Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman
2014-03-01
The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into the brain. © 2013 International Society for Neurochemistry.
Secular trends in ischemic stroke subtypes and stroke risk factors.
Bogiatzi, Chrysi; Hackam, Daniel G; McLeod, A Ian; Spence, J David
2014-11-01
Early diagnosis and treatment of a stroke improves patient outcomes, and knowledge of the cause of the initial event is crucial to identification of the appropriate therapy to maximally reduce risk of recurrence. Assumptions based on historical frequency of ischemic subtypes may need revision if stroke subtypes are changing as a result of recent changes in therapy, such as increased use of statins. We analyzed secular trends in stroke risk factors and ischemic stroke subtypes among patients with transient ischemic attack or minor or moderate stroke referred to an urgent transient ischemic attack clinic from 2002 to 2012. There was a significant decline in low-density lipoprotein cholesterol and blood pressure, associated with a significant decline in large artery stroke and small vessel stroke. The proportion of cardioembolic stroke increased from 26% in 2002 to 56% in 2012 (P<0.05 for trend). Trends remained significant after adjusting for population change. With more intensive medical management in the community, a significant decrease in atherosclerotic risk factors was observed, with a significant decline in stroke/transient ischemic attack caused by large artery atherosclerosis and small vessel disease. As a result, cardioembolic stroke/transient ischemic attack has increased significantly. Our findings suggest that more intensive investigation for cardiac sources of embolism and greater use of anticoagulation may be warranted. © 2014 American Heart Association, Inc.
Internet-based information-seeking behavior for transient ischemic attack.
Abedi, Vida; Mbaye, Marieme; Tsivgoulis, Georgios; Male, Shailesh; Goyal, Nitin; Alexandrov, Andrei V; Zand, Ramin
2015-12-01
In recent years, Internet became an increasingly important tool for accessing health information and is being used more frequently to promote public health. To use Google search data to explore information seeking behavior for transient ischemic attack. We selected two groups of keywords related to transient ischemic attack: 'Transient Ischemic Attack' and 'Mini Stroke'. We obtained all available online search data performed in the United States from the Google search engine for a 10-year span--January 2004 to December 2013. The monthly and daily search data for the selected keywords were analyzed--using moving average--to explore the trends, peaks, and declining effects. There were three significant concurrent peaks in the Google search data for the selected keywords. Each peak was directly associated with media coverage and news headlines related to the incident of transient ischemic attack in a public figure. Following each event, it took three- to seven-days for the search trend to return to its respective average value. Furthermore, the trend was steady for 'Transient Ischemic Attack'; however, the search interest for the keyword 'Mini Stroke' shows a steady increase. The overall search interest for the selected keywords was significantly higher in the southeastern United States. Our study shows that changes in online search behavior can be associated with media coverage of key events (in our case transient ischemic attack) in public figures. These findings suggest that multimedia health promotion campaigns might be more effective, if increased promptly after similar media coverage. © 2015 World Stroke Organization.
Huang, Bing; Zhou, Xiaoya; Wang, Menglong; Li, Xuefei; Zhou, Liping; Meng, Guannan; Wang, Yuhong; Wang, Zhuo; Wang, Songyun; Yu, Lilei; Jiang, Hong
2018-06-01
Blood pressure elevation in response to transient renal nerve stimulation (RNS) has been used to determine the ablation target and endpoint of renal denervation. This study aimed to evaluate the safety of transient RNS in canines with normal or ischaemic hearts. In ten normal (Group 1) and six healed myocardial infarction (HMI) (Group 2) canines, a large-tip catheter was inserted into the left or right renal artery to perform transient RNS. The left stellate ganglion neural activity (LSGNA) and ventricular electrophysiological parameters were measured at baseline and during transient RNS. In another 20 acute myocardial infarction (AMI) canines, RNS (Group 3, n = 10) or sham RNS (Group 4, n = 10) was intermittently (1 min ON and 4 min OFF) performed for 1 h following AMI induction. The LSGNA and AMI-induced ventricular arrhythmias were analysed. In normal and HMI canines, although transient RNS significantly increased the LSGNA and facilitated the action potential duration (APD) alternans, it did not induce any ventricular arrhythmias and did not change the ventricular effective refractory period, APD or maximum slope of the APD restitution curve. In AMI canines, transient RNS significantly exacerbated LSG activation and promoted the incidence of ventricular arrhythmias. Transient RNS did not increase the risk of ventricular arrhythmias in normal or HMI hearts, but it significantly promoted the occurrence of ventricular arrhythmias in AMI hearts. Therefore, electrical stimulation-based renal nerve mapping may be unsafe in AMI patients and in patients with a high risk for malignant ventricular arrhythmias.
Inhibition of Xenobiotic-Degrading Hydrolases by Organophosphinates
1985-07-01
transient increase in the salicylic acid hydrolysis product was observed. Pretreatment with 4-nitrophenyl methyl(phenyl)phosphinate had no significant...h. Hydroly- sis of aspirin was not reduced in pretreated mice, although a transient increase in the salicylic acid hydrolysis product was observed...26 Figure 1. Pathways of aspirin metabolism in mammals: CE is carboxylester hydrolase, SA is salicylic acid, SU is salicyluric
Lee, Jae-Chul; Kim, Yang Hee; Lee, Tae-Kyeong; Kim, In Hye; Cho, Jeong Hwi; Cho, Geum-Sil; Shin, Bich-Na; Park, Joon Ha; Ahn, Ji Hyeon; Shin, Myoung Cheol; Cho, Jun Hwi; Kang, Il Jun; Won, Moo-Ho; Seo, Jeong Yeol
2017-01-01
Ischemic preconditioning (IPC) is induced by exposure to brief durations of transient ischemia, which results in ischemic tolerance to a subsequent longer or lethal period of ischemia. In the present study, the effects of IPC (2 min of transient cerebral ischemia) were examined on immunoreactivity of platelet-derived growth factor (PDGF)-BB and on neuroprotection in the gerbil hippocampal CA1 region following lethal transient cerebral ischemia (LTCI; 5 min of transient cerebral ischemia). IPC was subjected to a 2-min sublethal ischemia and a LTCI was given 5-min transient ischemia. The animals in all of the groups were given recovery times of 1, 2 and 5 days and change in PDGF-BB immunoreactivity was examined as was the neuronal damage/death in the hippocampus induced by LTCI. LTCI induced a significant loss of pyramidal neurons in the hippocampal CA1 region 5 days after LTCI, and significantly decreased PDGF-BB immunoreactivity in the CA1 pyramidal neurons from day 1 after LTCI. Conversely, IPC effectively protected the CA1 pyramidal neurons from LTCI and increased PDGF-BB immunoreactivity in the CA1 pyramidal neurons post-LTCI. In conclusion, the results demonstrated that LTCI significantly altered PDGF-BB immunoreactivity in pyramidal neurons in the hippocampal CA1 region, whereas IPC increased the immunoreactivity. These findings indicated that PDGF-BB may be associated with IPC-mediated neuroprotection. PMID:28627606
Transient Suppression of TGFβ Receptor Signaling Facilitates Human Islet Transplantation
Fischbach, Shane; Song, Zewen; Gaffar, Iljana; Zimmerman, Ray; Wiersch, John; Prasadan, Krishna; Shiota, Chiyo; Guo, Ping; Ramachandran, Sabarinathan; Witkowski, Piotr
2016-01-01
Although islet transplantation is an effective treatment for severe diabetes, its broad application is greatly limited due to a shortage of donor islets. Suppression of TGFβ receptor signaling in β-cells has been shown to increase β-cell proliferation in mice, but has not been rigorously examined in humans. Here, treatment of human islets with a TGFβ receptor I inhibitor, SB-431542 (SB), significantly improved C-peptide secretion by β-cells, and significantly increased β-cell number by increasing β-cell proliferation. In addition, SB increased cell-cycle activators and decreased cell-cycle suppressors in human β-cells. Transplantation of SB-treated human islets into diabetic immune-deficient mice resulted in significant improvement in blood glucose control, significantly higher serum and graft insulin content, and significantly greater increases in β-cell proliferation in the graft, compared with controls. Thus, our data suggest that transient suppression of TGFβ receptor signaling may improve the outcome of human islet transplantation, seemingly through increasing β-cell number and function. PMID:26872091
Radon inhalation protects against transient global cerebral ischemic injury in gerbils.
Kataoka, Takahiro; Etani, Reo; Takata, Yuji; Nishiyama, Yuichi; Kawabe, Atsushi; Kumashiro, Masayuki; Taguchi, Takehito; Yamaoka, Kiyonori
2014-10-01
Although brain disorders are not the main indication for radon therapy, our previous study suggested that radon inhalation therapy might mitigate brain disorders. In this study, we assessed whether radon inhalation protects against transient global cerebral ischemic injury in gerbils. Gerbils were treated with inhaled radon at a concentration of 2,000 Bq/m(3) for 24 h. After radon inhalation, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that transient global cerebral ischemia induced neuronal damage in hippocampal CA1, and the number of damaged neurons was significantly increased compared with control. However, radon treatment inhibited ischemic damage. Superoxide dismutase (SOD) activity in the radon-treated gerbil brain was significantly higher than that in sham-operated gerbils. These findings suggested that radon inhalation activates antioxidative function, especially SOD, thereby inhibiting transient global cerebral ischemic injury in gerbils.
Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible memory deficit.
Takeda, Atsushi; Takada, Shunsuke; Nakamura, Masatoshi; Suzuki, Miki; Tamano, Haruna; Ando, Masaki; Oku, Naoto
2011-01-01
The translocation of synaptic Zn(2+) to the cytosolic compartment has been studied to understand Zn(2+) neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn(2+) in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn(2+) in the hippocampus was induced with clioquinol (CQ), a zinc ionophore. Zn(2+) delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP) in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn(2+) levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl(2) into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn(2+) in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn(2+) and/or the preferential vulnerability to Zn(2+) in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn(2+) in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn(2+). The present study indicates that the transient increase in cytosolic Zn(2+) in CA1 pyramidal neurons reversibly impairs object recognition memory.
Transient Increase in Zn2+ in Hippocampal CA1 Pyramidal Neurons Causes Reversible Memory Deficit
Takeda, Atsushi; Takada, Shunsuke; Nakamura, Masatoshi; Suzuki, Miki; Tamano, Haruna; Ando, Masaki; Oku, Naoto
2011-01-01
The translocation of synaptic Zn2+ to the cytosolic compartment has been studied to understand Zn2+ neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn2+ in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn2+ in the hippocampus was induced with clioquinol (CQ), a zinc ionophore. Zn2+ delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP) in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn2+ levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl2 into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn2+ in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn2+ and/or the preferential vulnerability to Zn2+ in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn2+ in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn2+. The present study indicates that the transient increase in cytosolic Zn2+ in CA1 pyramidal neurons reversibly impairs object recognition memory. PMID:22163318
Milani-Nejad, Nima; Chung, Jae-Hoon; Canan, Benjamin D; Fedorov, Vadim V; Whitson, Bryan A; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L
2018-01-01
Cross-bridge attachment allows force generation to occur, and rate of tension redevelopment (k tr ) is a commonly used index of cross-bridge cycling rate. Tension overshoots have been observed briefly after a slack-restretch k tr maneuver in various species of animal models and humans. In this study, we set out to determine the properties of these overshoots and their possible underlying mechanism. Utilizing human cardiac trabeculae, we have found that tension overshoots are temperature-dependent and that they do not occur at resting states. In addition, we have found that myosin cross-bridge cycle is vital to these overshoots as inhibition of the cycle results in the blunting of the overshoots and the magnitude of the overshoots are dependent on the level of myofilament activation. Lastly, we show that the number of cross-bridges transiently increase during tension overshoots. These findings lead us to conclude that tension overshoots are likely due to a transient enhancement of the recruitment of myosin heads into the cross-bridge cycling, regulated by the myocardium, and with potential physiological significance in determining cardiac output. We show that isolated human myocardium is capable of transiently increasing its maximal force generation capability by increasing cross-bridge recruitment following slack-restretch maneuver. This process can potentially have important implications and significance in cardiac contraction in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.
Energetic ion leakage from foreshock transient cores
NASA Astrophysics Data System (ADS)
Liu, Terry Z.; Angelopoulos, Vassilis; Hietala, Heli
2017-07-01
Earth's foreshock is filled with backstreaming particles that can interact with the ambient solar wind and its discontinuities to form foreshock transients. Many foreshock transients have a core with low dynamic pressure that can significantly perturb the bow shock and the magnetosphere-ionosphere system. Foreshock transients have also been recently recognized as sites of particle acceleration, which may be important for seeding the parent shock with energetic particles. A relevant step of this seeding would be energetic ion leakage into the surrounding foreshock environment. On the other hand, such leakage would also suppress the energetic particle flux contrast across foreshock transients' boundaries masking their perceived contribution to ion energization. To further examine this hypothesis of ion leakage, we report on multipoint case studies of three foreshock transient events selected from a large database. The cases were selected to exemplify, in increasing complexity, the nature and consequences of energetic ion leakage. Ion energy dispersion, observed upstream and/or downstream of the foreshock transients, is explained with a simple, ballistic model of ions leaking from the foreshock transients. Larger energies are required for leaked ions to reach the spacecraft as the distance between the transient and spacecraft increases. Our model, which explains well the observed ion energy dispersion and velocity distributions, can also be used to reveal the shape of the foreshock transients in three dimensions. Our results suggest that ion leakage from foreshock transient cores needs to be accounted for both in statistical studies and in global models of ion acceleration under quasi-parallel foreshock conditions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ye, Sheng; Covino, Timothy P.; Sivapalan, Murugesu
In this paper, we use a dynamic network flow model, coupled with a transient storage zone biogeochemical model, to simulate dissolved nutrient removal processes at the channel network scale. We have explored several scenarios in respect of the combination of rainfall variability, and the biological and geomorphic characteristics of the catchment, to understand the dominant controls on removal and delivery of dissolved nutrients (e.g., nitrate). These model-based theoretical analyses suggested that while nutrient removal efficiency is lower during flood events compared to during baseflow periods, flood events contribute significantly to bulk nutrient removal, whereas bulk removal during baseflow periods ismore » less. This is due to the fact that nutrient supply is larger during flood events; this trend is even stronger in large rivers. However, the efficiency of removal during both periods decreases in larger rivers, however, due to (i) increasing flow velocities and thus decreasing residence time, and (ii) increasing flow depth, and thus decreasing nutrient uptake rates. Besides nutrient removal processes can be divided into two parts: in the main channel and in the hyporheic transient storage zone. When assessing their relative contributions the size of the transient storage zone is a dominant control, followed by uptake rates in the main channel and in the transient storage zone. Increasing size of the transient storage zone with downstream distance affects the relative contributions to nutrient removal of the water column and the transient storage zone, which also impacts the way nutrient removal rates scale with increasing size of rivers. Intra-annual hydrologic variability has a significant impact on removal rates at all scales: the more variable the streamflow is, compared to mean discharge, the less nutrient is removed in the channel network. A scale-independent first order uptake coefficient, ke, estimated from model simulations, is highly dependent on the relative size of the transient storage zone and how it changes in the downstream direction, as well as the nature of hydrologic variability.« less
Zhong, Bao-Liang; Chen, Shu-Lin; Conwell, Yeates
2016-01-01
Objectives Loneliness is a risk factor for poor cognitive function in older adults (OAs), however, to date, no studies have explored whether transient and chronic loneliness have differential effects on OAs’ cognitive function. The present study evaluates the impacts of transient versus chronic loneliness on cognitive function in OAs. Design A 6-year follow-up cohort study. Setting Rural and urban communities of 23 provinces in China. Participants 2995 OAs who were cognitively healthy (the modified Mini-mental State Examination [mMMSE] ≥ 14) and completed the 2005, 2008 and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. Measurements Self-report loneliness and mMMSE. Results Both transient (β=−0.389, t=−2.191, df=2994, P=0.029) and chronic loneliness (β=−0.640, t=−2.109, df=2994, P=0.035) were significantly associated with lower mMMSE scores six years later, net of potential confounding effects of baseline covariates. Sensitivity analyses found that regression coefficients of mMMSE scores on transient loneliness were statistically significant and relatively stable across samples with various levels of cognitive function. In contrast, coefficients of mMMSE scores on chronic loneliness were statistically significant only among samples with normal cognitive function and the absolute values of these coefficients increased with the degree of cognitive health of the analytic sample. In the sample with mMMSE≥21, the coefficient of chronic loneliness was 2.59 times as large as that of transient loneliness (−1.017 versus −0.392). Conclusions Both transient and chronic loneliness are significant predictors of cognitive decline in OAs. Relative to transient loneliness, chronic loneliness has more pronounced negative effects on the brain health of OAs. PMID:26905049
Cholinergic Interneurons Underlie Spontaneous Dopamine Release in Nucleus Accumbens
2017-01-01
The release of dopamine from terminals in the NAc is regulated by a number of factors, including voltage-gated ion channels, D2-autoreceptors, and nAChRs. Cholinergic interneurons (CINs) drive dopamine release through activation of nAChRs on dopamine terminals. Using cyclic voltammetry in mouse brain slices, nAChR-dependent spontaneous dopamine transients and the mechanisms underlying the origin were examined in the NAc. Spontaneous events were infrequent (0.3 per minute), but the rate and amplitude were increased after blocking Kv channels with 4-aminopyridine. Although the firing frequency of CINs was increased by blocking glutamate reuptake with TBOA and the Sk blocker apamin, only 4-aminopyridine increased the frequency of dopamine transients. In contrast, inhibition of CIN firing with the μ/δ selective opioid [Met5]enkephalin (1 μm) decreased spontaneous dopamine transients. Cocaine increased the rate and amplitude of dopamine transients, suggesting that the activity of the dopamine transporter limits the detection of these events. In the presence of cocaine, the rate of spontaneous dopamine transients was further increased after blocking D2-autoreceptors. Blockade of muscarinic receptors had no effect on evoked dopamine release, suggesting that feedback inhibition of acetylcholine release was not involved. Thus, although spontaneous dopamine transients are reliant on nAChRs, the frequency was not strictly governed by the activity of CINs. The increase in frequency of spontaneous dopamine transients induced by cocaine was not due to an increase in cholinergic tone and is likely a product of an increase in detection resulting from decreased dopamine reuptake. SIGNIFICANCE STATEMENT The actions of dopamine in the NAc are thought to be responsible for endogenous reward and the reinforcing properties of drugs of abuse, such as psychostimulants. The present work examines the mechanisms underlying nAChR-induced spontaneous dopamine release. This study demonstrates that spontaneous dopamine release is (1) dependent of the activation of nicotinic receptors, (2) independent on the spontaneous activity of cholinergic interneurons, and (3) that cocaine increased the detection of dopamine transients by prolonging the presence and increasing the diffusion of dopamine in the extracellular space. The release of acetylcholine is therefore responsible for spontaneous dopamine transients, and cocaine augments dopamine tone without altering activity of cholinergic interneurons. PMID:28115487
The distribution of calcium in toad cardiac pacemaker cells during spontaneous firing.
Ju, Y K; Allen, D G
2000-12-01
Isolated, spontaneously active pacemaker cells from the sinus venosus region of the toad heart were loaded with the calcium indicator fluo-3. The cells were examined with a confocal microscope to investigate the distribution of calcium during spontaneous activity. Three classes of calcium-related signals were present. First, intense, localised, time-invariant signals were detected from structures distributed across the cell interior. Based on the insensitivity to saponin and the distribution in the cell, these signals appear to arise from fluo-3 located in the sarcoplasmic reticulum and the nuclear envelope. Second, spatially uniform signals from the cytoplasm were present at rest and showed spontaneous increases in [Ca2+]i which propagated along the cell. These Ca2+ transients were uniform in intensity across the diameter of the cell and we could detect no significant delay in the middle of the cell compared to the edges. However, within the nucleus the Ca2+ transient showed a clear delay compared to the cytoplasm. Third, localised, transient increases in [Ca2+]i (Ca2+ sparks) which did not propagate were also detectable. These could be detected both near the surface membrane and in the interior of the cell and reduced in magnitude and increased in duration in the presence of ryanodine. The frequency of firing of Ca2+ sparks significantly increased in the 200-ms period preceding a spontaneous Ca2+ transient. These results suggest that pacemaker cells contain sarcoplasmic reticulum which is distributed across the cell. The Ca2+ transient is uniform across the cell indicating that near-synchronous release of Ca2+ from the sarcoplasmic reticulum is achieved. Ca2+ sparks occur in pacemaker cells though their role in pacemaker function remains to be elucidated.
Lederballe Pedersen, O; Mikkelsen, E; Lanng Nielsen, J; Christensen, N J
1979-04-17
Chronic treatment with beta-blockers was interrupted abruptly in six patients with arterial hypertension. Three patients, who had experienced symptoms during a previous withdrawal, again complained of transient palpitations, tremor, sweating, headache and general malaise. A significant increase in standing blood pressure (BP) and heart rate (HR) was noted after 24 h. The standing HR reached a maximum after 48 h and had decreased significantly on the 7th day (p less than 0.005). There was a strong tendency to greater increase in standing BP and HR in the patients who experienced symptoms than in those who did not. Plasma concentrations of noradrenaline, adrenaline and prolactin did not change significantly. Thus, beta-blocker withdrawal symptoms are reproducible and are indicative of a transient sympathetic hyperresponse. The increased activity is not likely to be caused by increased production of circulating catecholamines, but rather by increased sensitivity of the beta-receptor.
Analytical Assessment for Transient Stability Under Stochastic Continuous Disturbances
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ju, Ping; Li, Hongyu; Gan, Chun
Here, with the growing integration of renewable power generation, plug-in electric vehicles, and other sources of uncertainty, increasing stochastic continuous disturbances are brought to power systems. The impact of stochastic continuous disturbances on power system transient stability attracts significant attention. To address this problem, this paper proposes an analytical assessment method for transient stability of multi-machine power systems under stochastic continuous disturbances. In the proposed method, a probability measure of transient stability is presented and analytically solved by stochastic averaging. Compared with the conventional method (Monte Carlo simulation), the proposed method is many orders of magnitude faster, which makes itmore » very attractive in practice when many plans for transient stability must be compared or when transient stability must be analyzed quickly. Also, it is found that the evolution of system energy over time is almost a simple diffusion process by the proposed method, which explains the impact mechanism of stochastic continuous disturbances on transient stability in theory.« less
T.R. Jackson; R. Haggerty; S.V. Apte; A. Coleman; K.J. Drost
2012-01-01
Surface transient storage (STS) has functional significance in stream ecosystems because it increases solute interaction with sediments. After volume, mean residence time is the most important metric of STS, but it is unclear how this can be measured accurately or related to other timescales and field-measureable parameters. We studied mean residence time of lateral...
Calcagno, B; Eyles, D; van Alphen, B; van Swinderen, B
2013-01-08
It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the "dopamine ontogeny hypothesis of schizophrenia". To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia.
NASA Astrophysics Data System (ADS)
Huber, A.; Sergienko, G.; Wirtz, M.; Steudel, I.; Arakcheev, A.; Brezinsek, S.; Burdakov, A.; Dittmar, T.; Esser, H. G.; Kreter, A.; Linke, J.; Linsmeier, Ch; Mertens, Ph; Möller, S.; Philipps, V.; Pintsuk, G.; Reinhart, M.; Schweer, B.; Shoshin, A.; Terra, A.; Unterberg, B.
2016-02-01
The impact on the deuterium retention of simultaneous exposure of tungsten to a steady-state plasma and transient cyclic heat loads has been studied in the linear PSI-2 facility with the main objective of qualifying tungsten (W) as plasma-facing material. The transient heat loads were applied by a high-energy laser, a Nd:YAG laser (λ = 1064 nm) with an energy per pulse of up to 32 J and a duration of 1 ms. A pronounced increase in the D retention by a factor of 13 has been observed during the simultaneous transient heat loads and plasma exposure. These data indicate that the hydrogen clustering is enhanced by the thermal shock exposures, as seen on the increased blister size due to mobilization and thermal production of defects during transients. In addition, the significant increase of the D retention during the simultaneous loads could be explained by an increased diffusion of D atoms into the W material due to strong temperature gradients during the laser pulse exposure and to an increased mobility of D atoms along the shock-induced cracks. Only 24% of the retained deuterium is located inside the near-surface layer (d<4 μm). Enhanced blister formation has been observed under combined loading conditions at power densities close to the threshold for damaging. Blisters are not mainly responsible for the pronounced increase of the D retention.
Zitting, A; Savolainen, H
1982-07-01
Rats were injected intraperitoneally (150 mg/kg) with a mixture of nitroglycerin and ethylene glycol dinitrate (1:3). Treatment caused a transient small increase in methemoglobin contents in blood and diminished contents of reduced glutathione in liver and brain. Hepatic cytochrome P-450 concentration and ethoxycoumarin deethylase activity decreased shortly after exposure but later the effect disappeared. Succinate dehydrogenase activity decreased in liver, kidney and brain. In brain, activity of creatine kinase increased significantly and slight increase in hepatic UDPglucuronosyltransferase and epoxide hydrolase activity was observed. Renal ethoxycoumarin activity increased transiently. The results point to interaction of hydrolytically released nitrite with hemoproteins.
Zhong, Bao-Liang; Chen, Shu-Lin; Conwell, Yeates
2016-05-01
Loneliness is a risk factor for poor cognitive function in older adults (OAs); to date, however, no studies have explored whether transient and chronic loneliness have differential effects on OAs' cognitive function. The present study evaluates the impacts of transient versus chronic loneliness on cognitive function in OAs. A 6-year follow-up cohort study. Rural and urban communities of 22 provinces in China. 2,995 OAs who were cognitively healthy (the modified Mini-Mental State Examination [mMMSE] ≥ 14) and completed the 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. Self-report loneliness and mMMSE. Both transient (β = -0.389, t = -2.191, df = 2994, p = 0.029) and chronic loneliness (β = -0.640, t = -2.109, df = 2994, p = 0.035) were significantly associated with lower mMMSE scores 6 years later, net of potential confounding effects of baseline covariates. Sensitivity analyses found that regression coefficients of mMMSE scores on transient loneliness were statistically significant and relatively stable across samples with various levels of cognitive function. In contrast, coefficients of mMMSE scores on chronic loneliness were statistically significant only among samples with normal cognitive function and the absolute values of these coefficients increased with the degree of cognitive health of the analytic sample. In the sample with mMMSE greater than or equal to 21, the coefficient of chronic loneliness was 2.59 times as large as that of transient loneliness (-1.017 versus -0.392). Both transient and chronic loneliness are significant predictors of cognitive decline in OAs. Relative to transient loneliness, chronic loneliness has more pronounced negative effects on the brain health of OAs. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Shigeyasu, Chika; Hirano, Shinichiro; Akune, Yoko; Yamada, Masakazu
2015-09-01
This study was undertaken to determine the effect of topical application of diquafosol tetrasodium on proteins and mucin-like substances from tears of clinically healthy subjects. Tears were collected from both the eyes of 10 healthy volunteers. Diquafosol tetrasodium solution (3%) was applied once to the right eye and 0.9% sodium chloride solution (saline) once to the left eye. Tear samples were collected by Schirmer test strips before application and 5, 15, 30 and 60 min after application. Sialic acid, a marker of mucin-like substances, and major tear proteins including secretory IgA, lactoferrin, lipocalin-1, and lysozyme were measured by high performance liquid chromatography. Levels of total protein, sIgA and lysozyme were transiently decreased in both groups but returned to baseline levels within 15 min after application. The concentration of lactoferrin and lipocalin-1 did not change significantly in both groups. Sialic acid in tears was significantly decreased 5 min after saline application, but significantly increased 5 min after diquafosol application. No significant difference in sialic acid was seen after 15 min in both groups. Topical application of saline and diquafosol resulted in transient decrease of tear proteins possibly due to wash out or dilution effects. In contrast, diquafosol application significantly increased sialic acid, although the effect was transient. This suggests diquafosol stimulates the secretion of mucins from ocular tissues of healthy human subjects.
Saitoh, Yasukazu; Ikeshima, Minoru; Kawasaki, Naho; Masumoto, Aoi; Miwa, Nobuhiko
2016-01-01
In our previous study, we demonstrated that combined treatment with hydrogen (H2) and platinum nanocolloid (Pt-nc) exerted markedly antiproliferative effects on cancer cells compared with each treatment alone. However, because the related mechanisms remain unclear, we investigated carcinostatic mechanisms of the combined treatment with H2 + Pt-nc. Significant suppression of cell proliferation was confirmed at 52 h following combined treatment, and the similar effect was also observed by the 30- or 40-min transient treatment with H2 + Pt-nc. The transient treatments led to changes in cell size and morphology, loss of microvilli, and apoptosis-like cell death at 120 h after treatment. Moreover, transient combined treatment with H2 + Pt-nc induced cell-cycle arrest, as reflected by decreased proportions of G1-phase cells and accumulation of G2/M-phase cells. In contrast, intracellular peroxide levels were temporarily and significantly increased immediately after H2 + Pt-nc treatment but not after treatment with H2 or Pt-nc alone. Additionally, combined treatment-induced carcinostatic effects were significantly diminished in the presence of catalase, and marked hydrogen peroxide (H2O2) generation was confirmed after mixing Pt-nc into cell culture media containing a high concentration of H2. These changes are in agreement with the results that carcinostatic effects were induced after only 40 min of treatment with H2 + Pt-nc. Thus, transient and marked generation of H2O2 is responsible for the carcinostatic effects of combined treatment with H2 + Pt-nc.
Yu, Yan; Oberlaender, Kristin; Bengtson, C Peter; Bading, Hilmar
2017-07-01
Neurons undergo dramatic changes in their gene expression profiles in response to synaptic stimulation. The coupling of neuronal excitation to gene transcription is well studied and is mediated by signaling pathways activated by cytoplasmic and nuclear calcium transients. Despite this, the minimum synaptic activity required to induce gene expression remains unknown. To address this, we used cultured hippocampal neurons and cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH) that allows detection of nascent transcripts in the cell nucleus. We found that a single burst of action potentials, consisting of 24.4±5.1 action potentials during a 6.7±1.9s depolarization of 19.5±2.0mV causing a 9.3±0.9s somatic calcium transient, is sufficient to activate transcription of the immediate early gene arc (also known as Arg3.1). The total arc mRNA yield produced after a single burst-induced nuclear calcium transient was very small and, compared to unstimulated control neurons, did not lead to a significant increase in arc mRNA levels measured using quantitative reverse transcriptase PCR (qRT-PCR) of cell lysates. Significantly increased arc mRNA levels became detectable in hippocampal neurons that had undergone 5-8 consecutive burst-induced nuclear calcium transients at 0.05-0.15Hz. These results indicate that a single burst-induced nuclear calcium transient can activate gene expression and that transcription is rapidly shut off after synaptic stimulation has ceased. Copyright © 2017 Elsevier Ltd. All rights reserved.
