity patterns in technetium-99m pyrophosphate myocardial scintigraphy.

PubMed

Cowley, M J; Mantle, J A; Rogers, W J; Russell, R O; Rackley, C E; Logic, J R

1979-06-01

It has been suggested that diffuse Tc-99m pyrophosphate precordial activity may be due to persistent blood-pool activity in routine delayed views during myocardial imaging. To answer this question, we reviewed myocardial scintigrams recorded 60--90 min following the injection of 12--15 mCi of Tc-99m pyrophosphate for the presence of diffuse precordial activity, and compared these with early images of the blood pool in 265 patients. Diffuse activity in the delayed images was identified in 48 patients: in 20 with acute myocardial infarction and in 28 with no evidence of it. Comparison of these routine delayed images with early views of the blood pool revealed two types of patterns. In patients with acute infarction, 95% had delayed images that were distinguishable from blood pool either because the activity was smaller than the early blood pool, or by the presence of localized activity superimposed on diffuse activity identical to blood pool. In those without infarction, 93% had activity distribution in routine delayed views matching that in the early blood-pool images. The usefulness of the diffuse TcPPi precordial activity in myocardial infarction is improved when early blood-pool imaging is used to exclude persistence of blood-pool activity as its cause. Moreover, it does not require additional amounts of radioactivity nor complex computer processing, a feature that may be of value in the community hospital using the technique to "rule out" infarction 24--72 hr after onset of suggestive symptoms.

Serotonin delays habituation of leech swim response to touch.

PubMed

Alkatout, Bilal A; Marvin, Nicole M; Crisp, Kevin M

2007-08-22

Serotonin, acting through a cAMP-signaling pathway, delayed habituation to criterion of the leech's swim response to touch. This delay was reversed by crushing the connective between serotonin-exposed and serotonin-naive ganglia, and correlated with an increase in spontaneous impulse activity in this connective. We suggest that increased activity in intersegmental interneurons may play a role in maintaining swim responsiveness when concentrations of serotonin are elevated.

Relationship between Respiration and Photosynthesis in Guard Cell and Mesophyll Cell Protoplasts of Commelina communis L

PubMed Central

Gautier, Hélène; Vavasseur, Alain; Gans, Pierre; Lascève, Gérard

1991-01-01

A mass spectrometric method combining 16O/18O and 12C/13C isotopes was used to quantify the unidirectional fluxes of O2 and CO2 during a dark to light transition for guard cell protoplasts and mesophyll cell protoplasts of Commelina communis L. In darkness, O2 uptake and CO2 evolution were similar on a protein basis. Under light, guard cell protoplasts evolved O2 (61 micromoles of O2 per milligram of chlorophyll per hour) almost at the same rate as mesophyll cell protoplasts (73 micromoles of O2 per milligram of chlorophyll per hour). However, carbon assimilation was totally different. In contrast with mesophyll cell protoplasts, guard cell protoplasts were able to fix CO2 in darkness at a rate of 27 micromoles of CO2 per milligram of chlorophyll per hour, which was increased by 50% in light. At the onset of light, a delay observed for guard cell protoplasts between O2 evolution and CO2 fixation and a time lag before the rate of saturation suggested a carbon metabolism based on phosphoenolpyruvate carboxylase activity. Under light, CO2 evolution by guard cell protoplasts was sharply decreased (37%), while O2 uptake was slowly inhibited (14%). A control of mitochondrial activity by guard cell chloroplasts under light via redox equivalents and ATP transfer in the cytosol is discussed. From this study on protoplasts, we conclude that the energy produced at the chloroplast level under light is not totally used for CO2 assimilation and may be dissipated for other purposes such as ion uptake. PMID:16668030

Respiratory-related activity in hypoglossal neurons across sleep-waking states in cats.

PubMed

Richard, C A; Harper, R M

1991-02-22

Activity of behaviorally identified neurons in the hypoglossal nuclei supplying the genioglossal muscles was assessed in intact, unanesthetized cats across sleep-wake states. Nineteen of 37 recorded cells discharged on a breath-by-breath or tonic basis with the respiratory cycle in at least one state. Most respiratory-related cells discharged more slowly during quiet sleep, whereas rates during rapid eye movement sleep were similar to those of waking.

Kinetic, pharmacological and activity-dependent separation of two Ca2+ signalling pathways mediated by type 1 metabotropic glutamate receptors in rat Purkinje neurones

PubMed Central

Canepari, Marco; Ogden, David

2006-01-01

Type 1 metabotropic glutamate receptors (mGluR1) in Purkinje neurones (PNs) are important for motor learning and coordination. Here, two divergent mGluR1 Ca2+-signalling pathways and the associated membrane conductances were distinguished kinetically and pharmacologically after activation by 1-ms photorelease of l-glutamate or by bursts of parallel fibre (PF) stimulation. A new, mGluR1-mediated transient K+ conductance was seen prior to the slow EPSC (sEPSC). It was seen only in PNs previously allowed to fire spontaneously or held at depolarized potentials for several seconds and was slowly inhibited by agatoxin IVA, which blocks P/Q-type Ca2+ channels. It peaked in 148 ms, had well-defined kinetics and, unlike the sEPSC, was abolished by the phospholipase C (PLC) inhibitor U73122. It was blocked by the BK Ca2+-activated K+ channel blocker iberiotoxin and unaffected by apamin, indicating selective activation of BK channels by PLC-dependent store-released Ca2+. The K+ conductance and underlying transient Ca2+ release showed a highly reproducible delay of 99.5 ms following PF burst stimulation, with a precision of 1–2 ms in repeated responses of the same PN, and a subsequent fast rise and fall of Ca2+ concentration. Analysis of Ca2+ signals showed that activation of the K+ conductance by Ca2+ release occured in small dendrites and subresolution structures, most probably spines. The results show that PF burst stimulation activates two pathways of mGluR1 signalling in PNs. First, transient, PLC-dependent Ca2+ release from stores with precisely reproducible timing and second, slower Ca2+ influx in the cation-permeable sEPSC channel. The priming by prior Ca2+ influx in P/Q-type Ca2+ channels may determine the path of mGluR1 signalling. The precise timing of PLC-mediated store release may be important for interactions of PF mGluR1 signalling with other inputs to the PN. PMID:16497716

Bi-frontal direct current stimulation affects delay discounting choices.

PubMed

Hecht, David; Walsh, Vincent; Lavidor, Michal

2013-01-01

In delay discounting tasks, participants decide between receiving a certain amount of money now or a larger sum sometime in the future. This study investigated the effects of transcranial direct current stimulation on delay discounting. Participants made delay discounting choices while receiving a bi-frontal stimulation of right-hemisphere anodal/left-hemisphere cathodal, left-hemisphere anodal/right-hemisphere cathodal, and sham stimulation, in three separate sessions. When the difference between the alternatives was 10% or more, participants generally preferred to wait for the larger sum. Nevertheless, there were more choices of smaller "immediate" gains, instead of the larger delayed options, when the left dorsolateral prefrontal cortex (DLPFC) was facilitated and the right DLPFC inhibited, compared to the sham stimulation. These observations indicate the significant role of the prefrontal cortex in delay discounting choices, and demonstrate that increased left frontal activation combined with decreased right frontal activation can alter decision-making by intensifying a tendency to choose immediate gains.

An interpolated activity during the knowledge-of-results delay interval eliminates the learning advantages of self-controlled feedback schedules.

PubMed

Carter, Michael J; Ste-Marie, Diane M

2017-03-01

The learning advantages of self-controlled knowledge-of-results (KR) schedules compared to yoked schedules have been linked to the optimization of the informational value of the KR received for the enhancement of one's error-detection capabilities. This suggests that information-processing activities that occur after motor execution, but prior to receiving KR (i.e., the KR-delay interval) may underlie self-controlled KR learning advantages. The present experiment investigated whether self-controlled KR learning benefits would be eliminated if an interpolated activity was performed during the KR-delay interval. Participants practiced a waveform matching task that required two rapid elbow extension-flexion reversals in one of four groups using a factorial combination of choice (self-controlled, yoked) and KR-delay interval (empty, interpolated). The waveform had specific spatial and temporal constraints, and an overall movement time goal. The results indicated that the self-controlled + empty group had superior retention and transfer scores compared to all other groups. Moreover, the self-controlled + interpolated and yoked + interpolated groups did not differ significantly in retention and transfer; thus, the interpolated activity eliminated the typically found learning benefits of self-controlled KR. No significant differences were found between the two yoked groups. We suggest the interpolated activity interfered with information-processing activities specific to self-controlled KR conditions that occur during the KR-delay interval and that these activities are vital for reaping the associated learning benefits. These findings add to the growing evidence that challenge the motivational account of self-controlled KR learning advantages and instead highlights informational factors associated with the KR-delay interval as an important variable for motor learning under self-controlled KR schedules.

The effectiveness of graded activity for low back pain in occupational healthcare.

PubMed

Steenstra, I A; Anema, J R; Bongers, P M; de Vet, H C W; Knol, D L; van Mechelen, W

2006-11-01

Low back pain is a common medical and social problem associated with disability and absence from work. Knowledge on effective return to work (RTW) interventions is scarce. To determine the effectiveness of graded activity as part of a multistage RTW programme. Randomised controlled trial. Occupational healthcare. 112 workers absent from work for more than eight weeks due to low back pain were randomised to either graded activity (n = 55) or usual care (n = 57). Graded activity, a physical exercise programme aimed at RTW based on operant-conditioning behavioural principles. The number of days off work until first RTW for more then 28 days, total number of days on sick leave during follow up, functional status, and severity of pain. Follow up was 26 weeks. Graded activity prolonged RTW. Median time until RTW was equal to the total number of days on sick leave and was 139 (IQR = 69) days in the graded activity group and 111 (IQR = 76) days in the usual care group (hazard ratio = 0.52, 95% CI 0.32 to 0.86). An interaction between a prior workplace intervention and graded activity, together with a delay in the start of the graded activity intervention, explained most of the delay in RTW (hazard ratio = 0.86, 95% CI 0.40 to 1.84 without prior intervention and 0.39, 95% CI 0.19 to 0.81 with prior intervention). Graded activity did not improve pain or functional status clinically significantly. Graded activity was not effective for any of the outcome measures. Different interventions combined can lead to a delay in RTW. Delay in referral to graded activity delays RTW. In implementing graded activity special attention should be paid to the structure and process of care.

Spatial Analysis of Slowly Oscillating Electric Activity in the Gut of Mice Using Low Impedance Arrayed Microelectrodes

PubMed Central

Taniguchi, Mizuki; Kajioka, Shunichi; Shozib, Habibul B.; Sawamura, Kenta; Nakayama, Shinsuke

2013-01-01

Smooth and elaborate gut motility is based on cellular cooperation, including smooth muscle, enteric neurons and special interstitial cells acting as pacemaker cells. Therefore, spatial characterization of electric activity in tissues containing these electric excitable cells is required for a precise understanding of gut motility. Furthermore, tools to evaluate spatial electric activity in a small area would be useful for the investigation of model animals. We thus employed a microelectrode array (MEA) system to simultaneously measure a set of 8×8 field potentials in a square area of ∼1 mm2. The size of each recording electrode was 50×50 µm2, however the surface area was increased by fixing platinum black particles. The impedance of microelectrode was sufficiently low to apply a high-pass filter of 0.1 Hz. Mapping of spectral power, and auto-correlation and cross-correlation parameters characterized the spatial properties of spontaneous electric activity in the ileum of wild-type (WT) and W/Wv mice, the latter serving as a model of impaired network of pacemaking interstitial cells. Namely, electric activities measured varied in both size and cooperativity in W/Wv mice, despite the small area. In the ileum of WT mice, procedures suppressing the excitability of smooth muscle and neurons altered the propagation of spontaneous electric activity, but had little change in the period of oscillations. In conclusion, MEA with low impedance electrodes enables to measure slowly oscillating electric activity, and is useful to evaluate both histological and functional changes in the spatio-temporal property of gut electric activity. PMID:24124480

Positive and negative modulation of circadian activity rhythms by mGluR5 and mGluR2/3 metabotropic glutamate receptors.

PubMed

Gannon, Robert L; Millan, Mark J

2011-01-01

Glutamate released from retinal ganglion cells conveys information about the daily light:dark cycle to master circadian pacemaker neurons within the suprachiasmatic nucleus that then synchronize internal circadian rhythms with the external day-length. Glutamate activation of ionotropic glutamate receptors in the suprachiasmatic nucleus is well established, but the function of the metabotropic glutamate receptors that are also located in this nucleus is not known. Therefore, in this study we evaluated agonists and antagonists acting at orthosteric or allosteric sites for mGluR5 and mGluR2/3 metabotropic glutamate receptors for their ability to modulate light-induced phase advances and delays of hamster circadian activity rhythms. mGluR5 allosteric antagonists fenobam, MPEP and MTEP, each 10 mg/kg, potentiated light-induced phase advances of hamster circadian activity rhythms, while the mGluR5 agonists CHPG, (S)-3,5-DHPG or positive allosteric modulator CDPPB had no effect. Neither mGluR5 agonists nor antagonists had any effect on light-induced phase delays of activity rhythms. The competitive mGluR2/3 antagonist LY341495, 10 mg/kg, also potentiated light-induced phase advances, but inhibited light-induced phase delays. The mGluR2/3 agonists LY354740 and LY404039 were without effect on phase advances while a third agonist LY379268, 10 mg/kg, inhibited both light-induced advances and delays. Finally, mGluR2/3 agonists LY379268 and LY404039 also inhibited light-induced phase delays of activity rhythms. These results suggest that during light-induced phase advances, mGluR2/3 and mGluR5 receptors act to negatively modulate the effects of light on the circadian pacemaker or its output(s). mGluR5 receptors do not appear to be involved during light-induced phase delays. In contrast, the role for mGluR2/3 receptors during phase delays is more complicated as both agonists and antagonists inhibit light-induced phase delays. Dysfunctions in human circadian rhythms have been implicated in some forms of depression, and metabotropic glutamate receptor ligands, which are also being evaluated for antidepressant activity, are shown here to be capable of modifying light-induced phase shifts of circadian activity rhythms. Copyright © 2010 Elsevier Ltd. All rights reserved.

Does Early Versus Delayed Active Range of Motion Affect Rotator Cuff Healing After Surgical Repair? A Systematic Review and Meta-analysis.

PubMed

Kluczynski, Melissa A; Isenburg, Maureen M; Marzo, John M; Bisson, Leslie J

2016-03-01

The timing of passive range of motion (ROM) after surgical repair of the rotator cuff (RC) has been shown to affect healing. However, it is unknown if early or delayed active ROM affects healing. To determine whether early versus delayed active ROM affects structural results of RC repair surgery. Systematic review and meta-analysis. A systematic review of articles published between January 2004 and April 2014 was conducted. Structural results were compared for early (<6 weeks after surgery) versus delayed (≥6 weeks after surgery) active ROM using chi-square and Fisher exact tests, as well as relative risks (RRs) and 95% CIs. The analyses were stratified by tear size and repair method. A total of 37 studies (2251 repairs) were included in the analysis, with 10 (649 repairs) in the early group and 27 (1602 repairs) in the delayed group. For tears ≤3 cm, the risk of a structural tendon defect was higher in the early versus delayed group for transosseous plus single-row suture anchor repairs (39.7% vs 24.3%; RR, 1.63 [95% CI, 1.28-2.08]). For tears >3 cm, the risk of a structural tendon defect was higher in the early versus delayed group for suture bridge repairs (48% vs 17.5%; RR, 2.74 [95% CI, 1.59-4.73]) and all repair methods combined (40.5% vs 26.7%; RR, 1.52 [95% CI, 1.17-1.97]). For tears >5 cm, the risk of structural tendon defect was higher in the early versus delayed group for suture bridge repairs (100% vs 16.7%; RR, 6.00 [95% CI, 1.69-21.26]). There were no statistically significant associations for tears measuring ≤1, 1-3, or 3-5 cm. Early active ROM was associated with increased risk of a structural defect for small and large RC tears, and thus might not be advisable after RC repair. © 2015 The Author(s).

Activity-Based Restorative Therapies: Concepts and Applications in Spinal Cord Injury-Related Neurorehabilitation

ERIC Educational Resources Information Center

Sadowsky, Cristina L.; McDonald, John W.

2009-01-01

Physical rehabilitation following spinal cord injury-related paralysis has traditionally focused on teaching compensatory techniques, thus enabling the individual to achieve day-to-day function despite significant neurological deficits. But the concept of an irreparable central nervous system (CNS) is slowly being replaced with evidence related to…

Investigating Diffusion with Technology

ERIC Educational Resources Information Center

Miller, Jon S.; Windelborn, Augden F.

2013-01-01

The activities described here allow students to explore the concept of diffusion with the use of common equipment such as computers, webcams and analysis software. The procedure includes taking a series of digital pictures of a container of water with a webcam as a dye slowly diffuses. At known time points, measurements of the pixel densities…

Teaching Geophysics with a Vertical-Component Seismometer

ERIC Educational Resources Information Center

van Wijk, Kasper; Channel, Ted; Viskupic, Karen; Smith, Martin L.

2013-01-01

Earthquakes are some of the more dramatic expressions of the dynamics of our planet. The sudden release of stress built up slowly by tectonic or volcanic processes often has far-reaching consequences, and can be measured (in classrooms) around the world. This is one reason why designing and building seismometers has been a popular activity, and…

It's about time: Earlier rewards increase intrinsic motivation.

PubMed

Woolley, Kaitlin; Fishbach, Ayelet

2018-06-01

Can immediate (vs. delayed) rewards increase intrinsic motivation? Prior research compared the presence versus absence of rewards. By contrast, this research compared immediate versus delayed rewards, predicting that more immediate rewards increase intrinsic motivation by creating a perceptual fusion between the activity and its goal (i.e., the reward). In support of the hypothesis, framing a reward from watching a news program as more immediate (vs. delayed) increased intrinsic motivation to watch the program (Study 1), and receiving more immediate bonus (vs. delayed, Study 2; and vs. delayed and no bonus, Study 3) increased intrinsic motivation in an experimental task. The effect of reward timing was mediated by the strength of the association between an activity and a reward, and was specific to intrinsic (vs. extrinsic) motivation-immediacy influenced the positive experience of an activity, but not perceived outcome importance (Study 4). In addition, the effect of the timing of rewards was independent of the effect of the magnitude of the rewards (Study 5). (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Involvement of cannabinoid system in the nucleus accumbens on delay-based decision making in the rat.

PubMed

Fatahi, Zahra; Sadeghi, Bahman; Haghparast, Abbas

2018-01-30

The nucleus accumbens (NAc) plays a fundamental role in decision making and anticipation of reward. In addition, exogenous cannabinoids affect the behavior of humans and animals including disruption of short-term memory and cognitive impairments. Therefore, in this study, cannabinoid agonist and antagonist were administrated into the NAc to determine the effect of cannabinoid activation in the entire NAc on delay-based decision making. Rats were trained on a cost-benefit T-maze decision making task in which the animals were well-trained to choose between a small/immediate reward and a large/delay reward. After training, the animals were implanted with guide cannulae in the NAc. On test day, they received cannabinoid agonist (Win 55,212-2; 10, 50 and 100μM) and/or antagonist (AM251; 45μM) into the NAc. Percentage of high reward choice and latency of reward achievement were evaluated. Results showed that cannabinoid agonist administration caused a decrease in high reward choice such that rats selected small/immediate reward instead of large/delay reward. Moreover, in agonist-treated animals latency of reward achievement increased. Effects of cannabinoid activation on delay-based decision making with equivalent delays demonstrated that if the delay was equated on both arm goals, animals still had a preference for the high/delay reward, showing the results was not caused by an impairment of spatial preference or memory. These finding clarified that cannabinoid system activation in the entire NAc plays a critical role in the regulation of delay-based decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

Greater impulsivity is associated with decreased brain activation in obese women during a delay discounting task.

PubMed

Stoeckel, Luke E; Murdaugh, Donna L; Cox, James E; Cook, Edwin W; Weller, Rosalyn E

2013-06-01

Impulsivity and poor inhibitory control are associated with higher rates of delay discounting (DD), or a greater preference for smaller, more immediate rewards at the expense of larger, but delayed rewards. Of the many functional magnetic resonance imaging (fMRI) studies of DD, few have investigated the correlation between individual differences in DD rate and brain activation related to DD trial difficulty, with difficult DD trials expected to activate putative executive function brain areas involved in impulse control. In the current study, we correlated patterns of brain activation as measured by fMRI during difficult vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was defined by how much a reward choice deviated from an individual's 'indifference point', or the point where the subjective preference for an immediate and a delayed reward was approximately equivalent. We found that greater delay discounting was correlated with less modulation of activation in putative executive function brain areas, such as the middle and superior frontal gyri and inferior parietal lobule, in response to difficult compared to easy DD trials. These results support the suggestion that increased impulsivity is associated with deficient functioning of executive function areas of the brain.

Using time-delay to improve social play skills with peers for children with autism.

PubMed

Liber, Daniella B; Frea, William D; Symon, Jennifer B G

2008-02-01

Interventions that teach social communication and play skills are crucial for the development of children with autism. The time delay procedure is effective in teaching language acquisition, social use of language, discrete behaviors, and chained activities to individuals with autism and developmental delays. In this study, three boys with autism, attending a non-public school, were taught play activities that combined a play sequence with requesting peer assistance, using a graduated time delay procedure. A multiple-baseline across subjects design demonstrated the success of this procedure to teach multiple-step social play sequences. Results indicated an additional gain of an increase in pretend play by one of the participants. Two also demonstrated a generalization of the skills learned through the time delay procedure.

Nuclear reactor with internal thimble-type delayed neutron detection system

DOEpatents

Gross, Kenny C.; Poloncsik, John; Lambert, John D. B.

1990-01-01

This invention teaches improved apparatus for the method of detecting a breach in cladded fuel used in a nuclear reactor. The detector apparatus is located in the primary heat exchanger which conveys part of the reactor coolant past at least three separate delayed-neutron detectors mounted in this heat exchanger. The detectors are spaced apart such that the coolant flow time from the core to each detector is different, and these differences are known. The delayed-neutron activity at the detectors is a function of the delay time after the reaction in the fuel until the coolant carrying the delayed-neutron emitter passes the respective detector. This time delay is broken down into separate components including an isotopic holdup time required for the emitter to move through the fuel from the reaction to the coolant at the breach, and two transit times required for the emitter now in the coolant to flow from the breach to the detector loop and then via the loop to the detector. At least two of these time components are determined during calibrated operation of the reactor. Thereafter during normal reactor operation, repeated comparisons are made by the method of regression approximation of the third time component for the best-fit line correlating measured delayed-neutron activity against activity that is approximated according to specific equations. The equations use these time-delay components and known parameter values of the fuel and of the part and emitting daughter isotopes.

Excitotoxicity-induced prostaglandin D2 production induces sustained microglial activation and delayed neuronal death.

PubMed

Iwasa, Kensuke; Yamamoto, Shinji; Yagishita, Sosuke; Maruyama, Kei; Yoshikawa, Keisuke

2017-04-01

Excitotoxicity is the pivotal mechanism of neuronal death. Prostaglandins (PGs) produced during excitotoxicity play important roles in neurodegenerative conditions. Previously, we demonstrated that initial burst productions of PGD 2 , PGE 2 , and PGF 2α are produced by cyclooxygenase-2 (COX-2) in the hippocampus following a single systemic kainic acid (KA) administration. In addition, we showed that blocking of all PG productions ameliorated hippocampal delayed neuronal death at 30 days after KA administration. To investigate the role of individual PGs in the delayed neuronal death, we performed intracerebroventricular injection of PGD 2 , PGE 2 , or PGF 2α in rats whose hippocampal PG productions were entirely blocked by pretreatment of NS398, a COX-2 selective inhibitor. Administration of PGD 2 and PGF 2α had a latent contribution to the delayed neuronal death, sustained over 30 days after a single KA treatment. Furthermore, PGD 2 enhanced microglial activation, which may be involved in the delayed neuronal death in the hippocampus. These findings suggest that excitotoxic delayed neuronal death is mediated through microglia activated by PGD 2 . Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

MILITARY PAY: Processes for Retaining Injured Army National Guard and Reserve Soldiers on Active Duty Have Been Improved, but Some Challenges Remain

DTIC Science & Technology

2007-05-01

Active Duty Have Been Improved, but Some Challenges Remain The Army’s MRP program has largely resolved the widespread delays in order processing that...interviewed confirmed that they did not experience gaps in pay and associated benefits because of order processing delays. However, some of the...and injured reserve component soldiers we interviewed, these improvements have virtually eliminated the widespread delays in order processing that

Note: Large active area solid state photon counter with 20 ps timing resolution and 60 fs detection delay stability

NASA Astrophysics Data System (ADS)

Prochazka, Ivan; Kodet, Jan; Eckl, Johann; Blazej, Josef

2017-10-01

We are reporting on the design, construction, and performance of a photon counting detector system, which is based on single photon avalanche diode detector technology. This photon counting device has been optimized for very high timing resolution and stability of its detection delay. The foreseen application of this detector is laser ranging of space objects, laser time transfer ground to space and fundamental metrology. The single photon avalanche diode structure, manufactured on silicon using K14 technology, is used as a sensor. The active area of the sensor is circular with 200 μm diameter. Its photon detection probability exceeds 40% in the wavelength range spanning from 500 to 800 nm. The sensor is operated in active quenching and gating mode. A new control circuit was optimized to maintain high timing resolution and detection delay stability. In connection to this circuit, timing resolution of the detector is reaching 20 ps FWHM. In addition, the temperature change of the detection delay is as low as 70 fs/K. As a result, the detection delay stability of the device is exceptional: expressed in the form of time deviation, detection delay stability of better than 60 fs has been achieved. Considering the large active area aperture of the detector, this is, to our knowledge, the best timing performance reported for a solid state photon counting detector so far.

Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes.

PubMed

Navarro-Polanco, Ricardo A; Aréchiga-Figueroa, Iván A; Salazar-Fajardo, Pedro D; Benavides-Haro, Dora E; Rodríguez-Elías, Julio C; Sachse, Frank B; Tristani-Firouzi, Martin; Sánchez-Chapula, José A; Moreno-Galindo, Eloy G

2013-09-01

Choline (Ch) is a precursor and metabolite of the neurotransmitter acetylcholine (ACh). In canine and guinea pig atrial myocytes, Ch was shown to activate an outward K(+) current in a delayed rectifier fashion. This current has been suggested to modulate cardiac electrical activity and to play a role in atrial fibrillation pathophysiology. However, the exact nature and identity of this current has not been convincingly established. We recently described the unique ligand- and voltage-dependent properties of muscarinic activation of ACh-activated K(+) current (IKACh) and showed that, in contrast to ACh, pilocarpine induces a current with delayed rectifier-like properties with membrane depolarization. Here, we tested the hypothesis that Ch activates IKACh in feline atrial myocytes in a voltage-dependent manner similar to pilocarpine. Single-channel recordings, biophysical profiles, specific pharmacological inhibition and computational data indicate that the current activated by Ch is IKACh. Moreover, we show that membrane depolarization increases the potency and efficacy of IKACh activation by Ch and thus gives the appearance of a delayed rectifier activating K(+) current at depolarized potentials. Our findings support the emerging concept that IKACh modulation is both voltage- and ligand-specific and reinforce the importance of these properties in understanding cardiac physiology.

Facilitating tolerance of delayed reinforcement during functional communication training.

PubMed

Fisher, W W; Thompson, R H; Hagopian, L P; Bowman, L G; Krug, A

2000-01-01

Few clinical investigations have addressed the problem of delayed reinforcement. In this investigation, three individuals whose destructive behavior was maintained by positive reinforcement were treated using functional communication training (FCT) with extinction (EXT). Next, procedures used in the basic literature on delayed reinforcement and self-control (reinforcer delay fading, punishment of impulsive responding, and provision of an alternative activity during reinforcer delay) were used to teach participants to tolerate delayed reinforcement. With the first case, reinforcer delay fading alone was effective at maintaining low rates of destructive behavior while introducing delayed reinforcement. In the second case, the addition of a punishment component reduced destructive behavior to near-zero levels and facilitated reinforcer delay fading. With the third case, reinforcer delay fading was associated with increases in masturbation and head rolling, but prompting and praising the individual for completing work during the delay interval reduced all problem behaviors and facilitated reinforcer delay fading.

High-risk Long QT Syndrome Mutations in the Kv7.1 (KCNQ1) Pore Disrupt the Molecular Basis for Rapid K+ Permeation

PubMed Central

Burgess, Don E.; Bartos, Daniel C.; Reloj, Allison R.; Campbell, Kenneth S.; Johnson, Jonathan N.; Tester, David J.; Ackerman, Michael J.; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J.; Ohno, Seiko; Horie, Minoru; Delisle, Brian P.

2012-01-01

Type 1 long QT syndrome (LQT1) syndrome is caused by loss-of-function mutations in the KCNQ1, which encodes the K+ channel (Kv7.1) that underlies the slowly activating delayed rectifier K+ current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss-of-function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confer a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated non-functional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamic simulations (MDS) of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K+-K+ repulsive forces required for rapid K+ permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K+ channel selectivity filter. PMID:23092362

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

Bass, H.; Mosmann, T.; Strober, S.

Purified CD4+ BALB/c spleen T cells obtained 4-6 wk after total lymphoid irradiation (TLI) helped normal syngeneic B cells to produce a vigorous antibody response to TNP keyhole limpet hemocyanin in adoptive cell transfer experiments. However, the same cells failed to transfer delayed-type hypersensitivity to the adoptive hosts as measured by a foot pad swelling assay. In addition, purified CD4+ cells from TLI-treated mice were unable to induce graft vs. host disease in lethally irradiated allogeneic C57BL/Ka recipient mice. In response to mitogen stimulation, unfractionated spleen cells obtained from TLI mice secreted normal levels of IL-4 and IL-5, but markedlymore » reduced levels of IL-2 and INF-gamma. A total of 229 CD4+ clones from spleen cells of both normal and TLI-treated mice were established, and the cytokine secretion pattern from each clone was analyzed. The results demonstrate that the ratio of Th1- and Th2-like clones in the spleens of normal BALB/c mice is 1:0.6, whereas the ratio in TLI mice is approximately 1:7. These results suggest that Th2-like cells recover rapidly (at approximately 4-6 wk) after TLI treatment and account for the early return of antibody helper activity and secretion of IL-4 and IL-5, but Th1-like cells recover more slowly (in approximately 3 mo) after irradiation, and this accounts for the deficit in cell-mediated immunity and the reduced amount of IL-2 and IFN-gamma secretion.« less

Formation of mutagens in cooked foods. I. Beef.

PubMed

Spingarn, N E; Weisburger, J H

1979-09-01

Mutagens detectable by Salmonella typhimurium TA98, after activation by liver S-9 fraction, are formed when meat is cooked by frying, broiling and boiling. High levels of mutagenic activity are formed rapidly when frying, or more slowly during broiling. Formation of mutagens in boiled beef stock requires several days under reflux, but shows a strong concentration dependence. Time curves suggest that a period exists during which mutagens are not readily formed; however, after this period mutagen production is rapid. Hamburgers from commercial franchises were frequently mutagenically active.

Methods of Muscle Activation Onset Timing Recorded During Spinal Manipulation.

PubMed

Currie, Stuart J; Myers, Casey A; Krishnamurthy, Ashok; Enebo, Brian A; Davidson, Bradley S

2016-05-01

The purpose of this study was to determine electromyographic threshold parameters that most reliably characterize the muscular response to spinal manipulation and compare 2 methods that detect muscle activity onset delay: the double-threshold method and cross-correlation method. Surface and indwelling electromyography were recorded during lumbar side-lying manipulations in 17 asymptomatic participants. Muscle activity onset delays in relation to the thrusting force were compared across methods and muscles using a generalized linear model. The threshold combinations that resulted in the lowest Detection Failures were the "8 SD-0 milliseconds" threshold (Detection Failures = 8) and the "8 SD-10 milliseconds" threshold (Detection Failures = 9). The average muscle activity onset delay for the double-threshold method across all participants was 149 ± 152 milliseconds for the multifidus and 252 ± 204 milliseconds for the erector spinae. The average onset delay for the cross-correlation method was 26 ± 101 for the multifidus and 67 ± 116 for the erector spinae. There were no statistical interactions, and a main effect of method demonstrated that the delays were higher when using the double-threshold method compared with cross-correlation. The threshold parameters that best characterized activity onset delays were an 8-SD amplitude and a 10-millisecond duration threshold. The double-threshold method correlated well with visual supervision of muscle activity. The cross-correlation method provides several advantages in signal processing; however, supervision was required for some results, negating this advantage. These results help standardize methods when recording neuromuscular responses of spinal manipulation and improve comparisons within and across investigations. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Working memory for social cues recruits orbitofrontal cortex and amygdala: a functional magnetic resonance imaging study of delayed matching to sample for emotional expressions.

PubMed

LoPresti, Matthew L; Schon, Karin; Tricarico, Marisa D; Swisher, Jascha D; Celone, Kim A; Stern, Chantal E

2008-04-02

During everyday interactions, we continuously monitor and maintain information about different individuals and their changing emotions in memory. Yet to date, working memory (WM) studies have primarily focused on mechanisms for maintaining face identity, but not emotional expression, and studies investigating the neural basis of emotion have focused on transient activity, not delay related activity. The goal of this functional magnetic resonance imaging study was to investigate WM for two critical social cues: identity and emotion. Subjects performed a delayed match-to-sample task that required them to match either the emotional expression or the identity of a face after a 10 s delay. Neuroanatomically, our predictions focused on the orbitofrontal cortex (OFC) and the amygdala, as these regions have previously been implicated in emotional processing and long-term memory, and studies have demonstrated sustained OFC and medial temporal lobe activity during visual WM. Consistent with previous studies, transient activity during the sample period representing emotion and identity was found in the superior temporal sulcus and inferior occipital cortex, respectively. Sustained delay-period activity was evident in OFC, amygdala, and hippocampus, for both emotion and identity trials. These results suggest that, although initial processing of emotion and identity is accomplished in anatomically segregated temporal and occipital regions, sustained delay related memory for these two critical features is held by the OFC, amygdala and hippocampus. These regions share rich connections, and have been shown previously to be necessary for binding features together in long-term memory. Our results suggest a role for these regions in active maintenance as well.

Local conduction during acute myocardial infarction in rats: Interplay between central sympathetic activation and endothelin.

PubMed

Kolettis, Theofilos M; Kontonika, Marianthi; La Rocca, Vassilios; Vlahos, Antonios P; Baltogiannis, Giannis G; Kyriakides, Zenon S

2017-04-01

We investigated the effects of autonomic dysfunction and endothelin on local conduction and arrhythmogenesis during myocardial infarction. We recorded ventricular tachyarrhythmias, monophasic action potentials, and activation sequences in wild-type and ET B -deficient rats displaying high endothelin levels. Central sympathetic inputs were examined after clonidine administration. Clonidine mitigated early and delayed arrhythmogenesis in ET B -deficient and wild-type rats, respectively. The right ventricular activation delay increased in clonidine-treated ET B -deficient rats and slightly decreased in wild-type rats. The left ventricular voltage rise decreased in all groups, whereas the activation delay increased mainly in clonidine-treated ET B -deficient rats. Central sympathetic activation and endothelin modulate ischemia-induced arrhythmogenesis. Ischemia alters excitability, whereas endothelin impairs local conduction, an action partly counterbalanced by central sympathetic activity.

Altered entrainment to the day/night cycle attenuates the daily rise in circulating corticosterone in the mouse.

PubMed

Sollars, Patricia J; Weiser, Michael J; Kudwa, Andrea E; Bramley, Jayne R; Ogilvie, Malcolm D; Spencer, Robert L; Handa, Robert J; Pickard, Gary E

2014-01-01

The suprachiasmatic nucleus (SCN) is a circadian oscillator entrained to the day/night cycle via input from the retina. Serotonin (5-HT) afferents to the SCN modulate retinal signals via activation of 5-HT1B receptors, decreasing responsiveness to light. Consequently, 5-HT1B receptor knockout (KO) mice entrain to the day/night cycle with delayed activity onsets. Since circulating corticosterone levels exhibit a robust daily rhythm peaking around activity onset, we asked whether delayed entrainment of activity onsets affects rhythmic corticosterone secretion. Wheel-running activity and plasma corticosterone were monitored in mice housed under several different lighting regimens. Both duration of the light:dark cycle (T cycle) and the duration of light within that cycle was altered. 5-HT1B KO mice that entrained to a 9.5L:13.5D (short day in a T = 23 h) cycle with activity onsets delayed more than 4 h after light offset exhibited a corticosterone rhythm in phase with activity rhythms but reduced 50% in amplitude compared to animals that initiated daily activity <4 h after light offset. Wild type mice in 8L:14D (short day in a T = 22 h) conditions with highly delayed activity onsets also exhibited a 50% reduction in peak plasma corticosterone levels. Exogenous adrenocorticotropin (ACTH) stimulation in animals exhibiting highly delayed entrainment suggested that the endogenous rhythm of adrenal responsiveness to ACTH remained aligned with SCN-driven behavioral activity. Circadian clock gene expression in the adrenal cortex of these same animals suggested that the adrenal circadian clock was also aligned with SCN-driven behavior. Under T cycles <24 h, altered circadian entrainment to short day (winter-like) conditions, manifest as long delays in activity onset after light offset, severely reduces the amplitude of the diurnal rhythm of plasma corticosterone. Such a pronounced reduction in the glucocorticoid rhythm may alter rhythmic gene expression in the central nervous system and in peripheral organs contributing to an array of potential pathophysiologies.

Altered Entrainment to the Day/Night Cycle Attenuates the Daily Rise in Circulating Corticosterone in the Mouse

PubMed Central

Sollars, Patricia J.; Weiser, Michael J.; Kudwa, Andrea E.; Bramley, Jayne R.; Ogilvie, Malcolm D.; Spencer, Robert L.; Handa, Robert J.; Pickard, Gary E.

2014-01-01

The suprachiasmatic nucleus (SCN) is a circadian oscillator entrained to the day/night cycle via input from the retina. Serotonin (5-HT) afferents to the SCN modulate retinal signals via activation of 5-HT1B receptors, decreasing responsiveness to light. Consequently, 5-HT1B receptor knockout (KO) mice entrain to the day/night cycle with delayed activity onsets. Since circulating corticosterone levels exhibit a robust daily rhythm peaking around activity onset, we asked whether delayed entrainment of activity onsets affects rhythmic corticosterone secretion. Wheel-running activity and plasma corticosterone were monitored in mice housed under several different lighting regimens. Both duration of the light∶dark cycle (T cycle) and the duration of light within that cycle was altered. 5-HT1B KO mice that entrained to a 9.5L:13.5D (short day in a T = 23 h) cycle with activity onsets delayed more than 4 h after light offset exhibited a corticosterone rhythm in phase with activity rhythms but reduced 50% in amplitude compared to animals that initiated daily activity <4 h after light offset. Wild type mice in 8L:14D (short day in a T = 22 h) conditions with highly delayed activity onsets also exhibited a 50% reduction in peak plasma corticosterone levels. Exogenous adrenocorticotropin (ACTH) stimulation in animals exhibiting highly delayed entrainment suggested that the endogenous rhythm of adrenal responsiveness to ACTH remained aligned with SCN-driven behavioral activity. Circadian clock gene expression in the adrenal cortex of these same animals suggested that the adrenal circadian clock was also aligned with SCN-driven behavior. Under T cycles <24 h, altered circadian entrainment to short day (winter-like) conditions, manifest as long delays in activity onset after light offset, severely reduces the amplitude of the diurnal rhythm of plasma corticosterone. Such a pronounced reduction in the glucocorticoid rhythm may alter rhythmic gene expression in the central nervous system and in peripheral organs contributing to an array of potential pathophysiologies. PMID:25365210

Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking.

PubMed

Andersen, Martin N; Hefting, Louise L; Steffensen, Annette B; Schmitt, Nicole; Olesen, Søren-Peter; Olsen, Jesper V; Lundby, Alicia; Rasmussen, Hanne B

2015-11-15

The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, Kv7.1 and the accessory subunit KCNE1 forms the slowly activating delayed-rectifier potassium current current, which is enhanced by protein kinase A (PKA)-mediated phosphorylation. The observed current increase requires both phosphorylation of Kv7.1 and the presence of KCNE1. However, PKA also stimulates Kv7.1 currents in epithelial tissues, such as colon, where the channel does not coassemble with KCNE1. Here, we demonstrate that PKA activity significantly impacts the subcellular localization of Kv7.1 in Madin-Darby canine kidney cells. While PKA inhibition reduced the fraction of channels at the cell surface, PKA activation increased it. We show that PKA inhibition led to intracellular accumulation of Kv7.1 in late endosomes/lysosomes. By mass spectroscopy we identified eight phosphorylated residues on Kv7.1, however, none appeared to play a role in the observed response. Instead, we found that PKA acted by regulating endocytic trafficking involving the ubiquitin ligase Nedd4-2. We show that a Nedd4-2-resistant Kv7.1-mutant displayed significantly reduced intracellular accumulation upon PKA inhibition. Similar effects were observed upon siRNA knockdown of Nedd4-2. However, although Nedd4-2 is known to regulate Kv7.1 by ubiquitylation, biochemical analyses demonstrated that PKA did not influence the amount of Nedd4-2 bound to Kv7.1 or the ubiquitylation level of the channel. This suggests that PKA influences Nedd4-2-dependent Kv7.1 transport though a different molecular mechanism. In summary, we identify a novel mechanism whereby PKA can increase Kv7.1 current levels, namely by regulating Nedd4-2-dependent Kv7.1 transport. Copyright © 2015 the American Physiological Society.

Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking

PubMed Central

Andersen, Martin N.; Hefting, Louise L.; Steffensen, Annette B.; Schmitt, Nicole; Olesen, Søren-Peter; Olsen, Jesper V.; Lundby, Alicia

2015-01-01

The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, Kv7.1 and the accessory subunit KCNE1 forms the slowly activating delayed-rectifier potassium current current, which is enhanced by protein kinase A (PKA)-mediated phosphorylation. The observed current increase requires both phosphorylation of Kv7.1 and the presence of KCNE1. However, PKA also stimulates Kv7.1 currents in epithelial tissues, such as colon, where the channel does not coassemble with KCNE1. Here, we demonstrate that PKA activity significantly impacts the subcellular localization of Kv7.1 in Madin-Darby canine kidney cells. While PKA inhibition reduced the fraction of channels at the cell surface, PKA activation increased it. We show that PKA inhibition led to intracellular accumulation of Kv7.1 in late endosomes/lysosomes. By mass spectroscopy we identified eight phosphorylated residues on Kv7.1, however, none appeared to play a role in the observed response. Instead, we found that PKA acted by regulating endocytic trafficking involving the ubiquitin ligase Nedd4-2. We show that a Nedd4-2-resistant Kv7.1-mutant displayed significantly reduced intracellular accumulation upon PKA inhibition. Similar effects were observed upon siRNA knockdown of Nedd4-2. However, although Nedd4-2 is known to regulate Kv7.1 by ubiquitylation, biochemical analyses demonstrated that PKA did not influence the amount of Nedd4-2 bound to Kv7.1 or the ubiquitylation level of the channel. This suggests that PKA influences Nedd4-2-dependent Kv7.1 transport though a different molecular mechanism. In summary, we identify a novel mechanism whereby PKA can increase Kv7.1 current levels, namely by regulating Nedd4-2-dependent Kv7.1 transport. PMID:26405101

The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo.

PubMed Central

Bunn, H F; Haney, D N; Kamin, S; Gabbay, K H; Gallop, P M

1976-01-01

Hemoglobin A1c, the most abundant minor hemoglobin component in human erythrocytes, is formed by the condensation of glucose with the N-terminal amino groups of the beta-chains of Hb A. The biosynthesis of this glycosylated hemoglobin was studied in vitro by incubating suspensions of reticulocytes and bone marrow cells with [3H]leucine or 59Fe-bound transferrin. In all experiments, the specific activity of Hb A1c was significantly lower than that of Hb A, suggesting that the formation of Hb A1c is a posttranslational modification. The formation of Hb A1c in vivo was determined in two individuals who were given an infusion of 59Fe-labeled transferrin. As expected, the specific activity of Hb A rose promptly to a maximum during the 1st week and remained nearly constant thereafter. In contrast, the specific activity of Hb A1c and also of Hbs A1a and A1b rose slowly, reaching that of Hb A by about day 60. These results indicate that Hb A1c is slowly formed during the 120-day life-span of the erythrocyte, probably by a nonenzymatic process. Patients with shortened erythrocyte life-span due to hemolysis had markedly decreased levels of Hb A1c. PMID:932199

High throughput functional assays for P2X receptors.

PubMed

Namovic, Marian T; Jarvis, Michael F; Donnelly-Roberts, Diana

2012-06-01

Adenosine triphosphate (ATP) activates two receptor superfamilies, metabotropic P2Y and ionotropic P2X receptors. The P2X receptors are nonselective cation channels that are widely expressed on excitable cells including neurons, glia, and smooth muscle cells. The protocols in this unit are useful for evaluating ligands that interact with P2X receptors on native cells or that are cloned and expressed in recombinant heterologous cell systems. Calcium imaging methods are described for the pharmacological characterization of fast or slowly desensitizing P2X receptors. While these methods are readily applicable to a wide variety of ligand-gated ion channels, the protocols provided herein detail how they can be used to measure activation of homomeric P2X3 (fast desensitizing) and heteromeric P2X2/3 (slowly desensitizing) receptors. Appropriate agonists and/or calcium dyes can be substituted to assess activity at other P2X receptor subtypes. An additional protocol is provided for measuring P2X7 receptor-mediated pore formation in THP-1, a native human acute monocytic leukemia cell line that can be used to study homomeric P2X7 (non-desensitizing) receptors that are expressed on macrophages and microglial cells. © 2012 by John Wiley & Sons, Inc.

Effects of steam autoclave treatment on Geobacillus stearothermophilus spores.

PubMed

Huesca-Espitia, L C; Suvira, M; Rosenbeck, K; Korza, G; Setlow, B; Li, W; Wang, S; Li, Y-Q; Setlow, P

2016-11-01

To determine the mechanism of autoclave killing of Geobacillus stearothermophilus spores used in biological indicators (BIs) for steam autoclave sterilization, and rates of loss of spore viability and a spore enzyme used in BIs. Spore viability, dipicolinic acid (DPA) release, nucleic acid staining, α-glucosidase activity, protein structure and mutagenesis were measured during autoclaving of G. stearothermophilus spores. Loss of DPA and increases in spore core nucleic acid staining were slower than loss of spore viability. Spore core α-glucosidase was also lost more slowly than spore viability, although soluble α-glucosidase in spore preparations was lost more rapidly. However, spores exposed to an effective autoclave sterilization lost all viability and α-glucosidase activity. Apparently killed autoclaved spores were not recovered by artificial germination in supportive media, much spore protein was denatured during autoclaving, and partially killed autoclave-treated spore preparations did not acquire mutations. These results indicate that autoclave-killed spores cannot be revived, spore killing by autoclaving is likely by protein damage, and spore core α-glucosidase activity is lost more slowly than spore viability. This work provides insight into the mechanism of autoclave killing of spores of an organism used in BIs, and that a spore enzyme in a BI is more stable to autoclaving than spore viability. © 2016 The Society for Applied Microbiology.

Evaluation of takayasu arteritis with delayed contrast-enhanced MR imaging by a free-breathing 3D IR turbo FLASH.

PubMed

Liu, Min; Liu, Weifang; Li, Haoyuan; Shu, Xiaoming; Tao, Xincao; Zhai, Zhenguo

2017-12-01

The primary aim of our case-control study was to observe delayed contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with Takayasu arteritis (TA) in comparison with magnetic resonance angiography (MRA). Twenty-seven patients including 15 with active TA and 12 with stable TA who underwent both aortic MRA and DCE-MRI were included. A total of 27 sex- and age-matched healthy volunteers were enrolled as the control group. MRA were obtained with T1WI-volume-interpolated breath-hold examination sequence or fast low-angle shot (FLASH) sequence. DCE-MRI was acquired with a free-breathing three-dimensional inversion recovery Turbo fast low-angle shot (3D IR Turbo FLASH). Neither stenosis nor delayed enhancement of arterial wall was shown in the control group. In patients with stable TA, arterial stenosis was observed on MRA. On DCE-MR, delayed enhancement of arterial walls could be observed in the active TA group but not in the stable TA group or the control group. Stenotic arteries on MRA were comparable in the active TA and stable TA (χ = 2.70, P = .259); however, delayed enhancement of arterial walls in the active-TA group were more than those in the stable group (χ = 27.00, P < .001). Our results suggest that DCE-MRI with the free-breathing 3D IR Turbo FLASH sequence could assess TA and delayed enhancement on DCE-MRI is one characteristics of the active TA. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Periodicity and global exponential stability of generalized Cohen-Grossberg neural networks with discontinuous activations and mixed delays.

PubMed

Wang, Dongshu; Huang, Lihong

2014-03-01

In this paper, we investigate the periodic dynamical behaviors for a class of general Cohen-Grossberg neural networks with discontinuous right-hand sides, time-varying and distributed delays. By means of retarded differential inclusions theory and the fixed point theorem of multi-valued maps, the existence of periodic solutions for the neural networks is obtained. After that, we derive some sufficient conditions for the global exponential stability and convergence of the neural networks, in terms of nonsmooth analysis theory with generalized Lyapunov approach. Without assuming the boundedness (or the growth condition) and monotonicity of the discontinuous neuron activation functions, our results will also be valid. Moreover, our results extend previous works not only on discrete time-varying and distributed delayed neural networks with continuous or even Lipschitz continuous activations, but also on discrete time-varying and distributed delayed neural networks with discontinuous activations. We give some numerical examples to show the applicability and effectiveness of our main results. Copyright © 2013 Elsevier Ltd. All rights reserved.

Delayed ignition and propulsion of catalytic microrockets based on fuel-induced chemical dealloying of the inner alloy layer.

PubMed

Jodra, Adrián; Soto, Fernando; Lopez-Ramirez, Miguel Angel; Escarpa, Alberto; Wang, Joseph

2016-09-27

The delayed ignition and propulsion of catalytic tubular microrockets based on fuel-induced chemical dealloying of an inner alloy layer is demonstrated. Such timed delay motor activation process relies on the preferential gradual corrosion of Cu from the inner Pt-Cu alloy layer by the peroxide fuel. The dealloying process exposes the catalytically active Pt surface to the chemical fuel, thus igniting the microrockets propulsion autonomously without external stimuli. The delayed motor activation relies solely on the intrinsic material properties of the micromotor and the surrounding solution. The motor activation time can thus be tailored by controlling the composition of the Cu-Pt alloy layer and the surrounding media, including the fuel and NaCl concentrations and local pH. Speed acceleration in a given fuel solution is also demonstrated and reflects the continuous exposure of the Pt surface. The versatile "blastoff" control of these chemical microrockets holds considerable promise for designing self-regulated chemically-powered nanomachines with a "built-in" activation mechanism for diverse tasks.

Effect of unilateral and bilateral use of laterally wedged insoles with arch supports on impact loading in medial knee osteoarthritis.

PubMed

Abd El Megeid Abdallah, Amira Abdallah

2016-04-01

Increased impact loading is implicated in knee osteoarthritis development and progression. This study examined the impact ground reaction force (GRF) peak, its loading rate, its relative timing to stance phase timing, and walking speed during unilateral and bilateral use of laterally wedged insoles with arch supports. Within-subject design. Thirty-three female patients with medial knee osteoarthritis were examined with (unilateral 6° and 11°, and bilateral 0°, 6°, and 11°) and without insole use. Repeated measures MANOVA revealed that the impact force increased significantly in bilateral 11° versus unilateral 6° and without-insole conditions. The loading rate decreased significantly in unilateral 11° versus bilateral 6° insoles. The relative timing increased significantly in each of bilateral 6°, bilateral 11°, and unilateral 11° versus bilateral 0° insoles and in each of bilateral 11° and unilateral 11° versus without-insole condition. There were significant positive correlations between the walking speed and each of the force and loading rate. The Chi-square test revealed insignificant association between the insole condition and the presence of impact forces. Unilateral 11° insoles are capable of reducing impact loading possibly through increasing foot pronation. Walking slowly is another possible strategy to reduce loading. Unilaterally applied 11° laterally wedged insoles are capable of reducing and delaying the initial impact ground reaction forces and reducing their loading rates during walking in patients with medial knee osteoarthritis, thus reducing osteoarthritis progression. Walking slowly could also be used as a strategy to reduce impact loading. © The International Society for Prosthetics and Orthotics 2015.

An argument for weakly magnetized, slowly rotating progenitors of long gamma-ray bursts

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

Moreno Méndez, Enrique, E-mail: enriquemm@astro.unam.mx

2014-01-20

Using binary evolution with Case-C mass transfer, the spins of several black holes (BHs) in X-ray binaries (XBs) have been predicted and confirmed (three cases) by observations. The rotational energy of these BHs is sufficient to power up long gamma-ray bursts (GRBs) and hypernovae (HNe) and still leave a Kerr BH behind. However, strong magnetic fields and/or dynamo effects in the interior of such stars deplete their cores from angular momentum preventing the formation of collapsars. Thus, even though binaries can produce Kerr BHs, most of their rotation is acquired from the stellar mantle, with a long delay between BHmore » formation and spin up. Such binaries would not form GRBs. We study whether the conditions required to produce GRBs can be met by the progenitors of such BHs. Tidal-synchronization and Alfvén timescales are compared for magnetic fields of different intensities threading He stars. A search is made for a magnetic field range that allows tidal spin up all the way in to the stellar core but prevents its slow down during differential rotation phases. The energetics for producing a strong magnetic field during core collapse, which may allow for a GRB central engine, are also estimated. An observationally reasonable choice of parameters is found (B ≲ 10{sup 2} G threading a slowly rotating He star) that allows Fe cores to retain substantial angular momentum. Thus, the Case-C mass-transfer binary channel is capable of explaining long GRBs. However, the progenitors must have low initial spin and low internal magnetic field throughout their H-burning and He-burning phases.« less

Preload of slowly digestible carbohydrate microspheres decreases gastric emptying rate of subsequent meal in humans.

PubMed

Cisse, Fatimata; Pletsch, Elizabeth A; Erickson, Daniel P; Chegeni, Mohammad; Hayes, Anna M R; Hamaker, Bruce R

2017-09-01

Gastric emptying rate influences how fast the nutrients of a meal are delivered to the body, and when slow, it moderates glycemic response and may impact satiety. Carbohydrates are one of the macronutrients that trigger the ileal brake, and we hypothesized that slowly digestible carbohydrate (SDC) administered in a premeal load would delay gastric emptying. A crossover design study was conducted with 10 healthy adults using fabricated SDC-microspheres (cooked) that were given 20 minutes before a non-nutritive viscous paste meal. There were 4 treatment arms, each separated by a 1-week washout period, consisting of (1) the paste alone, (2) a rapidly digesting maltodextrin (Polycose) preload followed by the paste 20 minutes later, (3) an SDC-microsphere preload followed by the paste, and (4) a comparably slower SDC-microsphere preload followed by the paste. A 13 C-labeled octanoic acid breath test method was used to measure gastric emptying, with the label incorporated into the non-nutritive paste. The microspheres were less than 1 mm in diameter (a size that does not require breakdown in the stomach before emptying) and, after cooking, were of the same density value. Compared with the paste alone, both of the SDC-microsphere preloads (slow and comparably slower digesting) decreased gastric emptying rate of the paste, with the latter having the most effect (half-emptying times of 1.7, 2.3, and 2.8 hours, respectively [each different at P<.05]). In conclusion, SDCs decreased gastric emptying rate, and this was suggested to be due to a triggering of the ileal brake. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Ionizing Radiation on Human Adipose Derived Mesenchymal Stem Cells and their Differentiation towards the Osteoblastic Lineage

NASA Astrophysics Data System (ADS)

Konda, Bikash; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther; Lau, Patrick

Radiation exposure and musculoskeletal disuse are among the major challenges during space missions. Astronauts face the problem to lose bone calcium due to uncoupling of bone formation and resorption. Bone forming osteoblasts can be derived from the undifferentiated mesenchymal stem cell compartment (MSC). In this study, the ability of human adipose tissue derived stem cells (ATSC) to differentiate into the osteoblastic lineage was examined after radiation exposure in presence of medium supplementation with osteogenic additives (ß-glycerophosphate, ascorbic acid and dexamethasone). The SAOS-2 cell line (human osteosarcoma cell line) was used as control for osteoblastic differentiation. Changes in cellular morphology, cell cycle progression, as well as cellular radiation sensitivity were characterized after ionizing radiation exposure with X-rays and heavy ions (Ti). Rapidly proliferating SAOS-2 cells are less radiation-sensitive than slowly proliferating ATSC cells after X-ray (CFA: dose effect curves show D0 values of 1 Gy and 0.75 Gy for SAOS-2 and ATSC, respectively) exposure. Heavy ion (Ti) exposure resulted in a greater extent of cells accumulating in the G2/M phase of the cell cycle in a dose-dependent manner when compared to X-ray exposure. Differentiation of cells towards the osteoblastic lineage was quantified by hydroxyapatite (HA) deposition using Lonza OsteoImageTM mineralization assay. The deposition of HA after X- and Ti-irradiation for highly proliferating SAOS-2 cells showed a dose-dependent time delay while slowly proliferating ATSC showed no effect from radiation exposure. More detailed investigation is required to reveal the radiation dependent mechanism of bone loss in astronauts.

Teaching Students to Request the Continuation of Routine Activities by Using Time Delay and Decreasing Physical Assistance in the Context of Chain Interruption.

ERIC Educational Resources Information Center

Gee, Kathleen; And Others

1991-01-01

Three students (ages 5-10) with profound intellectual, sensory, and physical disabilities were taught to activate a communication device to request the continuation of activities in which they were involved. The intervention consisted of a consistent response interval and increasing time delay paired with decreasing physical assistance in…

The Effect of Delayed Auditory Feedback on Activity in the Temporal Lobe while Speaking: A Positron Emission Tomography Study

ERIC Educational Resources Information Center

Takaso, Hideki; Eisner, Frank; Wise, Richard J. S.; Scott, Sophie K.

2010-01-01

Purpose: Delayed auditory feedback is a technique that can improve fluency in stutterers, while disrupting fluency in many nonstuttering individuals. The aim of this study was to determine the neural basis for the detection of and compensation for such a delay, and the effects of increases in the delay duration. Method: Positron emission…

The role of early visual cortex in visual short-term memory and visual attention.

PubMed

Offen, Shani; Schluppeck, Denis; Heeger, David J

2009-06-01

We measured cortical activity with functional magnetic resonance imaging to probe the involvement of early visual cortex in visual short-term memory and visual attention. In four experimental tasks, human subjects viewed two visual stimuli separated by a variable delay period. The tasks placed differential demands on short-term memory and attention, but the stimuli were visually identical until after the delay period. Early visual cortex exhibited sustained responses throughout the delay when subjects performed attention-demanding tasks, but delay-period activity was not distinguishable from zero when subjects performed a task that required short-term memory. This dissociation reveals different computational mechanisms underlying the two processes.

76 FR 25240 - Clothianidin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... neurotoxicity were exhibited in both rats (decreased arousal, motor activity and locomotor activity) and mice... (decreased body weight gains and absolute thymus weights in pups, delayed sexual maturation and an increase.../day FQPA SF = 1x day.. based on decreased body weight gains and delayed sexual maturation, decreased...

Typology of nonlinear activity waves in a layered neural continuum.

PubMed

Koch, Paul; Leisman, Gerry

2006-04-01

Neural tissue, a medium containing electro-chemical energy, can amplify small increments in cellular activity. The growing disturbance, measured as the fraction of active cells, manifests as propagating waves. In a layered geometry with a time delay in synaptic signals between the layers, the delay is instrumental in determining the amplified wavelengths. The growth of the waves is limited by the finite number of neural cells in a given region of the continuum. As wave growth saturates, the resulting activity patterns in space and time show a variety of forms, ranging from regular monochromatic waves to highly irregular mixtures of different spatial frequencies. The type of wave configuration is determined by a number of parameters, including alertness and synaptic conditioning as well as delay. For all cases studied, using numerical solution of the nonlinear Wilson-Cowan (1973) equations, there is an interval in delay in which the wave mixing occurs. As delay increases through this interval, during a series of consecutive waves propagating through a continuum region, the activity within that region changes from a single-frequency to a multiple-frequency pattern and back again. The diverse spatio-temporal patterns give a more concrete form to several metaphors advanced over the years to attempt an explanation of cognitive phenomena: Activity waves embody the "holographic memory" (Pribram, 1991); wave mixing provides a plausible cause of the competition called "neural Darwinism" (Edelman, 1988); finally the consecutive generation of growing neural waves can explain the discontinuousness of "psychological time" (Stroud, 1955).

Encoding of Spatio-Temporal Input Characteristics by a CA1 Pyramidal Neuron Model

PubMed Central

Pissadaki, Eleftheria Kyriaki; Sidiropoulou, Kyriaki; Reczko, Martin; Poirazi, Panayiota

2010-01-01

The in vivo activity of CA1 pyramidal neurons alternates between regular spiking and bursting, but how these changes affect information processing remains unclear. Using a detailed CA1 pyramidal neuron model, we investigate how timing and spatial arrangement variations in synaptic inputs to the distal and proximal dendritic layers influence the information content of model responses. We find that the temporal delay between activation of the two layers acts as a switch between excitability modes: short delays induce bursting while long delays decrease firing. For long delays, the average firing frequency of the model response discriminates spatially clustered from diffused inputs to the distal dendritic tree. For short delays, the onset latency and inter-spike-interval succession of model responses can accurately classify input signals as temporally close or distant and spatially clustered or diffused across different stimulation protocols. These findings suggest that a CA1 pyramidal neuron may be capable of encoding and transmitting presynaptic spatiotemporal information about the activity of the entorhinal cortex-hippocampal network to higher brain regions via the selective use of either a temporal or a rate code. PMID:21187899

Modelling the human operator of slowly responding systems using linear models

NASA Technical Reports Server (NTRS)

Veldhuyzen, W.

1977-01-01

Control of slowly responding systems, such as, helmsman steering a large ship, is examined. It is shown that the describing function techniques are useful in analyzing the control behavior of the helmsman. Models are developed to describe the helmsman's control behavior. It is shown that the cross over model is applicable to the analysis of control of slowly responding systems.

Methylphenidate does not improve interference control during a working memory task in young patients with attention-deficit hyperactivity disorder.

PubMed

Prehn-Kristensen, Alexander; Krauel, Kerstin; Hinrichs, Hermann; Fischer, Jochen; Malecki, Ulrike; Schuetze, Hartmut; Wolff, Stephan; Jansen, Olav; Duezel, Emrah; Baving, Lioba

2011-05-04

Patients with attention-deficit/hyperactivity disorder (ADHD) show deficits in working memory (WM) which may be related to prefrontal dysfunction. Methylphenidate (MPH) can restore WM deficits in ADHD by enhancing prefrontal activity. At the same time, changes in striatal activation could cause ADHD patients to be more interference-sensitive during working memory tasks. However, it is unclear whether MPH reduces WM distractibility in ADHD. In this fMRI study, 12 ADHD patients and 12 healthy controls participated on two separate days in a delayed-match-to-sample test. During the delay interval, a distractor stimulus was presented in half of the trials. Children and adolescents with ADHD received MPH only on one of the two sessions. Behavioral data analyses revealed that MPH normalized WM in ADHD. However, MPH did not improve WM performance when a distractor was presented during the delay interval. Functional images showed that MPH enhanced prefrontal activity during the delay in ADHD patients when no distractor was present. If the delay was interrupted by a distractor, only healthy controls showed activation of the caudate. In patients with ADHD, however, in line with behavioral data, MPH did not enhance caudate activity. In healthy youth, caudate activity is involved in interference control allowing the successful maintenance of information in working memory even in the presence of distraction. Our findings suggest that interference control, linked to caudate activity, is not adequately enhanced by MPH in ADHD. Copyright © 2011 Elsevier B.V. All rights reserved.

Positive and negative sources of emotional arousal enhance long-term word-list retention when induced as long as 30 min after learning.

PubMed

Nielson, Kristy A; Powless, Mark

2007-07-01

The consolidation of newly formed memories occurs slowly, allowing memories to be altered by experience for some time after their formation. Various treatments, including arousal, can modulate memory consolidation when given soon after learning, but the degree of time-dependency of these treatments in humans has not been studied. Thus, 212 participants learned a word list, which was followed by either a positively or negatively valenced arousing video clip (i.e., comedy or surgery, respectively) after delays of 0, 10, 30 or 45 min. Arousal of either valence induced up to 30 min after learning, but not after 45 min, significantly enhanced one-week retrieval. The findings support (1) the time-dependency of memory modulation in humans and (2) other studies that suggest that it is the degree of arousal, rather than valence that modulates memory. Important implications for developing memory intervention strategies and for preserving and validating witness testimony are discussed.

The changing face of malignant hyperthermia: less fulminant, more insidious..

PubMed

Heytens, L; Forget, P; Scholtès, J L; Veyckemans, F

2015-07-01

Modern anaesthetic techniques have resulted in the clinical presentation of malignant hyperthermia to be more often indolent and/or insidious than truly fulminant, as previously known in the anaesthetic community. We present four recently referred cases to illustrate this point: one late-onset case, two patients with slowly progressive hypercapnia as the sole sign and a fourth patient with postoperative myalgias and elevated creatine kinase. We also discuss the reasons for the shift in typical clinical presentation. The more insidious character of malignant hyperthermia is most likely due to the lower triggering potency of modern volatile anaesthetics, the mitigating effects of several intravenous drugs (neuromuscular blocking agents, alpha 2 adrenergic receptor agonists, beta adrenergic blockade) or techniques (neuraxial anaesthesia) and the routine use of end-tidal CO2 monitoring leading to the early withdrawal of triggering drugs. Awareness among anaesthetists of this change in presentation is important since the clinical diagnosis is often more doubtful and, if corroborative evidence is not sought, the diagnosis may be delayed or missed altogether.

Lime as an Anti-Plasticizer for Self-Compacting Clay Concrete

PubMed Central

Landrou, Gnanli; Brumaud, Coralie; Winnefeld, Frank; Flatt, Robert J.; Habert, Guillaume

2016-01-01

This paper focuses on the modification of clay properties with inorganic additives to deflocculate and flocculate inorganic soil for the development of a material that would be as easy to use as the current concrete products, but with a much lower environmental impact. Considering that the rheological behaviour of clays is controlled by their surface charge, we first introduce potential determining ions to deflocculate the clay particles and to reduce the yield stress of the earth material. Their efficiency is characterized using zeta potential measurements and rheological tests. We then achieve the flocculation of clay particles by using natural minerals that slowly dissolve in the interstitial liquid and ultimately precipitate calcium silicate hydrate (C–S–H). The precipitation products are identified by X-ray diffraction and the consequences of this delayed precipitation are followed by oscillatory rheometric measurements. Finally, it is suggested that in this process, C–S–H precipitation is not used as a binding vector but as an anti-plasticizer that removes the inorganic dispersant additives. PMID:28773453

Lime as an Anti-Plasticizer for Self-Compacting Clay Concrete.

PubMed

Landrou, Gnanli; Brumaud, Coralie; Winnefeld, Frank; Flatt, Robert J; Habert, Guillaume

2016-04-29

This paper focuses on the modification of clay properties with inorganic additives to deflocculate and flocculate inorganic soil for the development of a material that would be as easy to use as the current concrete products, but with a much lower environmental impact. Considering that the rheological behaviour of clays is controlled by their surface charge, we first introduce potential determining ions to deflocculate the clay particles and to reduce the yield stress of the earth material. Their efficiency is characterized using zeta potential measurements and rheological tests. We then achieve the flocculation of clay particles by using natural minerals that slowly dissolve in the interstitial liquid and ultimately precipitate calcium silicate hydrate (C-S-H). The precipitation products are identified by X-ray diffraction and the consequences of this delayed precipitation are followed by oscillatory rheometric measurements. Finally, it is suggested that in this process, C-S-H precipitation is not used as a binding vector but as an anti-plasticizer that removes the inorganic dispersant additives.

Wound treatment and pain management: a stressful time.

PubMed

Matsuzaki, Kyoichi; Upton, Dominic

2013-12-01

This review and case study report considers the evidence to indicate that the progress of wound healing is negatively affected by the presence of stressors and in circumstances where patients are in pain. It considers the relationship between perceptions of pain, stress and delayed wound healing with a specific focus on guidance for clinical practice. It is appreciated that although the literature has examined these issues in the management of acute wounds, demonstrating that psychological stress can have detrimental effects on the wound-healing process, the evidence to support this link in relation to chronic wounds is limited. The review considers evidence indicating that punch biopsy wounds heal more slowly in subjects under stress on account of caring for family members with long-term illnesses and also considers briefly the relationship between cortisol secretion in response to stress and the consequent influences on cytokine levels and the wound-healing process. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

[Morphea or juvenile localised scleroderma: Case report].

PubMed

Strickler, Alexis; Gallo, Silvanna; Jaramillo, Pedro; de Toro, Gonzalo

2016-01-01

Morphea or juvenile localised scleroderma (JLS) is an autoimmune, inflammatory, chronic, slowly progressive connective tissue disease of unknown cause that preferably affects skin and underlying tissues. To report a case of Juvenil Localised scleroderma in an 8-year old girl, contributing to an early diagnosis and treatment. The case is presented of an 8 year-old girl who presented with indurated hypopigmented plaques, of linear distribution in the right upper extremity of two years onset, together with papery texture hyperpigmented indurated plaques with whitish areas of thinned skin in right lower extremity, and leg and ankle swelling. The clinical features and diagnostic tests, including histology were compatible with linear and pansclerotic JLS. She started with immunosuppressive therapy, physiotherapy, and occupational therapy. We report a case of linear and pansclerotic ELJ type, in which there was a 2 year delay in diagnosis, however the response to treatment was positive as expected. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Botulism from chopped garlic: delayed recognition of a major outbreak.

PubMed

St Louis, M E; Peck, S H; Bowering, D; Morgan, G B; Blatherwick, J; Banerjee, S; Kettyls, G D; Black, W A; Milling, M E; Hauschild, A H

1988-03-01

Diagnosis of botulism in two teenaged sisters in Montreal led to the identification of 36 previously unrecognized cases of type B botulism in persons who had eaten at a restaurant in Vancouver, British Columbia, during the preceding 6 weeks. A case-control study implicated a new vehicle for botulism, commercial chopped garlic in soybean oil (P less than 10(-4)). Relatively mild and slowly progressive illness, dispersion of patients over at least eight provinces and states in three countries, and a previously unsuspected vehicle had contributed to prolonged misdiagnoses, including myasthenia gravis (six patients), psychiatric disorders (four), stroke (three), and others. Ethnic background influenced severity of illness: 60% of Chinese patients but only 4% of others needed mechanical ventilation (P less than 10(-3]. Trypsinization of serum was needed to show toxemia in one patient. Electromyography results with high-frequency repetitive stimulation corroborated the diagnosis of botulism up to 2 months after onset. Although botulism is a life-threatening disease, misdiagnosis may be common and large outbreaks can escape recognition completely.

Nobody Is Perfect: ERP Effects Prior to Performance Errors in Musicians Indicate Fast Monitoring Processes

PubMed Central

Maidhof, Clemens; Rieger, Martina; Prinz, Wolfgang; Koelsch, Stefan

2009-01-01

Background One central question in the context of motor control and action monitoring is at what point in time errors can be detected. Previous electrophysiological studies investigating this issue focused on brain potentials elicited after erroneous responses, mainly in simple speeded response tasks. In the present study, we investigated brain potentials before the commission of errors in a natural and complex situation. Methodology/Principal Findings Expert pianists bimanually played scales and patterns while the electroencephalogram (EEG) was recorded. Event-related potentials (ERPs) were computed for correct and incorrect performances. Results revealed differences already 100 ms prior to the onset of a note (i.e., prior to auditory feedback). We further observed that erroneous keystrokes were delayed in time and pressed more slowly. Conclusions Our data reveal neural mechanisms in musicians that are able to detect errors prior to the execution of erroneous movements. The underlying mechanism probably relies on predictive control processes that compare the predicted outcome of an action with the action goal. PMID:19337379

[Prolonged states of virtual recovery after atypical pubertal schizophrenic episodes with over-valuation disorders of the "metaphysical intoxication" type].

PubMed

Bil'zho, A G

1986-01-01

Using clinical and follow-up methods of investigation the authors studied a number of patients with juvenile slowly progressive schizophrenia in whom the disease picture in youth was characterized by over-worship disturbances of the "metaphysical intoxication" type which were attended by marked social and occupational disadaptation. A group of patients (n = 25) was identified with a state of practical cure after youth. Three most characteristic patterns of personality changes in these patients were described. The dominant role in their structure was played by manifestations of delay of mental maturation and the syndrome of psychic juvenilism of a dissociated nature. A certain relationship was found between the level and nature of the patients' occupational adaptation and the type of their personality changes. The question is discussed about the determination of the disease stage in such cases. The authors consider them as recovery states with some personality changes which can be ascribed to residual schizophrenia.

Reasonable Temperature Schedules for Cold or Hot Charging of Continuously Cast Steel Slabs

NASA Astrophysics Data System (ADS)

Li, Yang; Chen, Xin; Liu, Ke; Wang, Jing; Wen, Jin; Zhang, Jiaquan

2013-12-01

Some continuously cast steel slabs are sensitive to transverse fracture problems during transportation or handling away from their storage state, while some steel slabs are sensitive to surface transverse cracks during the following rolling process in a certain hot charging temperature range. It is revealed that the investigated steel slabs with high fracture tendency under room cooling condition always contain pearlite transformation delayed elements, which lead to the internal brittle bainitic structure formation, while some microalloyed steels exhibit high surface crack susceptibility to hot charging temperatures due to carbonitride precipitation. According to the calculated internal cooling rates and CCT diagrams, the slabs with high fracture tendency during cold charging should be slowly cooled after cutting to length from hot strand or charged to the reheating furnace directly above their bainite formation temperatures. Based on a thermodynamic calculation for carbonitride precipitation in austenite, the sensitive hot charging temperature range of related steels was revealed for the determination of reasonable temperature schedules.