Howe, William M; Ji, Jinzhao; Parikh, Vinay; Williams, Sarah; Mocaër, Elisabeth; Trocmé-Thibierge, Caryn; Sarter, Martin
2010-01-01
Impairments in attention are a major component of the cognitive symptoms of neuropsychiatric and neurodegenerative disorders. Using an operant sustained attention task (SAT), including a distractor condition (dSAT), we assessed the putative pro-attentional effects of the selective α4β2* nicotinic acetylcholine receptor (nAChR) agonist S 38232 in comparison with the non-selective agonist nicotine. Neither drug benefited SAT performance. However, in interaction with the increased task demands implemented by distractor presentation, the selective agonist, but not nicotine, enhanced the detection of signals during the post-distractor recovery period. This effect is consistent with the hypothesis that second-long increases in cholinergic activity (‘transients') mediate the detection of cues and that nAChR agonists augment such transients. Electrochemical recordings of prefrontal cholinergic transients evoked by S 38232 and nicotine indicated that the α4β2* nAChR agonist evoked cholinergic transients that were characterized by a faster rise time and more rapid decay than those evoked by nicotine. Blockade of the α7 nAChR ‘sharpens' nicotine-evoked transients; therefore, we determined the effects of co-administration of nicotine and the α7 nAChR antagonist methyllycaconitine on dSAT performance. Compared with vehicle and nicotine alone, this combined treatment significantly enhanced the detection of signals. These results indicate that compared with nicotine, α4β2* nAChR agonists significantly enhance attentional performance and that the dSAT represents a useful behavioral screening tool. The combined behavioral and electrochemical evidence supports the hypothesis that nAChR agonist-evoked cholinergic transients, which are characterized by rapid rise time and fast decay, predict robust drug-induced enhancement of attentional performance. PMID:20147893
Kazumata, Ken; Uchino, Haruto; Tokairin, Kikutaro; Ito, Masaki; Shiga, Tohru; Osanai, Toshiya; Kawabori, Masahito
2018-06-01
Cerebral hyperperfusion complicates the postoperative course of patients with moyamoya disease after direct revascularization surgery. There is no clear distinction between cerebral hyperperfusion syndrome and benign postoperative increase in regional cerebral blood flow (rCBF). The present study aimed to determine clinically relevant changes in rCBF, anatomical correlations, and factors associated with transient neurologic symptoms after revascularization surgery in moyamoya disease. Whole-brain voxel-based perfusion mapping was used to identify regions involved in cerebral hyperperfusion and quantify the changes in 105 hemispheric surgeries with the use of single-photon computed tomography acquired on postoperative day 7. The changes in rCBF were quantitatively analyzed, and associations with cerebral hyperperfusion syndrome were determined. Transient neurologic symptoms appeared with rCBF increase in 37.9% of adults. Speech impairments were associated with an increase in rCBF in the operculo-insula region. Cheiro-oral syndrome was associated with the posterior insula as well as the prefrontal region. A receiver operating curve analysis yielded transient neurologic symptoms with maximum accuracy at >15.5% increase from baseline. Age and preoperative rCBF were independently associated with transient neurologic symptoms (P < 0.001). Areas showing rCBF increase during the experience of transient neurologic symptoms were spatially compatible with the known functional anatomy of the brain. An increase of approximately 15% from baseline was found to be critical, which is a far lower threshold than what has been reported previously. Increasing age was significantly associated with the occurrence of symptomatic hyperperfusion. Furthermore, patients with preserved rCBF also showed symptomatic hyperperfusion. Copyright © 2018 Elsevier Inc. All rights reserved.
Wang, Zhang-lian; Chen, Li-fang; Zhu, Wei-ming
2007-09-01
To observe on the transient analgesic effect of abdominal points transcutaneous electrical nerve stimulation (TENS) combined with abdominal acupuncture according to the holographic theory on pain of neck, shoulder, loin and legs. One hundred and twenty cases of pain of neck, shoulder, loin and legs were randomly divided into 4 groups: abdominal acupuncture TENS group, acupoints TENS group, electroacupuneture (EA) group, non-abdominal acupuncture TENS group, 30 cases in each group. All the cases were treated by the same stimulation parameters, but different stimulation points. The VAS scores were recorded before and after treatment. The VAS scores were significantly different before and after treatment in abdominal acupuncture TENS group (P < 0.01); the total effective rate of the transient analgesic effec t was 96.7% in the abdominal acupuncture TENS group, 93.3% in the acupoints TENS group, 96.7% in the EA group with no significant difference among the 3 groups, but with a very significant difference between the abdominal acupuncture TENS group and the non-abdominal acupunctureTENS group (10.0%), P < 0.01. Abdominal acupuncture TENS has a better transient analgesic effect and can use less stimulation points to increase the analgesic effect.
Effect of hypothermic pulmonary artery flushing on capillary filtration coefficient.
Andrade, R S; Wangensteen, O D; Jo, J K; Tsai, M Y; Bolman, R M
2000-07-27
We previously demonstrated that surfactant dilution and inhibition occur immediately after pulmonary artery flushing with hypothermic modified Euro-Collins solution. Consequently, we speculated that increased capillary permeability contributed to these surfactant changes. To test this hypothesis, we evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary capillary filtration coefficient (Kfc), and additionally performed a biochemical analysis of surfactant. We used a murine isolated, perfused lung model to measure the pulmonary capillary filtration coefficient and hemodynamic parameters, to determine the wet to dry weight ratio, and to evaluate surfactant by biochemical analysis of lung lavage fluid. We defined three study groups. In group I (controls), we harvested lungs without hypothermic pulmonary artery flushing, and measured Kfc immediately. In group II (in situ flush), we harvested lungs after hypothermic pulmonary artery flushing with modified Euro-Collins solution, and then measured Kfc. Experiments in groups I and II were designed to evaluate persistent changes in Kfc after pulmonary artery flushing. In group III (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfc during hypothermic pulmonary artery flushing. Groups I and II did not differ significantly in capillary filtration coefficient and hemodynamics. Group II showed significant alterations on biochemical surfactant analysis and a significant increase in wet-to-dry weight ratio, when compared with group I. In group III, we observed a significant transient increase in capillary filtration coefficient during pulmonary artery flushing. Hypothermic pulmonary artery flushing transiently increases the capillary filtration coefficient, leads to an increase in the wet to dry weight ratio, and induces biochemical surfactant changes. These findings could be explained by the effects of hypothermic modified Euro-Collins solution on pulmonary capillary permeability.
Pierce, Angela N.; Zhang, Zhen; Fuentes, Isabella M.; Wang, Ruipeng; Ryals, Janelle M.; Christianson, Julie A.
2015-01-01
Abstract Experiencing early life stress or injury increases a woman's likelihood of developing vulvodynia and concomitant dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. To investigate the outcome of neonatal vaginal irritation (NVI), female mouse pups were administered intravaginal zymosan on postnatal days 8 and 10 and were assessed as adults for vaginal hypersensitivity by measuring the visceromotor response to vaginal balloon distension (VBD). Western blotting and calcium imaging were performed to measure transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) in the vagina and innervating primary sensory neurons. Serum corticosterone (CORT), mast cell degranulation, and corticotropin-releasing factor receptor 1 (CRF1) expression were measured as indicators of peripheral HPA axis activation. Colorectal and hind paw sensitivity were measured to determine cross-sensitization resulting from NVI. Adult NVI mice had significantly larger visceromotor response during VBD than naive mice. TRPA1 protein expression was significantly elevated in the vagina, and calcium transients evoked by mustard oil (TRPA1 ligand) or capsaicin (TRPV1 ligand) were significantly decreased in dorsal root ganglion from NVI mice, despite displaying increased depolarization-evoked calcium transients. Serum CORT, vaginal mast cell degranulation, and CRF1 protein expression were all significantly increased in NVI mice, as were colorectal and hind paw mechanical and thermal sensitivity. Neonatal treatment with a CRF1 antagonist, NBI 35965, immediately before zymosan administration largely attenuated many of the effects of NVI. These results suggest that NVI produces chronic hypersensitivity of the vagina, as well as of adjacent visceral and distant somatic structures, driven in part by increased HPA axis activation. PMID:26098441
Startup of electrophoresis in a suspension of colloidal spheres.
Chiang, Chia C; Keh, Huan J
2015-12-01
The transient electrophoretic response of a homogeneous suspension of spherical particles to the step application of an electric field is analyzed. The electric double layer encompassing each particle is assumed to be thin but finite, and the effect of dynamic electroosmosis within it is incorporated. The momentum equation for the fluid outside the double layers is solved through the use of a unit cell model. Closed-form formulas for the time-evolving electrophoretic and settling velocities of the particles in the Laplace transform are obtained in terms of the electrokinetic radius, relative mass density, and volume fraction of the particles. The time scale for the development of electrophoresis and sedimentation is significantly smaller for a suspension with a higher particle volume fraction or a smaller particle-to-fluid density ratio, and the electrophoretic mobility at any instant increases with an increase in the electrokinetic particle radius. The transient electrophoretic mobility is a decreasing function of the particle volume fraction if the particle-to-fluid density ratio is relatively small, but it may increase with an increase in the particle volume fraction if this density ratio is relatively large. The particle interaction effect in a suspension on the transient electrophoresis is much weaker than that on the transient sedimentation of the particles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Valent, Francesca; Mariuz, Marika; Liva, Giulia; Bellomo, Fabrizio; De Corti, Daniela; Degan, Stefania; Ferrazzano, Alberto; Brusaferro, Silvio
2016-11-18
Transient exposure with acute effect has been shown to affect the risk of occupational injuries in various industrial settings and at the healthcare workplace. The objective of this study has been to identify transient exposures related to occupational injury risk in an Italian teaching hospital. A case-crossover study was conducted among the employees of the University Hospital of Udine who reported an occupational injury, commuting accident, or incident involving biological risk in a 15-month period in the years 2013 and 2014. The matched-pair interval approach was used to assess the role of acute sleep deprivation whereas the usual frequency approach was used for other 13 transient exposures. Sleep hours were not associated with the risk of injuries whereas a significant risk increase was associated with fatigue, rush, distraction, emergency situations, teaching to or being taught by someone, non-compliant patients, bloody operative/work field, excess noise, complex procedures, and anger. We identified transient exposures that increased the risk of occupational injuries in an Italian teaching hospital, providing indications for interventions to increase workers' safety at the healthcare workplace. Int J Occup Med Environ Health 2016;29(6):1001-1009. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.
Wang, Yu-Feng; Sun, Min-Yu; Hou, Qiuling; Hamilton, Kathryn A
2013-04-01
The neuropeptide vasopressin is crucial to mammalian osmotic regulation. Local hypoosmotic challenge transiently decreases and then increases vasopressin secretion. To investigate mechanisms underlying this transient response, we examined the effects of hypoosmotic challenge on the electrical activity of rat hypothalamic supraoptic nucleus (SON) vasopressin neurons using patch-clamp recordings. We found that 5 min exposure of hypothalamic slices to hypoosmotic solution transiently increased inhibitory postsynaptic current (IPSC) frequency and reduced the firing rate of vasopressin neurons. Recovery occurred by 10 min of exposure, even though the osmolality remained low. The γ-aminobutyric acid (GABA)A receptor blocker, gabazine, blocked the IPSCs and the hypoosmotic suppression of firing. The gliotoxin l-aminoadipic acid blocked the increase in IPSC frequency at 5 min and the recovery of firing at 10 min, indicating astrocytic involvement in hypoosmotic modulation of vasopressin neuronal activity. Moreover, β-alanine, an osmolyte of astrocytes and GABA transporter (GAT) inhibitor, blocked the increase in IPSC frequency at 5 min of hypoosmotic challenge. Confocal microscopy of immunostained SON sections revealed that astrocytes and magnocellular neurons both showed positive staining of vesicular GATs (VGAT). Hypoosmotic stimulation in vivo reduced the number of VGAT-expressing neurons, and increased co-localisation and molecular association of VGAT with glial fibrillary acidic protein that increased significantly by 10 min. By 30 min, neuronal VGAT labelling was partially restored, and astrocytic VGAT was relocated to the ventral portion while it decreased in the somatic zone of the SON. Thus, synergistic astrocytic and neuronal GABAergic inhibition could ensure that vasopressin neuron firing is only transiently suppressed under hypoosmotic conditions. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
NASA Astrophysics Data System (ADS)
Keitel, David
2016-05-01
Non-axisymmetries in rotating neutron stars emit quasi-monochromatic gravitational waves. These long-duration ‘continuous wave’ signals are among the main search targets of ground-based interferometric detectors. However, standard detection methods are susceptible to false alarms from instrumental artefacts that resemble a continuous-wave signal. Past work [Keitel, Prix, Papa, Leaci and Siddiqi 2014, Phys. Rev. D 89 064023] showed that a Bayesian approach, based on an explicit model of persistent single-detector disturbances, improves robustness against such artefacts. Since many strong outliers in semi-coherent searches of LIGO data are caused by transient disturbances that last only a few hours or days, I describe in a recent paper [Keitel D 2015, LIGO-P1500159] how to extend this approach to cover transient disturbances, and demonstrate increased sensitivity in realistic simulated data. Additionally, neutron stars could emit transient signals which, for a limited time, also follow the continuous-wave signal model. As a pragmatic alternative to specialized transient searches, I demonstrate how to make standard semi-coherent continuous-wave searches more sensitive to transient signals. Focusing on the time-scale of a single segment in the semi-coherent search, Bayesian model selection yields a simple detection statistic without a significant increase in computational cost. This proceedings contribution gives a brief overview of both works.
NASA Astrophysics Data System (ADS)
Chen, Hong-Yu; Luo, Lai-Ma; Zan, Xiang; Xu, Qiu; Tokunaga, Kazutoshi; Liu, Jia-Qin; Zhu, Xiao-Yong; Cheng, Ji-Gui; Wu, Yu-Cheng
2018-02-01
The transient thermal shock behaviors of W-ZrC/Sc2O3 composites with different ZrC contents were evaluated using transient thermal shock test by electron and laser beams. The effects of different ZrC doping contents on the surface morphology and thermal shock resistance of W-ZrC/Sc2O3 composites were then investigated. Similarity and difference between effects of electron and laser beam transient heat loading were also discussed in this study. Repeated heat loading resulted in thermal fatigue of the irradiated W-ZrC/Sc2O3 samples by thermal stress, leading to the rough surface morphologies with cracks. After different transient thermal tests, significant surface roughening, cracks, surface melting, and droplet ejection occurred. W-2vol.%Sc2O3 sample has superior thermal properties and greater resistance to surface modifications under transient thermal shock, and with the increasing ZrC content in W alloys, thermal shock resistance of W-Zr/Sc2O3 sample tends to be unsatisfied.
Heredia, María del Puy; Delgado, Carmen; Pereira, Laetitia; Perrier, Romain; Richard, Sylvain; Vassort, Guy; Bénitah, Jean-Pierre; Gómez, Ana María
2005-01-01
Neuropeptide Y (NPY) is the most abundant peptide in the mammalian heart, but its cardiac actions are not fully understood. Here we investigate the effect of NPY in intracellular Ca2+ release, using isolated rat cardiac myocytes and confocal microscopy. Cardiac myocytes were field-stimulated at 1 Hz. The evoked [Ca2+]i transient was of higher amplitude and of faster decay in the presence of 100 nM NPY. Cell contraction was also increased by NPY. We analyzed the occurrence of Ca2+ sparks and their characteristics after NPY application. NPY significantly increased Ca2+ sparks frequency in quiescent cells. The Ca2+ spark amplitude was enhanced by NPY but the other characteristics of Ca2+ sparks were not significantly altered. Because cardiac myocytes express both Y1 and Y2 NPY receptors, we repeated the experiments in the presence of the receptor blockers, BIBP3226 and BIIE0246. We found that Y1 NPY receptor blockade completely inhibited NPY effects on [Ca2+]i transient. PTX-sensitive G-proteins and/or phospholypase C (PLC) have been invoked to mediate NPY effects in other cell types. We tested these two hypotheses. In PTX-treated myocytes NPY was still effective, which suggests that the observed NPY actions are not mediated by PTX-sensitive G-proteins. In contrast, the increase in [Ca2+]i transient by NPY was completely inhibited by the PLC inhibitor U73122. In conclusion, we find that NPY has a positive inotropic effect in isolated rat cardiac myocytes, which involves increase in Ca2+ release after activation of Y1 NPY receptor and subsequent stimulation of PLC.
Olson, Marnie L; Kargacin, Margaret E; Ward, Christopher A; Kargacin, Gary J
2007-06-01
The effects of the phytoestrogens phloretin and phloridzin on Ca(2+) handling, cell shortening, the action potential, and Ca(2+) and K(+) currents in freshly isolated cardiac myocytes from rat ventricle were examined. Phloretin increased the amplitude and area and decreased the rate of decline of electrically evoked Ca(2+) transients in the myocytes. These effects were accompanied by an increase in the Ca(2+) load of the sarcoplasmic reticulum, as determined by the area of caffeine-evoked Ca(2+) transients. An increase in the extent of shortening of the myocytes in response to electrically evoked action potentials was also observed in the presence of phloretin. To further examine possible mechanisms contributing to the observed changes in Ca(2+) handling and contractility, the effects of phloretin on the cardiac action potential and plasma membrane Ca(2+) and K(+) currents were examined. Phloretin markedly increased the action potential duration in the myocytes, and it inhibited the Ca(2+)-independent transient outward K(+) current (I(to)). The inwardly rectifying K(+) current, the sustained outward delayed rectifier K(+) current, and L-type Ca(2+) currents were not significantly different in the presence and absence of phloretin, nor was there any evidence that the Na(+)/Ca(2+) exchanger was affected. The effects of phloretin on Ca(2+) handling in the myocytes are consistent with its effects on I(to). Phloridzin did not significantly alter the amplitude or area of electrically evoked Ca(2+) transients in the myocytes, nor did it have detectable effects on the sarcoplasmic reticulum Ca(2+) load, cell shortening, or the action potential.
Qi, Guo-Yan; Liu, Peng
2013-01-01
Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG) symptoms caused by high-dose steroids pulse therapy. Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT) and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW) were evaluated and compared with the clinical absolute scoring (AS) and relative scoring (RS) system. Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P < 0.000) in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2) significantly smaller (P < 0.05) than in the control group (24.9 ± 2.5). At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9) compared with at TW, although no significant difference compared with the control (9.7 ± 1.1). The TW lasted 1–6 days (mean 3.7) for the treatment group, significantly shorter (P < 0.05) than 2–12 days (mean 7.8) for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%), significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%). Slight side effects (18.75%) included maldigestion and rash in the treatment group. Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy. PMID:24348721
A potential risk of overestimating apparent diffusion coefficient in parotid glands.
Liu, Yi-Jui; Lee, Yi-Hsiung; Chang, Hing-Chiu; Huang, Teng-Yi; Chiu, Hui-Chu; Wang, Chih-Wei; Chiou, Ta-Wei; Hsu, Kang; Juan, Chun-Jung; Huang, Guo-Shu; Hsu, Hsian-He
2015-01-01
To investigate transient signal loss on diffusion weighted images (DWI) and overestimation of apparent diffusion coefficient (ADC) in parotid glands using single shot echoplanar DWI (EPDWI). This study enrolled 6 healthy subjects and 7 patients receiving radiotherapy. All participants received dynamic EPDWI with a total of 8 repetitions. Imaging quality of DWI was evaluated. Probability of severe overestimation of ADC (soADC), defined by an ADC ratio more than 1.2, was calculated. Error on T2WI, DWI, and ADC was computed. Statistical analysis included paired Student t testing and Mann-Whitney U test. A P value less than 0.05 was considered statistically significant. Transient signal loss was visually detected on some excitations of DWI but not on T2WI or mean DWI. soADC occurred randomly among 8 excitations and 3 directions of diffusion encoding gradients. Probability of soADC was significantly higher in radiotherapy group (42.86%) than in healthy group (24.39%). The mean error percentage decreased as the number of excitations increased on all images, and, it was smallest on T2WI, followed by DWI and ADC in an increasing order. Transient signal loss on DWI was successfully detected by dynamic EPDWI. The signal loss on DWI and overestimation of ADC could be partially remedied by increasing the number of excitations.
Weerateerangkul, Punate; Palee, Siripong; Chinda, Kroekkiat; Chattipakorn, Siriporn C; Chattipakorn, Nipon
2012-09-01
Although Kaempferia parviflora extract (KPE) and its flavonoids have positive effects on the nitric oxide (NO) signaling pathway, its mechanisms on the heart are still unclear. Because our previous studies demonstrated that KPE decreased defibrillation efficacy in swine similar to that of sildenafil citrate, the phosphodiesterase-5 inhibitor, it is possible that KPE may affect the cardiac NO signaling pathway. In the present study, the effects of KPE and sildenafil citrate on cyclic guanosine monophosphate (cGMP) level, modulation of cardiac function, and Ca transients in ventricular myocytes were investigated. In a rat model, cardiac cGMP level, cardiac function, and Ca transients were measured before and after treatment with KPE and sildenafil citrate. KPE significantly increased the cGMP level and decreased cardiac function and Ca transient. These effects were similar to those found in the sildenafil citrate-treated group. Furthermore, the nonspecific NOS inhibitor could abolish the effects of KPE and sildenafil citrate on Ca transient. KPE has positive effect on NO signaling in the heart, resulting in an increased cGMP level, similar to that of sildenafil citrate. This effect was found to influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes.
Gu, Lianzhi; Fink, Anne M.; Chowdhury, Shamim A.K.; Geenen, David L.; Piano, Mariann R.
2013-01-01
Aims: Excessive alcohol use in the form of binge drinking is associated with many adverse medical outcomes. Using an animal model, the primary objective of this study was to determine the effects of repeated episodes of binge drinking on myocardial structure, blood pressure (BP) and activation of mitogen-activated protein kinases (MAPKs). The effects of carvedilol, a beta-adrenergic blocker, were also examined in this animal model of binge drinking. Methods: Rats were randomized into three groups: control, binge and binge + carvedilol (20 mg/kg). Animals received intragastric administration of 5 g ethanol/kg in the morning × 4 days (Monday–Thursday) followed by no ethanol on Friday–Sunday. Animals were maintained on the protocol for 5 weeks. BP was measured using radiotelemetry methods. Animals underwent echocardiography at baseline, 2.5 and 5 weeks. Myocardial MAPKs were analyzed at 5 weeks using western blot techniques. Results: Over the course of 5 weeks, binge drinking was associated with significant transient increases in BP that were greater at 4 and 5 weeks compared with earlier time points. Carvedilol treatment significantly attenuated the binge-induced transient increases in BP at 4 and 5 weeks. No significant changes were found in echocardiographic parameters at any time period; however, binge drinking was associated with increased phosphorylation of p38 MAPK, which was blocked by carvedilol treatment. Conclusion: Repeated episodes of binge drinking result in progressive and transient increases in BP, no change in myocardial structure and differential regulation of MAPK activation. PMID:22878590
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hesselbarth, Nico; Pettinelli, Chiara; Gericke, Martin
Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I)more » significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects. - Highlights: • Tamoxifen treatment causes significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations. • Tamoxifen induces browning of subcutaneous AT and increased UCP-1 expression. • Tamoxifen changes adipocyte size distribution, and transient body composition.« less
Chen, Jing; Zhong, Jian; Yu, Hao; Xu, Xingsen; He, Hongbo; Yan, Zhencheng; Scholze, Alexandra; Liu, Daoyan; Zhu, Zhiming; Tepel, Martin
2012-01-01
Increased transient receptor potential canonical type 3 (TRPC3) channels have been observed in patients with essential hypertension. In the present study we tested the hypothesis that increased monocyte migration is associated with increased TRPC3 expression. Monocyte migration assay was performed in a microchemotaxis chamber using chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-α (TNF-α). Proteins were identified by immunoblotting and quantitative in-cell Western assay. The effects of TRP channel-inhibitor 2–aminoethoxydiphenylborane (2-APB) and small interfering RNA knockdown of TRPC3 were investigated. We observed an increased fMLP-induced migration of monocytes from hypertensive patients compared with normotensive control subjects (246±14% vs 151±10%). The TNF-α-induced migration of monocytes in patients with essential hypertension was also significantly increased compared to normotensive control subjects (221±20% vs 138±18%). In the presence of 2-APB or after siRNA knockdown of TRPC3 the fMLP-induced monocyte migration was significantly blocked. The fMLP-induced changes of cytosolic calcium were significantly increased in monocytes from hypertensive patients compared to normotensive control subjects. The fMLP-induced monocyte migration was significantly reduced in the presence of inhibitors of tyrosine kinase and phosphoinositide 3-kinase. We conclude that increased monocyte migration in patients with essential hypertension is associated with increased TRPC3 channels. PMID:22438881
Harada, K; Ide, Y; Tazunoki, Y; Imai, A; Yanagida, M; Kikuchi, Y; Imai, A; Ishii, H; Kawahara, J; Izumi, H; Kusaka, M; Tokiwa, T
1999-07-01
Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.
NASA Technical Reports Server (NTRS)
Richards, W. Lance
1996-01-01
Significant strain-gage errors may exist in measurements acquired in transient-temperature environments if conventional correction methods are applied. As heating or cooling rates increase, temperature gradients between the strain-gage sensor and substrate surface increase proportionally. These temperature gradients introduce strain-measurement errors that are currently neglected in both conventional strain-correction theory and practice. Therefore, the conventional correction theory has been modified to account for these errors. A new experimental method has been developed to correct strain-gage measurements acquired in environments experiencing significant temperature transients. The new correction technique has been demonstrated through a series of tests in which strain measurements were acquired for temperature-rise rates ranging from 1 to greater than 100 degrees F/sec. Strain-gage data from these tests have been corrected with both the new and conventional methods and then compared with an analysis. Results show that, for temperature-rise rates greater than 10 degrees F/sec, the strain measurements corrected with the conventional technique produced strain errors that deviated from analysis by as much as 45 percent, whereas results corrected with the new technique were in good agreement with analytical results.
Parihar, Mansingh; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar
2017-08-01
There is evidence for premature atherosclerosis and systemic arterial stiffening during follow-up of children with Kawasaki disease (KD) and coronary artery abnormalities (CAA). Moreover, patients with KD may also have subclinical myocardial involvement and inhomogeneous ventricular repolarization. The inhomogeneous ventricular repolarization manifests as increased QT dispersion on electrocardiography. There is a paucity of studies in endothelial dysfunction and QT dispersion in children with KD and transient CAA. Twenty children with KD and transient CAA were studied at least 1 year after resolution of CAA. Mean follow-up period between KD onset and enrolment in the study was 53.7 months. Twenty age and sex-matched controls were enrolled. High-resolution B-mode ultrasonography was used to analyze brachial artery dilatation in response to reactive hyperemia (cases and controls) and sublingual nitroglycerine (cases only). Carotid artery intima-media thickness (cIMT) and stiffness index were calculated. The difference between maximum and minimum QTc intervals on 12 lead electrocardiogram was calculated as QTc dispersion (QTcd). No statistically significant difference was noted in percent flow-mediated dilatation of brachial arteries in response to reactive hyperemia between cases (13.31 ± 10.41%) and controls (12.86 ± 7.09%). Sublingual nitroglycerine-mediated dilatation in children with KD was 14.88 ± 12.03%. Mean cIMT was similar in cases (0.036 ± 0.015 cm) and controls (0.035 ± 0.076 cm; p = 0.791). No statistically significant difference between groups was observed in mean QTcd values (0.057 ± 0.018 s vs. 0.059 ± 0.015 s in controls, p = 0.785). No evidence of significant endothelial dysfunction or increased QT dispersion in patients with KD and transient coronary artery abnormalities was found in our cohort when studied at a mean follow-up of 53.7 months. This is reassuring, and indicates that risk of subclinical atherosclerosis and myocarditis in a subset of children with KD and transient coronary artery abnormalities is not significant.
Shen, Changqing; Liu, Fang; Wang, Dong; Zhang, Ao; Kong, Fanrang; Tse, Peter W.