VLF wave growth and discrete emission triggering in the magnetosphere - A feedback model

NASA Technical Reports Server (NTRS)

Helliwell, R. A.; Inan, U. S.

1982-01-01

A simple nonlinear feedback model is presented to explain VLF wave growth and emission triggering observed in VLF transmission experiments. The model is formulated in terms of the interaction of electrons with a slowly varying wave in an inhomogeneous medium as in an unstable feedback amplifier with a delay line; constant frequency oscillations are generated on the magnetic equator, while risers and fallers are generated on the downstream and upstream sides of the equator, respectively. Quantitative expressions are obtained for the stimulated radiation produced by energy exchanged between energetic electrons and waves by Doppler-shifted cyclotron resonance, and feedback between the stimulated radiation and the phase bunched currents is incorporated in terms of a two-port discrete time model. The resulting model is capable of explaining the observed temporal growth and saturation effects, phase advance, retardation or frequency shift during growth in the context of a single parameter depending on the energetic particle distribution function, as well as pretermination triggering.

Acute deterioration in occult Chiari malformation following missile spinal trauma. Case report.

PubMed

Shahlaie, Kiarash; Hartman, Jonathan; Utter, Garth H; Schrot, Rudolph J

2008-04-01

Patients with Chiari malformation (CM) Type I typically experience chronic, slowly progressive symptoms. Rarely, however, do they suffer acute neurological deterioration following an iatrogenic decrease in caudal cerebrospinal fluid pressure due to, for example, a lumbar puncture. To our knowledge, acute neurological deterioration following missile spinal injury in CM has not been previously described. The authors report on a 16-year-old girl who was shot in the abdomen and lumbar spine. Although neurologically intact on initial workup, she developed precipitous quadriplegia and apnea in a delayed fashion. Tonsillar herniation with medullary compression and cerebellar infarction was diagnosed on magnetic resonance imaging. Suboccipital decompression resulted in significant neurological improvement. Well-formed tonsillar ectopia diagnosed at surgery suggested a preexisting CM. The authors conclude that missile spinal trauma can precipitate medullary compression and acute neurological decline, especially in patients with preexisting tonsillar ectopia. Immediate operative decompression to relieve impaction at the cervicomedullary junction can result in significant neurological recovery.

Photosynthetic activity during olive (Olea europaea) leaf development correlates with plastid biogenesis and Rubisco levels.

PubMed

Maayan, Inbar; Shaya, Felix; Ratner, Kira; Mani, Yair; Lavee, Shimon; Avidan, Benjamin; Shahak, Yosepha; Ostersetzer-Biran, Oren

2008-11-01

Olive leaves are known to mature slowly, reaching their maximum photosynthetic activity only after full leaf expansion. Poor assimilation rates, typical to young olive leaves, were previously associated with low stomata conductance. Yet, very little is known about chloroplast biogenesis throughout olive leaf development. Here, the photosynthetic activity and plastids development throughout leaf maturation is characterized by biochemical and ultrastructural analyses. Although demonstrated only low photosynthetic activity, the plastids found in young leaves accumulated both photosynthetic pigments and proteins required for photophosphorylation and carbon fixation. However, Rubisco (ribulose-1,5-bisphosphate carboxylase-oxygenase), which catalyzes the first major step of carbon fixation and one of the most abundant proteins in plants, could not be detected in the young leaves and only slowly accumulated throughout development. In fact, Rubisco levels seemed tightly correlated with the observed photosynthetic activities. Unlike Rubisco, numerous proteins accumulated in the young olive leaves. These included the early light induced proteins, which may be required to reduce the risk of photodamage, because of light absorption by photosynthetic pigments. Also, high levels of ribosomal L11 subunit, transcription factor elF-5A, Histones H2B and H4 were observed in the apical leaves, and in particular a plastidic-like aldolase, which accounted for approximately 30% of the total proteins. These proteins may upregulate in their levels to accommodate the high demand for metabolic energy in the young developing plant tissue, further demonstrating the complex sink-to-source relationship between young and photosynthetically active mature leaves.

Evidence for the absence of enzymatic reactions in the glassy state. A case study of xanthophyll cycle pigments in the desiccation-tolerant moss Syntrichia ruralis

PubMed Central

Fernández-Marín, Beatriz; Kranner, Ilse; Sebastián, María San; Artetxe, Unai; Laza, José Manuel; Vilas, José Luis; Pritchard, Hugh W.; Nadajaran, Jayanthi; Míguez, Fátima; Becerril, José María; García-Plazaola, José Ignacio

2013-01-01

Desiccation-tolerant plants are able to withstand dehydration and resume normal metabolic functions upon rehydration. These plants can be dehydrated until their cytoplasm enters a ‘glassy state’ in which molecular mobility is severely reduced. In desiccation-tolerant seeds, longevity can be enhanced by drying and lowering storage temperature. In these conditions, they still deteriorate slowly, but it is not known if deteriorative processes include enzyme activity. The storage stability of photosynthetic organisms is less studied, and no reports are available on the glassy state in photosynthetic tissues. Here, the desiccation-tolerant moss Syntrichia ruralis was dehydrated at either 75% or <5% relative humidity, resulting in slow (SD) or rapid desiccation (RD), respectively, and different residual water content of the desiccated tissues. The molecular mobility within dry mosses was assessed through dynamic mechanical thermal analysis, showing that at room temperature only rapidly desiccated samples entered the glassy state, whereas slowly desiccated samples were in a ‘rubbery’ state. Violaxanthin cycle activity, accumulation of plastoglobules, and reorganization of thylakoids were observed upon SD, but not upon RD. Violaxanthin cycle activity critically depends on the activity of violaxanthin de-epoxidase (VDE). Hence, it is proposed that enzymatic activity occurred in the rubbery state (after SD), and that in the glassy state (after RD) no VDE activity was possible. Furthermore, evidence is provided that zeaxanthin has some role in recovery apparently independent of its role in non-photochemical quenching of chlorophyll fluorescence. PMID:23761488

Computer laboratory notification system via short message service to reduce health care delays in management of tuberculosis in Taiwan.

PubMed

Chen, Tun-Chieh; Lin, Wei-Ru; Lu, Po-Liang; Lin, Chun-Yu; Lin, Shu-Hui; Lin, Chuen-Ju; Feng, Ming-Chu; Chiang, Horn-Che; Chen, Yen-Hsu; Huang, Ming-Shyan

2011-06-01

We investigated the impacts of introducing an expedited acid-fast bacilli (AFB) smear laboratory procedure and an automatic, real-time laboratory notification system by short message with mobile phones on delays in prompt isolation of patients with pulmonary tuberculosis (TB). We analyzed the data for all patients with active pulmonary tuberculosis at a hospital in Kaohsiung, Taiwan, a 1,600-bed medical center, during baseline (January 2004 to February 2005) and intervention (July 2005 to August 2006) phases. A total of 96 and 127 patients with AFB-positive TB was reported during the baseline and intervention phases, respectively. There were significant decreases in health care system delays (ie, laboratory delays: reception of sputum to reporting, P < .001; response delays: reporting to patient isolation, P = .045; and interval from admission to patient isolation, P < .001) during the intervention phase. Significantly fewer nurses were exposed to each patient with active pulmonary TB during the intervention phase (P = .039). Implementation of expedited AFB smear laboratory procedures and an automatic, real-time laboratory mobile notification system significantly decreased delays in the diagnosis and isolation of patients with active TB. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Ciprofloxacin and statin interaction: a cautionary tale of rhabdomyolysis.

PubMed

Goldie, Fraser Charles; Brogan, Amy; Boyle, James Graham

2016-07-28

A 62-year-old woman presented to hospital, on general practitioner (GP) advice, with a 15-day history of slowly progressing muscle weakness. Results showed newly deranged liver function and creatine kinase (CK) of >24 000. Prior medical history includes previous myocardial infarction and recurrent urinary tract infection. 4 days prior to symptom onset, the patient developed typical urinary tract infection symptoms, treated with ciprofloxacin. The patient had been taking simvastatin (40 mg nocte) for 13 years and had never previously taken ciprofloxacin. Initial management included intravenous crystalloid fluids and discontinuation of simvastatin. CK level fell, liver function slowly improved and renal function remained stable. Muscle weakness improved and the patient became independently able to perform activities of daily living. While the interactions between statins and other antibiotics are well documented, the interaction between statins and ciprofloxacin is less so. The consequences of this interaction can have potentially serious outcomes. 2016 BMJ Publishing Group Ltd.

Aerobic co-treatment of landfill leachate and domestic wastewater - are slowly biodegradable organics removed or simply diluted?

PubMed

Campos, R; Ferraz, F M; Vieira, E M; Povinelli, J

2014-01-01

This study investigated the co-treatment of landfill leachate/domestic wastewater in bench-scale activated sludge (AS) reactors to determine whether the slowly biodegradable organic matter (SBOM) was removed rather than diluted. The AS reactors were loaded with mixtures of raw leachate and leachate that was pretreated by air stripping. The tested volumetric ratios were 0%, 0.2%, 2% and 5%. For all of the tested conditions, the reactors performed better when pretreated leachate was used rather than raw leachate, and the best volumetric ratio was 2%. The following removals were obtained: 97% for the biochemical oxygen demand (BOD5,20), 79% for total suspended solids, 77% for dissolved organic carbon and 84% for soluble chemical oxygen demand. Most of the pretreated leachate SBOM (65%) was removed rather than diluted or adsorbed into the sludge, as confirmed by Fourier transform infrared (FTIR) spectroscopy analyses.

Monodisperse, polymeric microspheres produced by irradiation of slowly thawing frozen drops

NASA Technical Reports Server (NTRS)

Rhim, Won-Kyu (Inventor); Hyson, Michael T. (Inventor); Chung, Sang-Kun (Inventor); Colvin, Michael S. (Inventor); Chang, Manchium (Inventor)

1991-01-01

Monodisperse, polymeric microspheres are formed by injecting uniformly shaped droplets of radiation polymerizable monomers, preferably a biocompatible monomer, having covalent binding sites such as hydroxyethylmethacrylate, into a zone, impressing a like charge on the droplet so that they mutually repel each other, spheroidizing the droplets within the zone and collecting the droplets in a pool of cryogenic liquid. As the droplets enter the liquid, they freeze into solid, glassy microspheres, which vaporizes a portion of the cryogenic liquid to form a layer. The like-charged microspheres, suspended within the layer, move to the edge of the vessel holding the pool, are discharged, fall and are collected. The collected microspheres are irradiated while frozen in the cryogenic liquid to form latent free radicals. The frozen microspheres are then slowly thawed to activate the free radicals which polymerize the monomer to form evenly-sized, evenly-shaped, monodisperse polymeric microspheres.

Spectral models for early time SN 2011fe observations

NASA Astrophysics Data System (ADS)

Baron, E.; Hoeflich, P.; Friesen, Brian; Sullivan, M.; Hsiao, E.; Ellis, R. S.; Gal-Yam, A.; Howell, D. A.; Nugent, P. E.; Dominguez, I.; Krisciunas, K.; Phillips, M. M.; Suntzeff, N.; Wang, L.; Thomas, R. C.

2015-12-01

We use observed UV through near-IR spectra to examine whether SN 2011fe can be understood in the framework of Branch-normal Type Ia supernovae (SNe Ia) and to examine its individual peculiarities. As a benchmark, we use a delayed-detonation model with a progenitor metallicity of Z⊙/20. We study the sensitivity of features to variations in progenitor metallicity, the outer density profile, and the distribution of radioactive nickel. The effect of metallicity variations in the progenitor have a relatively small effect on the synthetic spectra. We also find that the abundance stratification of SN 2011fe resembles closely that of a delayed-detonation model with a transition density that has been fit to other Branch-normal SNe Ia. At early times, the model photosphere is formed in material with velocities that are too high, indicating that the photosphere recedes too slowly or that SN 2011fe has a lower specific energy in the outer ≈0.1 M⊙ than does the model. We discuss several explanations for the discrepancies. Finally, we examine variations in both the spectral energy distribution and in the colours due to variations in the progenitor metallicity, which suggests that colours are only weak indicators for the progenitor metallicity, in the particular explosion model that we have studied. We do find that the flux in the U band is significantly higher at maximum light in the solar metallicity model than in the lower metallicity model and the lower metallicity model much better matches the observed spectrum.

Actinomyces in Chronic Granulomatous Disease: An Emerging and Unanticipated Pathogen

PubMed Central

Reichenbach, Janine; Lopatin, Uri; Mahlaoui, Nizar; Beovic, Bojana; Siler, Ulrich; Zbinden, Reinhard; Seger, Reinhard A.; Galmiche, Louise; Brousse, Nicole; Kayal, Samer; Güngör, Tayfun; Blanche, Stéphane; Holland, Steven M.

2014-01-01

Background Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system that causes defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections, mostly by catalase-producing organisms. We report for the first time, to our knowledge, chronic infections with Actinomyces species in 10 patients with CGD. Actinomycosis is a chronic granulomatous condition that commonly manifests as cervicofacial, pulmonary, or abdominal disease, caused by slowly progressive infection with oral and gastrointestinal commensal Actinomyces species. Treatment of actinomycosis is usually simple in immunocompetent individuals, requiring long-term, high-dose intravenous penicillin, but is more complicated in those with CGD because of delayed diagnosis and an increased risk of chronic invasive or debilitating disease. Methods Actinomyces was identified by culture, staining, 16S ribosomal DNA polymerase chain reaction, and/ or a complement fixation test in 10 patients with CGD. Results All 10 patients presented with a history of fever and elevated inflammatory signs without evident focus. Diagnosis was delayed and clinical course severe and protracted despite high-dose intravenous antibiotic therapy and/or surgery. These results suggest an unrecognized and unanticipated susceptibility to weakly pathogenic Actinomyces species in patients with CGD because these are catalase-negative organisms previously thought to be nonpathogenic in CGD. Conclusions Actinomycosis should be vigorously sought and promptly treated in patients with CGD presenting with uncommon and prolonged clinical signs of infection. Actinomycosis is a catalase-negative infection important to consider in CGD. PMID:19874205

Heart Rate Recovery, Physical Activity Level, and Functional Status in Subjects With COPD.

PubMed

Morita, Andrea A; Silva, Laís K O; Bisca, Gianna W; Oliveira, Joice M; Hernandes, Nidia A; Pitta, Fabio; Furlanetto, Karina C

2018-05-15

A normal heart rate reflects the balance between the sympathetic and parasympathetic autonomic nervous system. When the difference between heart rate at the end of an exercise test and after 1 min of recovery, known as the 1-min heart rate recovery, is ≤ 12 beats/min, this may indicate an abnormal delay. We sought to compare physical activity patterns and subjects' functional status with COPD with or without delayed 1-min heart rate recovery after the 6-min walk test (6MWT). 145 subjects with COPD (78 men, median [interquartile range (IQR)] age 65 [60-73] y, body mass index 25 [21-30] kg/m 2 , FEV 1 45 ± 15% predicted) were underwent the following assessments: spirometry, 6MWT, functional status, and physical activity in daily life (PADL). A delayed heart rate recovery of 1 min was defined as ≤ 12 beats/min. Subjects with delayed 1-min heart rate recovery walked a shorter distance in the 6MWT compared to subjects without delayed heart rate recovery (median [IQR] 435 [390-507] m vs 477 [425-515] m, P = .01; 81 [71-87] vs 87 [79-98]% predicted, P = .002). Regarding PADL, subjects with delayed heart rate recovery spent less time in the standing position (mean ± SD 185 ± 89 min vs 250 ± 107 min, P = .002) and more time in sedentary positions (472 ± 110 min vs 394 ± 129 min, P = .002). Scores based on the self-care domain of the London Chest Activity of Daily Living questionnaire and the activity domain of the Pulmonary Functional Status and Dyspnea questionnaire were also worse in the group with delayed heart rate recovery (6 ± 2 points vs 5 ± 2 points; P = .039 and 29 ± 24 points vs 19 ± 17 points; P = .037, respectively). Individuals with COPD who exhibit delayed 1-min heart rate recovery after the 6MWT exhibited worse exercise capacity as well as a more pronounced sedentary lifestyle and worse functional status than those without delayed heart rate recovery. Despite its assessment simplicity, heart rate recovery after the 6MWT can be further explored as a promising outcome in COPD. Copyright © 2018 by Daedalus Enterprises.

Differential effects of dopamine and opioid receptor blockade on motivated Coca-Cola drinking behavior and associated changes in brain, skin and muscle temperatures.

PubMed

Kiyatkin, E A

2010-05-05

Although pharmacological blockade of both dopamine (DA) and opiate receptors has an inhibiting effect on appetitive motivated behaviors, it is still unclear which physiological mechanisms affected by these treatments underlie the behavioral deficit. To clarify this issue, we examined how pharmacological blockade of either DA (SCH23390+eticlopride at 0.2 mg/kg each) or opioid receptors (naloxone 1 mg/kg) affects motor activity and temperature fluctuations in the nucleus accumbens (NAcc), temporal muscle, and facial skin associated with motivated Coca-Cola drinking behavior in rats. In drug-free conditions, presentation of a cup containing 5 ml of Coca-Cola induced locomotor activation and rapid NAcc temperature increases, which both transiently decreased during drinking, and phasically increased again after the cup was emptied. Muscle temperatures followed this pattern, but increases were weaker and more delayed than those in the NAcc. Skin temperature rapidly dropped after cup presentation, remained at low levels during consumption, and slowly restored during post-consumption behavioral activation. By itself, DA receptor blockade induced robust decrease in spontaneous locomotion, moderate increases in brain and muscle temperatures, and a relative increase in skin temperatures, suggesting metabolic activation coupled with adynamia. Following this treatment (approximately 180 min), motor activation to cup presentation and Coca-Cola consumption were absent, but rats showed NAcc and muscle temperature increases following cup presentation comparable to control. Therefore, DA receptor blockade does not affect significantly central and peripheral autonomic responses to appetitive stimuli, but eliminates their behavior-activating effects, thus disrupting appetitive behavior and blocking consumption. Naloxone alone slightly decreased brain and muscle temperatures and increased skin temperatures, pointing at the enhanced heat loss and possible minor inhibition of basal metabolic activity. This treatment (approximately 60 min) had minimal effects on the latencies of drinking, but increased its total duration, with licking interrupted by pauses and retreats. This behavioral attenuation was coupled with weaker than in control locomotor activation and diminished temperature fluctuations in each recording location. Therefore, attenuation of normal behavioral and physiological responses to appetitive stimuli appears to underlie modest inhibiting effects of opiate receptor blockade on motivated behavior and consumption. (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Willing to wait: Elevated reward-processing EEG activity associated with a greater preference for larger-but-delayed rewards.

PubMed

Pornpattananangkul, Narun; Nusslock, Robin

2016-10-01

While almost everyone discounts the value of future rewards over immediate rewards, people differ in their so-called delay-discounting. One of the several factors that may explain individual differences in delay-discounting is reward-processing. To study individual-differences in reward-processing, however, one needs to consider the heterogeneity of neural-activity at each reward-processing stage. Here using EEG, we separated reward-related neural activity into distinct reward-anticipation and reward-outcome stages using time-frequency characteristics. Thirty-seven individuals first completed a behavioral delay-discounting task. Then reward-processing EEG activity was assessed using a separate reward-learning task, called a reward time-estimation task. During this EEG task, participants were instructed to estimate time duration and were provided performance feedback on a trial-by-trial basis. Participants received monetary-reward for accurate-performance on Reward trials, but not on No-Reward trials. Reward trials, relative to No-Reward trials, enhanced EEG activity during both reward-anticipation (including, cued-locked delta power during cue-evaluation and pre-feedback alpha suppression during feedback-anticipation) and reward-outcome (including, feedback-locked delta, theta and beta power) stages. Moreover, all of these EEG indices correlated with behavioral performance in the time-estimation task, suggesting their essential roles in learning and adjusting performance to maximize winnings in a reward-learning situation. Importantly, enhanced EEG power during Reward trials, as reflected by stronger 1) pre-feedback alpha suppression, 2) feedback-locked theta and 3) feedback-locked beta, was associated with a greater preference for larger-but-delayed rewards in a separate, behavioral delay-discounting task. Results highlight the association between a stronger preference toward larger-but-delayed rewards and enhanced reward-processing. Moreover, our reward-processing EEG indices detail the specific stages of reward-processing where these associations occur. Copyright © 2016 Elsevier Ltd. All rights reserved.

Persistent spatial information in the frontal eye field during object-based short-term memory.

PubMed

Clark, Kelsey L; Noudoost, Behrad; Moore, Tirin

2012-08-08

Spatial attention is known to gate entry into visual short-term memory, and some evidence suggests that spatial signals may also play a role in binding features or protecting object representations during memory maintenance. To examine the persistence of spatial signals during object short-term memory, the activity of neurons in the frontal eye field (FEF) of macaque monkeys was recorded during an object-based delayed match-to-sample task. In this task, monkeys were trained to remember an object image over a brief delay, regardless of the locations of the sample or target presentation. FEF neurons exhibited visual, delay, and target period activity, including selectivity for sample location and target location. Delay period activity represented the sample location throughout the delay, despite the irrelevance of spatial information for successful task completion. Furthermore, neurons continued to encode sample position in a variant of the task in which the matching stimulus never appeared in their response field, confirming that FEF maintains sample location independent of subsequent behavioral relevance. FEF neurons also exhibited target-position-dependent anticipatory activity immediately before target onset, suggesting that monkeys predicted target position within blocks. These results show that FEF neurons maintain spatial information during short-term memory, even when that information is irrelevant for task performance.

Drift in Neural Population Activity Causes Working Memory to Deteriorate Over Time.

PubMed

Schneegans, Sebastian; Bays, Paul M

2018-05-23

Short-term memories are thought to be maintained in the form of sustained spiking activity in neural populations. Decreases in recall precision observed with increasing number of memorized items can be accounted for by a limit on total spiking activity, resulting in fewer spikes contributing to the representation of each individual item. Longer retention intervals likewise reduce recall precision, but it is unknown what changes in population activity produce this effect. One possibility is that spiking activity becomes attenuated over time, such that the same mechanism accounts for both effects of set size and retention duration. Alternatively, reduced performance may be caused by drift in the encoded value over time, without a decrease in overall spiking activity. Human participants of either sex performed a variable-delay cued recall task with a saccadic response, providing a precise measure of recall latency. Based on a spike integration model of decision making, if the effects of set size and retention duration are both caused by decreased spiking activity, we would predict a fixed relationship between recall precision and response latency across conditions. In contrast, the drift hypothesis predicts no systematic changes in latency with increasing delays. Our results show both an increase in latency with set size, and a decrease in response precision with longer delays within each set size, but no systematic increase in latency for increasing delay durations. These results were quantitatively reproduced by a model based on a limited neural resource in which working memories drift rather than decay with time. SIGNIFICANCE STATEMENT Rapid deterioration over seconds is a defining feature of short-term memory, but what mechanism drives this degradation of internal representations? Here, we extend a successful population coding model of working memory by introducing possible mechanisms of delay effects. We show that a decay in neural signal over time predicts that the time required for memory retrieval will increase with delay, whereas a random drift in the stored value predicts no effect of delay on retrieval time. Testing these predictions in a multi-item memory task with an eye movement response, we identified drift as a key mechanism of memory decline. These results provide evidence for a dynamic spiking basis for working memory, in contrast to recent proposals of activity-silent storage. Copyright © 2018 Schneegans and Bays.

Escaping the impulse to immediate gratification: the prospect concept promotes a future-oriented mindset, prompting an inclination towards delayed gratification.

PubMed

Cheng, Ying-Yao; Shein, Paichi Pat; Chiou, Wen-Bin

2012-02-01

People's willingness to postpone receiving an immediate reward in order to gain additional benefits in the future, that is, a tendency to shallow delay discounting, is closely related to one's health, wealth, and happiness. We conducted two experiments investigating how the prospect concept can induce a future-oriented mindset and induce people to behave accordingly. We found that engaging in prospective imagery led the participants to focus on delayed utility over immediate utility in financial decisions (Experiment 1). Participants who received the prospect prime via a scrambled-sentence task decreased their desire to pursue hedonic activities for instant gratification (Experiment 2). Moreover, a state of future orientation mediated the effect of the prospect prime on measures of delayed gratification (Experiments 1 and 2). Thus, reminders of prospect may activate a mindset for future orientation by which delayed gratification is strengthened. ©2011 The British Psychological Society.

Delay selection by spike-timing-dependent plasticity in recurrent networks of spiking neurons receiving oscillatory inputs.

PubMed

Kerr, Robert R; Burkitt, Anthony N; Thomas, Doreen A; Gilson, Matthieu; Grayden, David B

2013-01-01

Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem.

Delay Selection by Spike-Timing-Dependent Plasticity in Recurrent Networks of Spiking Neurons Receiving Oscillatory Inputs

PubMed Central

Kerr, Robert R.; Burkitt, Anthony N.; Thomas, Doreen A.; Gilson, Matthieu; Grayden, David B.

2013-01-01

Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem. PMID:23408878

Willing to Wait: Elevated Reward-Processing EEG Activity Associated with a Greater Preference for Larger-But-Delayed Rewards

PubMed Central

Pornpattananangkul, Narun; Nusslock, Robin

2016-01-01

While almost everyone discounts the value of future rewards over immediate rewards, people differ in their so-called delay-discounting. One of the several factors that may explain individual differences in delay-discounting is reward-processing. To study individual-differences in reward-processing, however, one needs to consider the heterogeneity of neural-activity at each reward-processing stage. Here using EEG, we separated reward-related neural activity into distinct reward-anticipation and reward-outcome stages using time-frequency characteristics. Thirty-seven individuals completed a behavioral delay-discounting task. Reward-processing EEG activity was assessed using a separate reward-learning task, called a reward time-estimation task. During this task, participants were instructed to estimate time duration and were provided performance feedback on a trial-by-trial basis. Participants received monetary-reward for accurate-performance on Reward trials, but not on No-Reward trials. Reward trials, relative to No-Reward trials, enhanced EEG activity during both reward-anticipation stage (including, cued-locked delta power during cue-evaluation and pre-feedback alpha suppression during feedback-anticipation) and at the reward-outcome stage (including, feedback-locked delta, theta and beta power). Moreover, all of these EEG indices correlated with behavioral performance in the time-estimation task, suggesting their essential roles in learning and adjusting performance to maximize winnings in a reward-learning situation. Importantly, enhanced EEG power during Reward trials for 1) pre-feedback alpha suppression, 2) feedback-locked theta and 3) feedback-locked beta was associated with a greater preference for larger-but-delayed rewards. Results highlight the association between a stronger preference toward larger-but-delayed rewards and enhanced reward-processing. Moreover, our reward-processing EEG indices detail the specific stages of reward-processing where these associations occur. PMID:27477630

Delocalization of frontier orbitals induced red emission for heptazine based thermally activated delayed fluorescence molecule: First-principles study

NASA Astrophysics Data System (ADS)

Kang, Yongxiang; Zhao, Liyun; Leng, Jiancai

2018-04-01

Design of red organic emitting molecules with characteristic of thermally activated delayed fluorescence (TADF) remains a great challenge. Here, electronic and optical properties of a series of multi-branched TADF molecules have been investigated based on the newly-proposed optimal Hartree-Fock percentage method. Results show that, though enlarging the delocalization of HOMO and LUMO, the emission wavelength is redshift. The designed red TADF molecule possesses smaller reorganization energy than these for reported molecules. This indicates the non-radiative energy consumption of excited state is small and effective luminescence can be expected. Thus, a promising red thermally activated delayed fluorescence molecule is proposed.

A Demonstration of Precise Calibration of Tropospheric Delay Fluctuations with Water Vapor Radiometers

NASA Technical Reports Server (NTRS)

Teitelbaum, L. P.; Keihm, S. J.; Linfield, R. P.; Mahoney, M. J.; Resch, G. M.

1996-01-01

The ability of water vapor radiometers (WVRs) to calibrate changes in tropospheric delay was demonstrated during very long baseline radio interferometer (VLBI) observations at Goldstone, California. WVR measurements reduced the observed VLBI delay variations over a 13 hr period by a factor of approx. = 2.5. When applied to shorter time scales, a approx. = 50% reduction in 100-700 s delay variations was achieved during conditions of high tropospheric activity. Thermal WVR noise precluded calibration of short time scale delay fluctuations during quiet tropospheric conditions.

Differential Activation of Medullary Vagal Nuclei Caused by Stimulation of Different Esophageal Mechanoreceptors

PubMed Central

Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza

2010-01-01

Esophageal mechanorecptors, i.e. muscular slowly adapting tension receptors and mucosal rapidly adapting touch receptors, mediate different sets of reflexes. The aim of this study was to determine the medullary vagal nuclei involved in the reflex responses to activation of these receptors. Thirty-three cats were anesthetized with alpha-chloralose and the esophagus was stimulated by slow balloon or rapid air distension. The physiological effects of the stimuli (N=4) were identified by recording responses from the pharyngeal, laryngeal, and hyoid muscles, esophagus, and the lower esophageal sphincter (LES). The effects on the medullary vagal nuclei of the stimuli: slow distension (N=10), rapid distension (N=9), and in control animals (N=10) were identified using the immunohistochemical analysis of c-fos. The experimental groups were stimulated 3 times per minute for 3 hours. After the experiment, the brains were removed and processed for c-fos immunoreactivity or thioinin. We found that slow balloon distension activated the esophago-UES contractile reflex and esophago LES relaxation response, and rapid air injection activated the belch and its component reflexes. Slow balloon distension activated the NTSce, NTSdl, NTSvl, DMNc, DMNr and NAr; and rapid air injection primarily activated AP, NTScd, NTSim, NTSis, NTSdm, NTSvl, NAc and NAr. We concluded that different sets of medullary vagal nuclei mediate different reflexes of the esophagus activated from different sets of mechanoreceptors. The NTScd is the primary NTS subnucleus mediating reflexes from the mucosal rapidly adapting touch receptors, and the NTSce is the primary NTS subnucleus mediating reflexes from the muscular slowly adapting tension receptors. The AP may be involved in mediation of belching. PMID:20971087

Is There a Neighborhood Frequency Effect in English?: Evidence from Reading and Lexical Decision

ERIC Educational Resources Information Center

Sears, Christopher R.; Campbell, Crystal R.; Lupker, Stephen J.

2006-01-01

What is the effect of a word's higher frequency neighbors on its identification time? According to activation-based models of word identification (J. Grainger & A. M. Jacobs, 1996; J. L. McClelland & D. E. Rumelhart, 1981), words with higher frequency neighbors will be processed more slowly than words without higher frequency neighbors because of…

Effects of sorghum (Sorghum bicolor (L.) Moench) tannins on alpha-amylase activity and in vitro digestibility of starch in raw and processed flours

USDA-ARS?s Scientific Manuscript database

The effect of condensed tannins (CT) on in vitro starch digestibility in cooked, wholegrain sorghum flours and on corn starch was investigated. CT extracts were also tested for their inhibitory effect on alpha-amylases. Rapidly digestible starch, slowly digestible starch, and resistant starch were n...

Range Reference Notebook

DTIC Science & Technology

2006-10-15

EM 61 and a Schonstedt Magnetometer . The magnetometer was used to screen locations for stakes and other intrusive activities. Digital geophysics was...patterns from direct-fire weapons, such as anti-tank rockets, are expected to form ellipses that are highly elongated parallel to the line of fire...Trajectory of Indirect Fire Weapons Historically, precision development progressed more slowly for indirect-fire weapons because hitting an unseen target

Robinson during EVA 3

NASA Image and Video Library

2005-06-29

S114-E-6221 (3 August 2005) --- Astronaut Stephen K. Robinson, STS-114 mission specialist, on the end of the station’s Canadarm2 (out of frame), slowly and cautiously makes his way to the underside of Space Shuttle Discovery to remove gap fillers from between the orbiter’s heat-shielding tiles during the mission’s third session of extravehicular activity (EVA).

Robinson during EVA 3

NASA Image and Video Library

2005-08-03

S114-E-6215 (3 August 2005) --- Astronaut Stephen K. Robinson, STS-114 mission specialist, on the end of the station’s Canadarm2 (out of frame), slowly and cautiously makes his way to the underside of Space Shuttle Discovery to remove gap fillers from between the orbiter’s heat-shielding tiles during the mission’s third of three sessions of extravehicular activity (EVA).

Some Characteristics of an Effective Language Learning Program. CATESOL Occasional Papers, No. 1.

ERIC Educational Resources Information Center

Sutherland, Kenton

Children learn a second language quickly and easily simply by being exposed to it. Adults generally learn more slowly and less well. It is hypothesized that the brain in youth is extremely plastic, but hardens with adolescence and adulthood and becomes less receptive. Children learn in an active way, during play, and the language is reinforced by…

IKs channels open slowly because KCNE1 accessory subunits slow the movement of S4 voltage sensors in KCNQ1 pore-forming subunits

PubMed Central

Ruscic, Katarina J.; Miceli, Francesco; Villalba-Galea, Carlos A.; Dai, Hui; Mishina, Yukiko; Bezanilla, Francisco; Goldstein, Steve A. N.

2013-01-01

Human IKs channels activate slowly with the onset of cardiac action potentials to repolarize the myocardium. IKs channels are composed of KCNQ1 (Q1) pore-forming subunits that carry S4 voltage-sensor segments and KCNE1 (E1) accessory subunits. Together, Q1 and E1 subunits recapitulate the conductive and kinetic properties of IKs. How E1 modulates Q1 has been unclear. Investigators have variously posited that E1 slows the movement of S4 segments, slows opening and closing of the conduction pore, or modifies both aspects of electromechanical coupling. Here, we show that Q1 gating current can be resolved in the absence of E1, but not in its presence, consistent with slowed movement of the voltage sensor. E1 was directly demonstrated to slow S4 movement with a fluorescent probe on the Q1 voltage sensor. Direct correlation of the kinetics of S4 motion and ionic current indicated that slowing of sensor movement by E1 was both necessary and sufficient to determine the slow-activation time course of IKs. PMID:23359697

Differential Acetylcholine Release in the Prefrontal Cortex and Hippocampus During Pavlovian Trace and Delay Conditioning

PubMed Central

Flesher, M. Melissa; Butt, Allen E.; Kinney-Hurd, Brandee L.

2011-01-01

Pavlovian trace conditioning critically depends on the medial prefrontal cortex (mPFC) and hippocampus (HPC), whereas delay conditioning does not depend on these brain structures. Given that the cholinergic basal forebrain system modulates activity in both the mPFC and HPC, it was reasoned that the level of acetylcholine (ACh) release in these regions would show distinct profiles during testing in trace and delay conditioning paradigms. To test this assumption, microdialysis probes were implanted unilaterally into the mPFC and HPC of rats that were pre-trained in appetitive trace and delay conditioning paradigms using different conditional stimuli in the two tasks. On the day of microdialysis testing, dialysate samples were collected during a quiet baseline interval before trials were initiated, and again during performance in separate blocks of trace and delay conditioning trials in each animal. ACh levels were quantified using high performance liquid chromatography and electrochemical detection techniques. Consistent with our hypothesis, results showed that ACh release in the mPFC was greater during trace conditioning than during delay conditioning. The level of ACh released during trace conditioning in the HPC was also greater than the levels observed during delay conditioning. While ACh efflux in both the mPFC and HPC selectively increased during trace conditioning, ACh levels in the mPFC during trace conditioning testing showed the greatest increases observed. These results demonstrate a dissociation in cholinergic activation of the mPFC and HPC during performance in trace but not delay appetitive conditioning, where this cholinergic activity may contribute to attentional mechanisms, adaptive response timing, or memory consolidation necessary for successful trace conditioning. PMID:21514394

Model predictions of higher-order normal alkane ignition from dilute shock-tube experiments

NASA Astrophysics Data System (ADS)

Rotavera, B.; Petersen, E. L.

2013-07-01

Shock-induced oxidation of two higher-order linear alkanes was measured using a heated shock tube facility. Experimental overlap in stoichiometric ignition delay times obtained under dilute (99 % Ar) conditions near atmospheric pressure was observed in the temperature-dependent ignition trends of n-nonane ( n-C9H20) and n-undecane ( n-C11H24). Despite the overlap, model predictions of ignition using two different detailed chemical kinetics mechanisms show discrepancies relative to both the measured data as well as to one another. The present study therefore focuses on the differences observed in the modeled, high-temperature ignition delay times of higher-order n-alkanes, which are generally regarded to have identical ignition behavior for carbon numbers above C7. Comparisons are drawn using experimental data from the present study and from recent work by the authors relative to two existing chemical kinetics mechanisms. Time histories from the shock-tube OH* measurements are also compared to the model predictions; a double-peaked structure observed in the data shows that the time response of the detector electronics is crucial for properly capturing the first, incipient peak near time zero. Calculations using the two mechanisms were carried out at the dilution level employed in the shock-tube experiments for lean {({φ} = 0.5)}, stoichiometric, and rich {({φ} = 2.0)} equivalence ratios, 1230-1620 K, and for both 1.5 and 10 atm. In general, the models show differing trends relative to both measured data and to one another, indicating that agreement among chemical kinetics models for higher-order n-alkanes is not consistent. For example, under certain conditions, one mechanism predicts the ignition delay times to be virtually identical between the n-nonane and n-undecane fuels (in fact, also for all alkanes between at least C8 and C12), which is in agreement with the experiment, while the other mechanism predicts the larger fuels to ignite progressively more slowly.