2013-01-01
The condition of locomotive bearings, which are essential components in trains, is crucial to train safety. The Doppler effect significantly distorts acoustic signals during high movement speeds, substantially increasing the difficulty of monitoring locomotive bearings online. In this study, a new Doppler transient model based on the acoustic theory and the Laplace wavelet is presented for the identification of fault-related impact intervals embedded in acoustic signals. An envelope spectrum correlation assessment is conducted between the transient model and the real fault signal in the frequency domain to optimize the model parameters. The proposed method can identify the parameters used for simulated transients (periods in simulated transients) from acoustic signals. Thus, localized bearing faults can be detected successfully based on identified parameters, particularly period intervals. The performance of the proposed method is tested on a simulated signal suffering from the Doppler effect. Besides, the proposed method is used to analyze real acoustic signals of locomotive bearings with inner race and outer race faults, respectively. The results confirm that the periods between the transients, which represent locomotive bearing fault characteristics, can be detected successfully. PMID:24253191
Shen, Changqing; Liu, Fang; Wang, Dong; Zhang, Ao; Kong, Fanrang; Tse, Peter W
2013-11-18
The condition of locomotive bearings, which are essential components in trains, is crucial to train safety. The Doppler effect significantly distorts acoustic signals during high movement speeds, substantially increasing the difficulty of monitoring locomotive bearings online. In this study, a new Doppler transient model based on the acoustic theory and the Laplace wavelet is presented for the identification of fault-related impact intervals embedded in acoustic signals. An envelope spectrum correlation assessment is conducted between the transient model and the real fault signal in the frequency domain to optimize the model parameters. The proposed method can identify the parameters used for simulated transients (periods in simulated transients) from acoustic signals. Thus, localized bearing faults can be detected successfully based on identified parameters, particularly period intervals. The performance of the proposed method is tested on a simulated signal suffering from the Doppler effect. Besides, the proposed method is used to analyze real acoustic signals of locomotive bearings with inner race and outer race faults, respectively. The results confirm that the periods between the transients, which represent locomotive bearing fault characteristics, can be detected successfully.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sevik, James; Wallner, Thomas; Pamminger, Michael
The efficiency improvement and emissions reduction potential of lean and exhaust gas recirculation (EGR)-dilute operation of spark-ignition gasoline engines is well understood and documented. However, dilute operation is generally limited by deteriorating combustion stability with increasing inert gas levels. The combustion stability decreases due to reduced mixture flame speeds resulting in significantly increased combustion initiation periods and burn durations. A study was designed and executed to evaluate the potential to extend lean and EGR-dilute limits using a low-energy transient plasma ignition system. The low-energy transient plasma was generated by nanosecond pulses and its performance compared to a conventional transistorized coilmore » ignition (TCI) system operated on an automotive, gasoline direct-injection (GDI) single-cylinder research engine. The experimental assessment was focused on steady-state experiments at the part load condition of 1500 rpm 5.6 bar indicated mean effective pressure (IMEP), where dilution tolerance is particularly critical to improving efficiency and emission performance. Experimental results suggest that the energy delivery process of the low-energy transient plasma ignition system significantly improves part load dilution tolerance by reducing the early flame development period. Statistical analysis of relevant combustion metrics was performed in order to further investigate the effects of the advanced ignition system on combustion stability. Results confirm that at select operating conditions EGR tolerance and lean limit could be improved by as much as 20% (from 22.7 to 27.1% EGR) and nearly 10% (from λ = 1.55 to 1.7) with the low-energy transient plasma ignition system.« less
Transient Three-Dimensional Side Load Analysis of Out-of-Round Film Cooled Nozzles
NASA Technical Reports Server (NTRS)
Wang, Ten-See; Lin, Jeff; Ruf, Joe; Guidos, Mike
2010-01-01
The objective of this study is to investigate the effect of nozzle out-of-roundness on the transient startup side loads at a high altitude, with an anchored computational methodology. The out-of-roundness could be the result of asymmetric loads induced by hardware attached to the nozzle, asymmetric internal stresses induced by previous tests, and deformation, such as creep, from previous tests. The rocket engine studied encompasses a regeneratively cooled thrust chamber and a film cooled nozzle extension with film coolant distributed from a turbine exhaust manifold. The computational methodology is based on an unstructured-grid, pressure-based computational fluid dynamics formulation, and a transient inlet history based on an engine system simulation. Transient startup computations were performed with the out-of-roundness achieved by four different degrees of ovalization: one perfectly round, one slightly out-of-round, one more out-of-round, and one significantly out-of-round. The results show that the separation-line-jump is the peak side load physics for the round, slightly our-of-round, and more out-of-round cases, and the peak side load increases as the degree of out-of-roundness increases. For the significantly out-of-round nozzle, however, the peak side load reduces to comparable to that of the round nozzle and the separation line jump is not the peak side load physics. The counter-intuitive result of the significantly out-of-round case is found to be related to a side force reduction mechanism that splits the effect of the separation-line-jump into two parts, not only in the circumferential direction and most importantly in time.
Efficacy and Tolerability of Indiplon in Transient Insomnia
Rosenberg, Russell; Roth, Thomas; Scharf, Martin B.; Lankford, D. Alan; Farber, Robert
2007-01-01
Objectives: The efficacy of indiplon was evaluated by polysomnography (PSG) in an experimental model of transient insomnia consisting of the first night effect combined with a 2-hour phase advance. Methods: Healthy volunteers age 21–64 years (N=593; 62% female; mean (± SEM) years, 32±0.39) were randomized to double-blind treatment with a single nighttime dose of indiplon (10 mg or 20 mg) or placebo. PSG assessments included latency to persistent sleep (LPS, primary endpoint) and total sleep time (TST); self-report assessments included sleep quality (SQ); next day residual effects were evaluated by the Digit Symbol Substitution Test (DSST), Symbol Copying Test (SCT), and a Visual Analog Scale of sleepiness (VAS). Results: LPS mean (± SEM) values were significantly reduced on indiplon 10 mg (21.2±1.5 minutes) and indiplon 20 mg (16.8±1.1 minutes) compared to placebo (33.1±2.5minutes; p <0.0001 for both comparisons to placebo). TST mean (± SEM) values were significantly increased on indiplon 10 mg (414.5±3.9 minutes) and indiplon 20 mg (423.5±3.1 minutes) compared to placebo (402.9±3.9 minutes; p <0.005 for the 10 mg dose; p <0.0001 for the 20 mg dose). SQ was also significantly improved on both doses. There were no differences between indiplon and placebo on next day DSST, SCT, or VAS. Conclusions: Indiplon was effective in inducing sleep, increasing sleep duration, and improving overall sleep quality without next day residual effects in healthy volunteers in a model of transient insomnia. Citation: Rosenberg R; Roth T; Scharf MB et al. Efficacy and tolerability of indiplon in transient insomnia. J Clin Sleep Med 2007;3(4):374-379. PMID:17694726
Sangkatumvong, Suvimol; Khoo, Michael C. K.; Kato, Roberta; Detterich, Jon A.; Bush, Adam; Keens, Thomas G.; Meiselman, Herbert J.; Wood, John C.
2011-01-01
Rationale: Sickle cell disease is an inherited blood disorder characterized by vasoocclusive crises. Although hypoxia and pulmonary disease are known risk factors for these crises, the mechanisms that initiate vasoocclusive events are not well known. Objectives: To study the relationship between transient hypoxia, respiration, and microvascular blood flow in patients with sickle cell. Methods: We established a protocol that mimics nighttime hypoxic episodes and measured microvascular blood flow to determine if transient hypoxia causes a decrease in microvascular blood flow. Significant desaturations were induced safely by five breaths of 100% nitrogen. Measurements and Main Results: Desaturation did not induce change in microvascular perfusion; however, it induced substantial transient parasympathetic activity withdrawal in patients with sickle cell disease, but not controls subjects. Marked periodic drops in peripheral microvascular perfusion, unrelated to hypoxia, were triggered by sighs in 11 of 11 patients with sickle cell and 8 of 11 control subjects. Although the sigh frequency was the same in both groups, the probability of a sigh inducing a perfusion drop was 78% in patients with sickle cell and 17% in control subjects (P < 0.001). Evidence for sigh-induced sympathetic nervous system dominance was seen in patients with sickle cell (P < 0.05), but was not significant in control subjects. Conclusions: These data demonstrate significant disruption of autonomic nervous system balance, with marked parasympathetic withdrawal in response to transient hypoxia. They draw attention to an enhanced autonomic nervous system–mediated sigh–vasoconstrictor response in patients with sickle cell that could increase red cell retention in the microvasculature, promoting vasoocclusion. PMID:21616995
Design and Implementation of a Thermal Load Reduction System in a Hyundai PHEV
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kreutzer, Cory J; Rugh, John P
Increased market penetration of electric drive vehicles (EDVs) requires overcoming a number of hurdles including limited vehicle range and the elevated cost of EDVs as compared to conventional vehicles. Climate control loads have a significant impact on range, cutting it by over 50% in both cooling and heating conditions. In order to minimize the impact of climate control on EDV range, the National Renewable Energy Laboratory has partnered with Hyundai America and key industry partners to quantify the performance of thermal load reduction technologies on a Hyundai Sonata PHEV. Technologies that impact vehicle cabin heating in cold weather conditions andmore » cabin cooling in warm weather conditions were evaluated. Tests included thermal transient and steady-state periods for all technologies, including the development of a new test methodology to evaluate the performance of occupant thermal conditioning. Heated surfaces and increased insulation demonstrated significant reductions in energy use from steady-state heating, including a 29% - 59% reduction from heated surfaces. Solar control glass packages demonstrated significant reductions in energy use for both transient and steady-state cooling, with up to a 42% reduction in transient and 12.8% reduction in steady-state energy use for the packages evaluated. Technologies that demonstrated significant climate control load reduction were selected for incorporation into a complete thermal load reduction package. The complete package is set to be evaluated in the second phase of the ongoing project.« less
The Catalina Sky Survey for Near-Earth Objects
NASA Astrophysics Data System (ADS)
Christensen, E.
The Catalina Sky Survey (CSS) specializes in the detection of the closest transients in our transient universe: near-Earth objects (NEOs). CSS is the leading NEO survey program since 2005, with a discovery rate of 500-600 NEOs per year. This rate is set to substantially increase starting in 2014 with the deployment of wider FOV cameras at both survey telescopes, while a proposed 3-telescope system in Chile would provide a new and significant capability in the Southern Hemisphere beginning as early as 2015. Elements contributing to the success of CSS may be applied to other surveys, and include 1) Real-time processing, identification, and reporting of interesting transients; 2) Human-assisted validation to ensure a clean transient stream that is efficient to the limits of the system (˜ 1σ); 3) an integrated follow-up capability to ensure threshold or high-priority transients are properly confirmed and followed up. Additionally, the open-source nature of the CSS data enables considerable secondary science (i.e. CRTS), and CSS continues to pursue collaborations to maximize the utility of the data.
NASA Astrophysics Data System (ADS)
Zhao, X.; Chang, Y.; Peng, F.; Wu, J.
2016-12-01
Study of solute transport in karst conduit is of great significance for prediction and prevention of groundwater pollution in southwest karst region. Solute transport in karst conduit is strongly influenced by pools which often develop along karst conduit. In order to investigate the effect of transient storage within pools on solute transport in the conduit, a pool-pipe system was built in the laboratory and some tracer tests were performed in various flow conditions to characterize the solute transport in different pool-pipe structures. The Qtracer2 program was used to obtain solute transport parameters. We used retardation coefficient R to characterize the difference between the 1-D analytical solution of the classical advection-dispersion equation and experimental results. The experimental results reveal that the concentration peak decreases with the number of pools whereas the dispersion coefficient and dispersivity increase gradually. Adding transient storage increases retardation as tailing of the breakthrough curve(BTC) is growing with the number of pools. This demonstrates that transient storage within pools is transformed to retardation. The symmetrical pool has longer tails compared to the asymmetrical pool. The concentration peak lag behind significantly due to the asymmetrical pool. A decrease in dispersivity and tailing of the BTC is observed in all pipes with the increase of flow velocities. The 1-D analytical solution of the classical advection-dispersion equation is well fitted to BTC of a single pipe in maximum flow velocity but is poorly fitted to other BTCs with appreciable tails. Therefore, it requires an appropriate model to explain tailing of the BTC. The conclusion has important significance for understanding of solute transport process in karst conduit. Future work will focus on using the appropriate model to explain tailing of the BTC.
Do osmotic forces play a role in the uptake of water by human skin?
van Kemenade, Patricia M; Houben, Mark M J; Huyghe, Jacques M; Douven, Lucien F A
2004-05-01
To describe the water and ion transport through the skin under different conditions, we developed a three-component mixture model. This model has proven to describe the transient change in transepidermal water loss (TEWL) after a change in relative humidity and the result of damage to the skin. Osmotic forces arc present in the model. To assess the influence of osmotic forces on the water uptake of the skin, we investigated transient TEWL values after 1 h application of salt solutions of different molarities (0, 1, and 4 M NaCl). Filters saturated with 0, 1, and 4 M NaCl solution were applied for 1 h under occlusion. TEWL was measured 50-90 min after removal of the solution. The transient water loss curves were fit with an exponential function. The area under the fitted curve was calculated and regarded as a measure for the amount of extra water absorbed in the skin. For all molarities, TEWL is increased immediately after removal of the solution. In time, this increase decays until pre-application values are reached again. The rate of decrease differs significantly for all three molarities. Ninety-five per cent of the increase has been reversed after 30, 19, and 6 min for the 0, 1, and 4 M case, respectively. The amount of water absorbed differs significantly between the three molarities 7.3+/-2.0; 3.9+/-1.0; 2.0+/-0.5 g/m(2), respectively. In all cases, there was an increase in TEWL immediately after removal of the solution. The significant differences in decay time and amount of water absorbed between the three molarities indicate that osmotic forces do play an important role in the water uptake.
Greyling, Arno; Schreuder, Tim H A; Landman, Thijs; Draijer, Richard; Verheggen, Rebecca J H M; Hopman, Maria T E; Thijssen, Dick H J
2015-03-01
Hyperglycemia, commonly present after a meal, causes transient impairment in endothelial function. We examined whether increases in blood flow (BF) protect against the hyperglycemia-mediated decrease in endothelial function in healthy subjects and patients with type 2 diabetes mellitus (T2DM). Ten healthy subjects and 10 age- and sex-matched patients with T2DM underwent simultaneous bilateral assessment of brachial artery endothelial function by means of flow-mediated dilation (FMD) using high-resolution echo-Doppler. FMD was examined before and 60, 120, and 150 min after a 75-g oral glucose challenge. We unilaterally manipulated BF by heating one arm between minute 30 and minute 60. Oral glucose administration caused a statistically significant, transient increase in blood glucose in both groups (P < 0.001). Forearm skin temperature, brachial artery BF, and shear rate significantly increased in the heated arm (P < 0.001), and to a greater extent compared with the nonheated arm in both groups (interaction effect P < 0.001). The glucose load caused a transient decrease in FMD% (P < 0.05), whereas heating significantly prevented the decline (interaction effect P < 0.01). Also, when correcting for changes in diameter and shear rate, we found that the hyperglycemia-induced decrease in FMD can be prevented by local heating (P < 0.05). These effects on FMD were observed in both groups. Our data indicate that nonmetabolically driven elevation in BF and shear rate can similarly prevent the hyperglycemia-induced decline in conduit artery endothelial function in healthy volunteers and in patients with type 2 diabetes. Additional research is warranted to confirm that other interventions that increase BF and shear rate equally protect the endothelium when challenged by hyperglycemia. Copyright © 2015 the American Physiological Society.
Dan, Yinghui; Zhang, Song; Zhong, Heng; Yi, Hochul; Sainz, Manuel B
2015-02-01
Agrobacterium tumefaciens caused tissue browning leading to subsequent cell death in plant transformation and novel anti-oxidative compounds enhanced Agrobacterium -mediated plant transformation by mitigating oxidative stress. Browning and death of cells transformed with Agrobacterium tumefaciens is a long-standing and high impact problem in plant transformation and the agricultural biotechnology industry, severely limiting the production of transgenic plants. Using our tomato cv. MicroTom transformation system, we demonstrated that Agrobacterium caused tissue browning (TB) leading to subsequent cell death by our correlation study. Without an antioxidant (lipoic acid, LA) TB was severe and associated with high levels of GUS transient expression and low stable transformation frequency (STF). LA addition shifted the curve in that most TB was intermediate and associated with the highest levels of GUS transient expression and STF. We evaluated 18 novel anti-oxidative compounds for their potential to enhance Agrobacterium-mediated transformation, by screening for TB reduction and monitoring GUS transient expression. Promising compounds were further evaluated for their effect on MicroTom and soybean STF. Among twelve non-antioxidant compounds, seven and five significantly (P < 0.05) reduced TB and increased STF, respectively. Among six antioxidants four of them significantly reduced TB and five of them significantly increased STF. The most efficient compound found to increase STF was melatonin (MEL, an antioxidant). Optimal concentrations and stages to use MEL in transformation were determined, and Southern blot analysis showed that T-DNA integration was not affected by MEL. The ability of diverse compounds with different anti-oxidative mechanisms can reduce Agrobacterium-mediated TB and increase STF, strongly supporting that oxidative stress is an important limiting factor in Agrobacterium-mediated transformation and the limiting factor can be controlled by these compounds at different levels.
Marshall, Iain J; Wang, Yanzhong; McKevitt, Christopher; Rudd, Anthony G; Wolfe, Charles D A
2013-07-01
Vascular risk factors are suboptimally managed internationally. This study investigated time trends in risk factors diagnosed before stroke and their treatment, and factors associated with appropriate medication use. A total of 4416 patients with a first stroke were registered in the population-based South London Stroke Register from 1995 to 2011. Previously diagnosed risk factors and usual medications were collected from patients' primary care and hospital records. Trends and associations were assessed using multivariate logistic regression. Seventy-two percent of patients were diagnosed previously with 1 or more risk factors; 30% had diagnosed risk factors that were untreated. Hypercholesterolemia increased significantly during the study period; myocardial infarction and transient ischemic attack prevalences decreased. Antiplatelet prescription increased in atrial fibrillation (AF), myocardial infarction, and transient ischemic attack (AF, 37%-51%, P<0.001; myocardial infarction, 48%-69%, P<0.001; transient ischemic attack, 49%-61%, P=0.015). Anticoagulant prescription for AF showed a nonsignificant increase (12%-23%; P=0.059). Fewer older patients with AF were prescribed anticoagulants (age, >85 versus <65 years; adjusted relative risk, 0.19; 95% confidence interval, 0.08-0.41). Black ethnicity (adjusted relative risk, 1.17; 95% confidence interval, 1.10-1.23) and female sex (adjusted relative risk, 1.09; 95% confidence interval, 1.03-1.15) were associated with increased antihypertensive drug prescription; other medications did not vary by ethnicity or sex. Antiplatelet and cholesterol-lowering treatment prescribing have improved significantly over time; however, only a minority with AF received anticoagulants, and this did not improve significantly. Overall, 30% of strokes occurred in patients with previously diagnosed but untreated risk factors.
Experimental fault characterization of a neural network
NASA Technical Reports Server (NTRS)
Tan, Chang-Huong
1990-01-01
The effects of a variety of faults on a neural network is quantified via simulation. The neural network consists of a single-layered clustering network and a three-layered classification network. The percentage of vectors mistagged by the clustering network, the percentage of vectors misclassified by the classification network, the time taken for the network to stabilize, and the output values are all measured. The results show that both transient and permanent faults have a significant impact on the performance of the measured network. The corresponding mistag and misclassification percentages are typically within 5 to 10 percent of each other. The average mistag percentage and the average misclassification percentage are both about 25 percent. After relearning, the percentage of misclassifications is reduced to 9 percent. In addition, transient faults are found to cause the network to be increasingly unstable as the duration of a transient is increased. The impact of link faults is relatively insignificant in comparison with node faults (1 versus 19 percent misclassified after relearning). There is a linear increase in the mistag and misclassification percentages with decreasing hardware redundancy. In addition, the mistag and misclassification percentages linearly decrease with increasing network size.
Slow-Down in Diffusion in Crowded Protein Solutions Correlates with Transient Cluster Formation.
Nawrocki, Grzegorz; Wang, Po-Hung; Yu, Isseki; Sugita, Yuji; Feig, Michael
2017-12-14
For a long time, the effect of a crowded cellular environment on protein dynamics has been largely ignored. Recent experiments indicate that proteins diffuse more slowly in a living cell than in a diluted solution, and further studies suggest that the diffusion depends on the local surroundings. Here, detailed insight into how diffusion depends on protein-protein contacts is presented based on extensive all-atom molecular dynamics simulations of concentrated villin headpiece solutions. After force field adjustments in the form of increased protein-water interactions to reproduce experimental data, translational and rotational diffusion was analyzed in detail. Although internal protein dynamics remained largely unaltered, rotational diffusion was found to slow down more significantly than translational diffusion as the protein concentration increased. The decrease in diffusion is interpreted in terms of a transient formation of protein clusters. These clusters persist on sub-microsecond time scales and follow distributions that increasingly shift toward larger cluster size with increasing protein concentrations. Weighting diffusion coefficients estimated for different clusters extracted from the simulations with the distribution of clusters largely reproduces the overall observed diffusion rates, suggesting that transient cluster formation is a primary cause for a slow-down in diffusion upon crowding with other proteins.
Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient
Shimojima, Masaya; Yuasa, Shinsuke; Motoda, Chikaaki; Yozu, Gakuto; Nagai, Toshihiro; Ito, Shogo; Lachmann, Mark; Kashimura, Shin; Takei, Makoto; Kusumoto, Dai; Kunitomi, Akira; Hayashiji, Nozomi; Seki, Tomohisa; Tohyama, Shugo; Hashimoto, Hisayuki; Kodaira, Masaki; Egashira, Toru; Hayashi, Kenshi; Nakanishi, Chiaki; Sakata, Kenji; Yamagishi, Masakazu; Fukuda, Keiichi
2017-01-01
Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transient is partly independent of the cytosolic Ca2+ transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca2+ homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca2+ transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca2+ transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca2+ transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca2+ transient. Thus, emerin and the nuclear Ca2+ transient are possible therapeutic targets in heart failure and EDMD. PMID:28290476
Ejaz, Sohail; Emmrich, Julius V; Sitnikov, Sergey L; Hong, Young T; Sawiak, Stephen J; Fryer, Tim D; Aigbirhio, Franklin I; Williamson, David J; Baron, Jean-Claude
2016-03-01
'True' transient ischaemic attacks are characterized not only clinically, but also radiologically by a lack of corresponding changes on magnetic resonance imaging. During a transient ischaemic attack it is assumed that the affected tissue is penumbral but rescued by early spontaneous reperfusion. There is, however, evidence from rodent studies that even brief focal ischaemia not resulting in tissue infarction can cause extensive selective neuronal loss associated with long-lasting sensorimotor impairment but normal magnetic resonance imaging. Selective neuronal loss might therefore contribute to the increasingly recognized cognitive impairment occurring in patients with transient ischaemic attacks. It is therefore relevant to consider treatments to reduce brain damage occurring with transient ischaemic attacks. As penumbral neurons are threatened by markedly constrained oxygen delivery, improving the latter by increasing arterial O2 content would seem logical. Despite only small increases in arterial O2 content, normobaric oxygen therapy experimentally induces significant increases in penumbral O2 pressure and by such may maintain the penumbra alive until reperfusion. Nevertheless, the effects of normobaric oxygen therapy on infarct volume in rodent models have been conflicting, although duration of occlusion appeared an important factor. Likewise, in the single randomized trial published to date, early-administered normobaric oxygen therapy had no significant effect on clinical outcome despite reduced diffusion-weighted imaging lesion growth during therapy. Here we tested the hypothesis that normobaric oxygen therapy prevents both selective neuronal loss and sensorimotor deficits in a rodent model mimicking true transient ischaemic attack. Normobaric oxygen therapy was applied from the onset and until completion of 15 min distal middle cerebral artery occlusion in spontaneously hypertensive rats, a strain representative of the transient ischaemic attack-prone population. Whereas normoxic controls showed normal magnetic resonance imaging but extensive cortical selective neuronal loss associated with microglial activation (present both at Day 14 in vivo and at Day 28 post-mortem) and marked and long-lasting sensorimotor deficits, normobaric oxygen therapy completely prevented sensorimotor deficit (P < 0.02) and near-completely Day 28 selective neuronal loss (P < 0.005). Microglial activation was substantially reduced at Day 14 and completely prevented at Day 28 (P = 0.002). Our findings document that normobaric oxygen therapy administered during ischaemia nearly completely prevents the neuronal death, microglial inflammation and sensorimotor impairment that characterize this rodent true transient ischaemic attack model. Taken together with the available literature, normobaric oxygen therapy appears a promising therapy for short-lasting ischaemia, and is attractive clinically as it could be started at home in at-risk patients or in the ambulance in subjects suspected of transient ischaemic attack/early stroke. It may also be a straightforward adjunct to reperfusion therapies, and help prevent subtle brain damage potentially contributing to long-term cognitive and sensorimotor impairment in at-risk populations. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
NASA Astrophysics Data System (ADS)
Kawo, Nafyad Serre; Zhou, Yangxiao; Magalso, Ronnell; Salvacion, Lasaro
2018-05-01
A coupled simulation-optimization approach to optimize an artificial-recharge-pumping system for the water supply in the Maghaway Valley, Cebu, Philippines, is presented. The objective is to maximize the total pumping rate through a system of artificial recharge and pumping while meeting constraints such as groundwater-level drawdown and bounds on pumping rates at each well. The simulation models were coupled with groundwater management optimization to maximize production rates. Under steady-state natural conditions, the significant inflow to the aquifer comes from river leakage, whereas the natural discharge is mainly the subsurface outflow to the downstream area. Results from the steady artificial-recharge-pumping simulation model show that artificial recharge is about 20,587 m3/day and accounts for 77% of total inflow. Under transient artificial-recharge-pumping conditions, artificial recharge varies between 14,000 and 20,000 m3/day depending on the wet and dry seasons, respectively. The steady-state optimisation results show that the total optimal abstraction rate is 37,545 m3/day and artificial recharge is increased to 29,313 m3/day. The transient optimization results show that the average total optimal pumping rate is 36,969 m3/day for the current weir height. The transient optimization results for an increase in weir height by 1 and 2 m show that the average total optimal pumping rates are increased to 38,768 and 40,463 m3/day, respectively. It is concluded that the increase in the height of the weir can significantly increase the artificial recharge rate and production rate in Maghaway Valley.
Effects of transients in LIGO suspensions on searches for gravitational waves
NASA Astrophysics Data System (ADS)
Walker, M.; Abbott, T. D.; Aston, S. M.; González, G.; Macleod, D. M.; McIver, J.; Abbott, B. P.; Abbott, R.; Adams, C.; Adhikari, R. X.; Anderson, S. B.; Ananyeva, A.; Appert, S.; Arai, K.; Ballmer, S. W.; Barker, D.; Barr, B.; Barsotti, L.; Bartlett, J.; Bartos, I.; Batch, J. C.; Bell, A. S.; Betzwieser, J.; Billingsley, G.; Birch, J.; Biscans, S.; Biwer, C.; Blair, C. D.; Bork, R.; Brooks, A. F.; Ciani, G.; Clara, F.; Countryman, S. T.; Cowart, M. J.; Coyne, D. C.; Cumming, A.; Cunningham, L.; Danzmann, K.; Da Silva Costa, C. F.; Daw, E. J.; DeBra, D.; DeRosa, R. T.; DeSalvo, R.; Dooley, K. L.; Doravari, S.; Driggers, J. C.; Dwyer, S. E.; Effler, A.; Etzel, T.; Evans, M.; Evans, T. M.; Factourovich, M.; Fair, H.; Fernández Galiana, A.; Fisher, R. P.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Giaime, J. A.; Giardina, K. D.; Goetz, E.; Goetz, R.; Gras, S.; Gray, C.; Grote, H.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hall, E. D.; Hammond, G.; Hanks, J.; Hanson, J.; Hardwick, T.; Harry, G. M.; Heintze, M. C.; Heptonstall, A. W.; Hough, J.; Izumi, K.; Jones, R.; Kandhasamy, S.; Karki, S.; Kasprzack, M.; Kaufer, S.; Kawabe, K.; Kijbunchoo, N.; King, E. J.; King, P. J.; Kissel, J. S.; Korth, W. Z.; Kuehn, G.; Landry, M.; Lantz, B.; Lockerbie, N. A.; Lormand, M.; Lundgren, A. P.; MacInnis, M.; Márka, S.; Márka, Z.; Markosyan, A. S.; Maros, E.; Martin, I. W.; Martynov, D. V.; Mason, K.; Massinger, T. J.; Matichard, F.; Mavalvala, N.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McIntyre, G.; Mendell, G.; Merilh, E. L.; Meyers, P. M.; Miller, J.; Mittleman, R.; Moreno, G.; Mueller, G.; Mullavey, A.; Munch, J.; Nuttall, L. K.; Oberling, J.; Oliver, M.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; Ottaway, D. J.; Overmier, H.; Palamos, J. R.; Paris, H. R.; Parker, W.; Pele, A.; Penn, S.; Phelps, M.; Pierro, V.; Pinto, I.; Principe, M.; Prokhorov, L. G.; Puncken, O.; Quetschke, V.; Quintero, E. A.; Raab, F. J.; Radkins, H.; Raffai, P.; Reid, S.; Reitze, D. H.; Robertson, N. A.; Rollins, J. G.; Roma, V. J.; Romie, J. H.; Rowan, S.; Ryan, K.; Sadecki, T.; Sanchez, E. J.; Sandberg, V.; Savage, R. L.; Schofield, R. M. S.; Sellers, D.; Shaddock, D. A.; Shaffer, T. J.; Shapiro, B.; Shawhan, P.; Shoemaker, D. H.; Sigg, D.; Slagmolen, B. J. J.; Smith, B.; Smith, J. R.; Sorazu, B.; Staley, A.; Strain, K. A.; Tanner, D. B.; Taylor, R.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thrane, E.; Torrie, C. I.; Traylor, G.; Tuyenbayev, D.; Vajente, G.; Valdes, G.; van Veggel, A. A.; Vecchio, A.; Veitch, P. J.; Venkateswara, K.; Vo, T.; Vorvick, C.; Ward, R. L.; Warner, J.; Weaver, B.; Weiss, R.; Weßels, P.; Willke, B.; Wipf, C. C.; Worden, J.; Wu, G.; Yamamoto, H.; Yancey, C. C.; Yu, Hang; Yu, Haocun; Zhang, L.; Zucker, M. E.; Zweizig, J.
2017-12-01
This paper presents an analysis of the transient behavior of the Advanced LIGO (Laser Interferometer Gravitational-wave Observatory) suspensions used to seismically isolate the optics. We have characterized the transients in the longitudinal motion of the quadruple suspensions during Advanced LIGO's first observing run. Propagation of transients between stages is consistent with modeled transfer functions, such that transient motion originating at the top of the suspension chain is significantly reduced in amplitude at the test mass. We find that there are transients seen by the longitudinal motion monitors of quadruple suspensions, but they are not significantly correlated with transient motion above the noise floor in the gravitational wave strain data, and therefore do not present a dominant source of background noise in the searches for transient gravitational wave signals. Using the suspension transfer functions, we compared the transients in a week of gravitational wave strain data with transients from a quadruple suspension. Of the strain transients between 10 and 60 Hz, 84% are loud enough that they would have appeared above the sensor noise in the top stage quadruple suspension monitors if they had originated at that stage at the same frequencies. We find no significant temporal correlation with the suspension transients in that stage, so we can rule out suspension motion originating at the top stage as the cause of those transients. However, only 3.2% of the gravitational wave strain transients are loud enough that they would have been seen by the second stage suspension sensors, and none of them are above the sensor noise levels of the penultimate stage. Therefore, we cannot eliminate the possibility of transient noise in the detectors originating in the intermediate stages of the suspension below the sensing noise.