Activity In Children With ADHD During Waiting Situations In The Classroom: A Pilot Study

ERIC Educational Resources Information Center

Antrop, Inge; Buysse, Ann; Roeyers, Herbert; Van Oost, Paulette

2005-01-01

Background: According to the optimal stimulation theory and the delay aversion hypothesis, children with attention deficit hyperactivity disorder (ADHD) experience difficulties when they are confronted with low levels of stimulation and delay, respectively. Aim: This study investigated the activity level of children with ADHD during waiting…

The role of social toxicity in responses to a slowly-evolving environmental disaster: the case of amphibole asbestos exposure in Libby, Montana, USA.

PubMed

Cline, Rebecca J W; Orom, Heather; Chung, Jae Eun; Hernandez, Tanis

2014-09-01

Experiencing a disaster has significant negative effects on psychological adjustment. Case study accounts point to two consistent trends in slowly-evolving environmental disasters: (a) patterns of negative social dynamics, and (b) relatively worse psychological outcomes than in natural disasters. Researchers have begun to explicitly postulate that the social consequences of slowly-evolving environmental disasters (e.g., community conflict) have their own effects on victims' psychological outcomes. This study tested a model of the relationship between those social consequences and psychological adjustment of victims of a slowly-evolving environmental disaster, specifically those whose health has been compromised by the amphibole asbestos disaster in Libby, MT. Results indicate that experiencing greater community conflict about the disaster was associated with greater family conflict about the disaster which, in turn, was associated with greater social constraints on talking with others about their disease, both directly and indirectly through experiencing stigmatization. Experiencing greater social constraints was associated with worse psychological adjustment, both directly and indirectly through failed social support. Findings have implications for understanding pathways by which social responses create negative effects on mental health in slowly-evolving environmental disasters. These pathways suggest points for prevention and response (e.g., social support, stigmatization of victims) for communities experiencing slowly-evolving environmental disasters.

Comparing Active Delay and Procrastination from a Self-Regulated Learning Perspective

ERIC Educational Resources Information Center

Corkin, Danya M.; Yu, Shirley L.; Lindt, Suzanne F.

2011-01-01

Researchers have proposed that the act of postponing academic work may be divided into a traditional definition of procrastination, viewed as maladaptive, and adaptive forms of delay. Adaptive forms of delay may be more consistent with certain facets of self-regulated learning. The current study investigated this issue by examining whether the…

Global exponential stability of octonion-valued neural networks with leakage delay and mixed delays.

PubMed

Popa, Călin-Adrian

2018-06-08

This paper discusses octonion-valued neural networks (OVNNs) with leakage delay, time-varying delays, and distributed delays, for which the states, weights, and activation functions belong to the normed division algebra of octonions. The octonion algebra is a nonassociative and noncommutative generalization of the complex and quaternion algebras, but does not belong to the category of Clifford algebras, which are associative. In order to avoid the nonassociativity of the octonion algebra and also the noncommutativity of the quaternion algebra, the Cayley-Dickson construction is used to decompose the OVNNs into 4 complex-valued systems. By using appropriate Lyapunov-Krasovskii functionals, with double and triple integral terms, the free weighting matrix method, and simple and double integral Jensen inequalities, delay-dependent criteria are established for the exponential stability of the considered OVNNs. The criteria are given in terms of complex-valued linear matrix inequalities, for two types of Lipschitz conditions which are assumed to be satisfied by the octonion-valued activation functions. Finally, two numerical examples illustrate the feasibility, effectiveness, and correctness of the theoretical results. Copyright © 2018 Elsevier Ltd. All rights reserved.

Translating working memory into action: behavioral and neural evidence for using motor representations in encoding visuo-spatial sequences.

PubMed

Langner, Robert; Sternkopf, Melanie A; Kellermann, Tanja S; Grefkes, Christian; Kurth, Florian; Schneider, Frank; Zilles, Karl; Eickhoff, Simon B

2014-07-01

The neurobiological organization of action-oriented working memory is not well understood. To elucidate the neural correlates of translating visuo-spatial stimulus sequences into delayed (memory-guided) sequential actions, we measured brain activity using functional magnetic resonance imaging while participants encoded sequences of four to seven dots appearing on fingers of a left or right schematic hand. After variable delays, sequences were to be reproduced with the corresponding fingers. Recall became less accurate with longer sequences and was initiated faster after long delays. Across both hands, encoding and recall activated bilateral prefrontal, premotor, superior and inferior parietal regions as well as the basal ganglia, whereas hand-specific activity was found (albeit to a lesser degree during encoding) in contralateral premotor, sensorimotor, and superior parietal cortex. Activation differences after long versus short delays were restricted to motor-related regions, indicating that rehearsal during long delays might have facilitated the conversion of the memorandum into concrete motor programs at recall. Furthermore, basal ganglia activity during encoding selectively predicted correct recall. Taken together, the results suggest that to-be-reproduced visuo-spatial sequences are encoded as prospective action representations (motor intentions), possibly in addition to retrospective sensory codes. Overall, our study supports and extends multi-component models of working memory, highlighting the notion that sensory input can be coded in multiple ways depending on what the memorandum is to be used for. Copyright © 2013 Wiley Periodicals, Inc.

Feasibility study of 235U and 239Pu characterization in radioactive waste drums using neutron-induced fission delayed gamma rays

NASA Astrophysics Data System (ADS)

Nicol, T.; Pérot, B.; Carasco, C.; Brackx, E.; Mariani, A.; Passard, C.; Mauerhofer, E.; Collot, J.

2016-10-01

This paper reports a feasibility study of 235U and 239Pu characterization in 225 L bituminized waste drums or 200 L concrete waste drums, by detecting delayed fission gamma rays between the pulses of a deuterium-tritium neutron generator. The delayed gamma yields were first measured with bare samples of 235U and 239Pu in REGAIN, a facility dedicated to the assay of 118 L waste drums by Prompt Gamma Neutron Activation Analysis (PGNAA) at CEA Cadarache, France. Detectability in the waste drums is then assessed using the MCNPX model of MEDINA (Multi Element Detection based on Instrumental Neutron Activation), another PGNAA cell dedicated to 200 L drums at FZJ, Germany. For the bituminized waste drum, performances are severely hampered by the high gamma background due to 137Cs, which requires the use of collimator and shield to avoid electronics saturation, these elements being very penalizing for the detection of the weak delayed gamma signal. However, for lower activity concrete drums, detection limits range from 10 to 290 g of 235U or 239Pu, depending on the delayed gamma rays of interest. These detection limits have been determined by using MCNPX to calculate the delayed gamma useful signal, and by measuring the experimental gamma background in MEDINA with a 200 L concrete drum mock-up. The performances could be significantly improved by using a higher interrogating neutron emission and an optimized experimental setup, which would allow characterizing nuclear materials in a wide range of low and medium activity waste packages.

Delayed bleeding and hemorrhage of mucosal defects after gastric endoscopic submucosal dissection on second-look endoscopy.

PubMed

Ono, Shoko; Ono, Masayoshi; Nakagawa, Manabu; Shimizu, Yuichi; Kato, Mototsugu; Sakamoto, Naoya

2016-04-01

Although second-look endoscopy is performed within several days after gastric endoscopic submucosal dissection (ESD), there has been no evidence supporting the usefulness of the intervention. We investigated the relationship between delayed bleeding and hemorrhage of mucosal defects after ESD on second-look endoscopy and analyzed risk factors of active bleeding on second-look endoscopy. A total of 441 consecutive ESD cases with gastric cancer or adenoma were retrospectively analyzed. Second-look endoscopy was performed in the morning after the day of ESD. Bleeding of mucosal defects on second-look endoscopy was classified according to the Forrest classification, and active bleeding was defined as Forrest Ia or Ib. Delayed bleeding was defined as hematemesis or melena after second-look endoscopy. A total of 406 second-look endoscopies were performed, and delayed bleeding occurred in 11 patients. The incidence rate of delayed bleeding after second-look endoscopy in patients with Forrest Ia or Ib was significantly higher than that in patients with Forrest IIa, IIb or III (7.69 vs. 2.02 %, p < 0.05). Complication of a histological ulcer, large size of the resected specimen and long ESD procedure time were shown to be risk factors for hemorrhage of mucosal defects after ESD on second-look endoscopy by univariate analysis. Multivariate analysis indicated that only large size of the resected specimen was a risk factor. In a specimen size of >35 mm, the odds ratio of active bleeding on second-look endoscopy was 1.9. Active bleeding of mucosal defects on second-look endoscopy is a risk factor for delayed bleeding.

Effect of delayed anthrax vaccine dose on Bacillus anthracis protective antigen IgG response and lethal toxin neutralization activity.

PubMed

Pittman, Phillip R; Fisher, Diana; Quinn, Xiaofei; Schmader, Trevor; Barrera-Oro, Julio G

2013-10-17

We describe the Bacillus anthracis protective antigen IgG antibody response and the B. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (AVA, BioThrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti-PA IgG before the boost, compared to 99.2% (P<0.0001) 28 days after the boost. Geometric mean anti-PA IgG concentration (GMC) was 1.66 μg/mL before and 887.82 μg/mL after the boost (P<0.0001). The proportion of individuals with four-fold increase in GMC following the boost ranged from 93.8% to 100%. Robust anti-PA IgG levels and B. anthracis lethal toxin neutralization activity are induced when an AVA dose is delayed as long as two years. These data support continuing with the vaccination schedule when a dose is delayed as long as two years rather than restarting the series. Published by Elsevier Ltd.

Electromechanical delay of the knee flexor muscles is impaired after harvesting hamstring tendons for anterior cruciate ligament reconstruction.

PubMed

Ristanis, Stavros; Tsepis, Elias; Giotis, Dimitrios; Stergiou, Nicholas; Cerulli, Guiliano; Georgoulis, Anastasios D

2009-11-01

Changes in electromechanical delay during muscle activation are expected when there are substantial alterations in the structural properties of the musculotendinous tissue. In anterior cruciate ligament reconstruction, specific tendons are being harvested for grafts. Thus, there is an associated scar tissue development at the tendon that may affect the corresponding electromechanical delay. This study was conducted to investigate whether harvesting of semitendinosus and gracilis tendons for anterior cruciate ligament reconstruction will affect the electromechanical delay of the knee flexors. Case-control study; Level of evidence, 3. The authors evaluated 12 patients with anterior cruciate ligament reconstruction with a semitendinosus and gracilis autograft, 2 years after the reconstruction, and 12 healthy controls. Each participant performed 4 maximally explosive isometric contractions with a 1-minute break between contractions. The surface electromyographic activity of the biceps femoris and the semitendinosus was recorded from both legs during the contractions. The statistical comparisons revealed significant increases of the electromechanical delay of the anterior cruciate ligament-reconstructed knee for both investigated muscles. Specifically, the electromechanical delay values were increased for both the biceps femoris (P = .029) and the semitendinosus (P = .005) of the reconstructed knee when compared with the intact knee. Comparing the anterior cruciate ligament-reconstructed knee against healthy controls revealed similar significant differences for both muscles (semitendinosus, P = .011; biceps femoris, P = .024). The results showed that harvesting the semitendinosus and gracilis tendons for anterior cruciate ligament reconstruction significantly increased the electromechanical delay of the knee flexors. Increased hamstring electromechanical delay might impair knee safety and performance by modifying the transfer time of muscle tension to the tibia and therefore affecting muscle response during sudden movements in athletic activities. However, further investigation is required to identify whether the increased electromechanical delay of the hamstrings can actually influence optimal sports performance and increase the risk for knee injury in athletes with anterior cruciate ligament reconstructions.

[Determinants of tuberculosis diagnosis delay in limited resources countries].

PubMed

Ndeikoundam Ngangro, N; Chauvin, P; Halley des Fontaines, V

2012-02-01

Delayed diagnoses of pulmonary tuberculosis contribute to the spread of the epidemic. This study aims to identify risk factors associated with patient delay (from symptoms onset to the first visit), health system delay (from the first visit to the tuberculosis treatment initiation) and total delay (sum of the patient and the health system delay) in low income and high tuberculosis burden countries. A systematic literature review has been performed using the keywords: "tuberculosis"; "delay", care seeking"; "health care seeking behavior"; "diagnosis" and "treatment". Only quantitative studies showing delays for pulmonary tuberculosis adult cases were included in this review. Low income, gender, rural life, unemployment, ageing and misunderstanding the microbial cause of tuberculosis are associated with delayed diagnoses. Systemic factors including low health care coverage, patient expenditures and entry into the health system by consulting a traditional healer or a non-skilled professional delay the beginning of tuberculosis treatment. Delays can be used as indicators to evaluate tuberculosis control programs. Active case finding in the households of contagious patients can help to diminish diagnostic delays in low-income countries with high endemicity. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Parietal and premotor cortices: activation reflects imitation accuracy during observation, delayed imitation and concurrent imitation.

PubMed

Krüger, Britta; Bischoff, Matthias; Blecker, Carlo; Langhanns, Christine; Kindermann, Stefan; Sauerbier, Isabell; Reiser, Mathias; Stark, Rudolf; Munzert, Jörn; Pilgramm, Sebastian

2014-10-15

This study investigated whether activation within areas belonging to the action observation and imitation network reveals a linear relation to the subsequent accuracy of imitating a bimanual rhythmic movement measured via a motion capturing system. 20 participants were scanned with functional magnetic resonance imaging (fMRI) when asked to imitate observed bimanual movements either concurrently versus with a delay (2s) or simply to observe the movements without imitation. Results showed that action observation relates to activation within classic mirror-related areas. Activation patterns were more widespread when participants were asked to imitate the movement. During observation with concurrent imitation, activation in the left inferior parietal lobe (IPL) was associated negatively with imitation accuracy. During observation in the delayed imitation condition, higher subsequent imitation accuracy was coupled with higher activation in the right superior parietal lobe (SPL) and the left parietal operculum (POp). During the delayed imitation itself, a negative association between imitation accuracy and brain activation was revealed in the right ventral premotor cortex (vPMC). We conclude that the IPL is involved in online comparison and visuospatial attention processes during imitation, the SPL provides a kinesthetic blueprint during movement observation, the POp preserves body identity, and the vPMC recruits motor representations--especially when no concurrent visual guidance is possible. Copyright © 2014 Elsevier Inc. All rights reserved.

Voltage-clamp analysis of membrane currents and excitation-contraction coupling in a crustacean muscle.

PubMed

Weiss, T; Erxleben, C; Rathmayer, W

2001-01-01

A single fibre preparation from the extensor muscle of a marine isopod crustacean is described which allows the analysis of membrane currents and simultaneously recorded contractions under two-electrode voltage-clamp conditions. We show that there are three main depolarisation-gated currents, two are outward and carried by K+, the third is an inward Ca2+ current, I(Ca). Normally, the K+ currents which can be isolated by using K+ channel blockers, mask I(Ca). I(Ca) activates at potentials more positive than -40 mV, is maximal around 0 mV, and shows strong inactivation at higher depolarisation. Inactivation depends on current rather than voltage. Ba2+, Sr2+ and Mg2+ can substitute for Ca2+. Ba2+ currents are about 80% larger than Ca2+ currents and inactivate little. The properties of I(Ca) characterise it as a high threshold L-type current. The outward current consists primarily of a fast, transient A current, I(K(A)) and a maintained, delayed rectifier current, I(K(V)). In some fibres, a small Ca2+-dependent K+ current is also present. I(K(A)) activates fast at depolarisation above -45 mV, shows pronounced inactivation and is almost completely inactivated at holding potentials more positive than -40 mV. I(K(A)) is half-maximally blocked by 70 microM 4-aminopyridine (4-AP), and 70 mM tetraethylammonium (TEA). I(K(V)) activates more slowly, at about -30 mV, and shows no inactivation. It is half-maximally blocked by 2 mM TEA but rather insensitive to 4-AP. Physiologically, the two K+ currents prevent all-or-nothing action potentials and determine the graded amplitude of active electrical responses and associated contractions. Tension development depends on and is correlated with depolarisation-induced Ca2+ influx mediated by I(Ca). The voltage dependence of peak tension corresponds directly to the voltage dependence of the integrated I(Ca). The threshold potential for contraction is at about -38 mV. Peak tension increases with increasing voltage steps, reaches maximum at around 0 mV, and declines with further depolarisation.

Walking delays anticipatory postural adjustments but not reaction times in a choice reaction task.

PubMed

Haridas, C; Gordon, I T; Misiaszek, J E

2005-06-01

During standing, anticipatory postural adjustments (APAs) and focal movements are delayed while performing a choice reaction task, compared with a simple reaction task. We hypothesized that APAs and focal movements of a choice reaction task would be similarly delayed during walking. Furthermore, reaction times are delayed during walking compared with standing. We further hypothesized that APAs and focal movements would be delayed during walking, compared with standing, for both simple and choice reaction tasks. Subjects either walked or stood on a treadmill while holding on to stable handles. They were asked to push or pull on the handles in response to a visual cue. Muscle activity was recorded from muscles of the leg (APA) and arm (RT). Our results were in agreement with previous work showing APA onset was delayed in the choice reaction task compared with the simple reaction task. In addition, the interval between the onset of APA and focal movement activity increased with choice reaction tasks. The task of walking did not delay the onset of focal movement for either the simple or choice reaction tasks. Walking did delay the onset of the APA, but only during choice reaction tasks. The results suggest the added demand of walking does not significantly modify the control of focal arm movements. However, additional attentional demands while walking may compromise anticipatory postural control.

Transition from Target to Gaze Coding in Primate Frontal Eye Field during Memory Delay and Memory-Motor Transformation.

PubMed

Sajad, Amirsaman; Sadeh, Morteza; Yan, Xiaogang; Wang, Hongying; Crawford, John Douglas

2016-01-01

The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T-G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T-G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T-G delay codes to a "pure" G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory-memory-motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation.

The Origin of Powerful Radio Sources

NASA Astrophysics Data System (ADS)

Wilson, A. S.; Colbert, E. J. M.

1995-05-01

Radio-loud active galaxies are associated with elliptical or elliptical-like galaxies, many of which appear to be the result of a recent merger. In contrast, radio-quiet active galaxies prefer spiral hosts. Despite the very large difference in radio luminosities between the two classes, their continua and line spectra from infrared through X-ray frequencies are very similar. In this paper, we describe recent developments of our model (Ap. J. 438, 62 1995) in which the radio-loud phenomenon is the result of a merger of two galaxies, with each galaxy nucleus containing a slowly (or non-) rotating supermassive black hole. It is envisaged that the two black holes eventually coalesce. For the small fraction of mergers in which the two holes are both massive and of comparable mass, a rapidly-spinning, high-mass hole results. The spin energy of a rapidly rotating 10(8-9) solar mass hole suffices to provide the ~ 10(60) ergs in relativistic particles and magnetic fields in the most energetic radio sources. Luminous radio-quiet active galaxies contain high-mass, slowly-rotating holes, with the infrared through X-ray emission of both classes being fuelled by accretion as commonly assumed. We discuss constraints on the model from the luminosity functions of radio-loud and radio-quiet galaxies and from the known cosmological evolution of the radio source population; this evolution is assumed to reflect higher galaxy merger rates in the past.

Challenges of including nitrogen effects on decomposition in earth system models

NASA Astrophysics Data System (ADS)

Hobbie, S. E.

2011-12-01

Despite the importance of litter decomposition for ecosystem fertility and carbon balance, key uncertainties remain about how this fundamental process is affected by nitrogen (N) availability. Nevertheless, resolving such uncertainties is critical for mechanistic inclusion of such processes in earth system models, towards predicting the ecosystem consequences of increased anthropogenic reactive N. Towards that end, we have conducted a series of experiments examining nitrogen effects on litter decomposition. We found that both substrate N and externally supplied N (regardless of form) accelerated the initial decomposition rate. Faster initial decomposition rates were linked to the higher activity of carbohydrate-degrading enzymes associated with externally supplied N and the greater relative abundances of Gram negative and Gram positive bacteria associated with green leaves and externally supplied organic N (assessed using phospholipid fatty acid analysis, PLFA). By contrast, later in decomposition, externally supplied N slowed decomposition, increasing the fraction of slowly decomposing litter and reducing lignin-degrading enzyme activity and relative abundances of Gram negative and Gram positive bacteria. Our results suggest that elevated atmospheric N deposition may have contrasting effects on the dynamics of different soil carbon pools, decreasing mean residence times of active fractions comprising very fresh litter, while increasing those of more slowly decomposing fractions including more processed litter. Incorporating these contrasting effects of N on decomposition processes into models is complicated by lingering uncertainties about how these effects generalize across ecosystems and substrates.

Effects of acute ethanol administration on nocturnal pineal serotonin N-acetyltransferase activity

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

Creighton, J.A.; Rudeen, P.K.

The effect of acute ethanol administration on pineal serotonin N-acetyltransferase (NAT) activity, norepinephrine and indoleamine content was examined in male rats. When ethanol was administered in two equal doses (2 g/kg body weight) over a 4 hour period during the light phase, the nocturnal rise in NAT activity was delayed by seven hours. The nocturnal pineal norepinephrine content was not altered by ethanol except for a delay in the reduction of NE with the onset of the following light phase. Although ethanol treatment led to a significant reduction in nocturnal levels of pineal serotonin content, there was no significant effectmore » upon pineal content of 5-hydroxyindoleacetic acid (5-HIAA). The data indicate that ethanol delays the onset of the rise of nocturnal pineal NAT activity.« less

Specific and Nonspecific Neural Activity during Selective Processing of Visual Representations in Working Memory

ERIC Educational Resources Information Center

Oh, Hwamee; Leung, Hoi-Chung

2010-01-01

In this fMRI study, we investigated prefrontal cortex (PFC) and visual association regions during selective information processing. We recorded behavioral responses and neural activity during a delayed recognition task with a cue presented during the delay period. A specific cue ("Face" or "Scene") was used to indicate which one of the two…

Role of spiral wave pinning in inhomogeneous active media in the termination of atrial fibrillation by electrical cardioversion.

PubMed

Kuklik, Pawel; Wong, Christopher X; Brooks, Anthony G; Zebrowski, Jan Jacek; Sanders, Prashanthan

2010-03-01

Atrial fibrillation is the most common type of arrhythmia to affect humans. One of the treatment modalities for atrial fibrillation is an electrical cardioversion. Electrical cardioversion can result in one of three outcomes: an immediate termination of arrhythmic activity, a delayed termination or unsuccessful termination. The mechanism of delayed termination is unknown. Here we present a model of an atrial fibrillation as a coexistence of several spiral waves pinned to the inhomogeneities in active media. We show that in inhomogeneous system delayed termination can be explained as the unpinning of a spiral wave from inhomogeneities and its termination after collision with the edge of the system. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Analysis of functions of delayed echolalia in autistic children.

PubMed

Prizant, B M; Rydell, P J

1984-06-01

This study was a preliminary attempt to determine how autistic children used delayed echolalia in naturalistic interactions with familiar people. Fourteen functional categories of delayed echolalia were derived based on videotape analyses of linguistic, extralinguistic, and paralinguistic features. Individual differences in functional usage were apparent across the three subjects. Delayed echolalia was found to vary along the dimensions of interactiveness, comprehension of the utterance produced, and relevance to linguistic or situational context. The diversity of delayed echolalic behavior is discussed in reference to its conventionality, the presence or absence of communicative intent, and its status as symbolic communicative activity.

Teaching self-control with qualitatively different reinforcers.

PubMed

Passage, Michael; Tincani, Matt; Hantula, Donald A

2012-01-01

This study examined the effectiveness of using qualitatively different reinforcers to teach self-control to an adolescent boy who had been diagnosed with an intellectual disability. First, he was instructed to engage in an activity without programmed reinforcement. Next, he was instructed to engage in the activity under a two-choice fixed-duration schedule of reinforcement. Finally, he was exposed to self-control training, during which the delay to a more preferred reinforcer was initially short and then increased incrementally relative to the delay to a less preferred reinforcer. Self-control training effectively increased time on task to earn the delayed reinforcer.

75 FR 41920 - Agency Information Collection; Activity Under OMB Review; Airline Service Quality Performance...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-19

... and analyze air traffic delays. Wheels-up and wheels-down times are used in conjunction with departure and arrival times to show the extent of ground delays. Actual elapsed flight time, wheels-down minus wheels- up time, is compared to scheduled elapsed flight time to identify airborne delays. The reporting...

Management of the slowly emerging zoonosis, Hendra virus, by private veterinarians in Queensland, Australia: a qualitative study.

PubMed

Mendez, Diana H; Kelly, Jenny; Buttner, Petra; Nowak, Madeleine; Speare, Rick

2014-09-17

Veterinary infection control for the management of Hendra virus (HeV), an emerging zoonosis in Australia, remained suboptimal until 2010 despite 71.4% (5/7) of humans infected with HeV being veterinary personnel or assisting a veterinarian, three of whom died before 2009. The aim of this study was to identify the perceived barriers to veterinary infection control and HeV management in private veterinary practice in Queensland, where the majority of HeV outbreaks have occurred in Australia. Most participants agreed that a number of key factors had contributed to the slow uptake of adequate infection control measures for the management of HeV amongst private veterinarians: a work culture characterised by suboptimal infection control standards and misconceptions about zoonotic risks; a lack of leadership and support from government authorities; the difficulties of managing biosecurity and public health issues from a private workforce perspective; and the slow pattern of emergence of HeV. By 2010, some infection control and HeV management changes had been implemented. Participants interviewed agreed that further improvements remained necessary; but also cautioned that this was a complex process which would require time. Private veterinarians and government authorities prior to 2009 were unprepared to handle new slowly emerging zoonoses, which may explain their mismanagement of HeV. Slowly emerging zoonoses may be of low public health significance but of high significance for specialised groups such as veterinarians. Private veterinarians, who are expected to fulfil an active biosecurity and public health role in the frontline management of such emerging zoonoses, need government agencies to better recognise their contribution, to consult with the veterinary profession when devising guidelines for the management of zoonoses and to provide them with greater leadership and support. We propose that specific infection control guidelines for the management of slowly emerging zoonoses in private veterinary settings need to be developed.

Efficacy of a Community-Based Technology-Enabled Physical Activity Counseling Program for People With Knee Osteoarthritis: Proof-of-Concept Study

PubMed Central

Sayre, Eric C; Xie, Hui; Falck, Ryan S; Best, John R; Liu-Ambrose, Teresa; Grewal, Navi; Hoens, Alison M; Noonan, Greg; Feehan, Lynne M

2018-01-01

Background Current practice guidelines emphasize the use of physical activity as the first-line treatment of knee osteoarthritis; however, up to 90% of people with osteoarthritis are inactive. Objective We aimed to assess the efficacy of a technology-enabled counseling intervention for improving physical activity in people with either a physician-confirmed diagnosis of knee osteoarthritis or having passed two validated criteria for early osteoarthritis. Methods We conducted a proof-of-concept randomized controlled trial. The immediate group received a brief education session by a physical therapist, a Fitbit Flex, and four biweekly phone calls for activity counseling. The delayed group received the same intervention 2 months later. Participants were assessed at baseline (T0) and at the end of 2 months (T1), 4 months (T2), and 6 months (T3). Outcomes included (1) mean time on moderate-to-vigorous physical activity (MVPA ≥3 metabolic equivalents [METs], primary outcome), (2) mean time on MVPA ≥4 METs, (3) mean daily steps, (4) mean time on sedentary activities, (5) Knee Injury and Osteoarthritis Outcome Score (KOOS), and (6) Partners in Health scale. Mixed-effects repeated measures analysis of variance was used to assess five planned contrasts of changes in outcome measures over measurement periods. The five contrasts were (1) immediate T1-T0 vs delayed T1-T0, (2) delayed T2-T1 vs delayed T1-T0, (3) mean of contrast 1 and contrast 2, (4) immediate T1-T0 vs delayed T2-T1, and (5) mean of immediate T2-T1 and delayed T3-T2. The first three contrasts estimate the between-group effects. The latter two contrasts estimate the effect of the 2-month intervention delay on outcomes. Results We recruited 61 participants (immediate: n=30; delayed: n=31). Both groups were similar in age (immediate: mean 61.3, SD 9.4 years; delayed: mean 62.1, SD 8.5 years) and body mass index (immediate: mean 29.2, SD 5.5 kg/m2; delayed: mean 29.2, SD 4.8 kg/m2). Contrast analyses revealed significant between-group effects in MVPA ≥3 METs (contrast 1 coefficient: 26.6, 95% CI 4.0-49.1, P=.02; contrast 3 coefficient: 26.0, 95% CI 3.1-49.0, P=.03), daily steps (contrast 1 coefficient: 1699.2, 95% CI 349.0-3049.4, P=.02; contrast 2 coefficient: 1601.8, 95% CI 38.7-3164.9, P=.045; contrast 3 coefficient: 1650.5, 95% CI 332.3-2968.7; P=.02), KOOS activity of daily living subscale (contrast 1 coefficient: 6.9, 95% CI 0.1-13.7, P=.047; contrast 3 coefficient: 7.2, 95% CI 0.8-13.6, P=.03), and KOOS quality of life subscale (contrast 1 coefficient: 7.4, 95% CI 0.0-14.7, P=.049; contrast 3 coefficient: 7.3, 95% CI 0.1-14.6, P=.048). We found no significant effect in any outcome measures due to the 2-month delay of the intervention. Conclusions Our counseling program improved MVPA ≥3 METs, daily steps, activity of daily living, and quality of life in people with knee osteoarthritis. These findings are important because an active lifestyle is an important component of successful self-management. Trial Registration ClinicalTrials.gov NCT02315664; https://clinicaltrials.gov/ct2/show/NCT02315664 (Archived by WebCite at http://www.webcitation.org/6ynSgUyUC) PMID:29712630

Dorsal Raphe Serotonergic Neurons Control Intertemporal Choice under Trade-off.

PubMed

Xu, Sangyu; Das, Gishnu; Hueske, Emily; Tonegawa, Susumu

2017-10-23

Appropriate choice about delayed reward is fundamental to the survival of animals. Although animals tend to prefer immediate reward, delaying gratification is often advantageous. The dorsal raphe (DR) serotonergic neurons have long been implicated in the processing of delayed reward, but it has been unclear whether or when their activity causally directs choice. Here, we transiently augmented or reduced the activity of DR serotonergic neurons, while mice decided between differently delayed rewards as they performed a novel odor-guided intertemporal choice task. We found that these manipulations, precisely targeted at the decision point, were sufficient to bidirectionally influence impulsive choice. The manipulation specifically affected choices with more difficult trade-off. Similar effects were observed when we manipulated the serotonergic projections to the nucleus accumbens (NAc). We propose that DR serotonergic neurons preempt reward delays at the decision point and play a critical role in suppressing impulsive choice by regulating decision trade-off. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia

PubMed Central

Asano, Teita; Aida, Shuji; Suemasu, Shintaro; Tahara, Kayoko; Tanaka, Ken-ichiro; Mizushima, Tohru

2015-01-01

Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here. PMID:26620883

Delayed Ejaculation

MedlinePlus

... your partner. Often, men might have difficulty reaching orgasm during sexual intercourse or other sexual activities with a partner. Some men can ejaculate only when masturbating. Delayed ejaculation is divided into the following types based on ...

Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation.

PubMed

Sameiro-Barbosa, Catia M; Geiser, Eveline

2016-01-01

The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system.

One Small Flare

NASA Image and Video Library

2018-02-15

The sun's only visible active region sputtered and spurted and eventually unleashed a small (C-class) flare (Feb. 7, 2018). The flare appears as a brief, bright flash about mid-way through the half-day clip. Normally, we do not pay much attention to flares this small, but it was just about the only real solar activity over the past week as the sun is slowly approaching its quiet period of the 11-year solar cycle. These images were taken in a wavelength of extreme ultraviolet light. Movies are available at https://photojournal.jpl.nasa.gov/catalog/PIA22244

Lateralized delay period activity marks the focus of spatial attention in working memory: evidence from somatosensory event-related brain potentials.

PubMed

Katus, Tobias; Eimer, Martin

2015-04-29

The short-term retention of sensory information in working memory (WM) is known to be associated with a sustained enhancement of neural activity. What remains controversial is whether this neural trace indicates the sustained storage of information or the allocation of attention. To evaluate the storage and attention accounts, we examined sustained tactile contralateral delay activity (tCDA component) of the event-related potential. The tCDA manifests over somatosensory cortex contralateral to task-relevant tactile information during stimulus retention. Two tactile sample sets (S1, S2) were presented sequentially, separated by 1.5 s. Each set comprised two stimuli, one per hand. Human participants memorized the location of one task-relevant stimulus per sample set and judged whether one of these locations was stimulated again at memory test. The two relevant pulses were unpredictably located on the same hand (stay trials) or on different hands (shift trials). Initially, tCDA components emerged contralateral to the relevant S1 pulse. Sequential loading of WM enhanced the tCDA after S2 was presented on stay trials. On shift trials, the tCDA's polarity reversed after S2 presentation, resulting in delay activity that was now contralateral to the task-relevant S2 pulse. The disappearance of a lateralized neural trace for the relevant S1 pulse did not impair memory accuracy for this stimulus on shift trials. These results contradict the storage account and suggest that delay period activity indicates the sustained engagement of an attention-based rehearsal mechanism. In conclusion, somatosensory delay period activity marks the current focus of attention in tactile WM. Copyright © 2015 the authors 0270-6474/15/356689-07$15.00/0.

Neural correlates of target selection for reaching movements in superior colliculus

PubMed Central

McPeek, Robert M.

2014-01-01

We recently demonstrated that inactivation of the primate superior colliculus (SC) causes a deficit in target selection for arm-reaching movements when the reach target is located in the inactivated field (Song JH, Rafal RD, McPeek RM. Proc Natl Acad Sci USA 108: E1433–E1440, 2011). This is consistent with the notion that the SC is part of a general-purpose target selection network beyond eye movements. To understand better the role of SC activity in reach target selection, we examined how individual SC neurons in the intermediate layers discriminate a reach target from distractors. Monkeys reached to touch a color oddball target among distractors while maintaining fixation. We found that many SC neurons robustly discriminate the goal of the reaching movement before the onset of the reach even though no saccade is made. To identify these cells in the context of conventional SC cell classification schemes, we also recorded visual, delay-period, and saccade-related responses in a delayed saccade task. On average, SC cells that discriminated the reach target from distractors showed significantly higher visual and delay-period activity than nondiscriminating cells, but there was no significant difference in saccade-related activity. Whereas a majority of SC neurons that discriminated the reach target showed significant delay-period activity, all nondiscriminating cells lacked such activity. We also found that some cells without delay-period activity did discriminate the reach target from distractors. We conclude that the majority of intermediate-layer SC cells discriminate a reach target from distractors, consistent with the idea that the SC contains a priority map used for effector-independent target selection. PMID:25505107

CAN LARGE TIME DELAYS OBSERVED IN LIGHT CURVES OF CORONAL LOOPS BE EXPLAINED IN IMPULSIVE HEATING?

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

Lionello, Roberto; Linker, Jon A.; Mikić, Zoran

The light curves of solar coronal loops often peak first in channels associated with higher temperatures and then in those associated with lower temperatures. The delay times between the different narrowband EUV channels have been measured for many individual loops and recently for every pixel of an active region observation. The time delays between channels for an active region exhibit a wide range of values. The maximum time delay in each channel pair can be quite large, i.e., >5000 s. These large time delays make-up 3%–26% (depending on the channel pair) of the pixels where a trustworthy, positive time delaymore » is measured. It has been suggested that these time delays can be explained by simple impulsive heating, i.e., a short burst of energy that heats the plasma to a high temperature, after which the plasma is allowed to cool through radiation and conduction back to its original state. In this paper, we investigate whether the largest observed time delays can be explained by this hypothesis by simulating a series of coronal loops with different heating rates, loop lengths, abundances, and geometries to determine the range of expected time delays between a set of four EUV channels. We find that impulsive heating cannot address the largest time delays observed in two of the channel pairs and that the majority of the large time delays can only be explained by long, expanding loops with photospheric abundances. Additional observations may rule out these simulations as an explanation for the long time delays. We suggest that either the time delays found in this manner may not be representative of real loop evolution, or that the impulsive heating and cooling scenario may be too simple to explain the observations, and other potential heating scenarios must be explored.« less

Wound healing effects of collagen-laminin dermal matrix impregnated with resveratrol loaded hyaluronic acid-DPPC microparticles in diabetic rats.