1985-01-01
A microprocessor-controlled system of microinjections and microaspirations has been developed to change, within approximately 1 ms, the [free Ca2+] at the outer surface of the sarcoplasmic reticulum (SR) wrapped around individual myofibrils (0.3-0.4 micron radius) of a skinned canine cardiac Purkinje cell (2.5-4.5 micron overall radius) at different phases of a Ca2+ transient. Simultaneously monitoring tension and aequorin bioluminescence provided two methods for estimating the peak myoplasmic [free Ca2+] reached during the spontaneous cyclic Ca2+ release from the SR obtained in the continuous presence of a bulk solution [free Ca2+] sufficiently high to overload the SR. These methods gave results in excellent agreement for the spontaneous Ca2+ release under a variety of conditions of pH and [free Mg2+], and of enhancement of Ca2+ release by calmodulin. Disagreement was observed, however, when the Ca2+ transient was modified during its ascending phase. The experiments also permitted quantification of the aequorin binding within the myofibrils and determination of its operational apparent affinity constant for Ca2+ at various [free Mg2+] levels. An increase of [free Ca2+] at the outer surface of the SR during the ascending phase of the Ca2+ transient induced further release of Ca2+. In contrast, an increase of [free Ca2+] during the descending phase of the Ca2+ transient did not cause further Ca2+ release. Varying [free H+], [free Mg2+], or the [Na+]/[K+] ratio had no significant effect on the Ca2+ transient during which the modification was applied, but it altered the subsequent Ca2+ transient. Therefore, Ca2+ appears to be the major, if not the only, ion controlling Ca2+ release from the SR rapidly enough to alter a Ca2+ transient during its course. PMID:3981128
Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway.
Liu, Chao; Wu, Jiliang; Xu, Kui; Cai, Fei; Gu, Jun; Ma, Liqun; Chen, Jianguo
2010-03-01
Recently more evidences support baicalein (Bai) is neuroprotective in models of ischemic stroke. This study was conducted to determine the molecular mechanisms involved in this effect. Either permanent or transient (2 h) middle cerebral artery occlusion (MCAO) was induced in rats in this study. Permanent MCAO led to larger infarct volumes in contrast to transient MCAO. Only in transient MCAO, Bai administration significantly reduced infarct size. Baicalein also markedly reduced apoptosis in the penumbra of transient MCAO rats. Additionally, oxygen and glucose deprivation (OGD) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular reactive oxygen species level and nitrotyrosine formation induced by OGD was counteracted by Bai, which is parallel with attenuated cell injury. The reduction of phosphorylation Akt and glycogen synthase kinase-3beta (GSK3beta) induced by OGD was restored by Bai, which was associated with preserved levels of phosphorylation of PTEN, the phophatase that negatively regulates Akt. As a consequence, Bcl-2/Bcl-xL-associated death protein phosphorylation was increased and the protein level of Bcl-2 in motochondria was maintained, which subsequently antagonize cytochrome c released in cytosol. LY294002 blocked the increase in phospho-AKT evoked by Bai and abolished the associated protective effect. Together, these findings provide evidence that Bai protects neurons against ischemia injury and this neuroprotective effect involves PI3K/Akt and PTEN pathway.
Observations on autoregulation in skeletal muscle - The effects of arterial hypoxia
NASA Technical Reports Server (NTRS)
Pohost, G. M.; Newell, J. B.; Hamlin, N. P.; Powell, W. J., Jr.
1976-01-01
An experimental study was carried out on 25 mongrel dogs of both sexes to re-evaluate autoregulation of blood flow in skeletal muscle, with particular reference to the steady-state resistance and transient response in muscle blood flow following a square wave increase in arterial perfusion pressure and to the examination of the effect of arterial hypoxia on this transient response. The data emphasize the importance of considering the transient changes in blood flow in evaluating the autoregulatory response in skeletal muscle. For quantification purposes, a parameter termed alpha is introduced which represents the ratio between the increase in blood flow from baseline to peak and the return of blood flow from the peak to the new steady-state. Such a quantification of the transient response in flow with step increases in perfusion pressure demonstrates substantial transient responses under conditions of normal oxygenation and progressive attenuation of flow transients with increasing hypoxia.
Besançon-Watelet, C; De March, A K; Renoult, E; Kessler, M; Béné, M C; Faure, G C; Sarda, M N
2000-02-15
Cytomegalovirus (CMV) infection or reactivation is a frequent complication of renal transplantation. Diagnosis of these conditions relies on the detection of circulating antigen, or of specific IgM and/or IgG, which develop over several weeks. Evocative clinical features may be detected earlier, but lack specificity. Rapid and early changes in the partition of lymphocyte subsets could be an additional indication of pending CMV infection. A systematic follow-up of peripheral B lymphocytes identified immunophenotypically by the determination of surface immunoglobulins (sIg), performed in 97 kidney transplant recipients, allowed to identify transient increases apparently predictive of CMV primo-infection or reactivation over the next 3 months. To better define the nature of these B cells, an extended investigation was performed for 14 prospective patients. In addition to surface Ig, membrane CD19, HLA-DR, and CD80 expression were explored. The cytoplasmic presence of mu, kappa, and lambda chains was also examined. B cell function was investigated using the ELISPOT technique, which allows an enumeration of the populations of IgG, IgA, and IgM secreting B cells. Retrospective analysis of the clinical outcome of the cohort of 97 patients evidenced that early transient increases in B cell levels were significantly (P<0.0001) associated with CMV infection. The same trend was noted in the smaller series of patients who benefited from a more extensive investigation of B cells, 10 of whom presented clinical or biological signs of CMV infection. Mature B cells, expressing surface Ig, CD19, DR, and CD80 are those presenting transient increases. No significant variation of preB (cmu+/kappalambda-) or activated (spot-forming) cells was evidenced in these patients. Individual examination of each patient's immune reconstitution profile allows to detect transient peaks of mature B cell during the initial immunosuppressive therapy, that appear to be predictive of oncoming CMV infection or reactivation.
Transient adhesion in a non-fully detached contact.
Liu, Zheyu; Lu, Hongyu; Zheng, Yelong; Tao, Dashuai; Meng, Yonggang; Tian, Yu
2018-04-18
Continuous approaching and detaching displacement usually occurs in an adhesion test. Here, we found a transient adhesion force at the end of a non-fully detached contact. This force occurred when the nominal detaching displacement was less than the traditional quasi-static theory predicted zero force point. The transient adhesion force was ascribed to interfacial adhesion hysteresis, which was caused by the cracking process of the contact and the deformation competition between the sphere and supporting spring. Results indicated that the testing of adhesion can be significantly affected by different combinations of stiffnesses of the contact objects and the supporting spring cantilever. This combination should be carefully designed in an adhesion test. All these results enabled increased understanding of the nature of adhesion and can guide the design of adhesive actuators.
Techniques for improving transients in learning control systems
NASA Technical Reports Server (NTRS)
Chang, C.-K.; Longman, Richard W.; Phan, Minh
1992-01-01
A discrete modern control formulation is used to study the nature of the transient behavior of the learning process during repetitions. Several alternative learning control schemes are developed to improve the transient performance. These include a new method using an alternating sign on the learning gain, which is very effective in limiting peak transients and also very useful in multiple-input, multiple-output systems. Other methods include learning at an increasing number of points progressing with time, or an increasing number of points of increasing density.
Transient flow analysis linked to fast pressure disturbance monitored in pipe systems
NASA Astrophysics Data System (ADS)
Kueny, J. L.; Lourenco, M.; Ballester, J. L.
2012-11-01
EDF Hydro Division has launched the RENOUVEAU program in order to increase performance and improve plant availability through anticipation. Due to this program, a large penstocks fleet is equipped with pressure transducers linked to a special monitoring system. Any significant disturbance of the pressure is captured in a snapshot and the waveform of the signal is stored and analyzed. During these transient states, variations in flow are unknown. In order to determine the structural impact of such overpressure occurring during complex transients conditions over the entire circuit, EDF DTG has asked ENSE3 GRENOBLE to develop a code called ACHYL CF*. The input data of ACHYL CF are circuit topology and pressure boundaries conditions. This article provide a description of the computer code developed for modeling the transient flow in a pipe network using the signals from pressure transducers as boundary conditions. Different test cases will be presented, simulating real hydro power plants for which measured pressure signals are available.
Szentandrássy, Norbert; Birinyi, Péter; Szigeti, Gyula; Farkas, Attila; Magyar, János; Tóth, András; Csernoch, László; Varró, András; Nánási, Péter P
2008-07-01
SEA0400 is a recently developed inhibitor of the Na+/Ca2+ exchanger (NCX) shown to suppress both forward and reverse mode operation of NCX. Present experiments were designed to study the effect of partial blockade of NCX on Ca handling and contractility in Langendorff-perfused guinea pig hearts loaded with the fluorescent Ca-sensitive dye fura-2. Left ventricular pressure and intracellular calcium concentration ([Ca2+]i) were synchronously recorded before and after cumulative superfusion with 0.3 and 1 muM SEA0400. SEA0400 caused no significant change in the systolic and diastolic values of left ventricular pressure and [Ca2+]i. Accordingly, pulse pressure and amplitude of the [Ca2+]i transient also remained unchanged in the presence of SEA0400. SEA0400 had no influence either on the time required to reach peak values of pressure and [Ca2+)]i or on half relaxation time. On the other hand, both 0.3 and 1 microM SEA0400 significantly increased the decay time constant of [Ca2+]i transients, obtained by fitting its descending limb between 30% and 90% of relaxation, from 127 +/- 7 to 165 +/- 7 and 177 +/- 14 ms, respectively (P < 0.05, n=6). In contrast to the guinea pig hearts, rat hearts responded to SEA0400 treatment with increased [Ca2+]i transients and contractility. These interspecies differences observed in the effect of SEA0400 can be explained by the known differences in calcium handling between the two species.
Transient Side Load Analysis of Out-of-Round Film-Cooled Nozzle Extensions
NASA Technical Reports Server (NTRS)
Wang, Ten-See; Lin, Jeff; Ruf, Joe; Guidos, Mike
2012-01-01
There was interest in understanding the impact of out-of-round nozzle extension on the nozzle side load during transient startup operations. The out-of-round nozzle extension could be the result of asymmetric internal stresses, deformation induced by previous tests, and asymmetric loads induced by hardware attached to the nozzle. The objective of this study was therefore to computationally investigate the effect of out-of-round nozzle extension on the nozzle side loads during an engine startup transient. The rocket engine studied encompasses a regeneratively cooled chamber and nozzle, along with a film cooled nozzle extension. The computational methodology is based on an unstructured-grid, pressure-based computational fluid dynamics formulation, and transient inlet boundary flow properties derived from an engine system simulation. Six three-dimensional cases were performed with the out-of-roundness achieved by three different degrees of ovalization, elongated on lateral y and z axes: one slightly out-of-round, one more out-of-round, and one significantly out-of-round. The results show that the separation line jump was the primary source of the peak side loads. Comparing to the peak side load of the perfectly round nozzle, the peak side loads increased for the slightly and more ovalized nozzle extensions, and either increased or decreased for the two significantly ovalized nozzle extensions. A theory based on the counteraction of the flow destabilizing effect of an exacerbated asymmetrical flow caused by a lower degree of ovalization, and the flow stabilizing effect of a more symmetrical flow, created also by ovalization, is presented to explain the observations obtained in this effort.
Nilsen, Tom O.; Ebbesson, Lars O.E.; Madsen, Steffen S.; McCormick, Stephen D.; Andersson, Eva; Bjornsson, Bjorn Thrandur; Prunet, Patrick; Stefansson, Sigurd O.
2007-01-01
This study examines changes in gill Na+,K+-ATPase (NKA) α- and β-subunit isoforms, Na+,K+,2Cl- cotransporter (NKCC) and cystic fibrosis transmembrane conductance regulator (CFTR I and II) in anadromous and landlocked strains of Atlantic salmon during parr-smolt transformation, and after seawater (SW) transfer in May/June. Gill NKA activity increased from February through April, May and June among both strains in freshwater (FW), with peak enzyme activity in the landlocked salmon being 50% below that of the anadromous fish in May and June. Gill NKA-α1b, -α3, -β1 and NKCC mRNA levels in anadromous salmon increased transiently, reaching peak levels in smolts in April/May, whereas no similar smolt-related upregulation of these transcripts occurred in juvenile landlocked salmon. Gill NKA-α1a mRNA decreased significantly in anadromous salmon from February through June, whereas α1a levels in landlocked salmon, after an initial decrease in April, remained significantly higher than those of the anadromous smolts in May and June. Following SW transfer, gill NKA-α1b and NKCC mRNA increased in both strains, whereas NKA-α1a decreased. Both strains exhibited a transient increase in gill NKA α-protein abundance, with peak levels in May. Gill α-protein abundance was lower in SW than corresponding FW values in June. Gill NKCC protein abundance increased transiently in anadromous fish, with peak levels in May, whereas a slight increase was observed in landlocked salmon in May, increasing to peak levels in June. Gill CFTR I mRNA levels increased significantly from February to April in both strains, followed by a slight, though not significant increase in May and June. CFTR I mRNA levels were significantly lower in landlocked than anadromous salmon in April/June. Gill CFTR II mRNA levels did not change significantly in either strain. Our findings demonstrates that differential expression of gill NKA-α1a, -α1b and -α3 isoforms may be important for potential functional differences in NKA, both during preparatory development and during salinity adjustments in salmon. Furthermore, landlocked salmon have lost some of the unique preparatory upregulation of gill NKA, NKCC and, to some extent, CFTR anion channel associated with the development of hypo-osmoregulatory ability in anadromous salmon.
As trees age and increase in size, the resistance along the water transport path has been hypothesized to increase and potentially limit the ultimate size a tree can reach. Past research has demonstrated that branches are a source of significant resistance in the transport path....
Transient elastography with the XL probe rapidly identifies patients with nonhepatic ascites.
Kohlhaas, Anna; Durango, Esteban; Millonig, Gunda; Bastard, Cecile; Sandrin, Laurent; Golriz, Mohammad; Mehrabi, Arianeb; Büchler, Markus W; Seitz, Helmut Karl; Mueller, Sebastian
2012-01-01
In contrast with other elastographic techniques, ascites is considered an exclusion criterion for assessment of fibrosis stage by transient elastography. However, a normal liver stiffness could rule out hepatic causes of ascites at an early stage. The aim of the present study was to determine whether liver stiffness can be generally determined by transient elastography through an ascites layer, to determine whether the ascites-mediated increase in intra-abdominal pressure affects liver stiffness, and to provide initial data from a pilot cohort of patients with various causes of ascites. Using the XL probe in an artificial ascites model, we demonstrated (copolymer phantoms surrounded by water) that a transient elastography-generated shear wave allows accurate determination of phantom stiffness up to a water lamella of 20 mm. We next showed in an animal ascites model that increased intra-abdominal pressure does not affect liver stiffness. Liver stiffness was then determined in 24 consecutive patients with ascites due to hepatic (n = 18) or nonhepatic (n = 6) causes. The cause of ascites was eventually clarified using routine clinical, imaging, laboratory, and other tools. Valid (75%) or acceptable (25%) liver stiffness data could be obtained in 23 patients (95.8%) with ascites up to an ascites lamella of 39 mm. The six patients (25%) with nonhepatic causes of ascites (eg, pancreatitis, peritoneal carcinomatosis) had a significantly lower liver stiffness (<8 kPa) as compared with the remaining patients with hepatic ascites (>30 kPa). Mean liver stiffness was 5.4 kPa ± 1.3 versus 66.2 ± 13.3 kPa. In conclusion, the presence of ascites and increased intra-abdominal pressure does not alter underlying liver stiffness as determined by transient elastography. We suggest that, using the XL probe, transient elastography can be used first-line to identify patients with nonhepatic ascites at an early stage.
Transient elastography with the XL probe rapidly identifies patients with nonhepatic ascites
Kohlhaas, Anna; Durango, Esteban; Millonig, Gunda; Bastard, Cecile; Sandrin, Laurent; Golriz, Mohammad; Mehrabi, Arianeb; Büchler, Markus W; Seitz, Helmut Karl; Mueller, Sebastian
2012-01-01
Background In contrast with other elastographic techniques, ascites is considered an exclusion criterion for assessment of fibrosis stage by transient elastography. However, a normal liver stiffness could rule out hepatic causes of ascites at an early stage. The aim of the present study was to determine whether liver stiffness can be generally determined by transient elastography through an ascites layer, to determine whether the ascites-mediated increase in intra-abdominal pressure affects liver stiffness, and to provide initial data from a pilot cohort of patients with various causes of ascites. Methods and results Using the XL probe in an artificial ascites model, we demonstrated (copolymer phantoms surrounded by water) that a transient elastography-generated shear wave allows accurate determination of phantom stiffness up to a water lamella of 20 mm. We next showed in an animal ascites model that increased intra-abdominal pressure does not affect liver stiffness. Liver stiffness was then determined in 24 consecutive patients with ascites due to hepatic (n = 18) or nonhepatic (n = 6) causes. The cause of ascites was eventually clarified using routine clinical, imaging, laboratory, and other tools. Valid (75%) or acceptable (25%) liver stiffness data could be obtained in 23 patients (95.8%) with ascites up to an ascites lamella of 39 mm. The six patients (25%) with nonhepatic causes of ascites (eg, pancreatitis, peritoneal carcinomatosis) had a significantly lower liver stiffness (<8 kPa) as compared with the remaining patients with hepatic ascites (>30 kPa). Mean liver stiffness was 5.4 kPa ± 1.3 versus 66.2 ± 13.3 kPa. Conclusion In conclusion, the presence of ascites and increased intra-abdominal pressure does not alter underlying liver stiffness as determined by transient elastography. We suggest that, using the XL probe, transient elastography can be used first-line to identify patients with nonhepatic ascites at an early stage. PMID:24367229
Estimating the impact of oyster restoration scenarios on transient fish production
McCoy, Elizabeth; Borrett, Stuart R.; LaPeyre, Megan K.; Peterson, Bradley J.
2017-01-01
Oyster reef restoration projects are increasing in number both to enhance oyster density and to retain valuable ecosystem services provided by oyster reefs. Although some oyster restoration projects have demonstrated success by increasing density and biomass of transient fish, it still remains a challenge to quantify the effects of oyster restoration on transient fish communities. We developed a bioenergetics model to assess the impact of selected oyster reef restoration scenarios on associated transient fish species. We used the model to analyze the impact of changes in (1) oyster population carrying capacity; (2) oyster population growth rate; and (3) diet preference of transient fish on oyster reef development and associated transient fish species. Our model results indicate that resident fish biomass is directly affected by oyster restoration and oyster biomass, and oyster restoration can have cascading impacts on transient fish biomass. Furthermore, the results highlight the importance of a favorable oyster population growth rate during early restoration years, as it can lead to rapid increases in mean oyster biomass and biomass of transient fish species. The model also revealed that a transient fish's diet solely dependent on oyster reef-derived prey could limit the biomass of transient fish species, emphasizing the importance of habitat connectivity in estuarine areas to enhance transient fish species biomass. Simple bioenergetics models can be developed to understand the dynamics of a system and make qualitative predictions of management and restoration scenarios.
Subclinical HSV-1 infections provide site-specific resistance to an unrelated pathogen
Rowe, Alexander M.; Yun, Hongming; Treat, Benjamin R.; Kinchington, Paul R.; Hendricks, Robert L.
2016-01-01
Herpes Simplex Virus-1 (HSV-1) infections of the cornea range in severity from minor transient discomfort to the blinding disease Herpes Stromal Keratitis (HSK), yet most patients experience a single episode of epithelial keratitis followed by reestablishment of a clear cornea. We asked if a single transient episode of HSV-1 epithelial keratitis causes long-term changes in the corneal microenvironment that influence immune responses to subsequent corneal infection or trauma. We showed that C57BL/6 mouse corneas infected with HSV-1 KOS, which induces transient herpes epithelial keratitis without HSK sequelae, possessed a significant leukocytic infiltrate comprised primarily of CD4+ T cells and macrophages along with elevated chemokines and cytokines that persisted without loss of corneal clarity (subclinical inflammation). Chemokine and cytokine expression was CD4+T cell-dependent, in that their production was significantly reduced by systemic CD4+T cell depletion starting before infection, although short-term (3 day) local CD4+ T cell depletion after infection did not influence chemokine levels in cornea. Corneas with subclinical inflammation developed significantly greater trauma-induced inflammation when they were recipients of syngeneic corneal transplants, but also exhibited significantly increased resistance to infections by unrelated pathogens such as pseudorabies virus (PRV). The resistance to PRV was CD4+ T cell-dependent, since it was eliminated by local CD4+T cell-depletion from the cornea. We conclude that transient HSV-1 corneal infections cause long-term alterations of the corneal microenvironment that provide CD4-dependent innate resistance to subsequent infections by antigenically unrelated pathogens. PMID:28062697
Johari, Yusuf B; Estes, Scott D; Alves, Christina S; Sinacore, Marty S; James, David C
2015-12-01
Based on an optimized electroporation protocol, we designed a rapid, milliliter-scale diagnostic transient production assay to identify limitations in the ability of Chinese hamster ovary (CHO) cells to produce a model "difficult-to-express" homodimeric Fc-fusion protein, Sp35Fc, that exhibited very low volumetric titer and intracellular formation of disulfide-bonded oligomeric aggregates post-transfection. As expression of Sp35Fc induced an unfolded protein response in transfected host cells, we utilized the transient assay to compare, in parallel, multiple functionally diverse strategies to engineer intracellular processing of Sp35Fc in order to increase production and reduce aggregation as two discrete design objectives. Specifically, we compared the effect of (i) co-expression of ER-resident molecular chaperones (BiP, PDI, CypB) or active forms of UPR transactivators (ATF6c, XBP1s) at varying recombinant gene load, (ii) addition of small molecules known to act as chemical chaperones (PBA, DMSO, glycerol, betaine, TMAO) or modulate UPR signaling (PERK inhibitor GSK2606414) at varying concentration, (iii) a reduction in culture temperature to 32°C. Using this information, we designed a biphasic, Sp35Fc-specific transient manufacturing process mediated by lipofection that utilized CypB co-expression at an optimal Sp35Fc:CypB gene ratio of 5:1 to initially maximize transfected cell proliferation, followed by addition of a combination of PBA (0.5 mM) and glycerol (1% v/v) at the onset of stationary phase to maximize cell specific production and eliminate Sp35Fc aggregation. Using this optimal, engineered process transient Sp35Fc production was significantly increased sixfold over a 12 day production process with no evidence of disulfide-bonded aggregates. Finally, transient production in clonally derived sub-populations (derived from parental CHO host) screened for a heritably improved capability to produce Sp35Fc was also significantly improved by the optimized process, showing that protein-specific cell/process engineering can provide a solution that exceeds the limits of genetic/functional diversity within heterogeneous host cell populations. . © 2015 Wiley Periodicals, Inc.
Immediate ventilatory response to sudden changes in venous return in humans.
Cummin, A R; Iyawe, V I; Jacobi, M S; Mehta, N; Patil, C P; Saunders, K B
1986-01-01
We changed venous return transiently by postural manoeuvres, and by lower body positive pressure, to see what happened simultaneously to ventilation. Cardiac output was measured by a Doppler technique. In seven subjects, after inflation of a pressure suit to 80 and 40 mmHg at 30 deg head-up tilt, both cardiac output and ventilation increased. Ventilation increased rapidly to a peak in the first 5 s, cardiac output more slowly to a steady state in about 20 s, at 80 mmHg inflation. After inflation to 80 mmHg in six subjects at 12.5 deg head-up and 30 deg head-down tilt, cardiac output did not change in the first, and fell in the second case. There were no significant changes in ventilation. On release of pressure there were transient increases in both cardiac output and ventilation, with ventilation lagging behind cardiac output, in contrast to (2) above. In five subjects, elevation of the legs at 30 deg head-up tilt caused a rise in both cardiac output and ventilation, but in two subjects neither occurred. In all seven subjects there was a transient increase in cardiac output and ventilation when the legs were lowered. Ventilation and cardiac output changes were approximately in phase. We were therefore unable to dissociate entirely increasing cardiac output from increasing ventilation. The relation between them was certainly not a simple proportional one. PMID:3612571
Transient MutS-Based Hypermutation System for Adaptive Evolution of Lactobacillus casei to Low pH.
Overbeck, Tom J; Welker, Dennis L; Hughes, Joanne E; Steele, James L; Broadbent, Jeff R
2017-10-15
This study explored transient inactivation of the gene encoding the DNA mismatch repair enzyme MutS as a tool for adaptive evolution of Lactobacillus casei MutS deletion derivatives of L. casei 12A and ATCC 334 were constructed and subjected to a 100-day adaptive evolution process to increase lactic acid resistance at low pH. Wild-type parental strains were also subjected to this treatment. At the end of the process, the Δ mutS lesion was repaired in representative L. casei 12A and ATCC 334 Δ mutS mutant isolates. Growth studies in broth at pH 4.0 (titrated with lactic acid) showed that all four adapted strains grew more rapidly, to higher cell densities, and produced significantly more lactic acid than untreated wild-type cells. However, the adapted Δ mutS derivative mutants showed the greatest increases in growth and lactic acid production. Further characterization of the L. casei 12A-adapted Δ mutS derivative revealed that it had a significantly smaller cell volume, a rougher cell surface, and significantly better survival at pH 2.5 than parental L. casei 12A. Genome sequence analysis confirmed that transient mutS inactivation decreased DNA replication fidelity in both L. casei strains, and it identified genetic changes that might contribute to the lactic acid-resistant phenotypes of adapted cells. Targeted inactivation of three genes that had acquired nonsense mutations in the adapted L. casei 12A Δ mutS mutant derivative showed that NADH dehydrogenase ( ndh ), phosphate transport ATP-binding protein PstB ( pstB ), and two-component signal transduction system (TCS) quorum-sensing histidine protein kinase ( hpk ) genes act in combination to increase lactic acid resistance in L. casei 12A. IMPORTANCE Adaptive evolution has been applied to microorganisms to increase industrially desirable phenotypes, including acid resistance. We developed a method to increase the adaptability of Lactobacillus casei 12A and ATCC 334 through transient inactivation of the DNA mismatch repair enzyme MutS. Here, we show this method was effective in increasing the resistance of L. casei to lactic acid at low pH. Additionally, we identified three genes that contribute to increased acid resistance in L. casei 12A. These results provide valuable insight on methods to enhance an organism's fitness to complex phenotypes through adaptive evolution and targeted gene inactivation. Copyright © 2017 American Society for Microbiology.
Transient MutS-Based Hypermutation System for Adaptive Evolution of Lactobacillus casei to Low pH
Overbeck, Tom J.; Welker, Dennis L.; Hughes, Joanne E.; Steele, James L.
2017-01-01
ABSTRACT This study explored transient inactivation of the gene encoding the DNA mismatch repair enzyme MutS as a tool for adaptive evolution of Lactobacillus casei. MutS deletion derivatives of L. casei 12A and ATCC 334 were constructed and subjected to a 100-day adaptive evolution process to increase lactic acid resistance at low pH. Wild-type parental strains were also subjected to this treatment. At the end of the process, the ΔmutS lesion was repaired in representative L. casei 12A and ATCC 334 ΔmutS mutant isolates. Growth studies in broth at pH 4.0 (titrated with lactic acid) showed that all four adapted strains grew more rapidly, to higher cell densities, and produced significantly more lactic acid than untreated wild-type cells. However, the adapted ΔmutS derivative mutants showed the greatest increases in growth and lactic acid production. Further characterization of the L. casei 12A-adapted ΔmutS derivative revealed that it had a significantly smaller cell volume, a rougher cell surface, and significantly better survival at pH 2.5 than parental L. casei 12A. Genome sequence analysis confirmed that transient mutS inactivation decreased DNA replication fidelity in both L. casei strains, and it identified genetic changes that might contribute to the lactic acid-resistant phenotypes of adapted cells. Targeted inactivation of three genes that had acquired nonsense mutations in the adapted L. casei 12A ΔmutS mutant derivative showed that NADH dehydrogenase (ndh), phosphate transport ATP-binding protein PstB (pstB), and two-component signal transduction system (TCS) quorum-sensing histidine protein kinase (hpk) genes act in combination to increase lactic acid resistance in L. casei 12A. IMPORTANCE Adaptive evolution has been applied to microorganisms to increase industrially desirable phenotypes, including acid resistance. We developed a method to increase the adaptability of Lactobacillus casei 12A and ATCC 334 through transient inactivation of the DNA mismatch repair enzyme MutS. Here, we show this method was effective in increasing the resistance of L. casei to lactic acid at low pH. Additionally, we identified three genes that contribute to increased acid resistance in L. casei 12A. These results provide valuable insight on methods to enhance an organism's fitness to complex phenotypes through adaptive evolution and targeted gene inactivation. PMID:28802267
Akuzawa-Tateyama, M; Tateyama, M; Ochi, R
1998-01-01
The effects of large reductions of [K+]o on membrane potential were studied in isolated rabbit ventricular myocytes using the whole-cell patch clamp technique.Decreasing [K+]o from the normal level of 5.4 mm to 0.1 mm increased resting membrane potential (Vrest) from −75.6 ± 0.3 to −140.3 ± 1.9 mV (means ± s.e.m; n = 127), induced irregular, transient depolarizations with mean maximal amplitudes of 19.5 ± 1.5 mV and elicited action potentials in 56.7 % of trials. The action potentials exhibited overshoots of 37.9 ± 1.5 mV (n = 72) and sustained plateaux.Addition of 0.1 mm La3+ in the presence of 0.1 mm[K+]o significantly increased Vrest but decreased the amplitude of transient depolarizations and suppressed the firing of action potentials.Replacement of external Na+ or Cl− with N-methyl-D-glucamine or aspartate, respectively, or internal dialysis with 10 mm EGTA or BAPTA had little effect on low [K+]o-induced membrane potential changes.Hyperpolarizing voltage clamp pulses to potentials between −110 and −200 mV activated irregular inward currents that increased in amplitude and frequency with increasing hyperpolarization and were depressed by 0.1 mm La3+.The generation of transient depolarizations by low [K+]o can be explained as being a consequence of decreasing the inward rectifier K+ current (IK1) and the appearance of inward currents reflecting electroporation resulting from strong electric fields across the membrane. PMID:9824717
Polyuria and impaired renal blood flow after asphyxia in preterm fetal sheep.