PubMed

Gokce, Evren H; Tuncay Tanrıverdi, Sakine; Eroglu, Ipek; Tsapis, Nicolas; Gokce, Goksel; Tekmen, Isıl; Fattal, Elias; Ozer, Ozgen

2017-10-01

An alternative formulation for the treatment of diabetic foot wounds that heal slowly is a requirement in pharmaceutical field. The aim of this study was to develop a dermal matrix consisting of skin proteins and lipids with an antioxidant that will enhance healing and balance the oxidative stress in the diabetic wound area due to the high levels of glucose. Thus a novel three dimensional collagen-laminin porous dermal matrix was developed by lyophilization. Resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine microparticles were combined with this dermal matrix. Characterization, in vitro release, microbiological and in vivo studies were performed. Spherical microparticles were obtained with a high RSV encapsulation efficacy. The microparticles were well dispersed in the dermal matrix from the surface to deeper layers. Collagenase degraded dermal matrix, however the addition of RSV loaded microparticles delayed the degradation time. The release of RSV was sustained and reached 70% after 6h. Histological changes and antioxidant parameters in different treatment groups were investigated in full-thickness excision diabetic rat model. Collagen fibers were intense and improved by the presence of formulation without any signs of inflammation. The highest healing score was obtained with the dermal matrix impregnated with RSV-microparticles with an increased antioxidant activity. Collagen-laminin dermal matrix with RSV microparticles was synergistically effective due to presence of skin components in the formulation and controlled release achieved. This combination is a safe and promising option for the treatment of diabetic wounds requiring long recovery. Copyright © 2017 Elsevier B.V. All rights reserved.

Reactivity and mobility of new and old mercury deposition in a boreal forest ecosystem during the first year of the METAALICUS study

USGS Publications Warehouse

Hintelmann, H.; Harris, R.; Heyes, A.; Hurley, J.P.; Kelly, C.A.; Krabbenhoft, D.P.; Lindberg, S.; Rudd, J.W.M.; Scott, K.J.; St. Louis, V.L.

2002-01-01

The METAALICUS (Mercury Experiment To Assess Atmospheric Loading In Canada and the US) project is a whole ecosystem experiment designed to study the activity, mobility, and availability of atmospherically deposited mercury. To investigate the dynamics of mercury newly deposited onto a terrestrial ecosystem, an enriched stable isotope of mercury (202Hg) was sprayed onto a Boreal forest subcatchment in an experiment that allowed us, for the first time, to monitor the fate of "new" mercury in deposition and to distinguish it from native mercury historically stored in the ecosystem. Newly deposited mercury was more reactive than the native mercury with respect to volatilization and methylation pathways. Mobility through runoff was very low and strongly decreased with time because of a rapid equilibration with the large native pool of "bound" mercury. Over one season, only ???8% of the added 202Hg volatilized to the atmosphere and less than 1% appeared in runoff. Within a few months, approximately 66% of the applied 202Hg remained associated with above ground vegetation, with the rest being incorporated into soils. The fraction of 202Hg bound to vegetation was much higher than seen for native Hg (<5% vegetation), suggesting that atmospherically derived mercury enters the soil pool with a time delay, after plants senesce and decompose. The initial mobility of mercury received through small rain events or dry deposition decreased markedly in a relatively short time period, suggesting that mercury levels in terrestrial runoff may respond slowly to changes in mercury deposition rates.

Bioinspired co-crystals of Imatinib providing enhanced kinetic solubility.

PubMed

Reggane, Maude; Wiest, Johannes; Saedtler, Marco; Harlacher, Cornelius; Gutmann, Marcus; Zottnick, Sven H; Piechon, Philippe; Dix, Ina; Müller-Buschbaum, Klaus; Holzgrabe, Ulrike; Meinel, Lorenz; Galli, Bruno

2018-05-04

Realizing the full potential of co-crystals enhanced kinetic solubility demands a comprehensive understanding of the mechanisms of dissolution, phase conversion, nucleation and crystal growth, and of the complex interplay between the active pharmaceutical ingredient (API), the coformer and co-existing forms in aqueous media. One blueprint provided by nature to keep poorly water-soluble bases in solution is the complexation with phenolic acids. Consequently, we followed a bioinspired strategy for the engineering of co-crystals of a poorly water-soluble molecule - Imatinib - with a phenolic acid, syringic acid (SYA). The dynamics of dissolution and solution-mediated phase transformations were monitored by Nuclear Magnetic Resonance (NMR) spectroscopy, providing mechanistic insights into the 60 fold-increased long lasting concentrations achieved by the syringate co-crystals as compared to Imatinib base and Imatinib mesylate. This lasting effect was linked to SYA's ability to delay the formation and nucleation of Imatinib hydrate - the thermodynamically stable form in aqueous media - through a metastable association of SYA with Imatinib in solution. Results from permeability studies evidenced that SYA did not impact Imatinib's permeability across membranes while suggesting improved bioavailability through higher kinetic solubility at the biological barriers. These results reflect that some degree of hydrophobicity of the coformer might be key to extend the kinetic solubility of co-crystals with hydrophobic APIs. Understanding how kinetic supersaturation can be shaped by the selection of an interactive coformer may help achieving the needed performance of new forms of poorly water-soluble, slowly dissolving APIs. Copyright © 2018. Published by Elsevier B.V.

Relationship between delayed embryonic development and metabolic factors and fat deposition in fruit bat Cynopterus sphinx.

PubMed

Banerjee, Arnab; Meenakumari, K J; Krishna, Amitabh

2007-01-01

The present study was undertaken in the fruit bat Cynopterus sphinx, which breeds twice in quick succession at Varanasi, India. Its gestation period varies significantly in the two successive pregnancies of the year owing to delayed embryonic development during the first (winter) pregnancy. The primary aim of the present study was to determine the role of metabolic factors in delayed embryonic development in the fruit bat C. sphinx. Variation in bodyweight, fat deposition, oxygen (O(2)) consumption rate, basal metabolic rate (BMR), body temperature (Tb) and hepatic succinate dehydrogenase (SDH) activity, along with circulating levels of thyroid hormones (tri-iodothyronine and thyroxine), were examined as metabolic factors during the two successive pregnancies in C. sphinx. The increase in bodyweight observed in November was due to accumulation of white adipose tissue in the posterior abdominal region. A significant decline in O(2) consumption rate, BMR, Tb and SDH activity was found in early winter in November-December, which coincides closely with the period of fat accumulation and with the period of delayed embryonic development in C. sphinx. A significantly higher O(2) consumption rate, BMR, Tb and SDH activity was noted during the second pregnancy in, when embryonic development was relatively faster. Thyroid hormone levels were high during the period of embryonic delay compared with levels during the remaining months. The results of the present study suggest that the delayed embryonic development in C. sphinx during early winter may be due to a low O(2) consumption rate, BMR, Tb and SDH activity in November-December. The energy saved by suppressing embryonic development in this species may be advantageous for fat accumulation. Increased thyroid hormone levels during the early winter period might facilitate fat accumulation in C. sphinx.

Is immediate adjunctive CBT more beneficial than delayed CBT in treating depression?: A Pilot Study.

PubMed

Rizvi, Sakina J; Zaretsky, Ari; Schaffer, Ayal; Levitt, Anthony

2015-03-01

Cognitive-behavioral therapy (CBT) is an efficacious first-line therapy for patients with major depressive disorder (MDD). Due to the limited accessibility of CBT, long wait lists result in delayed treatment, which may affect treatment outcomes. The goal of this pilot study was to obtain preliminary data from a randomized controlled trial to determine whether delayed CBT reduces the effectiveness of the therapy compared to immediate CBT in patients with MDD receiving pharmacotherapy. Patients were randomized to receive immediate CBT (n=18) or to begin CBT after 6 months (n=20) and received 14 weekly sessions, followed by two additional booster sessions. During the active treatment months, patients in the immediate group demonstrated reductions in scores on the Beck Depression Inventory II (BDI-II) that were similar to those in the delayed CBT group. However, when the analysis was performed using only data from patients in the delayed group who were still in a depressive episode, there was an overall greater decrease in BDI-II scores in the immediate group vs. the delayed group over the active treatment months, but not specifically at the 6-month endpoint. These findings suggest delays in depression treatment, similar to what occurs with real-world wait list times, may not have a significant impact on the effectiveness of CBT in patients who are already receiving treatment as usual. However, such delays may affect the effectiveness of CBT in those patients who remain depressed during the time delay. A larger trial is necessary to confirm these findings. (Journal of Psychiatric Practice 2015;21:107-113).

Neural Evidence for a Distinction between Short-Term Memory and the Focus of Attention

ERIC Educational Resources Information Center

Lewis-Peacock, Jarrod A.; Drysdale, Andrew T.; Oberauer, Klaus; Postle, Bradley R.

2012-01-01

It is widely assumed that the short-term retention of information is accomplished via maintenance of an active neural trace. However, we demonstrate that memory can be preserved across a brief delay despite the apparent loss of sustained representations. Delay period activity may, in fact, reflect the focus of attention, rather than STM. We…

Thermally activated delayed fluorescence of a Zr-based metal–organic framework

DOE PAGES

Mieno, H.; Kabe, R.; Allendorf, M. D.; ...

2017-12-22

Here, the first metal–organic framework exhibiting thermally activated delayed fluorescence (TADF) was developed. The zirconium-based framework (UiO-68-dpa) uses a newly designed linker composed of a terphenyl backbone, an electron-accepting carboxyl group, and an electron-donating diphenylamine and exhibits green TADF emission with a photoluminescence quantum yield of 30% and high thermal stability.

Dementia and driving

MedlinePlus

... getting more dangerous include: Getting lost on familiar roads Reacting more slowly in traffic Driving too slowly ... attention to traffic signs Taking chances on the road Drifting into other lanes Getting more agitated in ...

Factors Associated with Delayed Tuberculosis Test-seeking Behavior in the Peruvian Amazon

PubMed Central

Ford, Carolyn M.; Bayer, Angela M.; Gilman, Robert H.; Onifade, Dami; Acosta, Colleen; Cabrera, Lilia; Vidal, Carlos; Evans, Carlton A.

2010-01-01

This study aimed to determine the psychosocial factors associated with delayed test-seeking among tuberculosis patients. The duration of symptoms before seeking medical care was assessed by interview for 108 newly diagnosed pulmonary tuberculosis patients in the city of Iquitos in the Peruvian Amazon, which has high tuberculosis incidence. Beliefs associated with test-seeking behavior and delay was assessed in these patients. The median delay from symptom onset to seeking diagnostic testing was 61 days (inter-quartile range 30–91 days). The belief that tuberculosis is curable was associated with a 100% longer test-seeking delay; the perception that tuberculosis was common was associated with a 57% longer delay; male gender was associated with a 48% longer delay; and education less than complete secondary schooling was associated with a 44% longer delay. In conclusion, current health promotion activities that emphasize tuberculosis curability and high prevalence may paradoxically increase test-seeking delay and therefore require prospective evaluation. PMID:19996443

Neural evidence for a distinction between short-term memory and the focus of attention.

PubMed

Lewis-Peacock, Jarrod A; Drysdale, Andrew T; Oberauer, Klaus; Postle, Bradley R

2012-01-01

It is widely assumed that the short-term retention of information is accomplished via maintenance of an active neural trace. However, we demonstrate that memory can be preserved across a brief delay despite the apparent loss of sustained representations. Delay period activity may, in fact, reflect the focus of attention, rather than STM. We unconfounded attention and memory by causing external and internal shifts of attention away from items that were being actively retained. Multivariate pattern analysis of fMRI indicated that only items within the focus of attention elicited an active neural trace. Activity corresponding to representations of items outside the focus quickly dropped to baseline. Nevertheless, this information was remembered after a brief delay. Our data also show that refocusing attention toward a previously unattended memory item can reactivate its neural signature. The loss of sustained activity has long been thought to indicate a disruption of STM, but our results suggest that, even for small memory loads not exceeding the capacity limits of STM, the active maintenance of a stimulus representation may not be necessary for its short-term retention.

Shuttle Rocket Motor Program: NASA should delay awarding some construction contracts. Report to the Chair, Subcommittee on Government Activities and Transportation, Committee on Government Operations, House of Representatives

NASA Technical Reports Server (NTRS)

1992-01-01

Even though the executive branch has proposed terminating the Advanced Solid Rocket Motor (ASRM) program, NASA is proceeding with all construction activity planned for FY 1992 to avoid schedule slippage if the program is reinstated by Congress. However, NASA could delay some construction activities for at least a few months without affecting the current launch data schedule. For example, NASA could delay Yellow Creek's motor storage and dock projects, Stennis' dock project, and Kennedy's rotation processing and surge facility and dock projects. Starting all construction activities as originally planned could result in unnecessarily incurring additional costs and termination liability if the funding for FY 1993 is not provided. If Congress decides to continue the program, construction could still be completed in time to avoid schedule slippage.

Raising the Social Security Entitlement Age.

PubMed

Zissimopoulos, Julie; Blaylock, Barbara; Goldman, Dana P; Rowe, John W

2017-01-01

An aging America presents challenges but also brings social and economic capital. We quantify public revenues from, and public expenditures on, Americans aged 65 and older, the value of their unpaid, productive activities and financial gifts to family. Using microsimulation, we project the value of these activities, and government revenues and expenditures, under different scenarios of change to the Old Age and Survivors Insurance eligibility age through 2050. We find the value of unpaid productive activities and financial gifts are US$721 billion in 2010, while net (of tax revenues) spending on the 65 years and older is US$984 billion. Five-year delay in the full retirement age decreases federal spending by 10%, while 2-year delay in the early entitlement age increases it by 1.5%. The effect of 5-year delay on unpaid activities and transfers is small: US$4 billion decrease in services and US$4.5 billion increase in bequests and monetary gifts.

Convergence analysis of stochastic hybrid bidirectional associative memory neural networks with delays

NASA Astrophysics Data System (ADS)

Wan, Li; Zhou, Qinghua

2007-10-01

The stability property of stochastic hybrid bidirectional associate memory (BAM) neural networks with discrete delays is considered. Without assuming the symmetry of synaptic connection weights and the monotonicity and differentiability of activation functions, the delay-independent sufficient conditions to guarantee the exponential stability of the equilibrium solution for such networks are given by using the nonnegative semimartingale convergence theorem.

Airport Surface Delays and Causes: A Preliminary Analysis

NASA Technical Reports Server (NTRS)

Chin, David K.; Goldberg, Jay; Tang, Tammy

1997-01-01

This report summarizes FAA Program Analysis and Operations Research Service (ASD-400)/Lockheed Martin activities and findings related to airport surface delays and causes, in support of NASA Langley Research Center's Terminal Area Productivity (TAP) Program. The activities described in this report were initiated in June 1995. A preliminary report was published on September 30, 1995. The final report incorporates data collection forms filled out by traffic managers, other FAA staff, and an airline for the New York City area, some updates, data previously requested from various sources to support this analysis, and further quantification and documentation than in the preliminary report. This final report is based on data available as of April 12, 1996. This report incorporates data obtained from review and analysis of data bases and literature, discussions/interviews with engineers, air-traffic staff, other FAA technical personnel, and airline staff, site visits, and a survey on surface delays and causes. It includes analysis of delay statistics; preliminary findings and conclusions on surface movement, surface delay sources and causes, runway occupancy time (ROT), and airport characteristics impacting surface operations and delays; and site-specific data on the New York City area airports, which are the focus airports for this report.

Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones

PubMed Central

Olschewski, Andrea; Wolff, Matthias; Bräu, Michael E; Hempelmann, Gunter; Vogel, Werner; Safronov, Boris V

2002-01-01

Combining the patch-clamp recordings in slice preparation with the ‘entire soma isolation' method we studied action of several local anaesthetics on delayed-rectifier K+ currents in spinal dorsal horn neurones.Bupivacaine, lidocaine and mepivacaine at low concentrations (1–100 μM) enhanced delayed-rectifier K+ current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 μM). In isolated somata 0.1–10 μM bupivacaine enhanced delayed-rectifier K+ current by shifting its steady-state activation characteristic and the voltage-dependence of the activation time constant to more negative potentials by 10–20 mV.Detailed analysis has revealed that bupivacaine also increased the maximum delayed-rectifier K+ conductance by changing the open probability, rather than the unitary conductance, of the channel.It is concluded that local anaesthetics show a dual effect on delayed-rectifier K+ currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na+ conductance only. PMID:12055132

[Delayed reactions of active avoidance in white rats under conditions of an alternative choice].

PubMed

Ioseliani, T K; Sikharulidze, N I; Kadagishvili, A Ia; Mitashvili, E G

1995-01-01

It was shown that if the rats had been learned and then tested using conventional pain punishment of erroneous choice they were able to solve the problem of alternative choice only in the period of immediate action of conditioned stimuli. If the pain punishment for erroneously chosen compartment had not been applied in animal learning and testing, rats successfully solved the problem of alternative choice even after 5-second delay. Introduction of pain punishment led to the frustration of earlier elaborated delayed avoidance reactions. Analysis of the obtained results allows us to argue that the apparent incapability of white rats for solving the problems of delayed avoidance is caused by simultaneous action of two different mechanisms, i.e., those of the active and passive avoidance rather than short-term memory deficit.

Apparatus for and method of monitoring for breached fuel elements

DOEpatents

Gross, Kenny C.; Strain, Robert V.

1983-01-01

This invention teaches improved apparatus for the method of detecting a breach in cladded fuel used in a nuclear reactor. The detector apparatus uses a separate bypass loop for conveying part of the reactor coolant away from the core, and at least three separate delayed-neutron detectors mounted proximate this detector loop. The detectors are spaced apart so that the coolant flow time from the core to each detector is different, and these differences are known. The delayed-neutron activity at the detectors is a function of the dealy time after the reaction in the fuel until the coolant carrying the delayed-neutron emitter passes the respective detector. This time delay is broken down into separate components including an isotopic holdup time required for the emitter to move through the fuel from the reaction to the coolant at the breach, and two transit times required for the emitter now in the coolant to flow from the breach to the detector loop and then via the loop to the detector. At least two of these time components are determined during calibrated operation of the reactor. Thereafter during normal reactor operation, repeated comparisons are made by the method of regression approximation of the third time component for the best-fit line correlating measured delayed-neutron activity against activity that is approximated according to specific equations. The equations use these time-delay components and known parameter values of the fuel and of the part and emitting daughter isotopes.

Distributed value representation in the medial prefrontal cortex during intertemporal choices.

PubMed

Wang, Qiang; Luo, Shan; Monterosso, John; Zhang, Jintao; Fang, Xiaoyi; Dong, Qi; Xue, Gui

2014-05-28

The ability to resist current temptations in favor of long-term benefits is a critical human capacity. Despite the extensive studies on the neural mechanisms of intertemporal choices, how the subjective value of immediate and delayed rewards is represented and compared in the brain remains to be elucidated. The present fMRI study addressed this question by simultaneously and independently manipulating the magnitude of immediate and delayed rewards in an intertemporal decision task, combined with univariate analysis and multiple voxel pattern analysis. We found that activities in the posterior portion of the dorsal medial prefrontal cortex (DmPFC) were modulated by the value of immediate options, whereas activities in the adjacent anterior DmPFC were modulated by the subjective value of delayed options. Brain signal change in the ventral mPFC was positively correlated with the "relative value" (the absolute difference of subjective value between two intertemporal alternatives). In contrast, the dorsal anterior cingulate cortex activity was negatively correlated with the relative value. These results suggest that immediate and delayed rewards are separately represented in the dorsal mPFC and compared in the ventral mPFC to guide decisions. The functional dissociation of posterior and anterior DmPFC in representing immediate and delayed reward is consistent with the general structural and functional architecture of the prefrontal cortex and may provide a neural basis for human's unique capacity to delayed gratification. Copyright © 2014 the authors 0270-6474/14/347522-09$15.00/0.

Delay correction model for estimating bus emissions at signalized intersections based on vehicle specific power distributions.

PubMed

Song, Guohua; Zhou, Xixi; Yu, Lei

2015-05-01

The intersection is one of the biggest emission points for buses and also the high exposure site for people. Several traffic performance indexes have been developed and widely used for intersection evaluations. However, few studies have focused on the relationship between these indexes and emissions at intersections. This paper intends to propose a model that relates emissions to the two commonly used measures of effectiveness (i.e. delay time and number of stops) by using bus activity data and emission data at intersections. First, with a large number of field instantaneous emission data and corresponding activity data collected by the Portable Emission Measurement System (PEMS), emission rates are derived for different vehicle specific power (VSP) bins. Then, 2002 sets of trajectory data, an equivalent of about 140,000 sets of second-by-second activity data, are obtained from Global Position Systems (GPSs)-equipped diesel buses in Beijing. The delay and the emission factors of each trajectory are estimated. Then, by using baseline emission factors for two types of intersections, e.g. the Arterial @ Arterial Intersection and the Arterial @ Collector, delay correction factors are calculated for the two types of intersections at different congestion levels. Finally, delay correction models are established for adjusting emission factors for each type of intersections and different numbers of stops. A comparative analysis between estimated and field emission factors demonstrates that the delay correction model is reliable. Copyright © 2015 Elsevier B.V. All rights reserved.

Monkey prefrontal neurons during Sternberg task performance: full contents of working memory or most recent item?

PubMed

Konecky, R O; Smith, M A; Olson, C R

2017-06-01

To explore the brain mechanisms underlying multi-item working memory, we monitored the activity of neurons in the dorsolateral prefrontal cortex while macaque monkeys performed spatial and chromatic versions of a Sternberg working-memory task. Each trial required holding three sequentially presented samples in working memory so as to identify a subsequent probe matching one of them. The monkeys were able to recall all three samples at levels well above chance, exhibiting modest load and recency effects. Prefrontal neurons signaled the identity of each sample during the delay period immediately following its presentation. However, as each new sample was presented, the representation of antecedent samples became weak and shifted to an anomalous code. A linear classifier operating on the basis of population activity during the final delay period was able to perform at approximately the level of the monkeys on trials requiring recall of the third sample but showed a falloff in performance on trials requiring recall of the first or second sample much steeper than observed in the monkeys. We conclude that delay-period activity in the prefrontal cortex robustly represented only the most recent item. The monkeys apparently based performance of this classic working-memory task on some storage mechanism in addition to the prefrontal delay-period firing rate. Possibilities include delay-period activity in areas outside the prefrontal cortex and changes within the prefrontal cortex not manifest at the level of the firing rate. NEW & NOTEWORTHY It has long been thought that items held in working memory are encoded by delay-period activity in the dorsolateral prefrontal cortex. Here we describe evidence contrary to that view. In monkeys performing a serial multi-item working memory task, dorsolateral prefrontal neurons encode almost exclusively the identity of the sample presented most recently. Information about earlier samples must be encoded outside the prefrontal cortex or represented within the prefrontal cortex in a cryptic code. Copyright © 2017 the American Physiological Society.

Cognitive activities delay onset of memory decline in persons who develop dementia

PubMed Central

Hall, C B.; Lipton, R B.; Sliwinski, M; Katz, M J.; Derby, C A.; Verghese, J

2009-01-01

Background: Persons destined to develop dementia experience an accelerated rate of decline in cognitive ability, particularly in memory. Early life education and participation in cognitively stimulating leisure activities later in life are 2 factors thought to reflect cognitive reserve, which may delay the onset of the memory decline in the preclinical stages of dementia. Methods: We followed 488 initially cognitively intact community residing individuals with epidemiologic, clinical, and cognitive assessments every 12 to 18 months in the Bronx Aging Study. We assessed the influence of self-reported participation in cognitively stimulating leisure activities on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Results: Each additional self-reported day of cognitive activity at baseline delayed the onset of accelerated memory decline by 0.18 years. Higher baseline levels of cognitive activity were associated with more rapid memory decline after that onset. Inclusion of education did not significantly add to the fit of the model beyond the effect of cognitive activities. Conclusions: Our findings show that late life cognitive activities influence cognitive reserve independently of education. The effect of early life education on cognitive reserve may be mediated by cognitive activity later in life. Alternatively, early life education may be a determinant of cognitive reserve, and individuals with more education may choose to participate in cognitive activities without influencing reserve. Future studies should examine the efficacy of increasing participation in cognitive activities to prevent or delay dementia. GLOSSARY AD = Alzheimer disease; BL = baseline; CAS = Cognitive Activity Scale; CI = confidence interval; DSM = Diagnostic and Statistical Manual of Mental Disorders; dx = diagnosis; NIA = National Institute on Aging; SRT = Selective Reminding Test; WAIS VIQ = Wechsler Adult Intelligence Scale Verbal IQ. PMID:19652139

Validity of Different Activity Monitors to Count Steps in an Inpatient Rehabilitation Setting.

PubMed

Treacy, Daniel; Hassett, Leanne; Schurr, Karl; Chagpar, Sakina; Paul, Serene S; Sherrington, Catherine

2017-05-01

Commonly used activity monitors have been shown to be accurate in counting steps in active people; however, further validation is needed in slower walking populations. To determine the validity of activity monitors for measuring step counts in rehabilitation inpatients compared with visually observed step counts. To explore the influence of gait parameters, activity monitor position, and use of walkers on activity monitor accuracy. One hundred and sixty-six inpatients admitted to a rehabilitation unit with an average walking speed of 0.4 m/s (SD 0.2) wore 16 activity monitors (7 different devices in different positions) simultaneously during 6-minute and 6-m walks. The number of steps taken during the tests was also counted by a physical therapist. Gait parameters were assessed using the GAITRite system. To analyze the influence of different gait parameters, the percentage accuracy for each monitor was graphed against various gait parameters for each activity monitor. The StepWatch, Fitbit One worn on the ankle and the ActivPAL showed excellent agreement with observed step count (ICC 2,1 0.98; 0.92; 0.78 respectively). Other devices (Fitbit Charge, Fitbit One worn on hip, G-Sensor, Garmin Vivofit, Actigraph) showed poor agreement with the observed step count (ICC 2,1 0.12-0.40). Percentage agreement with observed step count was highest for the StepWatch (mean 98%). The StepWatch and the Fitbit One worn on the ankle maintained accuracy in individuals who walked more slowly and with shorter strides but other devices were less accurate in these individuals. There were small numbers of participants for some gait parameters. The StepWatch showed the highest accuracy and closest agreement with observed step count. This device can be confidently used by researchers for accurate measurement of step counts in inpatient rehabilitation in individuals who walk slowly. If immediate feedback is desired, the Fitbit One when worn on the ankle would be the best choice for this population. © 2017 American Physical Therapy Association

Premature rupture of membranes

MedlinePlus

... is fluid leaking from the vagina. It may leak slowly, or it may gush out. Some of ... the membranes break. The membranes may continue to leak. Sometimes when fluid leaks out slowly, women mistake ...

Advance in exploring the subsurface temporal evolution with Air-gun artificial source of Fujian, China

NASA Astrophysics Data System (ADS)

Yandan, H.; Jun, L.; Jin, X.; Tianyun, W.

2017-12-01

Geological disasters occur with the stress changes of subsurface medium. Since the stress changes slowly in the deep earth where only seismic wave can reach, monitoring the changes with repeatable seismic sources, ambient seismic noise and artificial sources has become a hot topic in seismology. The Fujian Earthquake Agency successfully constructed the Air-gun artificial source system and carried out over 6000 shots in six reservoirs. The correlation coefficient of signals can reach up to 0.99. Besides an excellent source, high recognition ability of seismic wave changes is required. It is common to use time delay estimation method based on cross-correlation to recognize the velocity changes. We investigate the accuracy of time delay detection of Air-gun source signals. Suppose that the medium does not change in a short time, we changed the explosion conditions of the air-gun array and recognized the subtle changes of signals by the time delay estimation method: (1) we changed the excitation depth from 8m to 30m, and found that the arriving time of bubble pulses advanced nearly 90ms. The results are quite consistent with the records of the OBS on the bottom of reservoir; (2) we changed the firing pressure from 800Psi to 2000Psi, and found that the bubble pulses were quite different but now we don't have any suitable numerical model to fit the changes; (3) we changed the excitation position of the air-gun, and divided the changed distance between the Air-gun and the near-shore seismograph by the corresponding changed travelling time. Then we got a velocity of 1.5km/s, which equals to the sound speed in water; (4) we controlled the microsecond of explosion moment from 0ms to 9ms, and counted the time delays of waveforms. Results are quite consistent with the theoretical value; (5) we changed the explosion mode, and quantitatively recognized the 0.1ms changes of the signal travel time. Our experiments show that the method is of high precision that can recognize the microsecond changes of the waves. Next step, we are planning to establish a fixed Air-gun signal transmitting station in Fujian, China.

Transition from Target to Gaze Coding in Primate Frontal Eye Field during Memory Delay and Memory–Motor Transformation123

PubMed Central

Sajad, Amirsaman; Sadeh, Morteza; Yan, Xiaogang; Wang, Hongying

2016-01-01

Abstract The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T–G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T–G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T–G delay codes to a “pure” G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory–memory–motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation. PMID:27092335

Behavioral characteristics of very-low-birth-weight infants of varying biologic risk at 6, 15, and 24 months of age.

PubMed

Oehler, J M; Thompson, R J; Goldstein, R F; Gustafson, K E; Brazy, J E

1996-01-01

To explore the relationship between developmental outcome and behavior of very-low-birth-weight (VLBW) infants (< or = 1500 g) at high and low biologic risk. Descriptive, ex post facto. Clinic for follow-up of infants at high risk. A convenience sample of 102 VLBW infants, free of major congenital anomalies, who completed 6-, 15-, and 24-month developmental testing and who were part of a larger study of 274 VLBW infants. Bayley Scales of Infant Development. Infants at high biologic risk, versus infants at low biologic risk, were less attentive and active through age 15 months and were less adept in gross and fine motor skills through age 24 months (p < or = 0.05-0.001). Infants with continuous delay were less attentive than infants with no delay or late delay through age 24 months, less active through age 15 months (p < or = 0.001-0.001), and less skilled in motor behaviors through age 24 months (p < or = 0.05-0.001). Infants at high biologic risk and infants with developmental delays are less attentive, less active, and less skilled in motor tasks during the first 15-24 months of life, suggesting an association between biologic risk and behavior and developmental delay and behavior.

Working memory performance and neural activity in prefrontal cortex of peripubertal monkeys

PubMed Central

Zhou, Xin; Zhu, Dantong; Qi, Xue-Lian; Lees, Cynthia J.; Bennett, Allyson J.; Salinas, Emilio; Stanford, Terrence R.

2013-01-01

The dorsolateral prefrontal cortex matures late into adolescence or early adulthood. This pattern of maturation mirrors working memory abilities, which continue to improve into adulthood. However, the nature of the changes that prefrontal neuronal activity undergoes during this process is poorly understood. We investigated behavioral performance and neural activity in working memory tasks around the time of puberty, a developmental event associated with the release of sex hormones and significant neurological change. The developmental stages of male rhesus monkeys were evaluated with a series of morphometric, hormonal, and radiographic measures. Peripubertal monkeys were trained to perform an oculomotor delayed response task and a variation of this task involving a distractor stimulus. We found that the peripubertal monkeys tended to abort a relatively large fraction of trials, and these were associated with low levels of task-related neuronal activity. However, for completed trials, accuracy in the delayed saccade task was high and the appearance of a distractor stimulus did not impact performance significantly. In correct trials delay period activity was robust and was not eliminated by the presentation of a distracting stimulus, whereas in trials that resulted in errors the sustained cue-related activity was significantly weaker. Our results show that in peripubertal monkeys the prefrontal cortex is capable of generating robust persistent activity in the delay periods of working memory tasks, although in general it may be more prone to stochastic failure than in adults. PMID:24047904

Brain activity in valuation regions while thinking about the future predicts individual discount rates.

PubMed

Cooper, Nicole; Kable, Joseph W; Kim, B Kyu; Zauberman, Gal

2013-08-07

People vary widely in how much they discount delayed rewards, yet little is known about the sources of these differences. Here we demonstrate that neural activity in ventromedial prefrontal cortex (VMPFC) and ventral striatum (VS) when human subjects are asked to merely think about the future--specifically, to judge the subjective length of future time intervals--predicts delay discounting. High discounters showed lower activity for longer time delays, while low discounters showed the opposite pattern. Our results demonstrate that the correlation between VMPFC and VS activity and discounting occurs even in the absence of choices about future rewards, and does not depend on a person explicitly evaluating future outcomes or judging their self-relevance. This suggests a link between discounting and basic processes involved in thinking about the future, such as temporal perception. Our results also suggest that reducing impatience requires not suppression of VMPFC and VS activity altogether, but rather modulation of how these regions respond to the present versus the future.

Annual reproductive synchronization in ovary and pineal gland function of female short-nosed fruit bat, Cynopterus sphinx.

PubMed

Haldar, Chandana; Yadav, Rajesh; Alipreeta

2006-08-01

We studied the annual correlation of ovarian activity and pineal gland in relation with seasonal variation and gestation of a tropical zone short-nosed fruit bat Cynopterus sphinx. Female bats showed bimodal polyestry (February/March and September/October) in their reproductive cycle. Plasma estradiol concentration ran parallel with ovarian activity and had an inverse relation with pineal mass and peripheral melatonin concentration. Due to the delayed embryonic development in the uterus (October-March) of female bats, interestingly, the uterine activity did not show a parallel relation with ovarian activity and estradiol level. Further, compared with normal non-pregnant females, melatonin level was high during gestation and delayed embryonic development phase. This suggests that the reproductive synchrony and annual variation in ovarian activity of this nocturnal flying mammal differ from other common tropical mammals. The delayed embryonic development in bats might be an adaptive strategy for the unfavorable conditions of the seasons and might be regulated by high peripheral estradiol and melatonin concentration.

Brain Activity in Valuation Regions while Thinking about the Future Predicts Individual Discount Rates

PubMed Central

Cooper, Nicole; Kim, B. Kyu; Zauberman, Gal

2013-01-01

People vary widely in how much they discount delayed rewards, yet little is known about the sources of these differences. Here we demonstrate that neural activity in ventromedial prefrontal cortex (VMPFC) and ventral striatum (VS) when human subjects are asked to merely think about the future—specifically, to judge the subjective length of future time intervals—predicts delay discounting. High discounters showed lower activity for longer time delays, while low discounters showed the opposite pattern. Our results demonstrate that the correlation between VMPFC and VS activity and discounting occurs even in the absence of choices about future rewards, and does not depend on a person explicitly evaluating future outcomes or judging their self-relevance. This suggests a link between discounting and basic processes involved in thinking about the future, such as temporal perception. Our results also suggest that reducing impatience requires not suppression of VMPFC and VS activity altogether, but rather modulation of how these regions respond to the present versus the future. PMID:23926268

Real-time detection of caspase-2 activation in a single living HeLa cell during cisplatin-induced apoptosis

NASA Astrophysics Data System (ADS)

Lin, Juqiang; Zhang, Zhihong; Yang, Jie; Zeng, Shaoqun; Liu, Bifeng; Luo, Qingming

2006-03-01

Caspase-2 is important for the mitochondrial apoptotic pathway, however, the mechanism by which caspase-2 executes apoptosis remains obscure. We carry out the first measurements of the dynamics of caspase-2 activation in a single living cell by a FRET (fluorescence resonance energy transfer) probe. Two FRET probes are constructed that each encoded a CRS (caspase-2 or caspase-3 recognition site) fused with a cyan fluorescent protein (CFP) and a red fluorescent protein (DsRed) (CFP-CRS-DsRed). Using these probes, we found that during cisplatin-induced apoptosis, caspase-2 activation occurred more slowly than did activation of caspase-3; additionally, caspase-2 activation was initiated much earlier than that of caspase-3.

Arterial Spin Labeling Perfusion Magnetic Resonance Image with Dual Postlabeling Delay: A Correlative Study with Acetazolamide Loading (123)I-Iodoamphetamine Single-Photon Emission Computed Tomography.

PubMed

Haga, Sei; Morioka, Takato; Shimogawa, Takafumi; Akiyama, Tomoaki; Murao, Kei; Kanazawa, Yuka; Sayama, Tetsuro; Arakawa, Shuji

2016-01-01

Perfusion magnetic resonance image with arterial spin labeling (ASL) provides a completely noninvasive measurement of cerebral blood flow (CBF). However, arterial transient times can have a marked effect on the ASL signal. For example, a single postlabeling delay (PLD) of 1.5 seconds underestimates the slowly streaming collateral pathways that maintain the cerebrovascular reserve (CVR). To overcome this limitation, we developed a dual PLD method. A dual PLD method of 1.5  and 2.5 seconds was compared with (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading to assess CVR in 10 patients with steno-occlusive cerebrovascular disease. In 5 cases (Group A), dual PLD-ASL demonstrated low CBF with 1.5-second PLD in the target area, whereas CBF was improved with 2.5-second PLD. In the other 5 cases (Group B), dual PLD-ASL depicted low CBF with 1.5-second PLD, and no improvement in CBF with 2.5-second PLD in the target area was observed. On single-photon emission computed tomography, CVR was maintained in Group A but decreased in Group B. Although dual PLD methods may not be a completely alternative test for (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading, it is a feasible, simple, noninvasive, and repeatable technique for assessing CVR, even when employed in a routine clinical setting. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Spectral models for early time SN 2011fe observations

DOE PAGES

Baron, E.; Hoeflich, P.; Friesen, Brian; ...

2015-10-13

We use observed UV through near-IR spectra to examine whether SN 2011fe can be understood in the framework of Branch-normal Type Ia supernovae (SNe Ia) and to examine its individual peculiarities. As a benchmark, we use a delayed-detonationmodel with a progenitormetallicity of Z ⊙/20. We study the sensitivity of features to variations in progenitor metallicity, the outer density profile, and the distribution of radioactive nickel. The effect of metallicity variations in the progenitor have a relatively small effect on the synthetic spectra. We also find that the abundance stratification of SN 2011fe resembles closely that of a delayed-detonation model withmore » a transition density that has been fit to other Branch-normal SNe Ia. At early times, the model photosphere is formed in material with velocities that are too high, indicating that the photosphere recedes too slowly or that SN 2011fe has a lower specific energy in the outer ≈0.1 M ⊙ than does the model. We discuss several explanations for the discrepancies. Lastly, we examine variations in both the spectral energy distribution and in the colours due to variations in the progenitor metallicity, which suggests that colours are only weak indicators for the progenitor metallicity, in the particular explosion model that we have studied. Here we do find that the flux in the U band is significantly higher at maximum light in the solar metallicity model than in the lower metallicity model and the lower metallicity model much better matches the observed spectrum.« less

Accessibility and use of Primary Health Care: how conclusive is the social-economical situation in Antwerp?

PubMed

Philips, H; Rotthier, P; Meyvis, L; Remmen, R

2015-04-01

The percentage of households that delays medical assistance due to financial reasons is slowly increasing. Moreover, some groups of the population do not ever find their way to primary health care and end up unnecessarily in the emergency department or with specialists. This study wants to examine how primary health care can be made accessible to these groups. In this study, we aim to discover whether in a city such as Antwerp primary health care is accessible to everyone. The statistics were collected from the Health Care Survey done by the Welfare Services Antwerp in cooperation with the City of Antwerp. The questions were asked in three different ways: a postal questionnaire, a telephone questionnaire and a face-to-face interview. We determined that people who live on social welfare delay medical help due to financial reasons more frequently than the global Antwerp population. They often do not have a regular general practitioner (GP). Especially single parents, house-wives and house-husbands, job-seekers, incapacitated people unable to work, unskilled workers and foreigners are among the vulnerable groups where accessibility to primary health care is a concern. If we hope to improve the accessibility of primary health care, we must first and foremost inform the above-mentioned groups of the insurability and how this is applied. When this is fulfilled, it will be easier for the GP to receive this vulnerable group within the primary care system, so that the help of specialized care, which is often unnecessary, can be reduced.

Solar flare microwave observations with high spectral resolution

NASA Astrophysics Data System (ADS)

Bruggmann, G.; Magun, A.; Benz, A. O.; Stehling, W.

1990-12-01

The solar flare radio emission in the 6-8 GHz range was observed with a high resolution spectrometer. The observed band corresponds to the plasma frequencies and gyrofrequencies of the transition region and the lowest part of the corona in active regions. Most of the emissions were found to be broadbanded, as expected from the gyrosynchrotron mechanism. In eight out of 46 observed events, spectral structures of three types were detected: spikes below the time resolution of 100 ms, slowly drifting broadband structures, and a narrow bandwidth patch of continuum emission. These first narrowband bursts spectrally recorded in the 6-8 GHz range are generally weak. Slowly drifting structures are the only type compatible with the gyrosynchrotron emission mechanism. A simple argument based on free-free absorption shows that plasma emission can only be propagated if the radiation originates in a dense region with a small density-scale length. The same holds for maser emission at a low harmonic of the electron gyrofrequency. Possible emission mechanisms and diagnostic capabilities are discussed.

Molecular turnover, the H3.3 dilemma and organismal aging (hypothesis)

PubMed Central

Saade, Evelyne; Pirozhkova, Iryna; Aimbetov, Rakhan; Lipinski, Marc; Ogryzko, Vasily

2015-01-01

The H3.3 histone variant has been a subject of increasing interest in the field of chromatin studies due to its two distinguishing features. First, its incorporation into chromatin is replication independent unlike the replication-coupled deposition of its canonical counterparts H3.1/2. Second, H3.3 has been consistently associated with an active state of chromatin. In accordance, this histone variant should be expected to be causally involved in the regulation of gene expression, or more generally, its incorporation should have downstream consequences for the structure and function of chromatin. This, however, leads to an apparent paradox: In cells that slowly replicate in the organism, H3.3 will accumulate with time, opening the way to aberrant effects on heterochromatin. Here, we review the indications that H3.3 is expected both to be incorporated in the heterochromatin of slowly replicating cells and to retain its functional downstream effects. Implications for organismal aging are discussed. PMID:25720734

NOTE: Total body-calcium measurements: comparison of two delayed-gamma neutron activation facilities

NASA Astrophysics Data System (ADS)

Ma, R.; Ellis, K. J.; Yasumura, S.; Shypailo, R. J.; Pierson, R. N., Jr.

1999-06-01

This study compares two independently calibrated delayed-gamma neutron activation (DGNA) facilities, one at the Brookhaven National Laboratory (BNL), Upton, New York, and the other at the Children's Nutrition Research Center (CNRC), Houston, Texas that measure total body calcium (TBCa). A set of BNL phantoms was sent to CNRC for neutron activation analysis, and a set of CNRC phantoms was measured at BNL. Both facilities showed high precision (<2%), and the results were in good agreement, within 5%.

Autonomous Mission Operations

NASA Technical Reports Server (NTRS)

Frank, Jeremy; Spirkovska, Lilijana; McCann, Rob; Wang, Lui; Pohlkamp, Kara; Morin, Lee

2012-01-01

NASA's Advanced Exploration Systems Autonomous Mission Operations (AMO) project conducted an empirical investigation of the impact of time-delay on todays mission operations, and of the effect of processes and mission support tools designed to mitigate time-delay related impacts. Mission operation scenarios were designed for NASA's Deep Space Habitat (DSH), an analog spacecraft habitat, covering a range of activities including nominal objectives, DSH system failures, and crew medical emergencies. The scenarios were simulated at time-delay values representative of Lunar (1.2-5 sec), Near Earth Object (NEO) (50 sec) and Mars (300 sec) missions. Each combination of operational scenario and time-delay was tested in a Baseline configuration, designed to reflect present-day operations of the International Space Station, and a Mitigation configuration in which a variety of software tools, information displays, and crew-ground communications protocols were employed to assist both crews and Flight Control Team (FCT) members with the long-delay conditions. Preliminary findings indicate: 1) Workload of both crew members and FCT members generally increased along with increasing time delay. 2) Advanced procedure execution viewers, caution and warning tools, and communications protocols such as text messaging decreased the workload of both flight controllers and crew, and decreased the difficulty of coordinating activities. 3) Whereas crew workload ratings increased between 50 sec and 300 sec of time-delay in the Baseline configuration, workload ratings decreased (or remained flat) in the Mitigation configuration.

The Effects of Constant Time Delay Embedded into Teaching Activities for Teaching the Names of Clothes for Preschool Children with Developmental Disabilities

ERIC Educational Resources Information Center

Odluyurt, Serhat

2011-01-01

The general purpose of this study was to examine the effectiveness of constant time delay embedded in activities for teaching clothes name for preschool children with developmental disabilities. This study included four participants having Down syndrome with an age range of 43-46 months. All experimental sessions were conducted in one to one…

Delayed mirror visual feedback presented using a novel mirror therapy system enhances cortical activation in healthy adults.

PubMed

Lee, Hsin-Min; Li, Ping-Chia; Fan, Shih-Chen

2015-07-11

Mirror visual feedback (MVF) generated in mirror therapy (MT) with a physical mirror promotes the recovery of hemiparetic limbs in patients with stroke, but is limited in that it cannot provide an asymmetric mode for bimanual coordination training. Here, we developed a novel MT system that can manipulate the MVF to resolve this issue. The aims of this pilot study were to examine the feasibility of delayed MVF on MT and to establish its effects on cortical activation in order to understand how it can be used for clinical applications in the future. Three conditions (no MVF, MVF, and 2-s delayed MVF) presented via our digital MT system were evaluated for their time-course effects on cortical activity by event-related desynchronization (ERD) of mu rhythm electroencephalography (EEG) during button presses in 18 healthy adults. Phasic ERD areas, defined as the areas of the relative ERD curve that were below the reference level and within -2-0 s (P0), 0-2 s (P1), and 2-4 s (P2) of the button press, were used. The overall (P0 to P2) and phasic ERD areas were higher when MVF was provided compared to when MVF was not provided for all EEG channels (C3, Cz, and C4). Phasic ERD areas in the P2 phase only increased during the delayed-MVF condition. Significant enhancement of cortical activation in the mirror neuron system and an increase in attention to the unseen limb may play major roles in the response to MVF during MT. In comparison to the no MVF condition, the higher phasic ERD areas that were observed during the P1 phase in the delayed-MVF condition indicate that the image of the still hand may have enhanced the cortical activation that occurred in response to the button press. This study is the first to achieve delayed MVF for upper-limb MT. Our approach confirms previous findings regarding the effects of MVF on cortical activation and contributes additional evidence supporting the use of this method in the future for upper-limb motor training in patients with stroke.

Progressive hemifacial atrophy (Parry-Romberg syndrome). Case report.

PubMed

Mazzeo, N; Fisher, J G; Mayer, M H; Mathieu, G P

1995-01-01

Progressive hemifacial atrophy (Parry-Romberg syndrome) is a slowly progressing facial atrophy of subcutaneous fat and the wasting of associated skin, cartilage, and bone. This disorder includes an active progressive phase (2 to 10 years) followed by a burning out of the atrophic process with subsequent stability. This article presents a review of the literature and a case report with unique dental involvement as a result of this disease process.

Use of Organic Substrates as a Best Management Practice for Active Ranges

DTIC Science & Technology

2011-11-30

is much more limited in high organic carbon soils due to a combination of enhanced sorption and degradation . Organic materials can enhance explosive... degradation by stimulating anaerobic biodegradation of the target contaminants and reducing naturally occurring Fe(III) to Fe(II), providing a reservoir...of reducing power to maintain anoxic conditions in the soil and enhance abiotic degradation . Humic materials slowly biodegrade, consuming oxygen

The Effects of Embedded Skill Instruction on the Acquisition of Target and Nontarget Skills in Preschoolers with Developmental Delays.

ERIC Educational Resources Information Center

Daugherty, Stefanie; Grisham-Brown, Jennifer; Hemmeter, Mary Louise

2001-01-01

In the current study, a constant time delay (CTD) procedure was embedded in classroom activities and routines to teach counting to three preschool children with speech and language delays. CTD was effective in teaching numbers to all three children. One child out of two also was able to acquire non-target information. (Contains references.) (CR)

Effects of Growth Rate and Limiting Substrate on Glucose Metabolism in Escherichia coli1

PubMed Central

Wright, D. N.; Lockhart, W. R.

1965-01-01

Wright, D. N. (Iowa State University, Ames), and W. R. Lockhart. Effects of growth rate and limiting substrate on glucose metabolism in Escherichia coli. J. Bacteriol. 89:1082–1085. 1965.—Escherichia coli was grown in continuous culture at various rates in a defined medium with either glucose of (NH4)2SO4 as the rate-limiting substrate. Cellular content of polysaccharide (“glycogen”) is greater in cells grown under nitrogen limitation with glucose available in excess, and is greater in rapidly grown than in slowly grown cells. The ability of cells to carry on endogenous respiration, as measured by tetrazolium reduction, can be correlated with their glycogen content. In carbon-limited cultures, the proportion of substrate glucose diverted to glycogen production is least for cells grown slowly, which may reflect greater energy requirements for cell maintenance in such cultures. The activity of glucose-6-phosphate dehydrogenase (indicating function of a C-1 preferential pathway for glucose degradation) is greater in rapidly grown cells, confirming earlier observations in batch cultures. Activity of this enzyme is also greater in nitrogen-limited than in carbon-limited cells, suggesting that there may be catabolic repression of the Embden-Meyerhoff pathway when glucose is available in excess. PMID:14276099

Dynamics of delay-coupled FitzHugh-Nagumo neural rings.

PubMed

Mao, Xiaochen; Sun, Jianqiao; Li, Shaofan

2018-01-01

This paper studies the dynamical behaviors of a pair of FitzHugh-Nagumo neural networks with bidirectional delayed couplings. It presents a detailed analysis of delay-independent and delay-dependent stabilities and the existence of bifurcated oscillations. Illustrative examples are performed to validate the analytical results and to discover interesting phenomena. It is shown that the network exhibits a variety of complicated activities, such as multiple stability switches, the coexistence of periodic and quasi-periodic oscillations, the coexistence of periodic and chaotic orbits, and the coexisting chaotic attractors.

Dynamics of delay-coupled FitzHugh-Nagumo neural rings

NASA Astrophysics Data System (ADS)

Mao, Xiaochen; Sun, Jianqiao; Li, Shaofan

2018-01-01

This paper studies the dynamical behaviors of a pair of FitzHugh-Nagumo neural networks with bidirectional delayed couplings. It presents a detailed analysis of delay-independent and delay-dependent stabilities and the existence of bifurcated oscillations. Illustrative examples are performed to validate the analytical results and to discover interesting phenomena. It is shown that the network exhibits a variety of complicated activities, such as multiple stability switches, the coexistence of periodic and quasi-periodic oscillations, the coexistence of periodic and chaotic orbits, and the coexisting chaotic attractors.

Group consensus control for networked multi-agent systems with communication delays.

PubMed

An, Bao-Ran; Liu, Guo-Ping; Tan, Chong

2018-05-01

This paper investigates group consensus problems in networked multi-agent systems (NMAS) with communication delays. Based on the sed state prediction scheme, the group consensus control protocol is designed to compensate the communication delay actively. In light of algebraic graph theories and matrix theories, necessary and(or) sufficient conditions of group consensus with respect to a given admissible control set are obtained for the NMAS with communication delays under mild assumptions. Finally, simulations are performed to demonstrate the effectiveness of the theoretical results. Copyright © 2018 ISA. All rights reserved.

Revitalizing the unused urban space, case study: Lhokseumawe, Aceh -Indonesia

NASA Astrophysics Data System (ADS)

Wahid, J.; Karsono, B.; Koesmeri, D. R. A.; Indriannisa, S. E.

2018-03-01

The phenomenon of urban decline in the highly industrialized nation is now slowly taking place in the developing world. Deindustrialization as defined as a decline in the manufacturing sectors led to the changes in social, economic and subsequently a shift in urban activities. By taking Lhokseumawe, Aceh, Republic of Indonesia as an example, this paper attempts to uncover the possibilities and opportunities in identifying the causes and tracing back on the decline. Lhokseumawe, Aceh was a well-known industrial region outside Java Island, and it has attracted thousands of workers from northern Sumatera and the nearby regions. After the downturn of the economy and the change in activities, the city slowly showed a decline. Scholars has estimated that one in six of the cities around the world that relied on oil and gas production activities will suffer from this phenomenological impact. Lhokseumawe is a good example of an industrial plants where PT Arun LNG (private limited company) operated since 1974 grew up rapidly and nicknamed “Petrodollar City”. The trickle effect of the activities from the petrodollar business led to a few settlements popping up at the periphery as a result of urban sprawl from Lhokseumawe, however, the glory of the economic growth outlived within a short period. This was resulted from the production of PT Arun NGL which had dropped dramatically in the 2000s and suddenly closed the operation in October 2014. From these perspectives, this paper attempts to investigate the impact of deindustrialization within the urban space and activity in Lhokseumawe which have consequences to urban declining phenomena. By taking one of the revitalized urban space formerly known as Cunda Plaza (CP) as a case study area, the paper will apply synoptic method through observation, space mapping and interview techniques for gathering and examining the data. The findings indicates that Cunda Plaza is a magnet as a central hub of urban activities which can be integrated with other thriving activities from urban conurbation of academic related activities within the city.

Checkpoints: it takes more than time to heal some wounds.

PubMed

Rhind, N; Russell, P

The S-phase DNA damage checkpoint seems to provide a twist on the checkpoint theme. Instead of delaying replication and allowing repair as a consequence, it may activate repair and delay replication as a consequence.

Delay in surgery predisposes to meniscal and chondral injuries in anterior cruciate ligament deficient knees.

PubMed

Gupta, Ravi; Masih, Gladson David; Chander, Gaurav; Bachhal, Vikas

2016-09-01

Despite improvements in instability after anterior cruciate ligament (ACL) reconstruction, associated intraarticular injuries remain a major cause of concern and important prognostic factor for long term results as it may lead to osteoarthritis. Delay in ACL reconstruction has been in variably linked to increase in these injuries but there is lack of consensus regarding optimal timing of reconstruction. The goal of this study was to investigate delay in surgery and other factors, associated with intraarticular injuries in ACL deficient knees. A total of 438 patients (42 females; 396 males) enrolled for this prospective observational study. The average age of patients was 26.43 (range 17-51 years) years with a mean surgical delay of 78.91 (range 1 week - 18 years) weeks after injury. We analyzed the factors of age, sex, surgical delay, instability, and level of activity for possible association with intraarticular injuries. Medial meniscus injuries had a significant association with surgical delay ( P = 0.000) after a delay of 6 months. Lateral meniscus injuries had a significant association with degree of instability ( P = 0.001). Medial-sided articular injuries were significantly affected by age (0.005) with an odds ratio (OR) of 1.048 (95% confidence interval [CI] of 1.014-1.082) reflecting 4.8% rise in incidence with each year. Lateral-sided injuries were associated with female sex ( P = 0.018) with OR of 2.846 (95% CI of 1.200-6.752). The level of activity failed to reveal any significant associations. Surgical delay predicts an increase in medial meniscal and lateral articular injuries justifying early rather than delayed reconstruction in ACL deficient knees. Increasing age is positively related to intraarticular injuries while females are more susceptible to lateral articular injuries.

Firing patterns transition and desynchronization induced by time delay in neural networks

NASA Astrophysics Data System (ADS)

Huang, Shoufang; Zhang, Jiqian; Wang, Maosheng; Hu, Chin-Kun

2018-06-01

We used the Hindmarsh-Rose (HR) model (Hindmarsh and Rose, 1984) to study the effect of time delay on the transition of firing behaviors and desynchronization in neural networks. As time delay is increased, neural networks exhibit diversity of firing behaviors, including regular spiking or bursting and firing patterns transitions (FPTs). Meanwhile, the desynchronization of firing and unstable bursting with decreasing amplitude in neural system, are also increasingly enhanced with the increase of time delay. Furthermore, we also studied the effect of coupling strength and network randomness on these phenomena. Our results imply that time delays can induce transition and desynchronization of firing behaviors in neural networks. These findings provide new insight into the role of time delay in the firing activities of neural networks, and can help to better understand the firing phenomena in complex systems of neural networks. A possible mechanism in brain that can cause the increase of time delay is discussed.

Sluggish gallbladder emptying and gastrointestinal transit after intake of common alcoholic beverages.

PubMed

Kasicka-Jonderko, A; Jonderko, K; Gajek, E; Piekielniak, A; Zawislan, R

2014-02-01

To study the movement along the gut and the effect upon the gallbladder volume of alcoholic beverages taken in the interdigestive state. The study comprised three research blocks attended by 12 healthy subjects each. Within a given research block volunteers underwent three examination sessions held on separate days, being offered an alcoholic beverage, or an aqueous ethanol solution of an identical proof, or a corresponding volume of isotonic glucose solution; the order of administration of the drinks was randomized. The beverages tested were: beer (4.7% vol, 400 ml), red wine (13.7% vol, 200 ml), whisky (43.5% vol, 100 ml) within the "Beer", "Wine", and "Whisky" research block, respectively. Gastric myoelectrical activity was examined electrogastrographically, gastric emptying with ¹³C-sodium acetate breath test, orocaecal transit with lactulose H₂ breath test, gallbladder emptying with ultrasonography, breath ethanol with alcotest. The study showed that alcoholic beverages were emptied from the stomach significantly slower than isotonic glucose. Alcoholic beverages produced by fermentation only (beer, red wine) were emptied from the stomach more slowly than ethanol solutions of identical proof, while gastric evacuation of whisky (distillation product) and matching alcohol solution was similar. The slower gastric evacuation of alcoholic beverages and ethanol solutions could not be ascribed to a disorganization of the gastric myoelectrical activity. The orocaecal transit of beer and red wine did not differ from that of isotonic glucose, whereas the orocaecal transit of whisky and high proof ethanol was markedly prolonged. Red wine and whisky, and to a similar extent control ethanol solutions caused an inhibition and delay of gallbladder emptying. We concluded that alcoholic beverages taken on an empty stomach exert a suppressive effect upon the transport function of the digestive tract and gallbladder emptying. The extent of this action depends on the type of a beverage (whether it is obtained from fermentation only, or fermentation followed by distillation) and ethanol concentration therein.

Canine left ventricle electromechanical behavior under different pacing modes.

PubMed

Vo Thang, Thanh-Thuy; Thibault, Bernard; Finnerty, Vincent; Pelletier-Galarneau, Matthieu; Khairy, Paul; Grégoire, Jean; Harel, François

2012-10-01

Cardiac resynchronization therapy may improve survival and quality of life in patients suffering from heart failure with left ventricular (LV) contraction dyssynchrony. While several studies have investigated electrical or mechanical determinants of synchronous contraction, few have focused on activation contraction coupling at a macroscopic level. The objective of the study was to characterize LV electromechanical behavior and response to pacing in a heart failure model. We analyzed data from 3D electroanatomic non-contact mapping and blood pool SPECT for 12 dogs with right ventricular (RV) tachycardia pacing-induced dilated cardiomyopathy. Surfaces generated by the two modalities were registered. Electrical signals were analyzed, and endocardial wall displacement curves were portrayed. Rapid pacing decreased the mean LV ejection fraction (LVEF) to 20.9 % and prolonged the QRS duration to 79 ± 10 ms (normal range: 40-50 ms). QRS duration remained unchanged with biventricular pacing (88.5 ms), while single site pacing further prolonged the QRS duration (113.3 ms for RV pacing and 111.6 ms for LV pacing). No trend was observed in LV systolic function. Activation duration time was significantly increased with all pacing modes compared to baseline. Finally, electromechanical delay, as defined by the delay between electrical activation and mechanical response, was increased by single site pacing (172.9 ms for RV pacing and 174.6 ms for LV pacing) but not by biventricular pacing (162.4 ms). Combined temporal and spatial coregistration electroanatomic maps and baseline gated blood pool SPECT imaging allowed us to quantify activation duration time, electromechanical delay, and LVEF for different pacing modes. Even if pacing modes did not significantly modify LVEF or activation duration, they produced alterations in electromechanical delay, with biventricular pacing significantly decreasing the electromechanical delay as measured by surface tracings and endocardial non-contact mapping.

Maternal immune activation during pregnancy in rats impairs working memory capacity of the offspring.

PubMed

Murray, Brendan G; Davies, Don A; Molder, Joel J; Howland, John G

2017-05-01

Maternal immune activation during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia in the offspring. Patients with schizophrenia display an array of cognitive symptoms, including impaired working memory capacity. Rodent models have been developed to understand the relationship between maternal immune activation and the cognitive symptoms of schizophrenia. The present experiment was designed to test whether maternal immune activation with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy affects working memory capacity of the offspring. Pregnant Long Evans rats were treated with either saline or polyI:C (4mg/kg; i.v.) on gestational day 15. Male offspring of the litters (2-3months of age) were subsequently trained on a nonmatching-to-sample task with odors. After a criterion was met, the rats were tested on the odor span task, which requires rats to remember an increasing span of different odors to receive food reward. Rats were tested using delays of approximately 40s during the acquisition of the task. Importantly, polyI:C- and saline-treated offspring did not differ in performance of the nonmatching-to-sample task suggesting that both groups could perform a relatively simple working memory task. In contrast, polyI:C-treated offspring had reduced span capacity in the middle and late phases of odor span task acquisition. After task acquisition, the rats were tested using the 40s delay and a 10min delay. Both groups showed a delay-dependent decrease in span, although the polyI:C-treated offspring had significantly lower spans regardless of delay. Our results support the validity of the maternal immune activation model for studying the cognitive symptoms of neurodevelopmental disorders such as schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural correlates of auditory recognition memory in the primate dorsal temporal pole

PubMed Central

Ng, Chi-Wing; Plakke, Bethany

2013-01-01

Temporal pole (TP) cortex is associated with higher-order sensory perception and/or recognition memory, as human patients with damage in this region show impaired performance during some tasks requiring recognition memory (Olson et al. 2007). The underlying mechanisms of TP processing are largely based on examination of the visual nervous system in humans and monkeys, while little is known about neuronal activity patterns in the auditory portion of this region, dorsal TP (dTP; Poremba et al. 2003). The present study examines single-unit activity of dTP in rhesus monkeys performing a delayed matching-to-sample task utilizing auditory stimuli, wherein two sounds are determined to be the same or different. Neurons of dTP encode several task-relevant events during the delayed matching-to-sample task, and encoding of auditory cues in this region is associated with accurate recognition performance. Population activity in dTP shows a match suppression mechanism to identical, repeated sound stimuli similar to that observed in the visual object identification pathway located ventral to dTP (Desimone 1996; Nakamura and Kubota 1996). However, in contrast to sustained visual delay-related activity in nearby analogous regions, auditory delay-related activity in dTP is transient and limited. Neurons in dTP respond selectively to different sound stimuli and often change their sound response preferences between experimental contexts. Current findings suggest a significant role for dTP in auditory recognition memory similar in many respects to the visual nervous system, while delay memory firing patterns are not prominent, which may relate to monkeys' shorter forgetting thresholds for auditory vs. visual objects. PMID:24198324

Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle

PubMed Central

Koh, S D; Ward, S M; Dick, G M; Epperson, A; Bonner, H P; Sanders, K M; Horowitz, B; Kenyon, J L

1999-01-01

We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm≈−60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1–10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, ⋧ 5 mM) caused continuous spiking.Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (τf = 96 ms, τs = 1.5 s at 0 mV). The half-activation voltage of the permeability was −27 mV, with significant activation at −50 mV.TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100–500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to −20 mV, potentials where TEA had no effect.Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvβ1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected.We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude. PMID:10050014

Slowly changing potential problems in Quantum Mechanics: Adiabatic theorems, ergodic theorems, and scattering

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

Fishman, S., E-mail: fishman@physics.technion.ac.il; Soffer, A., E-mail: soffer@math.rutgers.edu

2016-07-15

We employ the recently developed multi-time scale averaging method to study the large time behavior of slowly changing (in time) Hamiltonians. We treat some known cases in a new way, such as the Zener problem, and we give another proof of the adiabatic theorem in the gapless case. We prove a new uniform ergodic theorem for slowly changing unitary operators. This theorem is then used to derive the adiabatic theorem, do the scattering theory for such Hamiltonians, and prove some classical propagation estimates and asymptotic completeness.

Fraction eutectic measurements in slowly cooled Pb - 15 wt percent Sn alloys

NASA Technical Reports Server (NTRS)

Studer, Anthony C.; Laxmanan, V.

1988-01-01

A space shuttle experiment employing the General Purpose Furnace in its isothermal mode of operation is currently manifested for flight circa 1989. The aim of this experiment was to investigate the role of gravity in a slowly, and isothermally, cooled sample of a binary Pb - 15 wt percent Sn alloy. Ground based work in support of the microgravity experiment is discussed. In particular, it is shown that fraction eutectic measurements using an image analyzer, can be used to satisfactorily describe macrosegregation occurring in these slowly cooled ingots.

Time-varying delays compensation algorithm for powertrain active damping of an electrified vehicle equipped with an axle motor during regenerative braking

NASA Astrophysics Data System (ADS)

Zhang, Junzhi; Li, Yutong; Lv, Chen; Gou, Jinfang; Yuan, Ye

2017-03-01

The flexibility of the electrified powertrain system elicits a negative effect upon the cooperative control performance between regenerative and hydraulic braking and the active damping control performance. Meanwhile, the connections among sensors, controllers, and actuators are realized via network communication, i.e., controller area network (CAN), that introduces time-varying delays and deteriorates the control performances of the closed-loop control systems. As such, the goal of this paper is to develop a control algorithm to cope with all these challenges. To this end, the models of the stochastic network induced time-varying delays, based on a real in-vehicle network topology and on a flexible electrified powertrain, were firstly built. In order to further enhance the control performances of active damping and cooperative control of regenerative and hydraulic braking, the time-varying delays compensation algorithm for the electrified powertrain active damping during regenerative braking was developed based on a predictive scheme. The augmented system is constructed and the H∞ performance is analyzed. Based on this analysis, the control gains are derived by solving a nonlinear minimization problem. The simulations and hardware-in-loop (HIL) tests were carried out to validate the effectiveness of the developed algorithm. The test results show that the active damping and cooperative control performances are enhanced significantly.

Locomotor activity rhythms in dogs vary with age and cognitive status.

PubMed

Siwak, Christina T; Tapp, P Dwight; Zicker, Steven C; Murphey, Heather L; Muggenburg, Bruce A; Head, Elizabeth; Cotman, Carl W; Milgram, Norton W

2003-08-01

Beagle dogs exhibited diurnal patterns of locomotor activity that varied as a function of age, cognitive status, and housing environment. Aged dogs housed in an indoor facility showed a delayed onset of activity following lights on and displayed shorter bouts of activity, with more rest periods during the day, compared with young dogs. Cognitively impaired aged dogs were more active and showed a delayed peak of activity compared with unimpaired aged dogs. Housing in continuous light did not disrupt activity rhythms. The effect of age was less prominent in dogs housed in an indoor/outdoor facility. This suggests that bright sunlight and natural light-dark transitions are better able to consolidate and synchronize the activity rhythms of the dogs.

Modeling the influence of the VV delay for CRT on the electrical activation patterns in absence of conduction through the AV node

NASA Astrophysics Data System (ADS)

Romero, D. A.; Sebastián, Rafael; Plank, Gernot; Vigmond, Edward J.; Frangi, Alejandro F.

2008-03-01

From epidemiological studies, it has been shown that 0.2% of men and 0.1% of women suffer from a degree of atrioventricular (AV) block. In recent years, the palliative treatment for third degree AV block has included Cardiac Resynchronization Therapy (CRT). It was found that patients show more clinical improvement in the long term with CRT compared with single chamber devices. Still, an important group of patients does not improve their hemodynamic function as much as could be expected. A better understanding of the basis for optimizing the devices settings (among which the VV delay) will help to increase the number of responders. In this work, a finite element model of the left and right ventricles was generated using an atlas-based approach for their segmentation, which includes fiber orientation. The electrical activity was simulated with the electrophysiological solver CARP, using the Ten Tusscher et al. ionic model for the myocardium, and the DiFrancesco-Noble for Purkinje fibers. The model is representative of a patient without dilated or ischemic cardiomyopathy. The simulation results were analyzed for total activation times and latest activated regions at different VV delays and pre-activations (RV pre-activated, LV pre-activated). To optimize the solution, simulations are compared against the His-Purkinje network activation (normal physiological conduction), and interventricular septum activation (as collision point for the two wave fronts). The results were analyzed using Pearson's coefficient of correlation for point to point comparisons between simulation cases. The results of this study contribute to gain insight on the VV delay and how its adjustment might influence response to CRT and how it can be used to optimize the treatment.

[Presentation of Niemann-Pick type C disease with psychiatric disturbance in an adult].

PubMed

Tyvaert, L; Stojkovic, T; Cuisset, J-M; Vanier, M-T; Turpin, J-C; De Sèze, J; Vermersch, P

2005-03-01

Niemann-Pick Type C disease (NPC) is an autosomal recessive neurovisceral lysosomal lipid storage disorder. A 31-year-old right-handed woman had suffered from schizophrenia for 13 years. At 25 years of age, she developed a gait disorder with a static and kinetic cerebellar syndrome, dysarthria, vertical supranuclear gaze palsy and cognitive impairment. Brain MRI was normal. Abdominal ultrasonography was performed because of hypercholesterolemia and elevated transaminases and revealed hepatosplenomegaly, which in conjunction with other signs and symptoms, suggested the diagnosis of NPC. The diagnosis was confirmed by demonstration of lysosomal storage of unesterified cholesterol (filipin staining) and of a reduced rate of LDL-induced cholesterol esterification. Implication of the NPC1 gene was assessed by genetic complementation analysis. The phenotypic presentation of NPC is remarkably variable. The rarer adult-onset form has a slowly progressive course. Psychotic manifestations are often prominent and may precede neurologic symptoms. Exposure to neuroleptics delays the diagnosis of NPC. Psychotic manifestations associated with cerebellar syndrome, vertical supranuclear gaze palsy, and splenomegaly are very suggestive of NPC disease which can be reliably diagnosed on cultured skin fibroblasts by filipin staining.

Polypill: Progress and Challenges to Global Use--Update on the Trials and Policy Implementation.

PubMed

Webster, Ruth; Rodgers, Anthony

2015-12-01

Cardiovascular disease (CVD) is the leading cause of mortality globally. Most people with cardiovascular disease do not take long-term cholesterol-lowering, anti-platelet and blood pressure-lowering medications despite proven benefits. Fixed-dose combination pills ('polypills') have been shown to improve adherence to these recommended medications with corresponding improvements in risk factors such as blood pressure and low-density lipoprotein (LDL) cholesterol. Among patients not taking the full complement of recommended CVD preventive therapies, use of a polypill-based strategy (i.e. initiating treatment with single-pill combination medication then titrating further therapy as needed) has large potential benefits in reducing global morbidity and mortality. Despite this, few polypills are available on the market due to market failure in the funding of research and development for affordable non-communicable disease medicines. Additionally, defining a path to market has been problematic in that fixed-dose combinations with multiple different drug classes included are quite novel, and regulatory processes to review these types of applications are not well established. Despite these delays, progress is slowly being made.

Multiband optical-IR variability of the blazar PKS 0537-441

NASA Astrophysics Data System (ADS)

Li, Xiao-Pan; Wang, Li-Sha; Yang, Cheng; Yang, Hai-yan; Zhou, Li; Xu, Guang-Yang; Shan, Yu-Qiong; Liu, Jie; Luo, Yu-Hui; Zhang, Li

2018-06-01

We have reconsidered the simultaneous and homogeneous optical-IR light curves and the corresponding spectral indices curve of the blazar PKS 0537-441 from January 2011 to May 2015. All the curves show significant fluctuations on various timescales, and the flux variations seem to be more pronounced towards the IR bands. The relation between average fluxes and spectral indices reveals the existence of redder-when-brighter (RWB) and bluer-when-brighter (BWB) trends at different flux levels, along with a long-term achromatic trend and a mild RWB trend on short-term timescales. Cross-correlation analyses present an energy-dependent time delay that the lower-frequency variations follow higher-frequency ones by a few weeks and a hysteresis pattern between spectra and fluxes. Our analysis reveals some potential coherence between low-energy-peaked BL Lacs (LBLs) and FSRQs, and indicates that the observed flux variability and spectral changes could be due to the superposition of a dominant jet emission, an underlying thermal contribution from a more slowly varying disk and/or other geometric effects under the shock-in-jet scenario.

Treatment of Autism Spectrum Disorder in Children and Adolescents

PubMed Central

DeFilippis, Melissa; Wagner, Karen Dineen

2016-01-01

Autism spectrum disorder is a diagnosis that includes significant social communication deficits/delays along with restricted patterns of interests and behaviors. The prevalence of this diagnosis has increased over the past few decades, and it is unclear whether this is solely attributable to the increased awareness of milder forms of the disorder among medical providers. The current treatment options for the core symptoms of autism are limited to psychosocial therapies, such as applied behavior analysis. Medications have been most effective in treating the associated behavioral symptoms of autism, though studies have examined potential benefits in some of the core symptoms of autism with certain medications, especially the repetitive behaviors often seen with this diagnosis. Risperidone and aripiprazole are currently the only medications FDA approved for symptoms associated with autism spectrum disorders, targeting the irritability often seen with this diagnosis. Children and adolescents with autism spectrum disorder appear to be more susceptible to adverse effects with medications; therefore, initiation with low doses and titrating very slowly is recommended. Some complementary alternative treatments have been researched as possible treatments in autism, though evidence supporting many of these is very limited. PMID:27738378

Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome.

PubMed

Piekutowska-Abramczuk, Dorota; Mierzewska, Hanna; Bekiesińska-Figatowska, Monika; Ciara, Elżbieta; Trubicka, Joanna; Pronicki, Maciej; Rokicki, Dariusz; Rydzanicz, Małgorzata; Płoski, Rafał; Pronicka, Ewa

2016-01-01

Pathogenic molecular variants in the ADAR gene are a known cause of rare diseases, autosomal recessive Aicardi- Goutières syndrome type 6, severe infantile encephalopathy with intracranial calcifications and dominant dyschromatosis symmetrica hereditaria, demonstrated mainly in Asian adults. Recently, they have been also found in patients with nonsyndromic bilateral striatal necrosis accompanied by skin changes of the freckles-like type. Here, we present Polish siblings with acute onset and slowly progressive extrapyramidal syndrome with preserved intellectual abilities and basal ganglia changes found in MRI. A Leigh syndrome was considered for a long time as the most frequent cause of such lesions in children. Finally, two molecular variants in non-mitochondria-related ADAR gene c.3202+1G>A (p.?) and c.577C>G (p.Pro193Ala) were revealed by whole exome sequencing. We suggest that bilateral striatal necrosis should be always differentiated from LS to prevent the diagnosis delay. The striatal involvement accompanied by the presence of freckles-like skin changes should direct differential diagnosis to the ADAR gene mutations screening.

Maintenance treatment of recurrent ovarian cancer: Is it ready for prime time?