Quaedackers, J S; Roelfsema, V; Hunter, C J; Heineman, E; Gunn, A J; Bennet, L
2004-03-01
Renal impairment is common in preterm infants, often after exposure to hypoxia/asphyxia or other circulatory disturbances. We examined the hypothesis that this association is mediated by reduced renal blood flow (RBF), using a model of asphyxia induced by complete umbilical cord occlusion for 25 min (n = 13) or sham occlusion (n = 6) in chronically instrumented preterm fetal sheep (104 days, term is 147 days). During asphyxia there was a significant fall in RBF and urine output (UO). After asphyxia, RBF transiently recovered, followed within 30 min by a secondary period of hypoperfusion (P < 0.05). This was mediated by increased renal vascular resistance (RVR, P < 0.05); arterial blood pressure was mildly increased in the first 24 h (P < 0.05). RBF relatively normalized between 3 and 24 h, but hypoperfusion developed again from 24 to 60 h (P < 0.05, analysis of covariance). UO significantly increased to a peak of 249% of baseline between 3 and 12 h (P < 0.05), with increased fractional excretion of sodium, peak 10.5 +/- 1.4 vs. 2.6 +/- 0.6% (P < 0.001). Creatinine clearance returned to normal after 2 h; there was a transient reduction at 48 h to 0.32 +/- 0.02 ml.min(-1).g(-1) (vs. 0.45 +/- 0.04, P < 0.05) corresponding with the time of maximal depression of RBF. No renal injury was seen on histological examination at 72 h. In conclusion, severe asphyxia in the preterm fetus was associated with evolving renal tubular dysfunction, as shown by transient polyuria and natriuresis. Despite a prolonged increase in RVR, there was only a modest effect on glomerular function.
Yeung, John H K; Or, Penelope M Y
2007-06-01
The effects of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of PSP (1-4 micromole/kg, i.p.) produced a transient, dose-dependent depletion (10-37%) of hepatic GSH, with no effect on serum glutamic-pyruvic transaminase (SGPT) activity. Blood GSH was depleted (6-25%) at 3 h, followed by a rebound increase above the control GSH level (20%) at 18 h. The GSSG/GSH ratio, a measure of oxidative stress, was increased 3 h after PSP treatment but returned to normal levels at 24 h. Sub-chronic treatment of PSP (1-4 micromole/kg/day, i.p.) for seven days did not produce any significant changes in hepatic GSH levels and the GSSG/GSH ratio when measured 24 h after the final dose of PSP. PSP had little effect on glutathione transferase (GST), glutathione reductase (GSSG reductase) and glutathione peroxidase (GPX) activities in the liver. However, a dose-dependent increase in blood GPX activity (30-48%) was observed at 3h, which coincided with the increase in the GSSG/GSH ratio. The increase in blood GPX activity may be a responsive measure to deal with the transient oxidative stress induced by PSP treatment. The results showed that PSP only caused a transient perturbation on hepatic glutathione without affecting the GSH-related enzymes such as GST, GSSG reductase and GPX. The observed changes in blood GSH simply reflected the intra-organ translocation of glutathione, as the glutathione-related enzymes were not significantly affected by PSP treatment.
Castro, Michele M.; Cloutier, Anik; Bertagnolli, Mariane; Sartelet, Hervé; Germain, Nathalie; Comte, Blandine; Schulz, Richard; DeBlois, Denis; Nuyt, Anne Monique
2014-01-01
Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular rarefaction, vascular dysfunction and arterial (aorta) rigidity in adult rats. Whether structural changes are present in the matrix of aorta wall is unknown. Considering that elastin synthesis peaks in late fetal life in humans, and early postnatal life in rodents, we postulated that transient neonatal high-oxygen exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control) and were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to angiotensin II and to the acetylcholine analogue carbachol were not different between groups. Vascular superoxide anion production was similar between groups. There was no difference between groups in aortic cross sectional area, smooth muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta elastin/collagen content ratio was significantly decreased, the expression of elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1 staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced, indicating a shift in the balance towards degradation of the extra-cellular matrix and increased deposition of collagen. There was no significant difference in MMP-2 activity between groups as determined by gelatin zymography. Overall, these findings indicate that transient neonatal high oxygen exposure leads to vascular wall alterations (decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen) which are associated with increased rigidity. Importantly, these changes are present prior to the elevation of blood pressure and vascular dysfunction in this model, and may therefore be contributory. PMID:24743169
Jung, Sang-Kyu; McDonald, Karen A; Dandekar, Abhaya M
2015-01-01
Agrobacterium tumefaciens-mediated transient expression is known to be highly dependent on incubation temperature. Compared with early studies that were conducted at constant temperature, we examined the effect of variable leaf incubation temperature on transient expression. As a model system, synthetic endoglucanase (E1) and endoxylanase (Xyn10A) genes were transiently expressed in detached whole sunflower leaves via vacuum infiltration for biofuel applications. We found that the kinetics of transient expression strongly depended on timing of the temperature change as well as leaf incubation temperature. Surprisingly, we found that high incubation temperature (27-30 °C) which is suboptimal for T-DNA transfer, significantly enhanced transient expression if the high temperature was applied during the late phase (Day 3-6) of leaf incubation whereas incubation temperature in a range of 20-25 °C for an early phase (Day 0-2) resulted in higher production. On the basis of these results, we propose that transient expression is governed by both T-DNA transfer and protein synthesis in plant cells that have different temperature dependent kinetics. Because the phases were separated in time and had different optimal temperatures, we were then able to develop a novel two phase optimization strategy for leaf incubation temperature. Applying the time-varying temperature profile, we were able to increase the protein accumulation by fivefold compared with the control at a constant temperature of 20 °C. From our knowledge, this is the first report illustrating the effect of variable temperature profiling for improved transient expression. © 2015 American Institute of Chemical Engineers.
X-ray rebrightening of the Be/X-ray transient Swift J0243.6+6124
NASA Astrophysics Data System (ADS)
Rouco Escorial, A.; Degenaar, N.; van den Eijnden, J.; Wijnands, R.
2018-04-01
Swift J0243.6+6124 is a Be/X-ray transient that was discovered in October 2017 when it started a giant, type-II outburst (Atel #10809, Atel #10822). After reaching the peak around November 5th 2017, the source luminosity started to decay slowly over & sim;135 days, although the decay rate increased significantly around two weeks ago. To investigate how exactly the source would decay and potentially transit back into quiescence, we triggered a monitoring program (PI: Degenaar) on the system using the Neil Gehrels Swift observatory (Swift).
Li, Wennan; Chen, Xingjuan; Riley, Ashley M; Hiett, S Christopher; Temm, Constance J; Beli, Eleni; Long, Xin; Chakraborty, Saikat; Alloosh, Mouhamad; White, Fletcher A; Grant, Maria B; Sturek, Michael; Obukhov, Alexander G
2017-09-01
Coronary transient receptor potential canonical (TRPC) channel expression is elevated in metabolic syndrome (MetS). However, differential contribution of TRPCs to coronary pathology in MetS is not fully elucidated. We investigated the roles of TRPC1 and TRPC6 isoforms in coronary arteries of MetS pigs and determined whether long-term treatment with a mineralocorticoid receptor inhibitor, spironolactone, attenuates coronary TRPC expression and associated dysfunctions. MetS coronary arteries exhibited significant atherosclerosis, endothelial dysfunction, and increased histamine-induced contractions. Immunohistochemical studies revealed that TRPC6 immunostaining was significantly greater in the medial layer of MetS pig coronary arteries compared to that in Lean pigs, whereas little TRPC6 immunostaining was found in atheromas. Conversely, TRPC1 immunostaining was weak in the medial layer but strong in MetS atheromas, where it was predominantly localized to macrophages. Spironolactone treatment significantly decreased coronary TRPC expression and dysfunctions in MetS pigs. In vivo targeted delivery of the dominant-negative (DN)-TRPC6 cDNA to the coronary wall reduced histamine-induced calcium transients in the MetS coronary artery medial layer, implying a role for TRPC6 in mediating calcium influx in MetS coronary smooth muscles. Monocyte adhesion was increased in Lean pig coronary arteries cultured in the presence of aldosterone; and spironolactone antagonized this effect, suggesting that coronary mineralocorticoid receptor activation may regulate macrophage infiltration. TRPC1 expression in atheroma macrophages was associated with advanced atherosclerosis, whereas medial TRPC6 upregulation correlated with increased histamine-induced calcium transients and coronary contractility. We propose that long-term spironolactone treatment may be a therapeutic strategy to decrease TRPC expression and coronary pathology associated with MetS.
Trapping effect of metal nanoparticle mono- and multilayer in the organic field-effect transistor
NASA Astrophysics Data System (ADS)
Lee, Keanchuan; Weis, Martin; Lin, Jack; Taguchi, Dai; Majková, Eva; Manaka, Takaaki; Iwamoto, Mitsumasa
2011-03-01
The effect of silver nanoparticles self-assembled monolayer (Ag NPs SAM) on charge transport in pentacene organic field-effect transistors (OFET) was investigated by both steady-state and transient-state methods, which are current-voltage measurements in steady-state and time-resolved microscopic (TRM) second harmonic generation (SHG) in transient-state, respectively. The analysis of electronic properties revealed that OFET with SAM exhibited significant charge trapping effect due to the space-charge field formed by immobile charges. Lower transient-state mobility was verified by the direct probing of carrier motion by TRM-SHG technique. It was shown that the trapping effect rises together with increase of SAM layers suggesting the presence of traps in the bulk of NP films. The model based on the electrostatic charge barrier is suggested to explain the phenomenon.
Lindsey E. Rustad
2006-01-01
Evidence continues to accumulate that humans are significantly increasing atmospheric CO2 concentrations, resulting in unprecedented changes in the global climate system. Experimental manipulations of terrestrial ecosystems and their components have greatly increased our understanding of short-term responses to these global perturbations and have...
NASA Technical Reports Server (NTRS)
Mickley, L. J.; Leibensperger, E. M.; Jacob, D. J.; Rind, D.
2012-01-01
We use a general circulation model (NASA Goddard Institute for Space Studies GCM 3) to investigate the regional climate response to removal of aerosols over the United States. We perform a pair of transient 2010e2050 climate simulations following a scenario of increasing greenhouse gas concentrations, with and without aerosols over the United States and with present-day aerosols elsewhere. We find that removing U.S. aerosol significantly enhances the warming from greenhouse gases in a spatial pattern that strongly correlates with that of the aerosol. Warming is nearly negligible outside the United States, but annual mean surface temperatures increase by 0.4e0.6 K in the eastern United States. Temperatures during summer heat waves in the Northeast rise by as much as 1e2 K due to aerosol removal, driven in part by positive feedbacks involving soil moisture and low cloud cover. Reducing U.S. aerosol sources to achieve air quality objectives could thus have significant unintended regional warming consequences.
NASA Astrophysics Data System (ADS)
Shah, Syed Afaq Ali; Sayyad, Muhammad Hassan; Abdulkarim, Salem; Qiao, Qiquan
2018-05-01
A step-by-step heat treatment was applied to ruthenium-based N719 dye solution for its potential application in dye-sensitized solar cells (DSSCs). The effects were analyzed and compared with standard untreated devices. A significant increase in short circuit current density was observed by employing a step-by-step heating method for dye solution in DSSCs. This increase of J sc is attributed to the enhancement in dye adsorption by the surface of the semiconductor and the higher number of charge carriers generated. DSSCs fabricated by a heated dye solution have achieved an overall power conversion efficiency of 8.41% which is significantly higher than the efficiency of 7.31% achieved with DSSCs fabricated without heated dye. Electrochemical impedance spectroscopy and capacitance voltage studies were performed to understand the better performance of the device fabricated with heated dye. Furthermore, transient photocurrent and transient photovoltage measurements were also performed to gain an insight into interfacial charge carrier recombinations.
Sigurdarson, Sigurdur T; O'Shaughnessy, Patrick T; Watt, Janet A; Kline, Joel N
2004-10-01
Ammonia and endotoxin-rich dust are present in high concentrations in swine confinement facilities; exposure to this environment is linked to workers' respiratory problems. We hypothesized that experimental exposure to ammonia and dust would impair pulmonary function, and that these exposures would be synergistic. We exposed six normal subjects and eight subjects with mild asthma to ammonia (16-25 ppm) and/or endotoxin-rich grain dust (4 mg/m3). Pulmonary function and exhaled NOx were measured before and after exposure. There was no significant change in pulmonary function in the normal subjects following any of the exposure conditions. Among asthmatics, a significant transient decrease in FEV1 was induced by grain dust, but was not altered by ammonia; increased bronchial hyperreactivity was also noted in this group. In a vulnerable population, exposure to grain dust results in transient airflow obstruction. Short-term exposure to ammonia does not increase this response.
Colom, L V; Alexianu, M E; Mosier, D R; Smith, R G; Appel, S H
1997-08-01
A hybrid motoneuron cell line (VSC4.1) was used as a model system to study the relationship between alterations in intracellular calcium and subsequent cell death induced by immunoglobulin fractions purified from sera of patients with ALS. Using fluo-3 fluorescence imaging, immunoglobulins from 8 of 10 patients with ALS were found to induce transient increases in intracellular calcium ([Ca2+]i) in differentiated VSC4.1 cells. These transient [Ca2+]i increases required extracellular calcium entry through voltage-gated calcium channels sensitive to synthetic FTX and to high concentrations (>1 microM) of omega-agatoxin IVa. The incidence of transient [Ca2+]i increases induced by ALS immunoglobulins correlated with the extent of cytotoxicity induced by the same ALS immunoglobulins in parallel cultures of VSC4.1 cells. Furthermore, manipulations which blocked transient [Ca2+]i increases (addition of synthetic FTX or omega-agatoxin IVa) also inhibited the cytotoxic effects of ALS immunoglobulins. No transient calcium increases were observed in VSC4.1 cells following addition of immunoglobulins from 7 neurologic disease control patients. However, transient [Ca2+]i increases were observed following addition of immunoglobulins from 4 of 5 patients with myasthenia gravis (MG). The [Ca2+]i changes induced by MG immunoglobulins were not blocked by s-FTX, suggesting that they result from a different mechanism than those induced by ALS immunoglobulins. These results suggest that immunoglobulins from patients with ALS can induce transient increases in intracellular calcium in a motoneuron cell line, which may represent early events in the cascade of processes leading to injury and death of susceptible cells.
Wu, K W; Yang, P; Li, S S; Liu, C W; Sun, F Y
2015-07-09
We recently indicated that the vascular endothelial growth factor (VEGF) protects neurons against hypoxic death via enhancement of tyrosine phosphorylation of Kv1.2, an isoform of the delayed-rectifier potassium channels through activation of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway. The present study investigated whether VEGF could attenuate ischemia-induced increase of the potassium currents in the hippocampal pyramidal neurons of rats after ischemic injury. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) to induce brain ischemia. The whole-cell patch-clamp technique was used to record the potassium currents of hippocampal neurons in brain slices from the ischemically injured brains of the rats 24h after MCAO. We detected that transient MCAO caused a significant increase of voltage-gated potassium currents (Kv) and outward delayed-rectifier potassium currents (IK), but not outward transient potassium currents (IA), in the ipsilateral hippocampus compared with the sham. Moreover, we found that VEGF could acutely, reversibly and voltage-dependently inhibit the ischemia-induced IK increase. This inhibitory effect of VEGF could be completely abolished by wortmannin, an inhibitor of PI3-K. Our data indicate that VEGF attenuates the ischemia-induced increase of IK via activation of the PI3-K signaling pathway. Published by Elsevier Ltd.
Chen, Yih-Ru; Hsieh, Fang-I; Lien, Li-Ming; Hu, Chaur-Jong; Jeng, Jiann-Shing; Peng, Giia-Sheun; Tang, Sung-Chun; Chi, Nai-Fang; Sung, Yueh-Feng; Chiou, Hung-Yi
2018-06-02
The effect of RA on recurrent stroke is unknown. Therefore, we examined effects of rheumatoid arthritis (RA) on risk of stroke recurrence and investigated the interaction between RA and traditional cardiovascular risk factors on recurrence risk after ischemic stroke (IS) or transient ischemic attack (TIA). Of 3190 patients with IS or TIA recruited in this cohort study, 638 were comorbid with RA and 2552 without RA. Stroke recurrence, RA, lifestyle, lipid variables and other comorbidities were identified through linkage between a nationwide stroke database in Taiwan and the National Health Insurance claims database. Cox proportional hazard models with competing risk adjustment were used to evaluate the relationship between RA and recurrent stroke. Patients with RA showed a significantly increased risk of recurrent stroke, particular in recurrent IS/TIA. The increased risk of recurrent IS/TIA in RA patients may through the changes of triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio. A positive additive interaction was observed between RA and current smoking on the risk of recurrent IS/TIA. Significantly increased risks for recurrent IS/TIA were observed among RA patients who smoked > 40 years or those who smoked > 20 cigarettes/day. This study provides the first evidence that RA significantly increased recurrence IS/TIA risk. The changes of TG/HDL-C ratio may play some roles in the recurrence IS/TIA risk in RA patients. In addition, our results suggest that smoking increases the risk of recurrent IS/TIA in RA patients and reinforces the need for aggressive smoking cessation efforts in RA patients.
Charidimou, Andreas; Kakar, Puneet; Fox, Zoe; Werring, David J
2013-04-01
To evaluate cerebral microbleeds (CMBs) and future stroke risk (including intracerebral hemorrhage [ICH]) in patients with ischemic stroke (IS) or transient ischemic attack. A systematic review and meta-analysis of prospective cohorts with recent IS/transient ischemic attack. We critically appraised studies and calculated pooled odds ratios (ORs), using the Mantel-Haenszel fixed-effects method, for ICH or recurrent IS, in patients with versus without CMBs. We pooled data from 10 cohorts, including 3067 patients. CMBs were associated with a significant increased risk of any recurrent stroke (OR, 2.25; 95% confidence interval [95% CI], 1.70-2.98; P<0.0001), ICH (OR, 8.52; 95%CI, 4.23-17.18; P=0.007), and IS (OR, 1.55; 95%CI, 1.12-2.13; P<0.0001). When stratified by study population ethnicity (Asian versus Western [mainly white European]), the association of CMBs with ICH was significant for Asian cohorts (5 studies; n=1915; OR, 10.43; 95%CI, 4.59-23.72; P<0.0001) but borderline and of lower magnitude for Western cohorts (4 studies; n=885; OR, 3.87; 95%CI, 0.91-16.4; P=0.066). By contrast, there was a significant association of CMBs with recurrent IS in Western (3 studies; n=899) but not Asian cohorts (4 studies; n=1357; OR, 2.23; 95%CI, 1.29-3.85; P=0.004 compared with OR, 1.30; 95%CI, 0.88-1.93; P=0.192, respectively). There is consistent evidence of an increased risk of recurrent stroke after IS or transient ischemic attack in patients with CMBs. The risk for spontaneous ICH appears to be greater than the risk for recurrent IS. Our findings also suggest that the balance of risk for ICH versus IS differs between Asian and Western cohorts.
Kumas, Meltem; Altintas, Ozge; Karatas, Ersin; Kocyigit, Abdurrahim
2017-01-01
Background Remote ischemic preconditioning (IPreC) could provide tissue-protective effect at a remote site by anti-inflammatory, neuronal, and humoral signaling pathways. Objectives The aim of the study was to investigate the possible protective effects of remote IPreC on myocardium after transient middle cerebral artery occlusion (MCAo) in streptozotocin- induced diabetic (STZ) and non-diabetic rats. Methods 48 male Spraque Dawley rats were divided into eight groups: Sham, STZ, IPreC, MCAo, IPreC+MCAo, STZ+IPreC, STZ+MCAo and STZ+IPreC+MCAo groups. We induced transient MCAo seven days after STZ-induced diabetes, and performed IPreC 72 hours before transient MCAo. Remote myocardial injury was investigated histopathologically. Bax, Bcl2 and caspase-3 protein levels were measured by Western blot analysis. Total antioxidant status (TAS), total oxidant status (TOS) of myocardial tissue were measured by colorimetric assay. Oxidative stress index(OSI) was calculated as TOS-to-TAS ratio. For all statistical analysis, p values < 0.05 were considered significant. Results We observed serious damage including necrosis, congestion and mononuclear cell infiltration in myocardial tissue of the diabetic and ischemic groups. In these groups TOS and OSI levels were significantly higher; TAS levels were lower than those of IPreC related groups (p < 0.05). IPreC had markedly improved histopathological alterations and increased TAS levels in IPreC+MCAo and STZ+IPreC+MCAo compared to MCAo and STZ+MCAo groups (p < 0.05). In non-diabetic rats, MCAo activated apoptotic cell death via increasing Bax/Bcl2 ratio and caspase-3 levels. IPreC reduced apoptotic cell death by suppressing pro-apoptotic proteins. Diabetes markedly increased apoptotic protein levels and the effect did not reversed by IPreC. Conclusions We could suggest that IPreC attenuates myocardial injury via ameliorating histological findings, activating antioxidant mechanisms, and inducing antiapoptotic activity in diabetic rats. PMID:29160389
Adibhatla, Rao Muralikrishna; Hatcher, James F
2003-08-01
Neuroprotection by citicoline (CDP-choline) in transient cerebral ischemia has been demonstrated previously. Citicoline has undergone several Phase III clinical trials for stroke, and is being evaluated for treatment of Alzheimer's and Parkinson's diseases. Phospholipid degradation and generation of reactive oxygen species (ROS) are major factors causing neuronal injury in CNS trauma and neurodegenerative diseases. Oxidative metabolism of arachidonic acid (released by the action of phospholipases) contributes to ROS generation. We examined the effect of citicoline on phospholipase A(2) (PLA(2)) activity in relation to the attenuation of hydroxyl radical (OH.) generation after transient forebrain ischemia of gerbil. PLA(2) activity (requires mM Ca(2+)) increased significantly (P < 0.05) in both membrane (50.2 +/- 2.2 pmol/min/mg protein compared to sham 35.9 +/- 3.2) and mitochondrial fractions (77.0 +/- 1.2 pmol/min/mg protein compared to sham 33.9 +/- 1.2) after cerebral ischemia and 2 hr reperfusion in gerbil, which was significantly attenuated (P < 0.01) by citicoline (membrane, 39.9. +/- 2.2 and mitochondria, 41.9 +/- 3.2 pmol/min/mg protein). In vitro, citicoline and its components cytidine and choline had no effect on PLA(2) activity, and thus citicoline as such is not a PLA(2) inhibitor. Ischemia/reperfusion resulted in significant OH. generation (P < 0.01) and citicoline significantly (P < 0.01) attenuated their formation (expressed as 2,3-dihydroxybenzoic acid/salicylate ratio; ischemia/24 hr reperfusion, 6.30 +/- 0.23; sham, 2.56 +/- 0.27; ischemia/24 hr reperfusion + citicoline, 4.85 +/- 0.35). These results suggest that citicoline affects PLA(2) stimulation and decreases OH. generation after transient cerebral ischemia. Copyright 2003 Wiley-Liss, Inc.
Gadjanski, Ivana; Yodmuang, Supansa; Spiller, Kara; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana
2013-10-01
Formation of tissue-engineered cartilage is greatly enhanced by mechanical stimulation. However, direct mechanical stimulation is not always a suitable method, and the utilization of mechanisms underlying mechanotransduction might allow for a highly effective and less aggressive alternate means of stimulation. In particular, the purinergic, adenosine 5'-triphosphate (ATP)-mediated signaling pathway is strongly implicated in mechanotransduction within the articular cartilage. We investigated the effects of transient and continuous exogenous ATP supplementation on mechanical properties of cartilaginous constructs engineered using bovine chondrocytes and human mesenchymal stem cells (hMSCs) encapsulated in an agarose hydrogel. For both cell types, we have observed significant increases in equilibrium and dynamic compressive moduli after transient ATP treatment applied in the fourth week of cultivation. Continuous ATP treatment over 4 weeks of culture only slightly improved the mechanical properties of the constructs, without major changes in the total glycosaminoglycan (GAG) and collagen content. Structure-function analyses showed that transiently ATP-treated constructs, and in particular those based on hMSCs, had the highest level of correlation between compositional and mechanical properties. Transiently treated groups showed intense staining of the territorial matrix for GAGs and collagen type II. These results indicate that transient ATP treatment can improve functional mechanical properties of cartilaginous constructs based on chondrogenic cells and agarose hydrogels, possibly by improving the structural organization of the bulk phase and territorial extracellular matrix (ECM), that is, by increasing correlation slopes between the content of the ECM components (GAG, collagen) and mechanical properties of the construct.
2012-01-01
Background Rheumatoid arthritis (RA) is associated with increased morbidity and mortality from cardiovascular disease (CVD). This can be only partially attributed to traditional CVD risk factors such as dyslipidaemia and their downstream effects on endothelial function. The most common lipid abnormality in RA is reduced levels of high-density lipoprotein (HDL) cholesterol, probably due to active inflammation. In this longitudinal study we hypothesised that anti-tumor necrosis factor-α (anti-TNFα) therapy in patients with active RA improves HDL cholesterol, microvascular and macrovascular endothelial function. Methods Twenty-three RA patients starting on anti-TNFα treatment were assessed for HDL cholesterol level, and endothelial-dependent and -independent function of microvessels and macrovessels at baseline, 2-weeks and 3 months of treatment. Results Disease activity (CRP, fibrinogen, DAS28) significantly decreased during the follow-up period. There was an increase in HDL cholesterol levels at 2 weeks (p < 0.05) which was paralleled by a significant increase in microvascular endothelial-dependent function (p < 0.05). However, both parameters returned towards baseline at 12 weeks. Conclusion Anti-TNFα therapy in RA patients appears to be accompanied by transient but significant improvements in HDL cholesterol levels, which coexists with an improvement in microvascular endothelial-dependent function. PMID:22824166
Malinova, Irina; Steup, Martin; Fettke, Joerg
2013-09-01
Plants metabolize transitory starch by precisely coordinated plastidial and cytosolic processes. The latter appear to include the action of water-soluble heteroglycans (SHGin ) whose monosaccharide pattern is similar to that of apoplastic glycans (SHGex ) but, unlike SHGex , SHGin strongly interacts with glucosyl transferases. In this study, we analyzed starch metabolism using mesophyll protoplasts from wild-type plants and two knock-out mutants [deficient in the cytosolic transglucosidase, disproportionating isoenzyme 2 (DPE2) or the plastidial phosphoglucomutase (PGM1)] from Arabidopsis thaliana. Protoplasts prelabeled by photosynthetic (14) CO2 fixation were transferred to an unlabeled medium and were darkened or illuminated. Carbon transitions from the Calvin cycle or from starch to both SHGin and SHGex were analyzed. In illuminated protoplasts, starch turn-over was undetectable but darkened protoplasts continuously degraded starch. During illumination, neither the total (14) C content nor the labeling patterns of the sugar residues of SHGin were significantly altered but both the total amount and the labeling of the constituents of SHGex increased with time. In darkened protoplasts, the (14) C-content of most of the sugar residues of SHGin transiently and strongly increased and then declined. This effect was not observed in any SHGex constituent. In darkened DPE2-deficient protoplasts, none of the SHGin constituents exhibited an essential transient increase in labeling. In contrast, some residues of SHGin from the PGM1 mutant exhibited a transient increase in label but this effect significantly differed from that of the wild type. Two conclusions are reached: first, SHGin and SHGex exert different metabolic functions and second, SHGin is directly involved in starch degradation. © 2013 Scandinavian Plant Physiology Society.
Ruocco, Gaetano; Nuti, Ranuccio; Giambelluca, Amalia; Evangelista, Isabella; De Vivo, Oreste; Daniello, Cosimo; Palazzuoli, Alberto
2017-11-01
Worsening renal function (WRF) occurs in one-third of patients hospitalized for acute decompensated heart failure. Recently, WRF was categorized in two subtypes: persistent and transient WRF. Thus, we sought to investigate the different prognostic impact of persistent vs. transient WRF; we also evaluate the relation of two WRF phenotypes with congestion, B-type natriuretic peptide (BNP) changes, and diuretic response at discharge. The prospective was a single centre study including patients screened for interventional Diur-heart failure Trial (NCT01441245). Patients were eligible if they were admitted with a primary diagnosis of acute heart failure with evidence of volume overload. Persistent WRF was defined as a sustained creatinine increase by at least 0.3 mg/dl throughout the hospitalisation; transient WRF was defined as creatinine increase by at least 0.3 mg/dl within 72 h and a return to baseline levels at discharge. Patients were followed for 6 months after discharge. Our population included 192 acute decompensated heart failure patients. In total, 61 patients developed persistent WRF and 29 developed transient WRF. Patients with persistent WRF showed a lower mean urine output with respect to the transient WRF group and patients with preserved renal function (1618 ± 374 vs. 2132 ± 392 vs. 2075 ± 442 ml; P < 0.001). Similarly, patients with transient WRF demonstrated a higher rate of BNP decrease more than 30% than seen in patients with stable creatinine levels and in the persistent WRF group (95 vs. 76 vs. 54%; P = 0.001). Univariate Cox regression analysis demonstrated that BNP decrease less than 30% [HR 2.15 (1.40-3.40); P < 0.001] and persistent WRF [HR 1.70 (1.11-2.61); P = 0.01] were related to poor outcome; conversely, transient WRF should be considered as a protective factor [HR 0.42 (0.19-0.93); P = 0.03]. In the multivariable model, only persistent WRF appeared to be related to poor prognosis [HR 1.61 (1.02-2.57); P = 0.04]. WRF occurring during hospitalization has a different significance: transient deterioration appears to be associated with a favourable clinical course; conversely, persistent WRF is related to poor outcome.
Yon, Marianne; Pickavance, Lucy; Yanni Gerges, Joseph; Davis, Gershan; Wilding, John; Jian, Kun; Hart, George; Boyett, Mark
2016-01-01
Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR. Obese rats had significant upregulation of Cav1.2, HCN4, Kir2.1, RYR2, NCX1, SERCA2a, and RYR2 mRNA and downregulation of ERG mRNA. In the case of HCN4, it was confirmed that there was a significant increase in protein expression. The potential effects of the mRNA changes on the ventricular action potential and intracellular Ca2+ transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca2+ transient, both of which would be expected to be arrhythmogenic. Conclusion. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules. PMID:27747100
Roberts, B.J.; Mulholland, P.J.; Houser, J.N.
2007-01-01
Delivery of water, sediments, nutrients, and organic matter to stream ecosystems is strongly influenced by the catchment of the stream and can be altered greatly by upland soil and vegetation disturbance. At the Fort Benning Military Installation (near Columbus, Georgia), spatial variability in intensity of military training results in a wide range of intensities of upland disturbance in stream catchments. A set of 8 streams in catchments spanning this upland disturbance gradient was selected for investigation of the impact of disturbance intensity on hydrodynamics and nutrient uptake. The size of transient storage zones and rates of NH4+ uptake in all study streams were among the lowest reported in the literature. Upland disturbance did not appear to influence stream hydrodynamics strongly, but it caused significant decreases in instream nutrient uptake. In October 2003, coarse woody debris (CWD) was added to 1/2 of the study streams (spanning the disturbance gradient) in an attempt to increase hydrodynamic and structural complexity, with the goals of enhancing biotic habitat and increasing nutrient uptake rates. CWD additions had positive short-term (within 1 mo) effects on hydrodynamic complexity (water velocity decreased and transient storage zone cross-sectional area, relative size of the transient storage zone, fraction of the median travel time attributable to transient storage over a standardized length of 200 m, and the hydraulic retention factor increased) and nutrient uptake (NH4+ uptake rates increased). Our results suggest that water quality in streams with intense upland disturbances can be improved by enhancing instream biotic nutrient uptake capacity through measures such as restoring stream CWD. ?? 2007 by The North American Benthological Society.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kreutzer, Cory J.; Rugh, John; Tomerlin, Jeff
Increased market penetration of electric drive vehicles (EDVs) requires overcoming a number of hurdles, including limited vehicle range and the elevated cost in comparison to conventional vehicles. Climate control loads have a significant impact on range, cutting it by over 50% in both cooling and heating conditions. To minimize the impact of climate control on EDV range, the National Renewable Energy Laboratory has partnered with Hyundai America and key industry partners to quantify the performance of thermal load reduction technologies on a Hyundai Sonata plug-in hybrid electric vehicle. Technologies that impact vehicle cabin heating in cold weather conditions and cabinmore » cooling in warm weather conditions were evaluated. Tests included thermal transient and steady-state periods for all technologies, including the development of a new test methodology to evaluate the performance of occupant thermal conditioning. Heated surfaces demonstrated significant reductions in energy use from steady-state heating, including a 29%-59% reduction from heated surfaces. Solar control glass packages demonstrated significant reductions in energy use for both transient and steady-state cooling, with up to a 42% reduction in transient and 12.8% reduction in steady-state energy use for the packages evaluated. Technologies that demonstrated significant climate control load reduction were selected for incorporation into a complete thermal load reduction package. The complete package is set to be evaluated in the second phase of the ongoing project.« less
Kim, In Hye; Lee, Tae-Kyeong; Cho, Jeong Hwi; Lee, Jae-Chul; Park, Joon Ha; Ahn, Ji Hyeon; Shin, Bich-Na; Chen, Bai Hui; Tae, Hyun-Jin; Kim, Yang Hee; Kim, Jong-Dai; Kim, Young-Myeong; Won, Moo-Ho; Kang, Il Jun
2017-01-01
Chrysanthemum indicum Linné extract (CIL) is used in herbal medicine in East Asia. In the present study, gerbils were orally pre-treated with CIL, and changes of antioxidant enzymes including superoxide dismutase (SOD) 1 and SOD2, catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal CA1 region following 5 min of transient cerebral ischemia were investigated and the neuroprotective effect of CIL in the ischemic CA1 region was examined. SOD1, SOD2, CAT and GPX immunoreactivities were observed in the pyramidal cells of the CA1 region and their immunoreactivities were gradually decreased following ischemia-reperfusion and barely detectable at 5 days post-ischemia. CIL pre-treatment significantly increased immunoreactivities of SOD1, CAT and GPX, but not SOD2, in the CA1 pyramidal cells of the sham-operated animals. In addition, SOD1, SOD2, CAT and GPX immunoreactivities in the CA1 pyramidal cells were significantly higher compared with the ischemia-operated animals. Furthermore, it was identified that pre-treatment with CIL protected the CA1 pyramidal cells in the CA1 region using neuronal nuclei immunohistochemistry and Fluoro-Jade B histofluorescence staining; the protected CA1 pyramidal cells were 67.5% compared with the sham-operated animals. In conclusion, oral CIL pre-treatment increased endogenous antioxidant enzymes in CA1 pyramidal cells in the gerbil hippocampus and protected the cells from transient cerebral ischemic insult. This finding suggested that CIL is promising for the prevention of ischemia-induced neuronal damage. PMID:28534982
Chimeric Peptide Tat-HA-NR2B9c Improves Regenerative Repair after Transient Global Ischemia.
Zhou, Hai-Hui; Zhang, Li; Zhang, Hai-Xia; Zhang, Jin-Ping; Ge, Wei-Hong
2017-01-01
Transient global ischemia (TGI) is a major public health problem, and it heightens the need of effective treatments. The present study was undertaken to investigate whether recombinant polypeptide Tat-HA-NR2B9c improves spatial learning and memory deficits in rats after TGI. Rats were subjected to 20-min ischemia induced by four-vessel occlusion (4-VO) method and daily injected with Tat-HA-NR2B9c (1.12 mg/kg) for 1 week. Tat-HA-NR2B9c increased CREB activity, upregulated B-cell lymphoma-2 (Bcl-2) expression after treated for 24 h. There was a significant increase in dendrite spine density in hippocampal CA1 region and BrdU-positive cells and BrdU/NeuN-positive cells in the dentate gyrus after Tat-HA-NR2B9c treatment, compared with ischemia group at postischemic day 28. Inhibition of the CREB activation by recombinant lentivirus, LV-CREB133-GFP, abolished the upregulation effects of Tat-HA-NR2B9c on Bcl-2 expression. Moreover, Tat-HA-NR2B9c improved the impaired spatial learning and memory ability in Morris water maze. These results suggest that Tat-HA-NR2B9c substantially ameliorated the TGI-induced loss of dendrite spine in hippocampal CA1, increased neurogenesis in dentate gyrus, and significantly improved cognitive abilities by the CREB pathway in rats after transient global cerebral ischemia. It may be served as a treatment for TGI.
Vapor Flow Patterns During a Start-Up Transient in Heat Pipes
NASA Technical Reports Server (NTRS)
Issacci, F.; Ghoniem, N, M.; Catton, I.
1996-01-01
The vapor flow patterns in heat pipes are examined during the start-up transient phase. The vapor core is modelled as a channel flow using a two dimensional compressible flow model. A nonlinear filtering technique is used as a post process to eliminate the non-physical oscillations of the flow variables. For high-input heat flux, multiple shock reflections are observed in the evaporation region. The reflections cause a reverse flow in the evaporation and circulations in the adiabatic region. Furthermore, each shock reflection causes a significant increase in the local pressure and a large pressure drop along the heat pipe.
Correlation of transient adenosine release and oxygen changes in the caudate-putamen
Wang, Ying; Venton, B. Jill
2016-01-01
Adenosine is an endogenous nucleoside that modulates important physiological processes, such as vasodilation, in the central nervous system. A rapid, 2–4 seconds, mode of adenosine signaling has been recently discovered, but the relationship between this type of adenosine and blood flow change has not been characterized. In this study, adenosine and oxygen changes were simultaneously measured using fast-scan cyclic voltammetry. Oxygen changes occur when there is an increase in local cerebral blood flow and thus are a measure of vasodilation. About 34% of adenosine transients in the rat caudate-putamen are correlated with a subsequent transient change in oxygen. The amount of oxygen was correlated with the concentration of adenosine release and larger adenosine transients (over 0.4 μM) always had subsequent oxygen changes. The average duration of adenosine and oxygen transients were 3.2 seconds and 3.5 seconds, respectively. On average, the adenosine release starts and peaks 0.2 seconds prior to the oxygen. The A2a antagonist, SCH442416, decreased the number of both adenosine and oxygen transient events by about 32%. However, the A1 antagonist, DPCPX, did not significantly affect simultaneous adenosine and oxygen release. The nitric oxide (NO) synthase inhibitor L-NAME also did not affect the concentration or number of adenosine and oxygen release events. These results demonstrate that both adenosine and oxygen release are modulated via A2a receptors. The correlation of transient concentrations, time delay between adenosine and oxygen peaks, and effect of A2a receptors suggests adenosine modulates blood flow on a rapid, sub-second time scale. PMID:27314215
Jiang, Zheng; Li, Chun; Arrick, Denise M; Yang, Shu; Baluna, Alexandra E; Sun, Hong
2014-01-01
The role of nitric oxide synthases (NOSs) in early blood-brain barrier (BBB) disruption was determined using a new mouse model of transient focal cerebral ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA) at its M2 segment and reperfusion was induced by releasing the ligation. The diameter alteration of the MCA, arterial anastomoses and collateral arteries were imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. The reperfusion produced an extensive vasodilation and a sustained hyperemia. Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a non-specific NOS inhibitor) abolished reperfusion-induced vasodilation/hyperemia and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS (eNOS) inhibitor) significantly attenuated cerebral vasodilation but not BBB disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS) inhibitors) significantly reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine (AG) (an inducible NOS (iNOS) inhibitor) had less effect on either cerebral vasodilation or BBB disruption. On the other hand, papaverine (PV) not only increased the vasodilation/hyperemia but also significantly reduced BBB disruption. Combined treatment with L-NAME and PV preserved the vasodilation/hyperemia and significantly reduced BBB disruption. Our findings suggest that nNOS may play a major role in early BBB disruption following transient focal cerebral ischemia via a hyperemia-independent mechanism.
Farkas, Laszlo; Farkas, Daniela; Gauldie, Jack; Warburton, David; Shi, Wei; Kolb, Martin
2011-01-01
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease of the lung parenchyma, without curative treatment. Gremlin is a bone morphogenic protein (BMP) antagonist, its expression being increased in IPF lungs. It has been implicated in promoting myofibroblast accumulation, likely through inhibited fibroblast apoptosis and epithelial-to-mesenchymal transition. In the current study, we examined the effects of selective adenovirus-mediated overexpression of Gremlin in rat lungs. We show that transient Gremlin overexpression results in activation of alveolar epithelial cells with proliferation and apoptosis, as well as partly reversible lung fibrosis. We found myofibroblasts arranged in fibroblastic foci. Fibroblast proliferation occurred delayed as compared with epithelial changes. Fibrotic pathology significantly declined after Day 14, the reversal being associated with an increase of the epithelium-protective element, fibroblast growth factor (FGF)–10. Our data indicate that Gremlin-mediated BMP inhibition results in activation of epithelial cells and transient fibrosis, but also induction of epithelium-protective FGF10. A Gremlin–BMP–FGF10 loop may explain these results, and demonstrate that the interactions between different factors are quite complex in fibrotic lung disease. Increased Gremlin expression in human IPF tissue may be an expression of continuing epithelial injury, and Gremlin may be part of activated repair mechanisms. PMID:20705941
Fleming, J V; Hay, S M; Harries, D N; Rees, W D
1998-01-01
The growth-arrest genes (gas and gadd) are widely expressed during mammalian embryogenesis and may be useful as markers of nutritional stress in the embryo. F9 embryonal carcinoma cells have been used to characterize the effect of serum or amino acid deficiency on growth-arrest gene expression in a differentiating embryonic cell. The differentiation markers, homeobox B2 (HoxB2), collagen type IV and laminin B2, were not induced by growth arrest. Treatment with all-trans retinoic acid (RA) produced a dose-dependent increase in alkaline phosphatase activity, which was unchanged in lysine-deficient medium and reduced in low-serum medium. Low-serum medium also reduced HoxB2 expression. There was a transient 2-6-fold increase in mRNAs for C/EBP-beta, gadd153/CHOP-10 and gas5 genes 24 h after transfer to amino-acid-deficient media. The mRNAs for the gas2 and gas6 genes began to rise slowly by 5-10-fold after a delay of approx. 24 h. The transient increases did not occur in low-serum medium where there was a much smaller and slower increase. Differentiation caused 1-2-fold increases in gas2, gas3 and gas6 mRNA levels. The transient overexpression of gas5, gadd153/CHOP-10 and CCAAT-enhancer-binding protein-beta, and the later expression of gas6 mRNAs in response to amino acid deficiency, were not affected by differentiation. RA treatment increased the expression of gas3 and caused gas2 to be transiently overexpressed in amino-acid-deficient medium. Differentiation in serum-deficient medium did not significantly alter the levels of the growth-arrest gene mRNAs. These results show that in F9 cells the growth-arrest genes are expressed sequentially as a result of nutrient stress. PMID:9461558
Fleming, J V; Hay, S M; Harries, D N; Rees, W D
1998-02-15
The growth-arrest genes (gas and gadd) are widely expressed during mammalian embryogenesis and may be useful as markers of nutritional stress in the embryo. F9 embryonal carcinoma cells have been used to characterize the effect of serum or amino acid deficiency on growth-arrest gene expression in a differentiating embryonic cell. The differentiation markers, homeobox B2 (HoxB2), collagen type IV and laminin B2, were not induced by growth arrest. Treatment with all-trans retinoic acid (RA) produced a dose-dependent increase in alkaline phosphatase activity, which was unchanged in lysine-deficient medium and reduced in low-serum medium. Low-serum medium also reduced HoxB2 expression. There was a transient 2-6-fold increase in mRNAs for C/EBP-beta, gadd153/CHOP-10 and gas5 genes 24 h after transfer to amino-acid-deficient media. The mRNAs for the gas2 and gas6 genes began to rise slowly by 5-10-fold after a delay of approx. 24 h. The transient increases did not occur in low-serum medium where there was a much smaller and slower increase. Differentiation caused 1-2-fold increases in gas2, gas3 and gas6 mRNA levels. The transient overexpression of gas5, gadd153/CHOP-10 and CCAAT-enhancer-binding protein-beta, and the later expression of gas6 mRNAs in response to amino acid deficiency, were not affected by differentiation. RA treatment increased the expression of gas3 and caused gas2 to be transiently overexpressed in amino-acid-deficient medium. Differentiation in serum-deficient medium did not significantly alter the levels of the growth-arrest gene mRNAs. These results show that in F9 cells the growth-arrest genes are expressed sequentially as a result of nutrient stress.
Suppression of the PI3K subunit p85α delays embryoid body development and inhibits cell adhesion.
Gurney, Susan M R; Forster, Peter; Just, Ursula; Schwanbeck, Ralf
2011-12-01
Phosphatidylinositol-3-kinases (PI3Ks) exert a variety of signaling functions in eukaryotes. We suppressed the PI3K regulatory subunit p85α using a small interfering RNA (Pik3r1 siRNA) and examined the effects on embryoid body (EB) development in hanging drop culture. We observed a 150% increase in the volume of the treated EBs within 24 h, compared to the negative controls. Fluorescence Activated Cell Sorting (FACS) assays showed that this increase in volume is not due to increased cellular proliferation. Instead, the increase in volume appears to be due to reduced cellular aggregation and adherence. This is further shown by our observation that 40% of treated EBs form twin instead of single EBs, and that they have a significantly reduced ability to adhere to culture dishes when plated. A time course over the first 96 h reveals that the impaired adherence is transient and explained by an initial 12-hour delay in EB development. Quantitative PCR expression analysis suggests that the adhesion molecule integrin-β1 (ITGB1) is transiently downregulated by the p85α suppression. In conclusion we found that suppressing p85α leads to a delay in forming compact EBs, accompanied by a transient inability of the EBs to undergo normal cell-cell and cell-substrate adhesion. Copyright © 2011 Wiley Periodicals, Inc.
Dissection of the Effects of Quercetin on Mouse Myocardium.
Santos, Michel Santana; Oliveira, Evaleide Diniz; Santos-Miranda, Artur; Cruz, Jader Santos; Gondim, Antônio Nei Santana; Menezes-Filho, José Evaldo Rodrigues; Souza, Diego Santos; Pinho-da-Silva, Leidiane; Jesus, Itamar Couto Guedes; Roman-Campos, Danilo; Guatimosim, Silvia; Lara, Aline; Conde-Garcia, Eduardo Antônio; Vasconcelos, Carla Maria Lins
2017-06-01
Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an involvement of the sympathetic nervous system. In cardiomyocytes, 30 μM quercetin increased I Ca,L at 0 mV from -0.95 ± 0.01 A/F to -1.21 ± 0.08 A/F. The membrane potential at which 50% of the channels are activated (V 0.5 ) shifted towards more negative potentials from -13.06 ± 1.52 mV to -19.26 ± 1.72 mV and did not alter the slope factor. Furthermore, quercetin increased [Ca 2+ ] i transient by 28% when compared to control. Quercetin accelerated [Ca 2+ ] i transient decay time, which could be attributed to SERCA activation. In resting cardiomyocytes, quercetin did not change amplitude or frequency of Ca 2+ sparks. In isolated heart, quercetin increased heart rate and decreased PRi, QTc and duration of the QRS complex. Thus, we showed that quercetin activates β-adrenoceptors, leading to increased L-type Ca 2+ current and cell-wide intracellular Ca 2+ transient without visible changes in Ca 2+ sparks. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Machado, Gustavo C; Ferreira, Paulo H; Maher, Chris G; Latimer, Jane; Steffens, Daniel; Koes, Bart W; Li, Qiang; Ferreira, Manuela L
2016-12-01
A previous study has shown that transient physical and psychosocial activities increased the risk of developing low back pain. However, the link between these factors in triggering nonpersistent or persistent episodes remains unclear. We aimed to investigate the association of transient exposures to physical and psychosocial activities with the development of nonpersistent or persistent low back pain. This was a case-crossover study with 12 months follow-up. We included 999 consecutive participants seeking care for a sudden onset of low back pain. Development of low back pain was the outcome measure. At baseline, participants reported transient exposures to 12 predefined activities over the 4 days preceding pain onset. After 12 months, participants were asked whether they had recovered and the date of recovery. Exposures in the 2-hour period preceding pain onset (case window) were compared with the 2-hour period, 24 hours before pain onset (control window) in a case-crossover design for all participants. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI), and interaction analyses were used to compare estimates of nonpersistent (i.e., <6 weeks duration) and persistent cases. This study received funding from Australia's National Health and Medical Research Council (APP1003608). There were 832 participants (83%) who completed the 12 months follow-up successfully. Of these, 430 participants had nonpersistent low back pain (<6 weeks duration), whereas 352 reported persistent symptoms (≥6 weeks duration). Exposure to several transient activities, such as manual tasks involving heavy loads, awkward postures, live people or animals, moderate or vigorous physical activity, and being fatigued or tired during a task or activity, significantly increased the risk of both nonpersistent and persistent low back pain, with ORs ranging from 2.9 to 11.7. Overall, the risk of developing a persistent or a nonpersistent episode of low back pain associated with the included physical factors did not differ significantly. Our results revealed that previously identified triggers contribute equally to the development of both nonpersistent and persistent low back pain. Future prevention strategies should focus on controlling exposure to these triggers as they have the potential to decrease the burden associated with both acute and chronic low back pain. Copyright © 2016 Elsevier Inc. All rights reserved.
Yi, SangHak; Park, Young Ho; Jang, Jae-Won; Lim, Jae-Sung; Chun, In Kook; Kim, SangYun
2018-05-01
Perturbation of corticohippocampal circuits is a key step in the pathogenesis of transient global amnesia. We evaluated the spatial distribution of altered cerebral metabolism to determine the location of the corticohippocampal circuits perturbed during the acute stage of transient global amnesia. A consecutive series of 12 patients with transient global amnesia who underwent 18 F-fluorodeoxyglucose positron emission tomography within 3 days after symptom onset was identified. We used statistical parametric mapping with two contrasts to identify regions of decreased and increased brain metabolism in transient global amnesia patients compared with 25 age-matched controls. Transient global amnesia patients showed hypometabolic clusters in the left temporal and bilateral parieto-occipital regions that belong to the posterior medial network as well as, hypermetabolic clusters in the bilateral inferior frontal regions that belong to the anterior temporal network. The posterior medial and anterior temporal networks are the two main corticohippocampal circuits involved in memory-guided behavior. Decreased metabolism in the posterior medial network might explain the impairment of episodic memory observed during the acute stage of transient global amnesia. Concomitant increased metabolism within the anterior temporal network might occur as a compensatory mechanism.
Small gravitationally elicited voltage transients in pea stems
NASA Technical Reports Server (NTRS)
Pickard, B. G.
1984-01-01
Decapitated veritcal stem segments were observed for 45 min, noting the number of transients mu V for each 5-min interval. Results for two sets of stem segments are plotted. The average frequencies were 0.72 + or -0.05 and 0.66 + or - 0.04 per 5 min. One set of segments was swiveled gently to the horizontal position; then, recording continued for another 90 min. Transients continued in the vertical controls at a closely similar average rate 0.78 + or - 0.04 per 5 min. However, after the first 5-min interval the horizontally placed plants exhibited transients at an increased average rate of 1.08 + or - 0.04 per 5 min. The frequency of transients also increased following horizontal placement of intact shoots. However, it appears that this increase had two components: one due to gravity reception, and one due to the redistribution of indolacetic acid (IAA) believed to mediate gravitropic curvature (or, more specifically, to the increase of IAA in the lower tissue.
Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki
2017-01-01
Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380
A hybrid three-class brain-computer interface system utilizing SSSEPs and transient ERPs
NASA Astrophysics Data System (ADS)
Breitwieser, Christian; Pokorny, Christoph; Müller-Putz, Gernot R.
2016-12-01
Objective. This paper investigates the fusion of steady-state somatosensory evoked potentials (SSSEPs) and transient event-related potentials (tERPs), evoked through tactile simulation on the left and right-hand fingertips, in a three-class EEG based hybrid brain-computer interface. It was hypothesized, that fusing the input signals leads to higher classification rates than classifying tERP and SSSEP individually. Approach. Fourteen subjects participated in the studies, consisting of a screening paradigm to determine person dependent resonance-like frequencies and a subsequent online paradigm. The whole setup of the BCI system was based on open interfaces, following suggestions for a common implementation platform. During the online experiment, subjects were instructed to focus their attention on the stimulated fingertips as indicated by a visual cue. The recorded data were classified during runtime using a multi-class shrinkage LDA classifier and the outputs were fused together applying a posterior probability based fusion. Data were further analyzed offline, involving a combined classification of SSSEP and tERP features as a second fusion principle. The final results were tested for statistical significance applying a repeated measures ANOVA. Main results. A significant classification increase was achieved when fusing the results with a combined classification compared to performing an individual classification. Furthermore, the SSSEP classifier was significantly better in detecting a non-control state, whereas the tERP classifier was significantly better in detecting control states. Subjects who had a higher relative band power increase during the screening session also achieved significantly higher classification results than subjects with lower relative band power increase. Significance. It could be shown that utilizing SSSEP and tERP for hBCIs increases the classification accuracy and also that tERP and SSSEP are not classifying control- and non-control states with the same level of accuracy.
Features of Chaotic Transients in Excitable Media Governed by Spiral and Scroll Waves
NASA Astrophysics Data System (ADS)
Lilienkamp, Thomas; Christoph, Jan; Parlitz, Ulrich
2017-08-01
In excitable media, chaotic dynamics governed by spiral or scroll waves is often not persistent but transient. Using extensive simulations employing different mathematical models we identify a specific type-II supertransient by an exponential increase of transient lifetimes with the system size in 2D and an investigation of the dynamics (number and lifetime of spiral waves, Kaplan-Yorke dimension). In 3D, simulations exhibit an increase of transient lifetimes and filament lengths only above a critical thickness. Finally, potential implications for understanding cardiac arrhythmias are discussed.
Zhang, Liu-xia; Wang, Shu-zhong; Sui, Xiao-lei; Zhang, Zhen-xian
2011-09-01
This paper studied the effects of alternative furrow irrigation and nitrogen (N) application rate (no N, optimal N, and conventional N) on the photosynthesis, growth characteristics, yield formation, and fruit quality of cucumber (Cucumis sativus) cultivar Jinyu No. 5 in a solar greenhouse in winter-spring growth season and autumn-winter season. Under alternative furrow irrigation, the net photosynthetic rate of upper, middle, eand lower leaves was appreciably lower and the transpiration rate decreased significantly, and the transient water use efficiency of upper and middle leaves improved, as compared with those under conventional irrigation. Stomatal factor was the limiting factor of photosynthesis under alternative furrow irrigation. The photosynthesis and transient water use efficiency of functional leaves under alternative furrow irrigation increased with increasing N application rate. Comparing with conventional irrigation, alternative furrow irrigation decreased leaf chlorophyll content and plant biomass, but increased root biomass, root/shoot ratio, and dry matter allocation in root and fruit. The economic output under alternative furrow irrigation was nearly the same as that under conventional irrigation, whereas the water use efficiency for economic yield increased significantly, suggesting the beneficial effects of alternative furrow irrigation on root development and fruit formation. With the increase of N application rate, the leaf chlorophyll content, chlorophyll a/b, specific leaf mass, plant biomass, economic yield, and fruit Vc and soluble sugar contents under alternative furrow irrigation increased, but no significant difference was observed between the treatments optimal N and conventional N. N application had little effects on the water use efficiency for economic yield. The economic yield and biomass production of the cucumber were significantly higher in winter-spring growth season than in autumn-winter growth season.
Chatchaisak, Duangthip; Connor, Mark; Srikiatkhachorn, Anan; Chetsawang, Banthit
2018-05-01
Growing evidence suggests that calcitonin gene-related peptide (CGRP) participates in trigeminal nociceptive responses. However, the role of CGRP in sensitization or desensitization of nociceptive transduction remains poorly understood. In this study, we sought to further investigate the CGRP-induced up-regulation of transient receptor potential vanilloid-1 (TRPV1) and the responses of trigeminal neurons to nociceptive stimuli. Rat trigeminal ganglion (TG) organ cultures and isolated trigeminal neurons were incubated with CGRP. An increase in TRPV1 levels was observed in CGRP-incubated TG organ cultures. CGRP potentiated capsaicin-induced increase in phosphorylated CaMKII levels in the TG organ cultures. The incubation of the trigeminal neurons with CGRP significantly increased the inward currents in response to capsaicin challenge, and this effect was inhibited by co-incubation with the CGRP receptor antagonist, BIBN4068BS or the inhibitor of protein kinase A, H-89. These findings reveal that CGRP acting on trigeminal neurons may play a significant role in facilitating cellular events that contribute to the peripheral sensitization of the TG in nociceptive transmission.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bai, X. Y.; Liu, S. Q.; Su, J. T.
We report a subarcsecond penumbral transient brightening event with the high-spatial resolution observations from the 1.6 m New Solar Telescope (NST), Interface Region Imaging Spectrograph ( IRIS ), and the Solar Dynamics Observatory . The transient brightening, whose thermal energy is in the range of nanoflares, has signatures in the chromosphere, the transient region, and the corona. NST's H α channel reveals the fine structure of the event with a width as narrow as 101 km (0.″14), which is much smaller than the width from the previous observation. The transient brightening lasts for about 3 minutes. It is associated withmore » a redshift of about 17 km s{sup −1}, found in the Si iv 1402.77 Å line and exhibits an inward motion to the umbra with a speed of 87 km s{sup −1}. The small-scale energy released from the event has a multi-temperature component. Spectral analysis of the brightening region from IRIS shows that not only the transition region lines such as Si iv 1402.77 Å and C ii 1334.53 Å, but also the chromospheric Mg ii k 2796.35 Å line are significantly enhanced and broadened. In addition, the event can be found in all the extreme-ultraviolet passbands of the Atmospheric Imaging Assembly and the derived differential emission measure profile increases between 4 and 15 MK (or 6.6 ≤ log T ≤ 7.2) in the transient brightening phase. It is possible that the penumbral transient brightening event is caused by magnetic reconnection.« less
Effect of atherothrombotic aorta on outcomes of total aortic arch replacement.