PubMed

DiSilvestro, Paul; Alvarez Secord, Angeles

2018-06-05

Approximately 1% of women in the United States will be diagnosed with epithelial ovarian cancer (EOC) during their lifetime. It is most likely to present at a more advanced stage, requiring aggressive therapeutic measures, and most women will succumb to this illness. Due to advancements in therapy, the oncology community has begun to shift its focus to molecular targeted agents, alternative dosing schedules, and maintenance therapy. Women who achieve a response to initial adjuvant chemotherapy may be candidates for maintenance therapy, with the goal of inducing a lasting remission or prolonging the disease-free interval before recurrence. The rationale for maintenance therapy is to delay disease progression by eliminating residual, slowly-dying cancerous cells, or impeding cell turnover. This review discusses the goals of maintenance therapy for EOC with antiangiogenic agents or poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, and reviews clinical studies that have demonstrated improvements in survival outcomes. The side-effect profiles for PARP inhibitors and the implications for preserving quality of life during maintenance therapy will also be discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Stability switches and multistability coexistence in a delay-coupled neural oscillators system.

PubMed

Song, Zigen; Xu, Jian

2012-11-21

In this paper, we present a neural network system composed of two delay-coupled neural oscillators, where each of these can be regarded as the dynamical system describing the average activity of neural population. Analyzing the corresponding characteristic equation, the local stability of rest state is studied. The system exhibits the switch phenomenon between the rest state and periodic activity. Furthermore, the Hopf bifurcation is analyzed and the bifurcation curve is given in the parameters plane. The stability of the bifurcating periodic solutions and direction of the Hopf bifurcation are exhibited. Regarding time delay and coupled weight as the bifurcation parameters, the Fold-Hopf bifurcation is investigated in detail in terms of the central manifold reduction and normal form method. The neural system demonstrates the coexistence of the rest states and periodic activities in the different parameter regions. Employing the normal form of the original system, the coexistence regions are illustrated approximately near the Fold-Hopf singularity point. Finally, numerical simulations are performed to display more complex dynamics. The results illustrate that system may exhibit the rich coexistence of the different neuro-computational properties, such as the rest states, periodic activities, and quasi-periodic behavior. In particular, some periodic activities can evolve into the bursting-type behaviors with the varying time delay. It implies that the coexistence of the quasi-periodic activity and bursting-type behavior can be obtained if the suitable value of system parameter is chosen. Copyright © 2012 Elsevier Ltd. All rights reserved.

Aging transition in systems of oscillators with global distributed-delay coupling.

PubMed

Rahman, B; Blyuss, K B; Kyrychko, Y N

2017-09-01

We consider a globally coupled network of active (oscillatory) and inactive (nonoscillatory) oscillators with distributed-delay coupling. Conditions for aging transition, associated with suppression of oscillations, are derived for uniform and gamma delay distributions in terms of coupling parameters and the proportion of inactive oscillators. The results suggest that for the uniform distribution increasing the width of distribution for the same mean delay allows aging transition to happen for a smaller coupling strength and a smaller proportion of inactive elements. For gamma distribution with sufficiently large mean time delay, it may be possible to achieve aging transition for an arbitrary proportion of inactive oscillators, as long as the coupling strength lies in a certain range.

Identification of three signaling molecules required for calcineurin-dependent monopolar growth induced by the DNA replication checkpoint in fission yeast.

PubMed

Kume, Kazunori; Hashimoto, Tomoyo; Suzuki, Masashi; Mizunuma, Masaki; Toda, Takashi; Hirata, Dai

2017-09-30

Cell polarity is coordinately regulated with the cell cycle. Growth polarity of the fission yeast Schizosaccharomyces pombe transits from monopolar to bipolar during G2 phase, termed NETO (new end take off). Upon perturbation of DNA replication, the checkpoint kinase Cds1/CHK2 induces NETO delay through activation of Ca 2+ /calmodulin-dependent protein phosphatase calcineurin (CN). CN in turn regulates its downstream targets including the microtubule (MT) plus-end tracking CLIP170 homologue Tip1 and the Casein kinase 1γ Cki3. However, whether and which Ca 2+ signaling molecules are involved in the NETO delay remains elusive. Here we show that 3 genes (trp1322, vcx1 and SPAC6c3.06c encoding TRP channel, antiporter and P-type ATPase, respectively) play vital roles in the NETO delay. Upon perturbation of DNA replication, these 3 genes are required for not only the NETO delay but also for the maintenance of cell viability. Trp1322 and Vcx1 act downstream of Cds1 and upstream of CN for the NETO delay, whereas SPAC6c3.06c acts downstream of CN. Consistently, Trp1322 and Vcx1, but not SPAC6c3.06c, are essential for activation of CN. Interestingly, we have found that elevated extracellular Ca 2+ per se induces a NETO delay, which depends on CN and its downstream target genes. These findings imply that Ca 2+ -CN signaling plays a central role in cell polarity control by checkpoint activation. Copyright © 2017 Elsevier Inc. All rights reserved.

Viva la Evolucion!

ERIC Educational Resources Information Center

Haro, Robert P.

1979-01-01

Developments in library services to Hispanic Americans include special collection development and outreach services to non-users but change is coming too slowly for America's fastest growing minority. Professional education has responded slowly, if at all to the Hispanic population's needs. (MBR)

Gravitational instability of slowly rotating isothermal spheres

NASA Astrophysics Data System (ADS)

Chavanis, P. H.

2002-12-01

We discuss the statistical mechanics of rotating self-gravitating systems by allowing properly for the conservation of angular momentum. We study analytically the case of slowly rotating isothermal spheres by expanding the solutions of the Boltzmann-Poisson equation in a series of Legendre polynomials, adapting the procedure introduced by Chandrasekhar (1933) for distorted polytropes. We show how the classical spiral of Lynden-Bell & Wood (1967) in the temperature-energy plane is deformed by rotation. We find that gravitational instability occurs sooner in the microcanonical ensemble and later in the canonical ensemble. According to standard turning point arguments, the onset of the collapse coincides with the minimum energy or minimum temperature state in the series of equilibria. Interestingly, it happens to be close to the point of maximum flattening. We generalize the singular isothermal solution to the case of a slowly rotating configuration. We also consider slowly rotating configurations of the self-gravitating Fermi gas at non-zero temperature.

Biophysical models of protein evolution: Understanding the patterns of evolutionary sequence divergence

PubMed Central

Echave, Julian; Wilke, Claus O.

2018-01-01

For decades, rates of protein evolution have been interpreted in terms of the vague concept of “functional importance”. Slowly evolving proteins or sites within proteins were assumed to be more functionally important and thus subject to stronger selection pressure. More recently, biophysical models of protein evolution, which combine evolutionary theory with protein biophysics, have completely revolutionized our view of the forces that shape sequence divergence. Slowly evolving proteins have been found to evolve slowly because of selection against toxic misfolding and misinteractions, linking their rate of evolution primarily to their abundance. Similarly, most slowly evolving sites in proteins are not directly involved in function, but mutating them has large impacts on protein structure and stability. Here, we review the studies of the emergent field of biophysical protein evolution that have shaped our current understanding of sequence divergence patterns. We also propose future research directions to develop this nascent field. PMID:28301766

Thermally Activated Delayed Fluorescence in Polymers: A New Route toward Highly Efficient Solution Processable OLEDs.

PubMed

Nikolaenko, Andrey E; Cass, Michael; Bourcet, Florence; Mohamad, David; Roberts, Matthew

2015-11-25

Efficient intermonomer thermally activated delayed fluorescence is demonstrated for the first time, opening a new route to achieving high-efficiency solution processable polymer light-emitting device materials. External quantum efficiency (EQE) of up to 10% is achieved in a simple fully solution-processed device structure, and routes for further EQE improvement identified. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Checkpoints: It takes more than time to heal some wounds

PubMed Central

Rhind, Nicholas; Russell, Paul

2010-01-01

The S-phase DNA damage checkpoint seems to provide a twist on the checkpoint theme. Instead of delaying replication and allowing repair as a consequence, it may activate repair and delay replication as a consequence. PMID:11137027

Neural Evidence for a Distinction Between Short-Term Memory and the Focus of Attention

PubMed Central

Lewis-Peacock, Jarrod A.; Drysdale, Andrew T.; Oberauer, Klaus; Postle, Bradley R.

2011-01-01

It is widely assumed that the short-term retention of information is accomplished via maintenance of an active neural trace. However, we demonstrate that memory can be preserved across a brief delay despite the apparent loss of sustained representations. Delay-period activity may in fact reflect the focus of attention, rather than short-term memory. We unconfounded attention and memory by causing external and internal shifts of attention away from items that were being actively retained. Multivariate pattern analysis of fMRI indicated that only items within the focus of attention elicited an active neural trace. Activity corresponding to representations of items outside the focus quickly dropped to baseline. Nevertheless, this information was remembered after a brief delay. Our data also show that refocusing attention towards a previously unattended memory item can reactivate its neural signature. The loss of sustained activity has long been thought to indicate a disruption of short-term memory, but our results suggest that, even for small memory loads not exceeding the capacity limits of short-term memory, the active maintenance of a stimulus representation may not be necessary for its short-term retention. PMID:21955164

Analysis of virtual passive controllers for flexible space structures

NASA Technical Reports Server (NTRS)

Williams, Trevor W.

1992-01-01

The dynamics of flexible spacecraft are not usually well known before launch. This makes it important to develop controllers for such systems that can never be destabilized by perturbations in the structural model. Virtual passive controllers, or active vibration absorbers, possess this guaranteed stability property; they mimic a fictitious flexible structure attached to the true physical one. This report analyzes the properties of such controllers, and shows that disturbance absorption behavior can be naturally described in terms of a set of virtual zeros that they introduce into the closed-loop dynamics of the system. Based on this analysis, techniques are then derived for selecting the active vibration absorber internal parameters, i.e., the gain matrices of such controllers, so as to achieve specified control objectives. Finally, the effects on closed-loop stability of small delays in the feedback loop are investigated. Such delays would typically be introduced by a digital implementation of an active vibration absorber. It is shown that these delays only affect the real parts of the eigenvalues of a lightly-damped structure. Furthermore, it is only the high-frequency modes that are destabilized by delays; low-frequency modes are actually made more heavily damped. Eigenvalue perturbation methods are used to obtain accurate predictions of the critical delay at which a given system will become unstable; these methods also determine which mode is critical.

Highly pathogenic avian influenza H5N1 virus delays apoptotic responses via activation of STAT3

PubMed Central

Hui, Kenrie P. Y.; Li, Hung Sing; Cheung, Man Chun; Chan, Renee W. Y.; Yuen, Kit M.; Mok, Chris K. P.; Nicholls, John M.; Peiris, J. S. Malik; Chan, Michael C. W.

2016-01-01

Highly pathogenic avian influenza (HPAI) H5N1 virus continues to pose pandemic threat, but there is a lack of understanding of its pathogenesis. We compared the apoptotic responses triggered by HPAI H5N1 and low pathogenic H1N1 viruses using physiologically relevant respiratory epithelial cells. We demonstrated that H5N1 viruses delayed apoptosis in primary human bronchial and alveolar epithelial cells (AECs) compared to H1N1 virus. Both caspase-8 and -9 were activated by H5N1 and H1N1 viruses in AECs, while H5N1 differentially up-regulated TRAIL. H5N1-induced apoptosis was reduced by TRAIL receptor silencing. More importantly, STAT3 knock-down increased apoptosis by H5N1 infection suggesting that H5N1 virus delays apoptosis through activation of STAT3. Taken together, we demonstrate that STAT3 is involved in H5N1-delayed apoptosis compared to H1N1. Since delay in apoptosis prolongs the duration of virus replication and production of pro-inflammatory cytokines and TRAIL from H5N1-infected cells, which contribute to orchestrate cytokine storm and tissue damage, our results suggest that STAT3 may play a previously unsuspected role in H5N1 pathogenesis. PMID:27344974

Delayed expression of SAGs correlates with longevity in CMS wheat plants compared to its fertile plants.

PubMed

Semwal, Vimal Kumar; Singh, Bhupinder; Khanna-Chopra, Renu

2014-04-01

Reproductive sinks regulate monocarpic senescence in crop plants. Monocarpic senescence was studied in wheat fertile (cv. HW 2041) and its isonuclear cytoplasmic male sterile (CMS) line. CMS plants exhibited slower rate of senescence accompanied by longer green leaf area duration and slower deceleration in chlorophyll, protein content, PN and rubisco content coupled with lower protease activities than fertile (F) plants. CMS plants also exhibited lower ROS levels and less membrane damage than F plants. CMS plants maintained better antioxidant defense, less oxidative damage in chloroplast and higher transcript levels of both rbcL and rbcS genes during senescence than F plants. F plants exhibited early induction and higher expression of SAGs like serine and cysteine proteases, glutamine synthetases GS1 and GS2, WRKY53 transcription factor and decline in transcript levels of CAT1 and CAT2 genes than CMS plants. Hence, using genetically fertile and its CMS line of wheat it is confirmed that delayed senescence in the absence of reproductive sinks is linked with slower protein oxidation, rubisco degradation and delayed activation of SAGs. Better antioxidant defense in chloroplasts at later stages of senescence was able to mitigate the deleterious effects of ROS in CMS plants. We propose that delayed increase in ROS in cytoplasmic male sterile wheat plants resulted in delayed activation of WRKY53, SAGs and the associated biochemical changes than fertile plants.

Structural studies of 4-aminoantipyrine derivatives

NASA Astrophysics Data System (ADS)

Cunha, Silvio; Oliveira, Shana M.; Rodrigues, Manoel T.; Bastos, Rodrigo M.; Ferrari, Jailton; de Oliveira, Cecília M. A.; Kato, Lucília; Napolitano, Hamilton B.; Vencato, Ivo; Lariucci, Carlito

2005-10-01

Reaction of 4-aminoantipyrine with acetylacetone, ethyl acetoacetate, benzoyl isothiocyanate, phenyl isothiocyanate, maleic anhydride and methoxymethylene Meldrum's acid afforded a series of new antipyrine derivatives. The antibacterial activity of the synthesized compounds against Micrococcus luteus ATCC 9341, Staphilococcus aureus ATCC 29737, and Escherichia coli ATCC 8739 was evaluated and the minimal inhibitory concentration determined. Modest activity was found only to the maleamic acid obtained from the reaction of 4-aminoantipyrine and maleic anhydride. 1H NMR investigation of this maleamic acid showed that it is slowly converted to the corresponding toxic maleimide. The structures of three derivatives were determined by X-ray diffraction analysis.

The temporal profile of the reaction of microglia, astrocytes, and macrophages in the delayed onset paraplegia after transient spinal cord ischemia in rabbits.

PubMed

Matsumoto, Satoshi; Matsumoto, Mishiya; Yamashita, Atsuo; Ohtake, Kazunobu; Ishida, Kazuyoshi; Morimoto, Yasuhiro; Sakabe, Takefumi

2003-06-01

In the present study, we sought to elucidate the temporal profile of the reaction of microglia, astrocytes, and macrophages in the progression of delayed onset motor dysfunction after spinal cord ischemia (15 min) in rabbits. At 2, 4, 8, 12, 24, and 48 h after reperfusion (9 animals in each), hind limb motor function was assessed, and the lumbar spinal cord was histologically examined. Delayed motor dysfunction was observed in most animals at 48 h after ischemia, which could be predicted by a poor recovery of segmental spinal cord evoked potentials at 15 min of reperfusion. In the gray matter of the lumbar spinal cord, both microglia and astrocytes were activated early (2 h) after reperfusion. Microglia were diffusely activated and engulfed motor neurons irrespective of the recovery of segmental spinal cord evoked potentials. In contrast, early astrocytic activation was confined to the area where neurons started to show degeneration. Macrophages were first detected at 8 h after reperfusion and mainly surrounded the infarction area later. Although the precise roles of the activation of microglia, astrocytes, and macrophages are to be further determined, the results indicate that understanding functional changes of astrocytes may be important in the mechanism of delayed onset motor dysfunction including paraplegia. Microglia and macrophages play a role in removing tissue debris after transient spinal cord ischemia. Disturbance of astrocytic defense mechanism, breakdown of the blood-spinal cord barrier, or both seemed to be involved in the development of delayed motor dysfunction.

Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

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

Kiran, Shashi; Oddi, Vineesha; Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com

2015-02-01

Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose ofmore » doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT7 attenuated p38/JNK activation and also p53 response. • Overall, SIRT7 promoted cellular survival in conditions of genomic stress.« less

Volunteerism and socioemotional selectivity in later life.

PubMed

Hendricks, Jon; Cutler, Stephen J

2004-09-01

The goal of this work was to assess the applicability of socioemotional selectivity theory to the realm of volunteerism by analyzing data drawn from the September 2002 Current Population Survey Volunteer Supplement. Total number of organizations volunteered for and total number of hours engaged in volunteer activities were utilized to obtain measures of volunteer hours per organization and volunteer hours in the main organization to determine whether a selective process could be observed. Descriptive statistics on age patterns were followed by a series of curve estimations to identify the best-fitting curves. Logistic age patterns of slowly increasing then relatively stable volunteer activity suggest that socioemotional selectivity processes are operative in the realm of voluntary activities. Socioemotional selectivity theory is applicable to voluntary activities.

Glycation of myofibrillar proteins and ATPase activity after incubation with eleven sugars.

PubMed

Syrový, I

1994-01-01

Rat skeletal muscle myofibrils were incubated in the presence of D-glucose, D-fructose, D-galactose, D-ribose, D-tagatose, D-arabinose, D-xylose, D-mannose, L-sorbose, L-rhamnose or DL-glyceraldehyde and myofibrillar ATPase activity as well as the extent of glycation was measured. The attachment of sugars to proteins during glycation was generally dependent on the percentage of a given sugar present in the open-chain form. Glycation resulted in the decrease of myofibrillar ATPase activity. This decrease was low after incubation of myofibrillar proteins with slowly glycating sugars (e.g. glucose) and high with fast glycating sugars (e.g. ribose or glyceraldehyde). ATPase activity was less reduced in the presence of beta-mercaptoethanol.

A KCNQ1 mutation contributes to the concealed type 1 long QT phenotype by limiting the Kv7.1 channel conformational changes associated with protein kinase A phosphorylation.

PubMed

Bartos, Daniel C; Giudicessi, John R; Tester, David J; Ackerman, Michael J; Ohno, Seiko; Horie, Minoru; Gollob, Michael H; Burgess, Don E; Delisle, Brian P

2014-03-01

Type 1 long QT syndrome (LQT1) is caused by loss-of-function mutations in the KCNQ1-encoded Kv7.1 channel that conducts the slowly activating component of the delayed rectifier K(+) current (IKs). Clinically, the diagnosis of LQT1 is complicated by variable phenotypic expressivity, whereby approximately 25% of genotype-positive individuals present with concealed LQT1 (resting corrected QT [QTc] interval ≤460 ms). To determine whether a specific molecular mechanism contributes to concealed LQT1. We identified a multigenerational LQT1 family whereby 79% of the patients genotype-positive for p.Ile235Asn-KCNQ1 (I235N-Kv7.1) have concealed LQT1. We assessed the effect I235N-Kv7.1 has on IKs and the ventricular action potential (AP) by using in vitro analysis and computational simulations. Clinical data showed that all 10 patients with I235N-Kv7.1 have normal resting QTc intervals but abnormal QTc interval prolongation during the recovery phase of an electrocardiographic treadmill stress test. Voltage-clamping HEK293 cells coexpressing wild-type Kv7.1 and I235N-Kv7.1 (to mimic the patients' genotypes) showed that I235N-Kv7.1 generated relatively normal functioning Kv7.1 channels but were insensitive to protein kinase A (PKA) activation. Phosphomimetic and quinidine sensitivity studies suggest that I235N-Kv7.1 limits the conformational changes in Kv7.1 channels, which are necessary to upregulate IKs after PKA phosphorylation. Computational ventricular AP simulations predicted that the PKA insensitivity of I235N-Kv7.1 is primarily responsible for prolonging the AP with β-adrenergic stimulation, especially at slower cycle lengths. KCNQ1 mutations that generate relatively normal Kv7.1 channels, but limit the upregulation of IKs by PKA activation, likely contribute to concealed LQT1. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

High-efficiency electroluminescence and amplified spontaneous emission from a thermally activated delayed fluorescent near-infrared emitter

NASA Astrophysics Data System (ADS)

Kim, Dae-Hyeon; D'Aléo, Anthony; Chen, Xian-Kai; Sandanayaka, Atula D. S.; Yao, Dandan; Zhao, Li; Komino, Takeshi; Zaborova, Elena; Canard, Gabriel; Tsuchiya, Youichi; Choi, Eunyoung; Wu, Jeong Weon; Fages, Frédéric; Brédas, Jean-Luc; Ribierre, Jean-Charles; Adachi, Chihaya

2018-02-01

Near-infrared organic light-emitting diodes and semiconductor lasers could benefit a variety of applications including night-vision displays, sensors and information-secured displays. Organic dyes can generate electroluminescence efficiently at visible wavelengths, but organic light-emitting diodes are still underperforming in the near-infrared region. Here, we report thermally activated delayed fluorescent organic light-emitting diodes that operate at near-infrared wavelengths with a maximum external quantum efficiency of nearly 10% using a boron difluoride curcuminoid derivative. As well as an effective upconversion from triplet to singlet excited states due to the non-adiabatic coupling effect, this donor-acceptor-donor compound also exhibits efficient amplified spontaneous emission. By controlling the polarity of the active medium, the maximum emission wavelength of the electroluminescence spectrum can be tuned from 700 to 780 nm. This study represents an important advance in near-infrared organic light-emitting diodes and the design of alternative molecular architectures for photonic applications based on thermally activated delayed fluorescence.

Cingulo-opercular activity affects incidental memory encoding for speech in noise.

PubMed

Vaden, Kenneth I; Teubner-Rhodes, Susan; Ahlstrom, Jayne B; Dubno, Judy R; Eckert, Mark A

2017-08-15

Correctly understood speech in difficult listening conditions is often difficult to remember. A long-standing hypothesis for this observation is that the engagement of cognitive resources to aid speech understanding can limit resources available for memory encoding. This hypothesis is consistent with evidence that speech presented in difficult conditions typically elicits greater activity throughout cingulo-opercular regions of frontal cortex that are proposed to optimize task performance through adaptive control of behavior and tonic attention. However, successful memory encoding of items for delayed recognition memory tasks is consistently associated with increased cingulo-opercular activity when perceptual difficulty is minimized. The current study used a delayed recognition memory task to test competing predictions that memory encoding for words is enhanced or limited by the engagement of cingulo-opercular activity during challenging listening conditions. An fMRI experiment was conducted with twenty healthy adult participants who performed a word identification in noise task that was immediately followed by a delayed recognition memory task. Consistent with previous findings, word identification trials in the poorer signal-to-noise ratio condition were associated with increased cingulo-opercular activity and poorer recognition memory scores on average. However, cingulo-opercular activity decreased for correctly identified words in noise that were not recognized in the delayed memory test. These results suggest that memory encoding in difficult listening conditions is poorer when elevated cingulo-opercular activity is not sustained. Although increased attention to speech when presented in difficult conditions may detract from more active forms of memory maintenance (e.g., sub-vocal rehearsal), we conclude that task performance monitoring and/or elevated tonic attention supports incidental memory encoding in challenging listening conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Information and Biological Revolutions: Global Governance Challenges Summary of a Study Group

DTIC Science & Technology

2000-01-01

instruction and organize the classes. This change will come about slowly and then only if it proves to increase learning in the classroom. See Thomas K...dendrites and to form synaptic connections, then help to maintain and regulate synaptic activity responsible for learning and cognitive functions...testosterone may foster violent behavior is by the promotion of positive illusions about competitive ability . 77 Thus, an evolutionary history of raiding

Fermi-LAT Observations of Continued Gamma-ray Activity from Nova ASASSN-16ma

NASA Astrophysics Data System (ADS)

Li, Kwan-Lok; Chomiuk, Laura; Strader, Jay; Cheung, C. C.; Jean, P.; Shore, S. N.; Fermi Large Area Telescope Collaboration

2016-11-01

Following the report of a sudden gamma-ray onset detection of nova ASASSN-16ma coincident with the optical peak of 5.5 mag on November 8 (ATel #9736), ASASSN-16ma was observed to slowly decrease in gamma-rays but has remained bright enough to be detectable with Fermi-LAT over the last 9 days (test statistic, TS > 10 per day, except for November 17 with TS=5).

Implementation and adoption of nationwide electronic health records in secondary care in England: qualitative analysis of interim results from a prospective national evaluation

PubMed Central

Robertson, Ann; Cresswell, Kathrin; Takian, Amirhossein; Petrakaki, Dimitra; Crowe, Sarah; Cornford, Tony; Barber, Nicholas; Avery, Anthony; Fernando, Bernard; Jacklin, Ann; Prescott, Robin; Klecun, Ela; Paton, James; Lichtner, Valentina; Quinn, Casey; Ali, Maryam; Morrison, Zoe; Jani, Yogini; Waring, Justin; Marsden, Kate

2010-01-01

Objectives To describe and evaluate the implementation and adoption of detailed electronic health records in secondary care in England and thereby provide early feedback for the ongoing local and national rollout of the NHS Care Records Service. Design A mixed methods, longitudinal, multisite, socio-technical case study. Setting Five NHS acute hospital and mental health trusts that have been the focus of early implementation efforts and at which interim data collection and analysis are complete. Data sources and analysis Dataset for the evaluation consists of semi-structured interviews, documents and field notes, observations, and quantitative data. Qualitative data were analysed thematically with a socio-technical coding matrix, combined with additional themes that emerged from the data. Main results Hospital electronic health record applications are being developed and implemented far more slowly than was originally envisioned; the top-down, standardised approach has needed to evolve to admit more variation and greater local choice, which hospital trusts want in order to support local activity. Despite considerable delays and frustrations, support for electronic health records remains strong, including from NHS clinicians. Political and financial factors are now perceived to threaten nationwide implementation of electronic health records. Interviewees identified a range of consequences of long term, centrally negotiated contracts to deliver the NHS Care Records Service in secondary care, particularly as NHS trusts themselves are not party to these contracts. These include convoluted communication channels between different stakeholders, unrealistic deployment timelines, delays, and applications that could not quickly respond to changing national and local NHS priorities. Our data suggest support for a “middle-out” approach to implementing hospital electronic health records, combining government direction with increased local autonomy, and for restricting detailed electronic health record sharing to local health communities. Conclusions Experiences from the early implementation sites, which have received considerable attention, financial investment and support, indicate that delivering improved healthcare through nationwide electronic health records will be a long, complex, and iterative process requiring flexibility and local adaptability both with respect to the systems and the implementation strategy. The more tailored, responsive approach that is emerging is becoming better aligned with NHS organisations’ perceived needs and is, if pursued, likely to deliver clinically useful electronic health record systems. PMID:20813822

Nonresolving or slowly resolving pneumonia.

PubMed

Kuru, T; Lynch, J P

1999-09-01

Given the variability in rate of radiographic resolution, it remains controversial to decide when to initiate an invasive diagnostic work-up for nonresolving or slowly resolving pulmonary infiltrates. In immunocompetent patients who present with classical features of CAP (i.e., fever, chills, productive cough, new pulmonary infiltrate), clinical response to therapy is the most important determinant for further diagnostic studies. Within the first few days, persistence or even progression of infiltrates on chest radiographs is not unusual. Defervescence, diminished symptoms, and resolution of leukocytosis strongly support a response to antibiotic therapy, even when chest radiographic abnormalities persist. In this context, observation alone is reasonable, and invasive procedures can be deferred. Serial radiographs and clinical examinations dictate subsequent evaluation. In contrast, when clinical improvement has not occurred and chest radiographs are unchanged or worse, a more aggressive approach is warranted. In this setting, we advise fiberoptic bronchoscopy with BAL and appropriate cultures for bacteria, legionella, fungi, and mycobacteria. When endobronchial anatomy is normal and there is no purulence to suggest infection, TBBs should be done to exclude noninfectious causes (discussed earlier) or infections attributable to mycobacteria or fungi. An aggressive approach is also warranted in patients who are clinically stable or improving when the rate of radiographic resolution is delayed. As discussed earlier, what constitutes excessive delay is controversial, and depends upon the acuity of illness, specific pathogen, extent of involvement (i.e., lobar versus multilobar), comorbidities, and diverse host factors. Stable infiltrates even 2 to 4 weeks after institution of antibiotic therapy does not mandate intervention provided patients are improving clinically. Invasive techniques can also be deferred when unequivocal, albeit incomplete, radiographic resolution can be demonstrated. Lack of at least partial radiographic resolution by 6 weeks, even in asymptomatic patients, however, deserves consideration of alternative causes (e.g., endobronchial obstructing lesions, or noninfectious causes). Fiberoptic bronchoscopy with BAL and TBBs has minimal morbidity and is the preferred initial invasive procedure for detecting endobronchial lesions or substantiating noninfectious causes. The yield of bronchoscopy depends on demographics, radiographic features, and pre-test likelihood. In the absence of specific risk factors, the incidence of obstructing lesions (e.g., bronchogenic carcinomas, bronchial adenomas, obstructive foreign body) is low. Bronchogenic carcinoma is rare in nonsmoking, young (< 50 years) patients but is a legitimate consideration in older patients with a history of tobacco abuse. Non-neoplastic causes (e.g., pulmonary vasculitis, hypersensitivity pneumonia, etc.) should be considered when specific features are present (e.g., hematuria, appropriate epidemiologic exposures). Ancillary serologic tests or biopsies of extrapulmonary sites are invaluable in some cases. In rare instances, surgical (open or VATS) biopsy is necessary to diagnose refractory or non-resolving "pneumonias."

Versatile Molecular Functionalization for Inhibiting Concentration Quenching of Thermally Activated Delayed Fluorescence.

PubMed

Lee, Jiyoung; Aizawa, Naoya; Numata, Masaki; Adachi, Chihaya; Yasuda, Takuma

2017-01-01

Concentration quenching of thermally activated delayed fluorescence is found to be dominated by electron-exchange interactions, as described by the Dexter energy-transfer model. Owing to the short-range nature of the electron-exchange interactions, even a small modulation in the molecular geometric structure drastically affects the concentration-quenching, leading to enhanced solid-state photoluminescence and electroluminescence quantum efficiencies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

O(t-α)-synchronization and Mittag-Leffler synchronization for the fractional-order memristive neural networks with delays and discontinuous neuron activations.

PubMed

Chen, Jiejie; Chen, Boshan; Zeng, Zhigang

2018-04-01

This paper investigates O(t -α )-synchronization and adaptive Mittag-Leffler synchronization for the fractional-order memristive neural networks with delays and discontinuous neuron activations. Firstly, based on the framework of Filippov solution and differential inclusion theory, using a Razumikhin-type method, some sufficient conditions ensuring the global O(t -α )-synchronization of considered networks are established via a linear-type discontinuous control. Next, a new fractional differential inequality is established and two new discontinuous adaptive controller is designed to achieve Mittag-Leffler synchronization between the drive system and the response systems using this inequality. Finally, two numerical simulations are given to show the effectiveness of the theoretical results. Our approach and theoretical results have a leading significance in the design of synchronized fractional-order memristive neural networks circuits involving discontinuous activations and time-varying delays. Copyright © 2018 Elsevier Ltd. All rights reserved.

Donor-σ-Acceptor Motifs: Thermally Activated Delayed Fluorescence Emitters with Dual Upconversion.

PubMed

Geng, Yan; D'Aleo, Anthony; Inada, Ko; Cui, Lin-Song; Kim, Jong Uk; Nakanotani, Hajime; Adachi, Chihaya

2017-12-22

A family of organic emitters with a donor-σ-acceptor (D-σ-A) motif is presented. Owing to the weakly coupled D-σ-A intramolecular charge-transfer state, a transition from the localized excited triplet state ( 3 LE) and charge-transfer triplet state ( 3 CT) to the charge-transfer singlet state ( 1 CT) occurred with a small activation energy and high photoluminescence quantum efficiency. Two thermally activated delayed fluorescence (TADF) components were identified, one of which has a very short lifetime of 200-400 ns and the other a longer TADF lifetime of the order of microseconds. In particular, the two D-σ-A materials presented strong blue emission with TADF properties in toluene. These results will shed light on the molecular design of new TADF emitters with short delayed lifetimes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared with 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial

PubMed Central

Hanauer, Stephen B; Sandborn, William J; Dallaire, Christian; Archambault, André; Yacyshyn, Bruce; Yeh, Chyon; Smith-Hall, Nancy

2007-01-01

BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease. PATIENTS AND METHODS: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline. RESULTS: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated. CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day. PMID:18080055

The slowly reacting mode of combustion of gaseous mixtures in spherical vessels. Part 1: Transient analysis and explosion limits

NASA Astrophysics Data System (ADS)

Liñán, Amable; Moreno-Boza, Daniel; Iglesias, Immaculada; Sánchez, Antonio L.; Williams, Forman A.

2016-11-01

Frank-Kamenetskii's analysis of thermal explosions is revisited, using also a single-reaction model with an Arrhenius rate having a large activation energy, to describe the transient combustion of initially cold gaseous mixtures enclosed in a spherical vessel with a constant wall temperature. The analysis shows two modes of combustion. There is a flameless slowly reacting mode for low wall temperatures or small vessel sizes, when the temperature rise resulting from the heat released by the reaction is kept small by the heat-conduction losses to the wall, so as not to change significantly the order of magnitude of the reaction rate. In the other mode, the slow reaction rates occur only in an initial ignition stage, which ends abruptly when very large reaction rates cause a temperature runaway, or thermal explosion, at a well-defined ignition time and location, thereby triggering a flame that propagates across the vessel to consume the reactant rapidly. Explosion limits are defined, in agreement with Frank-Kamenetskii's analysis, by the limiting conditions for existence of the slowly reacting mode of combustion. In this mode, a quasi-steady temperature distribution is established after a transient reaction stage with small reactant consumption. Most of the reactant is burnt, with nearly uniform mass fraction, in a subsequent long stage during which the temperature follows a quasi-steady balance between the rates of heat conduction to the wall and of chemical heat release. The changes in the explosion limits caused by the enhanced heat-transfer rates associated with buoyant motion are described in an accompanying paper.

Liposome-encapsulated diacyl glycerol and inositol triphosphate-induced delayed oocyte activation and poor development of parthenotes.

PubMed

Nair, Ramya; Manikkath, Jyothsna; Hegde, Aswathi R; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

2017-09-01

To explore the ability of diacyl glycerol (DAG) and inositol triphosphate (IP3), two major secondary messengers in the calcium signaling pathway, in activating oocytes. Oocyte cumulus complex obtained from superovulated Swiss albino mice were incubated in M16 medium with liposome-encapsulated 1,2-Dipalmitoyl-sn-glycerol (LEDAG) and/or IP3 for 3 h. Strontium chloride was used as positive control. The activation potential, ploidy status, and blastocyst rate was calculated. Both DAG and IP3, individually, induced activation in ~98% of oocytes, which was significantly higher (p<0.01) than activation induced by strontium chloride (60%). Delayed pronucleus formation and a higher percentage of diploid parthenotes was observed in oocytes activated with LEDAG and/or IP3. However, these embryos failed to progress beyond the 6-8-cell stage. Only when the medium was supplemented with LEDAG (5 μg/mL) and IP3 (10 μg/mL) could activated oocytes progress till the blastocyst stage (5.26%), which was lower than the blastocyst rate in the positive controls (13.91%). The results of the present study indicate that DAG and IP3 can induce delayed oocyte activation and poor development of parthenotes in vitro.

77 FR 52246 - Clothianidin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

... concern. Clinical signs of neurotoxicity were exhibited in both rats (decreased arousal, motor activity..., delayed sexual maturation and an increase in stillbirths) was observed in the absence of maternal effects... weight gains and FQPA SF = 1X........ day. delayed sexual maturation, decreased absolute thymus weights...

14 CFR 1214.805 - Unforeseen customer delay.

Code of Federal Regulations, 2013 CFR

2013-01-01

... problem pose a threat of delay to the Shuttle launch schedule or critical off-line activities, NASA shall... availability of facilities, equipment, and personnel. In requesting NASA to make such special efforts, the customer shall agree to reimburse NASA the estimated additional cost incurred. ...

14 CFR 1214.805 - Unforeseen customer delay.

Code of Federal Regulations, 2011 CFR

2011-01-01

... problem pose a threat of delay to the Shuttle launch schedule or critical off-line activities, NASA shall... availability of facilities, equipment, and personnel. In requesting NASA to make such special efforts, the customer shall agree to reimburse NASA the estimated additional cost incurred. ...

14 CFR 1214.805 - Unforeseen customer delay.

Code of Federal Regulations, 2012 CFR

2012-01-01

... problem pose a threat of delay to the Shuttle launch schedule or critical off-line activities, NASA shall... availability of facilities, equipment, and personnel. In requesting NASA to make such special efforts, the customer shall agree to reimburse NASA the estimated additional cost incurred. ...

Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms

PubMed Central

Daneshzand, Mohammad; Faezipour, Miad; Barkana, Buket D.

2017-01-01

Deep brain stimulation (DBS) has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD). Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG) waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the performance of DBS devices. PMID:28848417

Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms.