Okada, Kenji; Omura, Atsushi; Kano, Hiroya; Inoue, Takeshi; Oka, Takanori; Minami, Hitoshi; Okita, Yutaka
2013-04-01
The effect of an atherothrombotic aorta on the short- and long-term outcomes of total aortic arch replacement, including postoperative neurologic deficits, remains unknown. We evaluated this relationship and also elucidated the synergistic effect of multiple other risk factors, in addition to an atherothrombotic aorta, on the neurologic outcome. A group of 179 consecutive patients undergoing total aortic arch replacement were studied. An atherothrombotic aorta was present in 34 patients (19%), more than moderate leukoaraiosis in 71 (39.7%), and significant extracranial carotid artery stenosis in 27 (15.1%). In-hospital deaths occurred in 2 patients, 1 (2.9%) of 34 patients with and 1 (0.7%) of 145 patients without an atherothrombotic aorta (P = .26). Permanent neurologic deficits occurred in 4 (2.2%) and transient neurologic deficits in 17 (9.5%) patients. Multivariate analysis demonstrated that the risk factors for transient neurologic deficits were an atherothrombotic aorta (odds ratio, 4.4), extracranial carotid artery stenosis (odds ratio, 5.5), moderate/severe leukoaraiosis (odds ratio, 3.6), and cardiopulmonary bypass time (odds ratio, 1.02). To calculate the probability of transient neurologic deficits, the following equation was derived: probability of transient neurologic deficits = {1 + exp [7.276 - 1.489 (atherothrombotic aorta) - 1.285 (leukoaraiosis) - 1.701 (extracranial carotid artery stenosis) - 0.017 (cardiopulmonary bypass time)]}(-1). An exponential increase occurred in the probability of transient neurologic deficits with presence of an atherothrombotic aorta and other risk factors in relation to the cardiopulmonary bypass time. Survival at 3 years after surgery was significantly reduced in patients with vs without an atherothrombotic aorta (75.0% ± 8.8% vs 89.2% ± 3.1%, P = .01). Patients with an atherothrombotic aorta and associated preoperative comorbidities might be predisposed to adverse short- and long-term outcomes, including transient neurologic deficits. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
Murata, Nobuhiro; Kaneko, Hidehiro; Yajima, Junji; Oikawa, Yuji; Oshima, Toru; Tanaka, Shingo; Kano, Hiroto; Matsuno, Shunsuke; Suzuki, Shinya; Kato, Yuko; Otsuka, Takayuki; Uejima, Tokuhisa; Nagashima, Kazuyuki; Kirigaya, Hajime; Sagara, Koichi; Sawada, Hitoshi; Aizawa, Tadanori; Yamashita, Takeshi
2015-10-01
The prognostic impact of worsening renal function (WRF) in acute coronary syndrome (ACS) patients is not fully understood in Japanese clinical practice, and clinical implication of persistent versus transient WRF in ACS patients is also unclear. With a single hospital-based cohort in the Shinken database 2004-2012 (n=19,994), we followed 604 ACS patients who underwent percutaneous coronary intervention (PCI). WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value. Persistent WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value and maintained until discharge, whereas transient WRF was defined as that WRF resolved at hospital discharge. WRF occurred in 78 patients (13%), persistent WRF 35 patients (6%) and transient WRF 43 patients (7%). WRF patients were older and had a higher prevalence of chronic kidney disease, history of myocardial infarction (MI), and ST elevation MI. WRF was associated with elevated inflammatory markers and reduced left ventricular (LV) ejection fraction in acute, chronic phase. Incidence of all-cause death and major adverse cardiac events (MACE: all-cause death, MI, and target lesion revascularization) was significantly higher in patients with WRF. Moreover, in the WRF group, incidences of all-cause death and MACE were higher in patients with persistent WRF than those with transient WRF. A multivariate analysis showed that as well as older age, female gender, and intubation, WRF was an independent determinant of the all-cause death in ACS patients who underwent PCI. In conclusion, WRF might have a prognostic impact among Japanese ACS patients who underwent PCI in association with enhanced inflammatory response and LV remodeling. Persistent WRF might portend increased events, while transient WRF might have association with favorable outcomes compared with persistent WRF. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Isgró, G; Addison, O; Fleming, G J P
2011-05-01
The effect of heat-pressing and subsequent pre-cementation (acid-etching) and resin-cementation operative techniques on the development of transient and residual stresses in different thicknesses of a lithium disilicate glass-ceramic were characterised using profilometry prior to biaxial flexure strength (BFS) determination. 60 IPS e.max Press discs were pressed and divested under controlled conditions. The discs were polished on one surface to thicknesses of 0.61±0.05, 0.84±0.08, and 1.06±0.07 mm (Groups A-C, respectively). The mean of the maximum deflection (acid-etching and resin-coating was determined using high resolution profilometery prior to BFS testing. Paired sample t-tests were performed (p<0.05) on the 20 individual samples in each group (Groups A-C) for each comparison. Differences between the baseline quantification and resin-cement coating deflection values and BFS values for Groups A-C were determined using a one-way ANOVA with post hoc Tukey tests (p<0.05). Baseline quantification for Groups A-C identified no significant differences between the group means of the maximum deflection values (p=0.341). Following HF acid-etching, a significant increase in deflection for all groups (p<0.001) was identified compared with the baseline quantification. Additionally, resin-cement coating significantly increased deflection for Group A (p<0.001), Group B (p<0.001) and Group C (p=0.001) specimens for the individual groups. The increased deflection from baseline quantification to resin-cement coating was significantly different (p<0.001) for the three specimen thicknesses, although the BFS values were not. The lower reported baseline quantification range of the mean of the maximum deflection for the IPS e.max(®) Press specimens was predominantly the result of specimen polishing regime inducing a tensile stress state across the surface defect integral which accounted for the observed surface convexity. Acid-etching and resin-cementation had a significant impact on the development and magnitude of the transient and residual stresses in the lithium disilicate glass-ceramic investigated. Copyright © 2011 Elsevier Ltd. All rights reserved.
Tako-tsubo cardiomyopathy observed in a patient with sepsis and transient hyperthyroidism.
Sarullo, Filippo M; Americo, Luigi; Accardo, Salvatore; Cicero, Sergio; Schicchi, Rossella; Schirò, Maria; Castello, Antonio
2009-03-01
A 55-years-old woman, with a history of hypertension and ischemic stroke with residual left hemiparesis, was admitted to our hospital because of dyspnoea with clinical evidence of acute pulmonary edema. She was found to have a sinus tachycardia with ST-elevation in leads D1, aVL and V1-V4 in the electrocardiogram, and akinesis of the left ventricular apex with overall left ventricular systolic function being severely impaired and an ejection fraction of 28% on echocardiography. Orotracheal intubation was performed and mechanical ventilation was immediately started. Emergency cardiac catheterization was performed 2 h after the symptom onset. Coronary angiography showed no significant coronary artery disease. Blood analysis revealed an increase in the creatine kinase MB fraction, a significant positive detection in troponin T, a white blood cell count of 35000 per microliter, C-reactive protein of 59,9 mg/dl, and transient elevation in the concentration of free triiodothyronine, free thyroxine, thyroid globulin antibody, and thyroid peroxidase antibody. The symptoms improved during the next days, and follow-up echocardiography 18 days later showed complete resolution of the left ventricular dysfunction. These data suggest that tako-tsubo cardiomyopathy may be induced in patients with sepsis and transient hyperthyroidism.
Joshi, Shailendra; Singh-Moon, Rajinder; Wang, Mei; Bruce, Jeffrey N.; Bigio, Irving J.; Mayevsky, Avraham
2014-01-01
Disruption of blood brain barrier (BBB) is used to enhance chemotherapeutic drug delivery. The purpose of this study was to understand the time course of hemodynamic and metabolic response to intraarterial (IA) mannitol infusions in order to optimize the delivery of drugs for treating brain tumors. Principal results We compared hemodynamic response, EEG changes, and mitochondrial function as judged by relative changes in tissue NADH concentrations, after intracarotid (IC) infusion of equal volumes of normal saline and mannitol in our rabbit IC drug delivery model. We observed significantly greater, though transient, hyperemic response to IC infusion of mannitol compared to normal saline. Infusion of mannitol also resulted in a greater increase in tissue NADH concentrations relative to the baseline. These hemodynamic, and metabolic changes returned to baseline within 5 min of mannitol injection. Conclusion Significant, though transient, changes in blood flow and brain metabolism occur with IA mannitol infusion. The observed transient hyperemia would suggest that intravenous (IV) chemotherapy should be administered either just before, or concurrent with IA mannitol injections. On the other hand, IA chemotherapy should be delayed until the peak hyperemic response has subsided. PMID:24440631
Verma, Santosh K; Lombardi, David A; Chang, Wen Ruey; Courtney, Theodore K; Huang, Yueng-Hsiang; Brennan, Melanye J; Mittleman, Murray A; Ware, James H; Perry, Melissa J
2011-08-01
This nested case-crossover study examined the association between rushing, distraction and walking on a contaminated floor and the rate of slipping, and whether the effects varied according to weekly hours worked, job tenure and use of slip-resistant shoes. At baseline, workers from 30 limited-service restaurants in the USA reported average work hours, average weekly duration of exposure to each transient risk factor and job tenure at the current location. Use of slip-resistant shoes was determined. During the following 12 weeks, participants reported weekly their slip experience and exposures to the three transient exposures at the time of slipping. The case-crossover design was used to estimate the rate ratios using the Mantel-Haenszel estimator for person-time data. Among 396 participants providing baseline information, 210 reported one or more slips with a total of 989 slips. Rate of slipping was 2.9 times higher when rushing as compared to working at a normal pace (95% CI 2.5 to 3.3). Rate of slipping was also significantly increased by distraction (rate ratio (RR) 1.7, 95% CI 1.5 to 2.0) and walking on a contaminated floor (RR 14.6, 95% CI 12.6 to 17.0). Use of slip-resistant shoes decreased the effects of rushing and walking on a contaminated floor. Rate ratios for all three transient factors decreased monotonically as job tenure increased. The results suggest the importance of these transient risk factors, particularly floor contamination, on rate of slipping in limited-service restaurant workers. Stable characteristics, such as slip-resistant shoes, reduced the effects of transient exposures.
Odnoshivkina, Yulia G; Sytchev, Vaycheslav I; Petrov, Alexey M
2017-06-01
Majority of cardiac β2-adrenoceptors is located in cholesterol-rich microdomains. Here, we have investigated the underlying mechanisms by which a slight to moderate cholesterol depletion with methyl-β-cyclodextrin (MβCD, 1 and 5mM) interferes with contractility and inotropic effect of β2-adrenergic agonist (fenoterol, 50μM) in the mouse atria. Treatment with MβCD itself increased amplitude of Ca 2+ transient but did not change the contraction amplitude due to a clamping action of elevated NO. Cholesterol depletion significantly attenuated the positive inotropic response to fenoterol which is accompanied by increase in NO generation and decrease in Ca 2+ transient. Influence of 1mM MβCD on the fenoterol-driven changes in both contractility and NO level was strongly attenuated by inhibition of G i -protein (pertussis toxin), Akt (Akt 1/2 kinase inhibitor) or NO-synthase (L-NAME). After exposure to 5mM MβCD, pertussis toxin or Akt inhibitor could recover the β2-agonist effects on contractility, NO production and Ca 2+ transient, while L-NAME only reduced NO level. An adenylyl cyclase activator (forskolin, 50nM) had no influence on the MβCD-induced changes in the β2-agonist effects. Obtained results suggest that slight cholesterol depletion upregulates G i -protein/Akt/NO-synthase signaling that attenuates the positive inotropic response to β2-adrenergic stimulation without altering the Ca 2+ transient. Whilst moderate cholesterol depletion additionally could suppress the enhancement of the Ca 2+ transient amplitude caused by the β2-adrenergic agonist administration in G i -protein/Akt-dependent but NO-independent manner. Copyright © 2016 Elsevier Ltd. All rights reserved.
Simultaneous recording of t-tubular electrical activity and Ca2+-release in heart failure
NASA Astrophysics Data System (ADS)
Crocini, C.; Coppini, R.; Ferrantini, C.; Yan, P.; Loew, L.; Tesi, C.; Poggesi, C.; Cerbai, E.; Pavone, F. S.; Sacconi, L.
2014-05-01
T-tubules (TT) are invaginations of the surface sarcolemma (SS) that mediate the rapid propagation of the action potential (AP) to the cardiomyocyte core. We employed the advantages of an ultrafast random access multi-photon (RAMP) microscope (Sacconi et al., PNAS 2012) with a double staining approach to optically record t-tubular AP and, simultaneously, the corresponding local Ca2+-release in different positions across the cardiomyocytes. Despite a uniform AP between SS and TT at steady-state stimulation, in control cardiomyocytes we observed a non-negligible be variability of local Ca2+-transient amplitude and kinetics. This variability was significantly reduced by applying 0.1μM Isoproterenol, which increases the opening probability of Ca2+-release units. In the rat heart failure model (HF), we previously demonstrated that some tubular elements fail to propagate AP. We found that the tubules unable to propagate AP, displayed a reduced correspondent Ca2+-transient amplitude as well as a slower Ca2+ rise compared to electrically coupled tubules. Moreover variability of Ca2+-transient kinetics were increased in HF. Finally, TT that did not show AP, occasionally exhibited spontaneous depolarizations that were never accompanied by local Ca2+-release in the absence of any pro-arrhythmogenic stimulation. Simultaneous recording of AP and Ca2+-transient allows us to probe the spatio-temporal variability of Ca2+-release, whereas the investigation of Ca2+-transient in HF discloses an unexpected uncoupling between t-tubular depolarization and Ca2+-release in remodeled tubules. This work was funded by the European Union 7th Framework Program (FP7/2007- 2013) under grant agreement n° 284464, 241526, by the Italian Ministry of University and Research (NANOMAX), and by Telethon-Italy (GGP13162).
Voltage stability analysis in the new deregulated environment
NASA Astrophysics Data System (ADS)
Zhu, Tong
Nowadays, a significant portion of the power industry is under deregulation. Under this new circumstance, network security analysis is more critical and more difficult. One of the most important issues in network security analysis is voltage stability analysis. Due to the expected higher utilization of equipment induced by competition in a power market that covers bigger power systems, this issue is increasingly acute after deregulation. In this dissertation, some selected topics of voltage stability analysis are covered. In the first part, after a brief review of general concepts of continuation power flow (CPF), investigations on various matrix analysis techniques to improve the speed of CPF calculation for large systems are reported. Based on these improvements, a new CPF algorithm is proposed. This new method is then tested by an inter-area transaction in a large inter-connected power system. In the second part, the Arnoldi algorithm, the best method to find a few minimum singular values for a large sparse matrix, is introduced into the modal analysis for the first time. This new modal analysis is applied to the estimation of the point of voltage collapse and contingency evaluation in voltage security assessment. Simulations show that the new method is very efficient. In the third part, after transient voltage stability component models are investigated systematically, a novel system model for transient voltage stability analysis, which is a logical-algebraic-differential-difference equation (LADDE), is offered. As an example, TCSC (Thyristor controlled series capacitors) is addressed as a transient voltage stabilizing controller. After a TCSC transient voltage stability model is outlined, a new TCSC controller is proposed to enhance both fault related and load increasing related transient voltage stability. Its ability is proven by the simulation.
Heat Pipe Vapor Dynamics. Ph.D. Thesis
NASA Technical Reports Server (NTRS)
Issacci, Farrokh
1990-01-01
The dynamic behavior of the vapor flow in heat pipes is investigated at startup and during operational transients. The vapor is modeled as two-dimensional, compressible viscous flow in an enclosure with inflow and outflow boundary conditions. For steady-state and operating transients, the SIMPLER method is used. In this method a control volume approach is employed on a staggered grid which makes the scheme very stable. It is shown that for relatively low input heat fluxes the compressibility of the vapor flow is low and the SIMPLER scheme is suitable for the study of transient vapor dynamics. When the input heat flux is high or the process under a startup operation starts at very low pressures and temperatures, the vapor is highly compressible and a shock wave is created in the evaporator. It is shown that for a wide range of input heat fluxes, the standard methods, including the SIMPLER scheme, are not suitable. A nonlinear filtering technique, along with the centered difference scheme, are then used for shock capturing as well as for the solution of the cell Reynolds-number problem. For high heat flux, the startup transient phase involves multiple shock reflections in the evaporator region. Each shock reflection causes a significant increase in the local pressure and a large pressure drop along the heat pipe. Furthermore, shock reflections cause flow reversal in the evaporation region and flow circulations in the adiabatic region. The maximum and maximum-averaged pressure drops in different sections of the heat pipe oscillate periodically with time because of multiple shock reflections. The pressure drop converges to a constant value at steady state. However, it is significantly higher than its steady-state value at the initiation of the startup transient. The time for the vapor core to reach steady-state condition depends on the input heat flux, the heat pipe geometry, the working fluid, and the condenser conditions. However, the vapor transient time, for an Na-filled heat pipe is on the order of seconds. Depending on the time constant for the overall system, the vapor transient time may be very short. Therefore, the vapor core may be assumed to be quasi-steady in the transient analysis of a heat pipe operation.
Kolbaev, S N; Aleksandrova, O P; Sharonova, I N; Skrebitsky, V G
2018-01-01
A neuroprotective and nootropic drug Noopept increased the frequency of spontaneous calcium transients in neurons of CA1 radial layer in cultured rat hippocampal slices. In contrast, the drug exerted no significant effect on intracellular calcium concentration and its dynamics in neurons of hippocampal CA1 pyramidal layer.
Thippeswamy, B S; Nagakannan, P; Shivasharan, B D; Mahendran, S; Veerapur, V P; Badami, S
2011-11-01
Embelia ribes is being used in Indian traditional herbal medicine for the treatment of mental disorders and as brain tonic. The present study was designed to investigate the protective effects of embelin from E. ribes on global ischemia/reperfusion-induced brain injury in rats. Transient global ischemia was induced by occluding bilateral common carotid arteries for 30 min followed by 24-h reperfusion. Neurological functions were measured using sensorimotor tests. Ischemia/reperfusion-induced neuronal injury was assessed by cerebral infarct area, biochemical and histopathological examination. Pretreatment of embelin (25 and 50 mg/kg, p.o.) significantly increased locomotor activity and hanging latency time and decreased beam walking latency when compared with ischemic control. The treatment also reduced significantly the lipid peroxidation and increased the total thiol content and glutathione-S-transferase activity in brain homogenates. The decreased cerebral infarction area in embelin-treated groups and histopathological observations confirmed the above findings. These observations suggested that embelin is a neuroprotective agent and may prove to be useful adjunct in the treatment of stroke.
Nakao, Shu; Wakabayashi, Shigeo; Nakamura, Tomoe Y
2015-01-01
In cardiomyocytes, intracellular calcium (Ca2+) transients are elicited by electrical and receptor stimulations, leading to muscle contraction and gene expression, respectively. Although such elevations of Ca2+levels ([Ca2+]) also occur in the nucleus, the precise mechanism of nuclear [Ca2+] regulation during different kinds of stimuli, and its relationship with cytoplasmic [Ca2+] regulation are not fully understood. To address these issues, we used a new region-specific fluorescent protein-based Ca2+ indicator, GECO, together with the conventional probe Fluo-4 AM. We confirmed that nuclear Ca2+ transients were elicited by both electrical and receptor stimulations in neonatal mouse ventricular myocytes. Kinetic analysis revealed that electrical stimulation-elicited nuclear Ca2+ transients are slower than cytoplasmic Ca2+ transients, and chelating cytoplasmic Ca2+ abolished nuclear Ca2+ transients, suggesting that nuclear Ca2+ are mainly derived from the cytoplasm during electrical stimulation. On the other hand, receptor stimulation such as with insulin-like growth factor-1 (IGF-1) preferentially increased nuclear [Ca2+] compared to cytoplasmic [Ca2+]. Experiments using inhibitors revealed that electrical and receptor stimulation-elicited Ca2+ transients were mainly mediated by ryanodine receptors and inositol 1,4,5-trisphosphate receptors (IP3Rs), respectively, suggesting different mechanisms for the two signals. Furthermore, IGF-1-elicited nuclear Ca2+ transient amplitude was significantly lower in myocytes lacking neuronal Ca2+ sensor-1 (NCS-1), a Ca2+ binding protein implicated in IP3R-mediated pathway in the heart. Moreover, IGF-1 strengthened the interaction between NCS-1 and IP3R. These results suggest a novel mechanism for receptor stimulation-induced nuclear [Ca2+] regulation mediated by IP3R and NCS-1 that may further fine-tune cardiac Ca2+ signal regulation.
Sun, Kai-Feng; Xu, Xiang-Rong; Duan, Shun-Shan; Wang, You-Shao; Cheng, Hao; Zhang, Zai-Wang; Zhou, Guang-Jie; Hong, Yi-Guo
2015-10-01
Organophosphate pesticides (OPs), as a replacement for the organochlorine pesticides, are generally considered non-toxic to plants and algae. Chlorpyrifos and dichlorvos are two OPs used for pest control all over the world. In this study, the dose-response of cyanobacteria Microcystis wesenbergii on OPs exposure and the stimulating effect of OPs with and without phosphorus source were investigated. The results showed that high concentrations of chlorpyrifos and dichlorvos caused significant decrease of chlorophyll a content. The median inhibitory concentrations (EC50) of chlorpyrifos and dichlorvos at 96 h were 15.40 and 261.16 μmol L(-1), respectively. Growth of M. wesenbergii under low concentration of OPs (ranged from 1/10,000 to 1/20 EC50), was increased by 35.85 % (chlorpyrifos) and 41.83 % (dichlorvos) at 120 h, respectively. Correspondingly, the highest enhancement on the maximum quantum yield (F v/F m) was 4.20 % (24 h) and 9.70 % (48 h), respectively. Chlorophyll fluorescence kinetics, known as O-J-I-P transients, showed significant enhancements in the O-J, J-I, and I-P transients under low concentrations of dichlorvos at 144 h, while enhancements of chlorophyll fluorescence kinetics induced by low concentrations of chlorpyrifos were only observed in the J-I transient at 144 h. Significant decreases of chlorophyll content, F v/F m and O-J-I-P transients with OPs as sole phosphorus source were found when they were compared with inorganic phosphate treatments. The results demonstrated an evidently hormetic dose-response of M. wesenbergii to both chlorpyrifos and dichlorvos, where high dose (far beyond environmental concentrations) exposure caused growth inhibition and low dose exposure induced enhancement on physiological processes. The stimulating effect of two OPs on growth of M. wesenbergii was negligible under phosphate limitation.
Choi, Hyun Young; Park, Joon Ha; Chen, Bai Hui; Shin, Bich Na; Lee, Yun Lyul; Kim, In Hye; Cho, Jeong-Hwi; Lee, Tae-Kyeong; Lee, Jae-Chul; Won, Moo-Ho; Ahn, Ji Hyeon; Tae, Hyun-Jin; Yan, Bing Chun; Hwang, In Koo; Cho, Jun Hwi; Kim, Young-Myeong; Kim, Sung Koo
2016-09-01
Lacosamide is a new antiepileptic drug which is widely used to treat partial-onset seizures. In this study, we examined the neuroprotective effect of lacosamide against transient ischemic damage and expressions of antioxidant enzymes such as Zn-superoxide dismutase (SOD1), Mn-superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal cornu ammonis 1 (CA1) region following 5 min of transient global cerebral ischemia in gerbils. We found that pre-treatment with 25 mg/kg lacosamide protected CA1 pyramidal neurons from transient global cerebral ischemic insult using hematoxylin-eosin staining and neuronal nuclear antigen immunohistochemistry. Transient ischemia dramatically changed expressions of SOD1, SOD2 and GPX, not CAT, in the CA1 pyramidal neurons. Lacosamide pre-treatment increased expressions of CAT and GPX, not SOD1 and 2, in the CA1 pyramidal neurons compared with controls, and their expressions induced by lacosamide pre-treatment were maintained after transient cerebral ischemia. In brief, pre-treatment with lacosamide protected hippocampal CA1 pyramidal neurons from ischemic damage induced by transient global cerebral ischemia, and the lacosamide-mediated neuroprotection may be closely related to increases of CAT and GPX expressions by lacosamide pre-treatment.
Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts
Bushinsky, David A.
2010-01-01
In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO3−])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco2)] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Cai). To determine whether Resp increases Cai, as does Met, we imaged Cai in primary cultures of bone cells. pH for Met = 7.07 ([HCO3−] = 11.8 mM) and for Resp = 7.13 (Pco2 = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Cai in individual bone cells; however, Met stimulated Cai to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Cai in Met than Resp. Both Met and Resp induced a marked, transient increase in Cai in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Cai by Met in primary bone cells is not a function of OGR1 alone, but must involve H+ receptors other than OGR1, or pathways sensitive to Pco2, HCO3−, or total CO2 that modify the effect of H+ in primary bone cells. PMID:20504884
Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts.
Frick, Kevin K; Bushinsky, David A
2010-08-01
In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO(3)(-)])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco(2))] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Ca(i)). To determine whether Resp increases Ca(i), as does Met, we imaged Ca(i) in primary cultures of bone cells. pH for Met = 7.07 ([HCO(3)(-)] = 11.8 mM) and for Resp = 7.13 (Pco(2) = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Ca(i) in individual bone cells; however, Met stimulated Ca(i) to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Ca(i) in Met than Resp. Both Met and Resp induced a marked, transient increase in Ca(i) in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Ca(i) by Met in primary bone cells is not a function of OGR1 alone, but must involve H(+) receptors other than OGR1, or pathways sensitive to Pco(2), HCO(3)(-), or total CO(2) that modify the effect of H(+) in primary bone cells.
Ward, Adam S.; Payn, Robert A.; Gooseff, Michael N.; McGlynn, Brian L.; Bencala, Kenneth E.; Kelleher, Christa A.; Wondzell, Steven M.; Wagener, Thorsten
2013-01-01
The accumulation of discharge along a stream valley is frequently assumed to be the primary control on solute transport processes. Relationships of both increasing and decreasing transient storage, and decreased gross losses of stream water have been reported with increasing discharge; however, we have yet to validate these relationships with extensive field study. We conducted transient storage and mass recovery analyses of artificial tracer studies completed for 28 contiguous 100 m reaches along a stream valley, repeated under four base-flow conditions. We calculated net and gross gains and losses, temporal moments of tracer breakthrough curves, and best fit transient storage model parameters (with uncertainty estimates) for 106 individual tracer injections. Results supported predictions that gross loss of channel water would decrease with increased discharge. However, results showed no clear relationship between discharge and transient storage, and further analysis of solute tracer methods demonstrated that the lack of this relation may be explained by uncertainty and equifinality in the transient storage model framework. Furthermore, comparison of water balance and transient storage approaches reveals complications in clear interpretation of either method due to changes in advective transport time, which sets a the temporal boundary separating transient storage and channel water balance. We have little ability to parse this limitation of solute tracer methods from the physical processes we seek to study. We suggest the combined analysis of both transient storage and channel water balance more completely characterizes transport of solutes in stream networks than can be inferred from either method alone.
Arvin, B; Lekieffre, D; Graham, J L; Moncada, C; Chapman, A G; Meldrum, B S
1994-04-01
The effect of the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) on ischaemia-induced changes in the microdialysate and tissue concentrations of glutamate, aspartate, and gamma-aminobutyric acid (GABA) was studied in rats. Twenty minutes of four-vessel occlusion resulted in a transient increase in microdialysate levels of glutamate, aspartate, and GABA in striatum, cortex, and hippocampus. Administration of GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min intravenously starting 20 min before onset of ischaemia) inhibited ischaemia-induced increases in microdialysate glutamate and GABA in striatum without affecting the increases in hippocampus or cortex. Twenty minutes of four-vessel occlusion resulted in immediate small decreases and larger delayed (72 h) decreases in tissue levels of glutamate and aspartate. Transient increases in tissue levels of GABA were shown in all three structures at the end of the ischaemic period. At 72 h, after the ischaemic period, significantly reduced GABA levels were observed in striatum and hippocampus. GYKI 52466, given under identical conditions as above, augmented the ischaemia-induced decrease in striatal tissue levels of glutamate and aspartate, without significantly affecting the decreases in hippocampus and cortex. Twenty minutes of ischaemia resulted in a large increase in microdialysate dopamine in striatum. GYKI 52466 failed to inhibit this increase. Kainic acid (500 microM infused through the probe for 20 min) caused increases in microdialysate glutamate and aspartate in the striatum. GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min) completely inhibited the kainic acid-induced glutamate release. In conclusion, the action of the non-NMDA antagonist, GYKI 52466, in the striatum is different from that in the cortex and hippocampus. The inhibition by GYKI 52466 of ischaemia-induced and kainate-induced increases in microdialysate glutamate concentration in the striatum may be related to the neuroprotection provided by GYKI 52466 in this region.
NASA Astrophysics Data System (ADS)
Dexter, Jason; McKinney, Jonathan C.; Markoff, Sera; Tchekhovskoy, Alexander
2014-05-01
Magnetically arrested accretion discs (MADs), where the magnetic pressure in the inner disc is dynamically important, provide an alternative mechanism for regulating accretion to what is commonly assumed in black hole systems. We show that a global magnetic field inversion in the MAD state can destroy the jet, significantly increase the accretion rate, and move the effective inner disc edge in to the marginally stable orbit. Reconnection of the MAD field in the inner radii launches a new type of transient outflow containing hot plasma generated by magnetic dissipation. This transient outflow can be as powerful as the steady magnetically dominated Blandford-Znajek jet in the MAD state. The field inversion qualitatively describes many of the observational features associated with the high-luminosity hard-to-soft state transition in black hole X-ray binaries: the jet line, the transient ballistic jet, and the drop in rms variability. These results demonstrate that the magnetic field configuration can influence the accretion state directly, and hence the magnetic field structure is an important second parameter in explaining observations of accreting black holes across the mass and luminosity scales.
Sadagurski, Marianna; Landeryou, Taylor; Cady, Gillian; Bartke, Andrzej; Bernal-Mizrachi, Ernesto; Miller, Richard A
2015-04-01
Transient nutrient restriction in the 3 weeks between birth and weaning (producing "crowded litter" or CL mice) leads to a significant increase in lifespan and is associated with permanent changes in energy homeostasis, leptin, and insulin sensitivity. Here, we show this brief period of early food restriction leads to permanent modulation of the arcuate nucleus of the hypothalamus (ARH), markedly increasing formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the paraventricular nucleus of the hypothalamus (PVH). An additional 4 weeks of caloric restriction, after weaning, does not further intensify the formation of AgRP and POMC projections. Acute leptin stimulation of 12-month-old mice leads to a stronger increase in the levels of hypothalamic pStat3 and cFos activity in CL mice than in controls, suggesting that preweaning food restriction leads to long-lasting enhancement of leptin signaling. In contrast, FoxO1 nuclear exclusion in response to insulin is equivalent in young adult CL and control mice, suggesting that hypothalamic insulin signaling is not modulated by the crowded litter intervention. Markers of hypothalamic reactive gliosis associated with aging, such as Iba1-positive microglia and GFAP-positive astrocytes, are significantly reduced in CL mice as compared to controls at 12 and 22 months of age. Lastly, age-associated overproduction of TNF-α in microglial cells is reduced in CL mice than in age-matched controls. Together, these results suggest that transient early life nutrient deprivation leads to long-term hypothalamic changes which may contribute to the longevity of CL mice. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Living within stories: Exploring the experiences of people with transient ischemic attack.
Crowfoot, Gary Mitchell; van der Riet, Pamela Jane; Maguire, Jane Margaret
2016-03-01
A transient ischemic attack (TIA) significantly increases a person's risk of ischemic stroke. However, little is known about the experiences of these people or what influences their decision to access care. This article explores the stories of three people who experienced a TIA. All participants were interviewed after receiving a diagnosis of TIA by a specialist neurologist. By utilizing a framework of narrative inquiry, several storylines were revealed across temporal, social, and geographical landscapes. The main storylines include: bodily disruption, time stasis, altered temporal perceptions, the roles of others, and help-seeking behavior. The primary author also reflects upon his own origin and explores how this inquiry has influenced his perceptions, career, and nursing practice. This inquiry may assist healthcare workers to gain insight into the experiences of people with TIA and suggests how involvement of significant others is beneficial when educating people at risk of TIA. © 2015 Wiley Publishing Asia Pty Ltd.
Effect of load transients on SOFC operation—current reversal on loss of load
NASA Astrophysics Data System (ADS)
Gemmen, Randall S.; Johnson, Christopher D.
The dynamics of solid oxide fuel cell (SOFC) operation have been considered previously, but mainly through the use of one-dimensional codes applied to co-flow fuel cell systems. In this paper several geometries are considered, including cross-flow, co-flow, and counter-flow. The details of the model are provided, and the model is compared with some initial experimental data. For parameters typical of SOFC operation, a variety of transient cases are investigated, including representative load increase and decrease and system shutdown. Of particular note for large load decrease conditions (e.g., shutdown) is the occurrence of reverse current over significant portions of the cell, starting from the moment of load loss up to the point where equilibrated conditions again provide positive current. Consideration is given as to when such reverse current conditions might most significantly impact the reliability of the cell.