PubMed

Daneshzand, Mohammad; Faezipour, Miad; Barkana, Buket D

2017-01-01

Deep brain stimulation (DBS) has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD). Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG) waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the performance of DBS devices.

Body temperature, activity and melatonin profiles in adults with attention-deficit/hyperactivity disorder and delayed sleep: a case-control study.

PubMed

Bijlenga, Denise; Van Someren, Eus J W; Gruber, Reut; Bron, Tannetje I; Kruithof, I Femke; Spanbroek, Elise C A; Kooij, J J Sandra

2013-12-01

Irregular sleep-wake patterns and delayed sleep times are common in adults with attention-deficit/hyperactivity disorder, but mechanisms underlying these problems are unknown. The present case-control study examined whether circadian abnormalities underlie these sleep problems in a naturalistic home setting. We included 12 medication-naïve patients with attention-deficit/hyperactivity disorder and delayed sleep phase syndrome, and 12 matched healthy controls. We examined associations between sleep/wake rhythm in attention-deficit/hyperactivity disorder and circadian parameters (i.e. salivary melatonin concentrations, core and skin temperatures, and activity patterns) of the patients and controls during five consecutive days and nights. Daily bedtimes were more variable within patients compared with controls (F = 8.19, P < 0.001), but melatonin profiles were equally stable within individuals. Dim-light melatonin onset was about 1.5 h later in the patient group (U = 771, Z = -4.63, P < 0.001). Patients slept about 1 h less on nights before work days compared with controls (F = 11.21, P = 0.002). The interval between dim-light melatonin onset and sleep onset was on average 1 h longer in patients compared with controls (U = 1117, Z = -2.62, P = 0.009). This interval was even longer in patients with extremely late chronotype. Melatonin, activity and body temperatures were delayed to comparable degrees in patients. Overall temperatures were lower in patients than controls. Sleep-onset difficulties correlated with greater distal-proximal temperature gradient (DPG; i.e. colder hands, r(2)  = -0.32, P = 0.028) in patients. Observed day-to-day bedtime variability of individuals with attention-deficit/hyperactivity disorder and delayed sleep phase syndrome were not reflected in their melatonin profiles. Irregular sleep-wake patterns and delayed sleep in individuals with attention-deficit/hyperactivity disorder and delayed sleep phase syndrome are associated with delays and dysregulations of the core and skin temperatures. © 2013 European Sleep Research Society.

A Simulation Based Approach for Contingency Planning for Aircraft Turnaround Operation System Activities in Airline Hubs

NASA Technical Reports Server (NTRS)

Adeleye, Sanya; Chung, Christopher

2006-01-01

Commercial aircraft undergo a significant number of maintenance and logistical activities during the turnaround operation at the departure gate. By analyzing the sequencing of these activities, more effective turnaround contingency plans may be developed for logistical and maintenance disruptions. Turnaround contingency plans are particularly important as any kind of delay in a hub based system may cascade into further delays with subsequent connections. The contingency sequencing of the maintenance and logistical turnaround activities were analyzed using a combined network and computer simulation modeling approach. Experimental analysis of both current and alternative policies provides a framework to aid in more effective tactical decision making.

Lag threads organize the brain’s intrinsic activity

PubMed Central

Mitra, Anish; Snyder, Abraham Z.; Blazey, Tyler; Raichle, Marcus E.

2015-01-01

It has been widely reported that intrinsic brain activity, in a variety of animals including humans, is spatiotemporally structured. Specifically, propagated slow activity has been repeatedly demonstrated in animals. In human resting-state fMRI, spontaneous activity has been understood predominantly in terms of zero-lag temporal synchrony within widely distributed functional systems (resting-state networks). Here, we use resting-state fMRI from 1,376 normal, young adults to demonstrate that multiple, highly reproducible, temporal sequences of propagated activity, which we term “lag threads,” are present in the brain. Moreover, this propagated activity is largely unidirectional within conventionally understood resting-state networks. Modeling experiments show that resting-state networks naturally emerge as a consequence of shared patterns of propagation. An implication of these results is that common physiologic mechanisms may underlie spontaneous activity as imaged with fMRI in humans and slowly propagated activity as studied in animals. PMID:25825720

Dynamically generated patterns in dense suspensions of active filaments

NASA Astrophysics Data System (ADS)

Prathyusha, K. R.; Henkes, Silke; Sknepnek, Rastko

2018-02-01

We use Langevin dynamics simulations to study dynamical behavior of a dense planar layer of active semiflexible filaments. Using the strength of active force and the thermal persistence length as parameters, we map a detailed phase diagram and identify several nonequilibrium phases in this system. In addition to a slowly flowing melt phase, we observe that, for sufficiently high activity, collective flow accompanied by signatures of local polar and nematic order appears in the system. This state is also characterized by strong density fluctuations. Furthermore, we identify an activity-driven crossover from this state of coherently flowing bundles of filaments to a phase with no global flow, formed by individual filaments coiled into rotating spirals. This suggests a mechanism where the system responds to activity by changing the shape of active agents, an effect with no analog in systems of active particles without internal degrees of freedom.

Ensemble codes involving hippocampal neurons are at risk during delayed performance tests.

PubMed

Hampson, R E; Deadwyler, S A

1996-11-26

Multielectrode recording techniques were used to record ensemble activity from 10 to 16 simultaneously active CA1 and CA3 neurons in the rat hippocampus during performance of a spatial delayed-nonmatch-to-sample task. Extracted sources of variance were used to assess the nature of two different types of errors that accounted for 30% of total trials. The two types of errors included ensemble "miscodes" of sample phase information and errors associated with delay-dependent corruption or disappearance of sample information at the time of the nonmatch response. Statistical assessment of trial sequences and associated "strength" of hippocampal ensemble codes revealed that miscoded error trials always followed delay-dependent error trials in which encoding was "weak," indicating that the two types of errors were "linked." It was determined that the occurrence of weakly encoded, delay-dependent error trials initiated an ensemble encoding "strategy" that increased the chances of being correct on the next trial and avoided the occurrence of further delay-dependent errors. Unexpectedly, the strategy involved "strongly" encoding response position information from the prior (delay-dependent) error trial and carrying it forward to the sample phase of the next trial. This produced a miscode type error on trials in which the "carried over" information obliterated encoding of the sample phase response on the next trial. Application of this strategy, irrespective of outcome, was sufficient to reorient the animal to the proper between trial sequence of response contingencies (nonmatch-to-sample) and boost performance to 73% correct on subsequent trials. The capacity for ensemble analyses of strength of information encoding combined with statistical assessment of trial sequences therefore provided unique insight into the "dynamic" nature of the role hippocampus plays in delay type memory tasks.

Solar flux forecasting using mutual information with an optimal delay

NASA Technical Reports Server (NTRS)

Ashrafi, S.; Conway, D.; Rokni, M.; Sperling, R.; Roszman, L.; Cooley, J.

1993-01-01

Solar flux F(sub 10.7) directly affects the atmospheric density, thereby changing the lifetime and prediction of satellite orbits. For this reason, accurate forecasting of F(sub 10.7) is crucial for orbit determination of spacecraft. Our attempts to model and forecast F(sub 10.7) uncovered highly entangled dynamics. We concluded that the general lack of predictability in solar activity arises from its nonlinear nature. Nonlinear dynamics allow us to predict F(sub 10.7) more accurately than is possible using stochastic methods for time scales shorter than a characteristic horizon, and with about the same accuracy as using stochastic techniques when the forecasted data exceed this horizon. The forecast horizon is a function of two dynamical invariants: the attractor dimension and the Lyapunov exponent. In recent years, estimation of the attractor dimension reconstructed from a time series has become an important tool in data analysis. In calculating the invariants of the system, the first necessary step is the reconstruction of the attractor for the system from the time-delayed values of the time series. The choice of the time delay is critical for this reconstruction. For an infinite amount of noise-free data, the time delay can, in principle, be chosen almost arbitrarily. However, the quality of the phase portraits produced using the time-delay technique is determined by the value chosen for the delay time. Fraser and Swinney have shown that a good choice for this time delay is the one suggested by Shaw, which uses the first local minimum of the mutual information rather than the autocorrelation function to determine the time delay. This paper presents a refinement of this criterion and applies the refined technique to solar flux data to produce a forecast of the solar activity.

A model for integrating elementary neural functions into delayed-response behavior.

PubMed

Gisiger, Thomas; Kerszberg, Michel

2006-04-01

It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning), and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task), or recalling from this image another one that has been associated with it during training (delayed-pair association task). The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

Selective involvement of superior frontal cortex during working memory for shapes.

PubMed

Yee, Lydia T S; Roe, Katherine; Courtney, Susan M

2010-01-01

A spatial/nonspatial functional dissociation between the dorsal and ventral visual pathways is well established and has formed the basis of domain-specific theories of prefrontal cortex (PFC). Inconsistencies in the literature regarding prefrontal organization, however, have led to questions regarding whether the nature of the dissociations observed in PFC during working memory are equivalent to those observed in the visual pathways for perception. In particular, the dissociation between dorsal and ventral PFC during working memory for locations versus object identities has been clearly present in some studies but not in others, seemingly in part due to the type of objects used. The current study compared functional MRI activation during delayed-recognition tasks for shape or color, two object features considered to be processed by the ventral pathway for perceptual recognition. Activation for the shape-delayed recognition task was greater than that for the color task in the lateral occipital cortex, in agreement with studies of visual perception. Greater memory-delay activity was also observed, however, in the parietal and superior frontal cortices for the shape than for the color task. Activity in superior frontal cortex was associated with better performance on the shape task. Conversely, greater delay activity for color than for shape was observed in the left anterior insula and this activity was associated with better performance on the color task. These results suggest that superior frontal cortex contributes to performance on tasks requiring working memory for object identities, but it represents different information about those objects than does the ventral frontal cortex.

Lysophosphatidylcholine hydrolases of human erythrocytes, lymphocytes, and brain: Sensitive targets of conserved specificity for organophosphorus delayed neurotoxicants

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

Vose, Sarah C.; Center for Children's Environmental Health Research, School of Public Health, University of California, Berkeley, CA 94720; Holland, Nina T.

2007-10-01

Brain neuropathy target esterase (NTE), associated with organophosphorus (OP)-induced delayed neuropathy, has the same OP inhibitor sensitivity and specificity profiles assayed in the classical way (paraoxon-resistant, mipafox-sensitive hydrolysis of phenyl valerate) or with lysophosphatidylcholine (LysoPC) as the substrate. Extending our earlier observation with mice, we now examine human erythrocyte, lymphocyte, and brain LysoPC hydrolases as possible sensitive targets for OP delayed neurotoxicants and insecticides. Inhibitor profiling of human erythrocytes and lymphocytes gave the surprising result of essentially the same pattern as with brain. Human erythrocyte LysoPC hydrolases are highly sensitive to OP delayed neurotoxicants, with in vitro IC{sub 50} valuesmore » of 0.13-85 nM for longer alkyl analogs, and poorly sensitive to the current OP insecticides. In agricultural workers, erythrocyte LysoPC hydrolyzing activities are similar for newborn children and their mothers and do not vary with paraoxonase status but have high intersample variation that limits their use as a biomarker. Mouse erythrocyte LysoPC hydrolase activity is also of low sensitivity in vitro and in vivo to the OP insecticides whereas the delayed neurotoxicant ethyl n-octylphosphonyl fluoride inhibits activity in vivo at 1-3 mg/kg. Overall, inhibition of blood LysoPC hydrolases is as good as inhibition of brain NTE as a predictor of OP inducers of delayed neuropathy. NTE and lysophospholipases (LysoPLAs) both hydrolyze LysoPC, yet they are in distinct enzyme families with no sequence homology and very different catalytic sites. The relative contributions of NTE and LysoPLAs to LysoPC hydrolysis and clearance from erythrocytes, lymphocytes, and brain remain to be defined.« less

Haem oxygenase delays programmed cell death in wheat aleurone layers by modulation of hydrogen peroxide metabolism

PubMed Central

Wu, Mingzhu; Huang, Jingjing; Xu, Sheng; Ling, Tengfang; Xie, Yanjie; Shen, Wenbiao

2011-01-01

Haem oxygenase-1 (HO-1) confers protection against a variety of oxidant-induced cell and tissue injury in animals and plants. In this report, it is confirmed that programmed cell death (PCD) in wheat aleurone layers is stimulated by GA and prevented by ABA. Meanwhile, HO activity and HO-1 protein expression exhibited lower levels in GA-treated layers, whereas the hydrogen peroxide (H2O2) content was apparently increased. The pharmacology approach illustrated that scavenging or accumulating H2O2 either delayed or accelerated GA-induced PCD. Furthermore, pretreatment with the HO-1 specific inhibitor, zinc protoporphyrin IX (ZnPPIX), before exposure to GA, not only decreased HO activity but also accelerated GA-induced PCD significantly. The application of the HO-1 inducer, haematin, and the enzymatic reaction product of HO, carbon monoxide (CO) aqueous solution, both of which brought about a noticeable induction of HO expression, substantially prevented GA-induced PCD. These effects were reversed when ZnPPIX was added, suggesting that HO in vivo played a role in delaying PCD. Meanwhile, catalase (CAT) and ascorbate peroxidase (APX) activities or transcripts were enhanced by haematin, CO, or bilirubin (BR), the catalytic by-product of HO. This enhancement resulted in a decrease in H2O2 production and a delay in PCD. In addition, the antioxidants butylated hydroxytoluene (BHT), dithiothreitol (DTT), and ascorbic acid (AsA) were able not only to delay PCD but also to mimic the effects of haematin and CO on HO up-regulation. Overall, the above results suggested that up-regulation of HO expression delays PCD through the down-regulation of H2O2 production. PMID:20797999

Stability Switches, Hopf Bifurcations, and Spatio-temporal Patterns in a Delayed Neural Model with Bidirectional Coupling

NASA Astrophysics Data System (ADS)

Song, Yongli; Zhang, Tonghua; Tadé, Moses O.

2009-12-01

The dynamical behavior of a delayed neural network with bi-directional coupling is investigated by taking the delay as the bifurcating parameter. Some parameter regions are given for conditional/absolute stability and Hopf bifurcations by using the theory of functional differential equations. As the propagation time delay in the coupling varies, stability switches for the trivial solution are found. Conditions ensuring the stability and direction of the Hopf bifurcation are determined by applying the normal form theory and the center manifold theorem. We also discuss the spatio-temporal patterns of bifurcating periodic oscillations by using the symmetric bifurcation theory of delay differential equations combined with representation theory of Lie groups. In particular, we obtain that the spatio-temporal patterns of bifurcating periodic oscillations will alternate according to the change of the propagation time delay in the coupling, i.e., different ranges of delays correspond to different patterns of neural activities. Numerical simulations are given to illustrate the obtained results and show the existence of bursts in some interval of the time for large enough delay.

Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

PubMed

Margoles, Lindsay M; Mittal, Rohit; Klingensmith, Nathan J; Lyons, John D; Liang, Zhe; Serbanescu, Mara A; Wagener, Maylene E; Coopersmith, Craig M; Ford, Mandy L

2016-01-01

Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

Dimensionality of brain networks linked to life-long individual differences in self-control.

PubMed

Berman, Marc G; Yourganov, Grigori; Askren, Mary K; Ayduk, Ozlem; Casey, B J; Gotlib, Ian H; Kross, Ethan; McIntosh, Anthony R; Strother, Stephen; Wilson, Nicole L; Zayas, Vivian; Mischel, Walter; Shoda, Yuichi; Jonides, John

2013-01-01

The ability to delay gratification in childhood has been linked to positive outcomes in adolescence and adulthood. Here we examine a subsample of participants from a seminal longitudinal study of self-control throughout a subject's life span. Self-control, first studied in children at age 4 years, is now re-examined 40 years later, on a task that required control over the contents of working memory. We examine whether patterns of brain activation on this task can reliably distinguish participants with consistently low and high self-control abilities (low versus high delayers). We find that low delayers recruit significantly higher-dimensional neural networks when performing the task compared with high delayers. High delayers are also more homogeneous as a group in their neural patterns compared with low delayers. From these brain patterns, we can predict with 71% accuracy, whether a participant is a high or low delayer. The present results suggest that dimensionality of neural networks is a biological predictor of self-control abilities.

Stability analysis for discrete-time stochastic memristive neural networks with both leakage and probabilistic delays.

PubMed

Liu, Hongjian; Wang, Zidong; Shen, Bo; Huang, Tingwen; Alsaadi, Fuad E

2018-06-01

This paper is concerned with the globally exponential stability problem for a class of discrete-time stochastic memristive neural networks (DSMNNs) with both leakage delays as well as probabilistic time-varying delays. For the probabilistic delays, a sequence of Bernoulli distributed random variables is utilized to determine within which intervals the time-varying delays fall at certain time instant. The sector-bounded activation function is considered in the addressed DSMNN. By taking into account the state-dependent characteristics of the network parameters and choosing an appropriate Lyapunov-Krasovskii functional, some sufficient conditions are established under which the underlying DSMNN is globally exponentially stable in the mean square. The derived conditions are made dependent on both the leakage and the probabilistic delays, and are therefore less conservative than the traditional delay-independent criteria. A simulation example is given to show the effectiveness of the proposed stability criterion. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nonselective Currents and Channels in Plasma Membranes of Protoplasts from Coats of Developing Seeds of Bean1

PubMed Central

Zhang, Wen-Hao; Skerrett, Martha; Walker, N. Alan; Patrick, John W.; Tyerman, Stephen D.

2002-01-01

In developing bean (Phaseolus vulgaris) seeds, phloem-imported nutrients move in the symplast from sieve elements to the ground parenchyma cells where they are transported across the plasma membrane into the seed apoplast. To study the mechanisms underlying this transport, channel currents in ground parenchyma protoplasts were characterized using patch clamp. A fast-activating outward current was found in all protoplasts, whereas a slowly activating outward current was observed in approximately 25% of protoplasts. The two currents had low selectivity for univalent cations, but the slow current was more selective for K+ over Cl− (PK:PCl = 3.6–4.2) than the fast current (PK:PCl = 1.8–2.5) and also displayed Ca2+ selectivity. The slow current was blocked by Ba2+, whereas both currents were blocked by Gd3+ and La3+. Efflux of K+ from seed coat halves was inhibited 25% by Gd3+ and La3+ but was stimulated by Ba2+ and Cs+, suggesting that only the fast current may be a component in the pathway for K+ release. An “instantaneous” inward current observed in all protoplasts exhibited similar pharmacology and permeability for univalent cations to the fast outward current. In outside-out patches, two classes of depolarization-activated cation-selective channels were observed: one slowly activating of low conductance (determined from nonstationary noise to be 2.4 pS) and another with conductances 10-fold higher. Both channels occurred at high density. The higher conductance channel in 10 mm KCl had PK:PCl = 2.8. Such nonselective channels in the seed coat ground parenchyma cell could function to allow some of the efflux of phloem-imported univalent ions into the seed apoplast. PMID:11842143

The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis - insights for early bactericidal activity?

PubMed

Pullan, Steven T; Allnutt, Jon C; Devine, Rebecca; Hatch, Kim A; Jeeves, Rose E; Hendon-Dunn, Charlotte L; Marsh, Philip D; Bacon, Joanna

2016-05-17

Pyrazinamide (PZA) plays an essential part in the shortened six-month tuberculosis (TB) treatment course due to its activity against slow-growing and non-replicating organisms. We tested whether PZA preferentially targets slow growing cells of Mycobacterium tuberculosis that could be representative of bacteria that remain after the initial kill with isoniazid (INH), by observing the response of either slow growing or fast growing bacilli to differing concentrations of PZA. M. tuberculosis H37Rv was grown in continuous culture at either a constant fast growth rate (Mean Generation Time (MGT) of 23.1 h) or slow growth rate (69.3 h MGT) at a controlled dissolved oxygen tension of 10 % and a controlled acidity at pH 6.3 ± 0.1. Cultures were exposed to step-wise increases in the concentration of PZA (25 to 500 μgml(-1)) every two MGTs, and bacterial survival was measured. PZA-induced global gene expression was explored for each increase in PZA-concentration, using DNA microarray. At a constant pH 6.3, actively dividing mycobacteria were susceptible to PZA, with similar responses to increasing concentrations of PZA at both growth rates. Three distinct phases of drug response could be distingished for both slow growing (69.3 h MGT) and fast growing (23.1 h MGT) bacilli. A bacteriostatic phase at a low concentration of PZA was followed by a recovery period in which the culture adapted to the presence of PZA and bacteria were actively dividing in steady-state. In contrast, there was a rapid loss of viability at bactericidal concentrations. There was a notable delay in the onset of the recovery period in quickly dividing cells compared with those dividing more slowly. Fast growers and slow growers adapted to PZA-exposure via very similar mechanisms; through reduced gene expression of tRNA, 50S, and 30S ribosomal proteins. PZA had an equivalent level of activity against fast growing and slow growing M. tuberculosis. At both growth rates drug-tolerance to sub-lethal concentrations may have been due to reduced expression of tRNA, 50S, and 30S ribosomal proteins. The findings from this study show that PZA has utility against more than one phenotypic sub-population of bacilli and could be re-assessed for its early bactericidal activity, in combination with other drugs, during TB treatment.

The Effects of Methylphenidate on Discounting of Delayed Rewards in ADHD

PubMed Central

Shiels, Keri; Hawk, Larry W.; Reynolds, Brady; Mazzullo, Rebecca; Rhodes, Jessica; Pelham, William E.; Waxmonsky, James G.; Gangloff, Brian P.

2010-01-01

Impulsivity is a central component of attention-deficit/hyperactivity disorder (ADHD). Delay discounting, or a preference for smaller, immediate rewards over larger, delayed rewards is considered an important aspect of impulsivity, and delay-related impulsivity has been emphasized in etiological models of ADHD. The current study examined whether stimulant medication, an effective treatment for ADHD, reduces discounting of delayed experiential and hypothetical rewards among 49 children (age 9–12 years) with ADHD. Following a practice day, participants completed a 3-day double-blind placebo-controlled acute medication assessment. Active doses were long-acting methylphenidate (Concerta), with the nearest equivalents of 0.3 and 0.6 mg/kg TID immediate-release methylphenidate. On each testing day, participants completed experiential (real-world money in real time) and hypothetical discounting tasks. Relative to placebo, methylphenidate reduced discounting of delayed experiential rewards, but not hypothetical rewards. Broadly consistent with etiological models that emphasize delay-related impulsivity among children with ADHD, these findings provide initial evidence that stimulant medication reduces delay discounting among those with the disorder. The present results also draw attention to task parameters that may influence the sensitivity of various delay discounting measures to medication effects. PMID:19803628

Charged particle induced delayed X-rays (DEX) for the analysis of intermediate and heavy elements

NASA Astrophysics Data System (ADS)

Pillay, A. E.; Erasmus, C. S.; Andeweg, A. H.; Sellschop, J. P. F.; Annegarn, H. J.; Dunn, J.

1988-12-01

The emission of K X-rays from proton-rich and metastable radionuclides, following proton activation of the stable isotopes of the elements of interest, has not been widely used as a means of analysis. The thrust of this paper proposes a nuclear technique using delayed X-rays for the analysis of low concentrations of intermediate and heavy elements. The method is similar to the delayed gamma-ray technique. Proton bombardment induces mainly (p, n) reactions whereas the delayed X-rays originate largely from e --capture and isomeric transition. Samples of rare earth and platinum group elements (PGE), in the form of compacted powders, were irradiated with an 11 MeV proton beam and delayed X-rays detected with a 100 mm 2 Ge detector. Single element spectra for a range of rare earths and PGEs are presented. Analytical conditions are demonstrated for Pd in the range 0.1-5%. Spectra from actual geological samples of a PGE ore, preconcentrated by fire-assay, and monazite are presented. All six platinum group elements are visible and interference-free in a single spectrum, a marked advance on other nuclear techniques for these elements, including PIXE and neutron activation analysis (NAA).

The neuroeconomics of nicotine dependence: a preliminary functional magnetic resonance imaging study of delay discounting of monetary and cigarette rewards in smokers.

PubMed

MacKillop, James; Amlung, Michael T; Wier, Lauren M; David, Sean P; Ray, Lara A; Bickel, Warren K; Sweet, Lawrence H

2012-04-30

Neuroeconomics integrates behavioral economics and cognitive neuroscience to understand the neurobiological basis for normative and maladaptive decision making. Delay discounting is a behavioral economic index of impulsivity that reflects capacity to delay gratification and has been consistently associated with nicotine dependence. This preliminary study used functional magnetic resonance imaging to examine delay discounting for money and cigarette rewards in 13 nicotine dependent adults. Significant differences between preferences for smaller immediate rewards and larger delayed rewards were evident in a number of regions of interest (ROIs), including the medial prefrontal cortex, anterior insular cortex, middle temporal gyrus, middle frontal gyrus, and cingulate gyrus. Significant differences between money and cigarette rewards were generally lateralized, with cigarette choices associated with left hemisphere activation and money choices associated with right hemisphere activation. Specific ROI differences included the posterior parietal cortex, medial and middle frontal gyrus, ventral striatum, temporoparietal cortex, and angular gyrus. Impulsivity as measured by behavioral choices was significantly associated with both individual ROIs and a combined ROI model. These findings provide initial evidence in support of applying a neuroeconomic approach to understanding nicotine dependence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Wigner time delay and spin-orbit activated confinement resonances

NASA Astrophysics Data System (ADS)

Keating, D. A.; Deshmukh, P. C.; Manson, S. T.

2017-09-01

A study of the photoionization of spin-orbit split subshells of high-Z atoms confined in C60 has been performed using the relativistic-random-phase approximation. Specifically, Hg@C60 5p, Rn@C60 6p and Ra@C60 5d were investigated and the near-threshold confinement resonances in the j = l - 1/2 channels were found to engender structures in the j = l + 1/2 cross sections via correlation in the form of interchannel coupling. These structures are termed spin-orbit induced confinement resonances and they are found to profoundly influence the Wigner time delay spectrum resulting in time delays of tens or hundreds of attoseconds along with dramatic swings in time delay over small energy intervals. Pronounced relativistic effects in time delay are also found. These structures, including their manifestation in time delay spectra, are expected to be general phenomena in the photoionization of spin-orbit doublets in confined high-Z atoms.

Left ventricular lead placement in the latest activated region guided by coronary venous electroanatomic mapping.

PubMed

Rad, Masih Mafi; Blaauw, Yuri; Dinh, Trang; Pison, Laurent; Crijns, Harry J; Prinzen, Frits W; Vernooy, Kevin

2015-01-01

Left ventricular (LV) lead placement in the latest activated region is an important determinant of response to cardiac resynchronization therapy (CRT). We investigated the feasibility of coronary venous electroanatomic mapping (EAM) to guide LV lead placement to the latest activated region. Twenty-five consecutive CRT candidates with left bundle-branch block underwent intra-procedural coronary venous EAM using EnSite NavX. A guidewire was used to map the coronary veins during intrinsic activation, and to test for phrenic nerve stimulation (PNS). The latest activated region, defined as the region with an electrical delay >75% of total QRS duration, was located anterolaterally in 18 (basal, n = 10; mid, n = 8) and inferolaterally in 6 (basal, n = 3; mid, n = 3). In one patient, identification of the latest activated region was impeded by limited coronary venous anatomy. In patients with >1 target vein (n = 12), the anatomically targeted inferolateral vein was rarely the vein with maximal electrical delay (n = 3). A concordant LV lead position was achieved in 18 of 25 patients. In six patients, this was hampered by PNS (n = 4), lead instability (n = 1), and coronary vein stenosis (n = 1). Coronary venous EAM can be used intraprocedurally to guide LV lead placement to the latest activated region free of PNS. This approach especially contributes to optimization of LV lead electrical delay in patients with multiple target veins. Conventional anatomical LV lead placement strategy does not target the vein with maximal electrical delay in many of these patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study

PubMed Central

Sundt, Danielle; Gamper, Nikita

2015-01-01

Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na+ channels. A model containing only fast voltage-gated Na+ and delayed-rectifier K+ channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca2+-dependent K+ current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na+-K+ pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca2+-dependent K+ current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain. PMID:26334005

[Knockdown of indoleamine 2, 3-dioxygenase 2 (IDO2)gene inhibits tumor growth and enhances immune function in mice bearing melanoma].

PubMed

Liu, Yanling; Liu, Huan; Xiang, Yingqing; Chen, Xiaoyan; Xu, Ping; Min, Weiping

2017-12-01

Objective To study the role of indoleamine 2, 3-dioxygenase 2 (IDO2) in anti-tumor therapy and its effect on the immune response when using IDO2 as therapeutic target. Methods B16-BL6 cells were used to construct mouse xenografted melanoma model. IDO2-shRNA that contained IDO2-siRNA or control shRNA (scrambled-shRNA) was injected hydrodynamically via the tail vein to treat melanoma. The tumor size was measured by vernier caliper. Flow cytometry was performed to analyze the percentage of regulatory T cells (Tregs), T cell apoptosis rate in draining lymph nodes and the expressions of co-stimulatory molecules on splenic dendritic cells (DCs) from different treatment groups. The lactate dehydrogenase (LDH) assay was used to determine the CD8 + cytotoxic T lymphocyte (CTL) activity. The serum levels of tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) were detected by ELISA. Results In the IDO2-shRNA treated group, the tumor formation time was delayed, tumor grew slowly, and excised tumor mass was significantly reduced. IDO2-shRNA treatment also decreased the percentage of Tregs and T cell apoptosis in draining lymph nodes and increased the expressions of co-stimulatory molecules CD80 and CD86 on splenic DCs. The capacity of CD8 + T cells to kill B16-BL6 cells was enhanced and the serum levels of TNF-α and IFN-γ were upregulated. Conclusion Silencing IDO2 can effectively inhibit the growth of melanoma and improve the anti-tumor immune response in vivo.

Effect of corticosterone on larval growth, antipredator behaviour and metamorphosis of Hylarana indica.

PubMed

Kulkarni, P S; Gramapurohit, N P

2017-09-15

Corticosterone (CORT), a principal glucocorticoid in amphibians, is known to regulate diverse physiological processes including growth and metamorphosis of anuran tadpoles. Environmental stressors activate the neuroendocrine stress axis (hypothalamus-pituitary-interrenal axis, HPI) leading to an acute increase in CORT, which in turn, helps in coping with particular stress. However, chronic increase in CORT can negatively affect other physiological processes such as growth and metamorphosis. Herein, we studied the effect of exogenous CORT on larval growth, antipredator behaviour and metamorphic traits of Hylarana indica. Embryonic exposure to 5 or 20μg/L CORT did not affect their development, hatching duration as well as larval growth and metamorphosis. Exposure of tadpoles to 10 or 20μg/L CORT throughout larval development caused slower growth and development leading to increased body mass at stage 37. However, body and tail morphology of tadpoles was not affected. Interestingly, larval exposure to 5, 10 or 20μg/L CORT enhanced their antipredator response against kairomones in a concentration-dependent manner. Further, larval exposure to increasing concentrations of CORT resulted in the emergence of heavier froglets at 10 and 20μg/L while, delaying metamorphosis at all concentrations. Interestingly, the heavier froglets had shorter hindlimbs and consequently shorter jump distances. Tadpoles exposed to 20μg/L CORT during early, mid or late larval stages grew and developed slowly but tadpole morphology was not altered. Interestingly, exposure during early or mid-larval stages resulted in an enhanced antipredator response. These individuals metamorphosed later but at higher body mass while SVL was unaffected. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes.

PubMed

Song, Yejia; Belardinelli, Luiz

2017-12-14

Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na + current (I NaL ); 3) inhibition of I NaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H 2 O 2 ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I NaL inhibitors GS967 and tetrodotoxin. The magnitude of I NaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the Na V 1.5-channel blocker MTSEA blocked the I NaL . There were no significant differences between myocytes from young and old GPs in L-type Ca 2+ current and the rapidly- and slowly-activating delayed rectifier K + currents, although the inward rectifier K + current was slightly decreased in myocytes from old GPs. H 2 O 2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H 2 O 2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na V 1.5-channel I NaL is responsible for the prolongation of APD, and 3) Inhibition of I NaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

Treatment of Myasthenia Gravis Based on Its Immunopathogenesis

PubMed Central

Kim, Jee Young; Park, Kee Duk

2011-01-01

The prognosis of myasthenia gravis (MG) has improved dramatically due to advances in critical-care medicine and symptomatic treatments. Its immunopathogenesis is fundamentally a T-cell-dependent autoimmune process resulting from loss of tolerance toward self-antigens in the thymus. Thymectomy is based on this immunological background. For MG patients who are inadequately controlled with sufficient symptomatic treatment or fail to achieve remission after thymectomy, remission is usually achieved through the addition of other immunotherapies. These immunotherapies can be classified into two groups: rapid induction and long-term maintenance. Rapid induction therapy includes intravenous immunoglobulin (IVIg) and plasma exchange (PE). These produce improvement within a few days after initiation, and so are useful for acute exacerbation including myasthenic crisis or in the perioperative period. High-dose prednisone has been more universally preferred for remission induction, but it acts more slowly than IVIg and PE, commonly only after a delay of several weeks. Slow tapering of steroids after a high-dose pulse offers a method of maintaining the state of remission. However, because of significant side effects, other immunosuppressants (ISs) are frequently added as "steroid-sparing agents". The currently available ISs exert their immunosuppressive effects by three mechanisms: 1) blocking the synthesis of DNA and RNA, 2) inhibiting T-cell activation and 3) depleting the B-cell population. In addition, newer drugs including antisense molecule, tumor necrosis factor alpha receptor blocker and complement inhibitors are currently under investigation to confirm their effectiveness. Until now, the treatment of MG has been based primarily on experience rather than gold-standard evidence from randomized controlled trials. It is hoped that well-organized studies and newer experimental trials will lead to improved treatments. PMID:22259613

Factors and facts in Hungarian HIV/AIDS epidemic, 1985-2000.

PubMed

Dömök, I

2001-01-01

In Hungary among others there were some special factors, which shaped the outcome of HIV/AIDS epidemic. (1) In the early period of pandemic the "iron curtain" delayed and limited the importation of HIV to Hungary. (2) In 1985, at the time of detection of first HIV infected persons the etiological diagnostic tools were already commercially available and laboratory facilities have been created immediately for HIV antibody tests in networks of blood banks, public health and venereological services. (3) Laboratory facilities together with introduced health regulations resulted in (a) elimination of possibility of nosocomial HIV transmission by blood, blood products and organ transplantation; (b) efficient case finding and contact tracing in population groups potentially playing a significant role in spreading of infection; (c) opportunities for voluntary HIV testing free of charge. (4) Broad scale education and information activities have been developed from the beginning by governmental and non-governmental organizations alike. (5) Parenteral drug abuse did not play a role in spreading of HIV, so far. The above factors resulted in a slowly developing moderate epidemic. The facts are as follows. By the end of 2000 altogether 879 HIV positive (666 male, 100 female and 113 anonymous) persons have been notified, 377 (344 male and 33 female) of whom showed already the characteristic features of AIDS and 229 died. 29% of registered HIV positive persons have been foreigners originating from 56 countries. The cumulative incidence rate of AIDS was 38 per million population. 73% of Hungarian HIV positive persons and 72% of patients with AIDS belonged to transmission group of men having sex with men. The age of HIV positive persons at the time of detection was between 20 and 49 years in 81% and 72% of them resided in or around Budapest.

Recombinant human type II collagen hydrogel provides a xeno-free 3D micro-environment for chondrogenesis of human bone marrow-derived mesenchymal stromal cells.

PubMed

Muhonen, Virpi; Narcisi, Roberto; Nystedt, Johanna; Korhonen, Matti; van Osch, Gerjo J V M; Kiviranta, Ilkka

2017-03-01

Recombinant human type II collagen (rhCII) hydrogel was tested as a xeno-free micro-environment for the chondrogenesis of human bone marrow-derived mesenchymal stromal cells (BM-MSCs). The rhCII hydrogels were seeded with BM-MSCs and cultured in a xeno-free chondro-inductive medium for 14, 28 and 84 days. High-density pellet cultures served as controls. The samples were subjected to biochemical, histological and gene expression analyses. Although the cells deposited glycosaminoglycans into the extracellular space significantly more slowly in the rhCII hydrogels compared to the high-density pellets, a similar potential of matrix deposition was reached by the end of the 84-day culture. At day 28 of culture, the gene expression level for cartilage marker genes (i.e. genes encoding for Sox9 transcription factor, Collagen type II and Aggrecan) were considerably lower in the rhCII hydrogels than in the high-density pellets, but at the end of the 84-day culture period, all the cartilage marker genes analysed were expressed at a similar level. Interestingly, the expression of the matrix metallopeptidases (MMP)-13, MMP-14 and MMP-8, i.e. extracellular collagen network-degrading enzymes, were transiently upregulated in the rhCII hydrogel, indicating active matrix reorganization. This study demonstrated that the rhCII hydrogel functions as a xeno-free platform for BM-MSC chondrogenesis, although the process is delayed. The reversible catabolic reaction evoked by the rhCII hydrogel might be beneficial in graft integration in vivo and pinpoints the need to further explore the use of hydrogels containing recombinant extracellular matrix (ECM) proteins to induce the chondrogenesis of MSCs. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.