Kakinohana, O; Hefferan, M P; Nakamura, S; Kakinohana, M; Galik, J; Tomori, Z; Marsala, J; Yaksh, T L; Marsala, M
2006-09-01
Transient spinal cord ischemia may lead to a progressive degeneration of spinal interneurons and subsequently to increased hind limb motor tone. In the present work we sought to characterize the rigidity and spasticity components of this altered motor function by: i) tonic electromyographic activity measured in gastrocnemius muscle before and after ischemia, ii) measurement of muscle resistance during the period of ankle flexion and corresponding changes in electromyographic activity, iii) changes in Hoffmann reflex, and, iv) motor evoked potentials. In addition the effect of intrathecal treatment with baclofen (GABAB receptor agonist; 1 microg), nipecotic acid (GABA uptake inhibitor; 300 microg) and dorsal L2-L5 rhizotomy on spasticity and rigidity was studied. Finally, the changes in spinal choline acetyltransferase (ChAT) and vesicular glutamate transporter 2 and 1 (VGLUT2 and VGLUT1) expression were characterized using immunofluorescence and confocal microscopy. At 3-7 days after ischemia an increase in tonic electromyographic activity with a variable degree of rigidity was seen. In animals with modest rigidity a velocity-dependent increase in muscle resistance and corresponding appearance in electromyographic activity (consistent with the presence of spasticity) was measured during ankle rotation (4-612 degrees /s rotation). Measurement of the H-reflex revealed a significant increase in Hmax/Mmax ratio and a significant loss of rate-dependent inhibition. In the same animals a potent increase in motor evoked potential amplitudes was measured and this change correlated positively with the increased H-reflex responses. Spasticity and rigidity were consistently present for a minimum of 3 months after ischemia. Intrathecal treatment with baclofen (GABA B receptor agonist) and nipecotic acid (GABA uptake inhibitor) provided a significant suppression of spasticity, rigidity, H-reflex or motor evoked potentials. Dorsal L2-L5 rhizotomy significantly decreased muscle resistance but had no effect on increased amplitudes of motor evoked potentials. Confocal analysis of spinal cord sections at 8 weeks-12 months after ischemia revealed a continuing presence of ChAT positive alpha-motoneurons, Ia afferents and VGLUT2 and VGLUT1-positive terminals but a selective loss of small presumably inhibitory interneurons between laminae V-VII. These data demonstrate that brief transient spinal cord ischemia in rat leads to a consistent development of spasticity and rigidity. The lack of significant suppressive effect of dorsal L2-L5 rhizotomy on motor evoked potentials response indicates that descending motor input into alpha-motoneurons is independent on Ia afferent couplings and can independently contribute to increased alpha-motoneuronal excitability. The pharmacology of this effect emphasizes the potent role of GABAergic type B receptors in regulating both the spasticity and rigidity.
Aslan, Selcuk; Hofvander, Per; Dutta, Paresh; Sitbon, Folke; Sun, Chuanxin
2015-01-01
The beta-ketoacyl-ACP synthase II (KASII) is an enzyme in fatty acid biosynthesis, catalyzing the elongation of 16:0-acyl carrier protein (ACP) to 18:0-ACP in plastids. Mutations in KASII genes in higher plants can lead to lethality, which makes it difficult to utilize the gene for lipid metabolic engineering. We demonstrated previously that transient expression of plastid-directed fatty acyl reductases and wax ester synthases could result in different compositions of wax esters. We hypothesized that changing the ratio between C16 (palmitoyl-compounds) and C18 (stearoyl-compounds) in the plastidic acyl-ACP pool by inhibition of KASII expression would change the yield and composition of wax esters via substrate preference of the introduced enzymes. Here, we report that transient inhibition of KASII expression by three different RNAi constructs in leaves of N. benthamiana results in almost complete inhibition of KASII expression. The transient RNAi approach led to a shift of carbon flux from a pool of C18 fatty acids to C16, which significantly increased wax ester production in AtFAR6-containing combinations. The results demonstrate that transient inhibition of KASII in vegetative tissues of higher plants enables metabolic studies towards industrial production of lipids such as wax esters with specific quality and composition. PMID:26063537
Joubert, Dirk Albert; O'Neill, Scott L
2017-01-01
Pathogen replication and transmission in Wolbachia infected insects are currently studied using three Wolbachia infection systems: naturally infected Wolbachia hosts, hosts transinfected with Wolbachia (stably maintained and inherited infections) and hosts transiently infected with Wolbachia. All three systems have been used to test the effect of Wolbachia on mosquito transmitted pathogens such as dengue virus (DENV), West Nile virus (WNV) and Plasmodium. From these studies it is becoming increasingly clear that the interaction between a particular pathogen and Wolbachia is heavily influenced by the host-Wolbachia interaction and the model of infection. In particular, there is some evidence that under very specific conditions, Wolbachia can enhance pathogen infection in some hosts. In this study, we compared the effect of Wolbachia in two infection models (stable transinfected and transiently infected) on the replication, infection- and transmission rates of two flaviviruses, DENV and WNV (Kunjin strain). Our results indicate that Wolbachia had similar blocking effects in both stable and transient models of infection, however, the magnitude of the blocking effect was significantly lower in mosquitoes transiently infected with Wolbachia. More importantly, no evidence was found for any enhancement of either DENV or WNV (Kunjin strain) infection in Ae. aegypti infected with Wolbachia, supporting a role for Wolbachia as an effective and safe means for restricting transmission of these viruses.
Lennmyr, F; Ericsson, A; Gerwins, P; Ahlström, H; Terént, A
2003-11-01
Focal cerebral ischemia activates intracellular signaling pathways including the mitogen-activated protein kinase p38, which may be involved in the process of ischemic brain injury. In this study, the effect of pretreatment with the p38-inhibitor SB203580 on infarct size and blood-brain barrier (BBB) breakdown was investigated with magnetic resonance imaging (MRI). Rats were given SB203580 (n = 6) or vehicle (n = 6) in the right lateral ventricle prior to transient (90 min) middle cerebral artery occlusion (MCAO) on the left side. The rats were examined with serial MRI during MCAO, at reperfusion and after 1 and 4 days. The mean infarct size on T2-weighted images after 1 day was significantly higher in the SB203580-treated group than in controls (300 +/- 95 mm3 vs 126 +/- 75 mm3; P < 0.01). Vascular gadolinium leakage, indicating BBB breakdown, was significantly larger in the SB203580-treated group than in controls after 1 day (median leakage score 18.5; range 15-21 vs 6.5; 4-17; P < 0.05) and 4 days (11; 6-15 vs 3.5; 1-9; P < 0.05), although no significant difference was seen initially. Pretreatment with SB203580 may aggravate ischemic brain injury and cerebral vascular leakage in the present model of transient ischemia.
Two dimensional, transient catalytic combustion of CO-air on platinum
NASA Technical Reports Server (NTRS)
Sinha, N.; Bruno, C.; Bracco, F. V.
1985-01-01
The light off transient of catalytic combustion of lean CO-air mixtures in a platinum coated channel of a honeycomb monolith is studied with a model that resolves transient radial and axial gradients in both the gas and the solid. For the conditions studied it is concluded that: the initial heat release occurs near the entrance at the gas-solid interface and is controlled by heterogeneous reactions; large spatial and temporal temperature gradients occur in the solid near the entrance controlled mostly by the availability of fuel; the temperature of the solid near the entrance achieves almost its steady state value before significant heating of the back; heterogeneous reactions and the gas heated up front and flowing downstream heat the back of the solid; the overall transient time is controlled by the thermal inertia of the solid and by forced convection; radiation significantly influences both transient and steady state particularly near the entrance; the oxidation of CO occurs mostly on the catalyst and becomes diffusion controlled soon into the transient.
Swelling and gas release in oxide fuels during fast temperature transients
NASA Astrophysics Data System (ADS)
Dollins, C. C.; Jursich, M.
1982-05-01
A previously reported intergranular swelling and gas release model for oxide fuels has been modified to predict fission gas behavior during fast temperature transients. Under steady state or slowly varying conditions it has been assumed in the previous model that the pressure caused by the fission gas within the gas bubbles is in equilibrium with the surface tension of the bubbles. During a fast transient, however, net vacancy migration to the bubbles may be insufficient to maintain this equilibrium. In order to ascertain the net vacancy flow, it is necessary to model the point defect behavior in the fuel. Knowing the net flow of vacancies to the bubble and the bubble size, the bubble diffusivity can be determined and the long range migration of the gas out of the fuel can be calculated. The model has also been modified to allow release of all the gas on the grain boundaries during a fast temperature transient. The gas release predicted by the revised model shows good agreement to fast transient gas release data from an EBR-II TREAT H-3 (Transient Reactor Test Facility) test. Agreement has also been obtained between predictions using the model and gas release data obtained by Argonne National Laboratory from out-of-reactor transient heating experiments on irradiated UO 2. It was found necessary to increase the gas bubble diffusivity used in the model by a factor of thirty during the transient to provide agreement between calculations and measurements. Other workers have also found that such an increase is necessary for agreement and attribute the increased diffusivity to yielding at the bubble surface due to the increased pressure.
Flight evaluation of modifications to a digital electronic engine control system in an F-15 airplane
NASA Technical Reports Server (NTRS)
Burcham, F. W., Jr.; Myers, L. P.; Zeller, J. R.
1983-01-01
The third phase of a flight evaluation of a digital electronic engine control system in an F-15 has recently been completed. It was found that digital electronic engine control software logic changes and augmentor hardware improvements resulted in significant improvements in engine operation. For intermediate to maximum power throttle transients, an increase in altitude capability of up to 8000 ft was found, and for idle to maximum transients, an increase of up to 4000 ft was found. A nozzle instability noted in earlier flight testing was investigated on a test engine at NASA Lewis Research Center, a digital electronic engine control software logic change was developed and evaluated, and no instability occurred in the Phase 3 flight evaluation. The backup control airstart modification was evaluated, and gave an improvement of airstart capability by reducing the minimum airspeed for successful airstarts by 50 to 75 knots.
Testing of neuroendocrine function in astronauts as related to fluid shifts
NASA Astrophysics Data System (ADS)
Sauseng-Fellegger, G.; König, E. M.; Hinghofer-Szalkay, H.; Jezová, D.; Vigas, M.
We addressed the question of optimal conditions for neuroendocrine and cardiovascular testing in astronauts. We tested stress reactions during LBNP of ≤-50 mm Hg. There was a mild transient elevation of plasma GH concentration and a nonsignificant rise of plasma ACTH, while PRL, insulin and glucose remained unchanged. Aldosterone was decreased 5 and 10 min after beginning of LBNP, thereafter rose significantly, and displayed a further significant concentration increase 5 min post-LBNP. The endocrine and cardiovascular responses to submaximal exercise were tested at 8.00 am and 8.00 pm. Exercise-induced changes of heart rate and blood pressure remained unchanged with daytime whereas plasma concentrations of epinephrine, GH and PRL in response to work load were significantly higher in the evening than in the morning. As expected, basal resting values of plasma cortisol were significantly lower in the evening than in the morning but were similar one hour after cessation of exercise. Our findings demonstrate the importance of frequent sampling in case of transient physiological phenomena, and contribute to existing knowledge on circadian influences upon neuroendocrine stress responses.
Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin
Sood, Shilpa; Choudhary, Shambhunath; Wang, Hwa-Chain Robert
2013-01-01
More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens and co-carcinogens. To identify co-carcinogens with abilities to induce cellular pre-malignancy, we studied the activity of triclocarban (TCC), an antimicrobial agent commonly used in household and personal care products. Here, we demonstrated, for the first time, that chronic exposure to TCC at physiologically-achievable nanomolar concentrations resulted in progressive carcinogenesis of human breast cells from non-cancerous to pre-malignant. Pre-malignant carcinogenesis was measured by increasingly-acquired cancer-associated properties of reduced dependence on growth factors, anchorage- independent growth and increased cell proliferation, without acquisition of cellular tumorigenicity. Long-term TCC exposure also induced constitutive activation of the Erk–Nox pathway and increases of reactive oxygen species (ROS) in cells. A single TCC exposure induced transient induction of the Erk–Nox pathway, ROS elevation, increased cell proliferation, and DNA damage in not only non-cancerous breast cells but also breast cancer cells. Using these constitutively- and transiently-induced changes as endpoints, we revealed that non-cytotoxic curcumin was effective in intervention of TCC-induced cellular pre-malignancy. Our results lead us to suggest that the co-carcinogenic potential of TCC should be seriously considered in epidemiological studies to reveal the significance of TCC in the development of sporadic breast cancer. Using TCC-induced transient and constitutive endpoints as targets will likely help identify non-cytotoxic preventive agents, such as curcumin, effective in suppressing TCC-induced cellular pre-malignancy. PMID:23942114
Chu, Hannah X; Kim, Hyun Ah; Lee, Seyoung; Moore, Jeffrey P; Chan, Christopher T; Vinh, Antony; Gelderblom, Mathias; Arumugam, Thiruma V; Broughton, Brad RS; Drummond, Grant R; Sobey, Christopher G
2014-01-01
We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed ∼15,000 leukocytes (CD45+high cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising ∼40% lymphoid cells and ∼60% myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to ∼5,000 as early as 3 hours after pMCAO. Several cell types (monocytes, macrophages, B lymphocytes, CD8+ T lymphocytes, and natural killer cells) were also increased at 3 hours to levels sustained for 24 hours, whereas others (CD4+ T cells, natural killer T cells, and dendritic cells) were unchanged at 3 hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis revealed that leukocytes typically had entered and widely dispersed throughout the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO, there were ∼50% fewer infiltrating leukocytes at 24 hours after transient MCAO (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally increased in both models. These findings indicate that a profound infiltration of inflammatory cells occurs in the brain early after focal ischemia, especially without reperfusion. PMID:24326388
Association of transient hyperthyroidism and severity of hyperemesis gravidarum.
Malek, Nor Zila Hassan; Kalok, Aida; Hanafiah, Zainal Abidin; Shah, Shamsul Azhar; Ismail, Nor Azlin Mohamed
2017-03-23
Background Transient non-immune hyperthyroidism in early pregnancy is hyperthyroidism diagnosed for the first time in early pregnancy, without evidence of thyroid autoimmunity or clinical findings of Grave's disease and resolved spontaneously as the pregnancy progressed. Hyperemesis gravidarum (HG) is the commonest cause with 66%-73% of women with severe HG were found to have elevated thyroid function. Materials and methods We conducted a cross sectional study to determine the prevalence of transient hyperthyroidism in patients with hyperemesis gravidarum and its relation to the severity of nausea and vomiting. Severity of nausea and vomiting in pregnancy was assessed using the modified pregnancy-unique quantification of emesis (PUQE) scoring system. Each patient had urine and blood investigations which also included a full blood count and thyroid and renal function tests. Patients with abnormal thyroid function were retested at 20 weeks of gestation. The patients' demographic data, electrolyte levels, thyroid function and their respective PUQE score were analyzed. Results The prevalence of transient hyperthyroidism in women with hyperemesis gravidarum was 4.8%. Although there was a significant association between the severity of the PUQE score and hypokalemia (p = 0.001), there was no significant association with transient hyperthyroidism in early pregnancy (p = 0.072). Free T4 and TSH values of all women with transient hyperthyroidism were normalized by 20 weeks of gestation. Conclusion Transient hyperthyroidism in pregnancy is not significantly associated with the severity of the PUQE score. Women with transient hyperthyroidism in pregnancy are normally clinically euthyroid, hence a routine thyroid function test is unnecessary unless they exhibit clinical signs or symptoms of hyperthyroidism.
Beebe, Stephen J; Chen, Yeong-Jer; Sain, Nova M; Schoenbach, Karl H; Xiao, Shu
2012-01-01
It is hypothesized that high frequency components of nanosecond pulsed electric fields (nsPEFs), determined by transient pulse features, are important for maximizing electric field interactions with intracellular structures. For monopolar square wave pulses, these transient features are determined by the rapid rise and fall of the pulsed electric fields. To determine effects on mitochondria membranes and plasma membranes, N1-S1 hepatocellular carcinoma cells were exposed to single 600 ns pulses with varying electric fields (0-80 kV/cm) and short (15 ns) or long (150 ns) rise and fall times. Plasma membrane effects were evaluated using Fluo-4 to determine calcium influx, the only measurable source of increases in intracellular calcium. Mitochondria membrane effects were evaluated using tetramethylrhodamine ethyl ester (TMRE) to determine mitochondria membrane potentials (ΔΨm). Single pulses with short rise and fall times caused electric field-dependent increases in calcium influx, dissipation of ΔΨm and cell death. Pulses with long rise and fall times exhibited electric field-dependent increases in calcium influx, but diminished effects on dissipation of ΔΨm and viability. Results indicate that high frequency components have significant differential impact on mitochondria membranes, which determines cell death, but lesser variances on plasma membranes, which allows calcium influxes, a primary determinant for dissipation of ΔΨm and cell death.
Energetic and metabolic transient response of Saccharomyces cerevisiae to benzoic acid.
Kresnowati, M T A P; van Winden, W A; van Gulik, W M; Heijnen, J J
2008-11-01
Saccharomyces cerevisiae is known to be able to adapt to the presence of the commonly used food preservative benzoic acid with a large energy expenditure. Some mechanisms for the adaptation process have been suggested, but its quantitative energetic and metabolic aspects have rarely been discussed. This study discusses use of the stimulus response approach to quantitatively study the energetic and metabolic aspects of the transient adaptation of S. cerevisiae to a shift in benzoic acid concentration, from 0 to 0.8 mM. The information obtained also serves as the basis for further utilization of benzoic acid as a tool for targeted perturbation of the energy system, which is important in studying the kinetics and regulation of central carbon metabolism in S. cerevisiae. Using this experimental set-up, we found significant fast-transient (< 3000 s) increases in O(2) consumption and CO(2) production rates, of approximately 50%, which reflect a high energy requirement for the adaptation process. We also found that with a longer exposure time to benzoic acid, S. cerevisiae decreases the cell membrane permeability for this weak acid by a factor of 10 and decreases the cell size to approximately 80% of the initial value. The intracellular metabolite profile in the new steady-state indicates increases in the glycolytic and tricarboxylic acid cycle fluxes, which are in agreement with the observed increases in specific glucose and O(2) uptake rates.
Cicchelero, Laetitia; Denies, Sofie; Vanderperren, Katrien; Stock, Emmelie; Van Brantegem, Leen; de Rooster, Hilde; Sanders, Niek N
2017-08-01
The immunological, anti-angiogenic and clinical effects of metronomic cyclophosphamide and 3 consecutive intratumoral interleukin (IL)-12 gene therapy (electrogene therapy (EGT)) treatments were evaluated in 6 dogs with spontaneous cancer. In all dogs, a decrease in peripheral leukocytes 2 days after IL-12 EGT coincided with erythema and swelling of the tumor. In the tumor, a transient increase in IL-12 levels was measured, whereas a continuous increase in interferon γ (IFNγ) and thrombospondin 1 (TSP-1) were determined in contrast to a continuous decrease in vascular endothelial growth factor (VEGF). In the serum, a transient increase in IL-12 and IL-10 levels were noted in contrast to a transient decrease in VEGF and TSP-1. The treatment resulted in a significant anti-angiogenic effect. Although all primary tumors continued to progress in time, this progression was slower than before treatment according to the contrast-enhanced ultrasound data. Besides the encouraging immunostimulatory and anti-angiogenic effects observed in all dogs we also noticed in 4 out of 6 dogs clinically relevant improvements in quality of life and weight. These results hold great promise for combinatorial strategies of IL-12 EGT and metronomic chemotherapy with conventional antitumor (immuno)therapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Bayguinov, Orline; Hagen, Brian; Sanders, Kenton M
2003-01-01
Neurokinins contribute to the neural regulation of gastrointestinal (GI) smooth muscles. We studied responses of murine colonic smooth muscle cells to substance P (SP) and NK1 and NK2 agonists using confocal microscopy and the patch clamp technique. Colonic myocytes generated localized Ca2+ transients that were coupled to spontaneous transient outward currents (STOCs). SP (10−10 M) increased Ca2+ transients and STOCs. Higher concentrations of SP (10−6 M) increased basal Ca2+ and inhibited Ca2+ transients and STOCs. Effects of SP were due to increased Ca2+ entry via L-type Ca2+ channels, and were mediated by protein kinase C (PKC). Nifedipine (10−6 M) and the PKC inhibitor, GF 109203X (10−6 M) reduced L-type Ca2+ current and blocked the effects of SP. SP responses depended upon parallel stimulation of NK1 and NK2 receptors. NK1 agonist ([Sar9,Met(O2)11]-substance P; SSP) and NK2 agonists (neurokinin A (NKA) or GR-64349) did not mimic the effects of SP alone, but NK1 and NK2 agonists were effective when added in combination (10−10–10−6 M). Consistent with this, either an NK1-specific antagonist (GR-82334; 10−7 M) or an NK2-specific antagonist (MEN 10,627; 10−7 M) blocked responses to SP (10−6 M). Ryanodine (10−5 M) blocked the increase in Ca2+ transients and STOCs in response to SP (10−10 M). Our findings show that low concentrations of SP, via PKC-dependent enhancement of L-type Ca2+ current and recruitment of ryanodine receptors, stimulate Ca2+ transients. At higher concentrations of SP (10−6 M), basal Ca2+ increases and spontaneous Ca2+ transients and STOCs are inhibited. PMID:12711623
Cárdenas, Luis; Martínez, Adán; Sánchez, Federico; Quinto, Carmen
2008-12-01
The role of reactive oxygen species (ROS) in root-nodule development and metabolism has been extensively studied. However, there is limited evidence showing ROS changes during the earliest stages of the interaction between legumes and rhizobia. Herein, using ratio-imaging analysis, increasing and transient ROS levels were detected at the tips of actively growing root hair cells within seconds after addition of Nod factors (NFs). This transient response (which lasted up to 3 min) was Nod-factor-specific, as chitin oligomers (pentamers) failed to induce a similar response. When chitosan, a fungal elicitor, or ATP was used instead, a sustained increasing signal was observed. As ROS levels are transiently elevated after the perception of NFs, we propose that this ROS response is characteristic of the symbiotic interaction. Furthermore, we discuss the remarkable spatial and temporal coincidences between ROS and transiently increased calcium levels observed in root hair cells immediately after the detection of NFs.
NASA Astrophysics Data System (ADS)
Sima, Wenxia; Zou, Mi; Yang, Ming; Yang, Qing; Peng, Daixiao
2018-05-01
Amorphous alloy is increasingly widely used in the iron core of power transformer due to its excellent low loss performance. However, its potential harm to the power system is not fully studied during the electromagnetic transients of the transformer. This study develops a simulation model to analyze the effect of transformer iron core materials on ferroresonance. The model is based on the transformer π equivalent circuit. The flux linkage-current (ψ-i) Jiles-Atherton reactor is developed in an Electromagnetic Transients Program-Alternative Transients Program and is used to represent the magnetizing branches of the transformer model. Two ferroresonance cases are studied to compare the performance of grain-oriented Si-steel and amorphous alloy cores. The ferroresonance overvoltage and overcurrent are discussed under different system parameters. Results show that amorphous alloy transformer generates higher voltage and current than those of grain-oriented Si-steel transformer and significantly harms the power system safety.
NASA Technical Reports Server (NTRS)
Branscome, Lee E.; Gutowski, William J., Jr.
1991-01-01
Atmospheric transient eddies contribute significantly to mid-latitude energy and water vapor transports. Changes in the global climate, as induced by greenhouse enhancement, will likely alter transient eddy behavior. Unraveling all the feedbacks that occur in general circulation models (GCMs) can be difficult. The transient eddies are isolated from the feedbacks and are focused on the response of the eddies to zonal-mean climate changes that result from CO2-doubling. Using a primitive-equation spectral model, the impact of climate change on the life cycles of transient eddies is examined. Transient eddy behavior in experiments is compared with initial conditions that are given by the zonal-mean climates of the GCMs with current and doubled amounts of CO2. The smaller meridional temperature gradient in a doubled CO2 climate leads to a reduction in eddy kinetic energy, especially in the subtropics. The decrease in subtropical eddy energy is related to a substantial reduction in equatorward flux of eddy activity during the latter part of the life cycle. The reduction in equatorward energy flux alters the moisture cycle. Eddy meridional transport of water vapor is shifted slightly poleward and subtropical precipitation is reduced. The water vapor transport exhibits a relatively small change in magnitude, compared to changes in eddy energy, due to the compensating effect of higher specific humidity in the doubled-CO2 climate. An increase in high-latitude precipitation is related to the poleward shift in eddy water vapor flux. Surface evaporation amplifies climatic changes in water vapor transport and precipitation in the experiments.
Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.
2018-01-01
The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. PMID:27038339
Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A
2016-06-01
The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Transient response of sap flow to wind speed.
Chu, Chia R; Hsieh, Cheng-I; Wu, Shen-Yuang; Phillips, Nathan G
2009-01-01
Transient responses of sap flow to step changes in wind speed were experimentally investigated in a wind tunnel. A Granier-type sap flow sensor was calibrated and tested in a cylindrical tube for analysis of its transient time response. Then the sensor was used to measure the transient response of a well-watered Pachira macrocarpa plant to wind speed variations. The transient response of sap flow was described using the resistance-capacitance model. The steady sap flow rate increased as the wind speed increased at low wind speeds. Once the wind speed exceeded 8.0 m s(-1), the steady sap flow rate did not increase further. The transpiration rate, measured gravimetrically, showed a similar trend. The response of nocturnal sap flow to wind speed variation was also measured and compared with the results in the daytime. Under the same wind speed, the steady sap flow rate was smaller than that in the daytime, indicating differences between diurnal and nocturnal hydraulic function, and incomplete stomatal closure at night. In addition, it was found that the temporal response of the Granier sensor is fast enough to resolve the transient behaviour of water flux in plant tissue.
Elsharkawy, Aisha; Alboraie, Mohamed; Fouad, Rabab; Asem, Noha; Abdo, Mahmoud; Elmakhzangy, Hesham; Mehrez, Mai; Khattab, Hany; Esmat, Gamal
2017-12-01
Transient elastography is widely used to assess fibrosis stage in chronic hepatitis C (CHC). We aimed to establish and validate different transient elastography cut-off values for significant fibrosis and cirrhosis in CHC genotype 4 patients. The data of 100 treatment-naive CHC patients (training set) and 652 patients (validation set) were analysed. The patients were subjected to routine pretreatment laboratory investigations, liver biopsy and histopathological staging of hepatic fibrosis according to the METAVIR scoring system. Transient elastography was performed before and in the same week as liver biopsy using FibroScan (Echosens, Paris, France). Transient elastography results were correlated to different stages of hepatic fibrosis in both the training and validation sets. ROC curves were constructed. In the training set, the best transient elastography cut-off values for significant hepatic fibrosis (≥F2 METAVIR), advanced hepatic fibrosis (≥F3 METAVIR) and cirrhosis (F4 METAVIR) were 7.1, 9 and 12.2 kPa, with sensitivities of 87%, 87.5% and 90.9% and specificities of 100%, 99.9% and 99.9%, respectively. The application of these cut-offs in the validation set showed sensitivities of 85.5%, 82.8% and 92% and specificities of 86%, 89.4% and 99.01% for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, respectively. Transient elastography performs well for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, with validated cut-offs of 7.1, 9 and 12.2 kPa, respectively, in genotype 4 CHC patients. Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Nagashima, Shuichi; Yagyu, Hiroaki; Tozawa, Ryuichi; Tazoe, Fumiko; Takahashi, Manabu; Kitamine, Tetsuya; Yamamuro, Daisuke; Sakai, Kent; Sekiya, Motohiro; Okazaki, Hiroaki; Osuga, Jun-ichi; Honda, Akira; Ishibashi, Shun
2015-01-01
Squalene synthase (SS) catalyzes the biosynthesis of squalene, the first specific intermediate in the cholesterol biosynthetic pathway. To test the feasibility of lowering plasma cholesterol by inhibiting hepatic SS, we generated mice in which SS is specifically knocked out in the liver (L-SSKO) using Cre-loxP technology. Hepatic SS activity of L-SSKO mice was reduced by >90%. In addition, cholesterol biosynthesis in the liver slices was almost eliminated. Although the hepatic squalene contents were markedly reduced in L-SSKO mice, the hepatic contents of cholesterol and its precursors distal to squalene were indistinguishable from those of control mice, indicating the presence of sufficient centripetal flow of cholesterol and/or its precursors from the extrahepatic tissues. L-SSKO mice showed a transient liver dysfunction with moderate hepatomegaly presumably secondary to increased farnesol production. In a fed state, the plasma total cholesterol and triglyceride were significantly reduced in L-SSKO mice, primarily owing to reduced hepatic VLDL secretion. In a fasted state, the hypolipidemic effect was lost. mRNA expression of liver X receptor α target genes was reduced, while that of sterol-regulatory element binding protein 2 target genes was increased. In conclusion, liver-specific ablation of SS inhibits hepatic cholesterol biosynthesis and induces hypolipidemia without increasing significant mortality. PMID:25755092
Bondarenko, Vladimir E.
2014-01-01
The β1-adrenergic signaling system plays an important role in the functioning of cardiac cells. Experimental data shows that the activation of this system produces inotropy, lusitropy, and chronotropy in the heart, such as increased magnitude and relaxation rates of [Ca2+]i transients and contraction force, and increased heart rhythm. However, excessive stimulation of β1-adrenergic receptors leads to heart dysfunction and heart failure. In this paper, a comprehensive, experimentally based mathematical model of the β1-adrenergic signaling system for mouse ventricular myocytes is developed, which includes major subcellular functional compartments (caveolae, extracaveolae, and cytosol). The model describes biochemical reactions that occur during stimulation of β1-adrenoceptors, changes in ionic currents, and modifications of Ca2+ handling system. Simulations describe the dynamics of major signaling molecules, such as cyclic AMP and protein kinase A, in different subcellular compartments; the effects of inhibition of phosphodiesterases on cAMP production; kinetics and magnitudes of phosphorylation of ion channels, transporters, and Ca2+ handling proteins; modifications of action potential shape and duration; magnitudes and relaxation rates of [Ca2+]i transients; changes in intracellular and transmembrane Ca2+ fluxes; and [Na+]i fluxes and dynamics. The model elucidates complex interactions of ionic currents upon activation of β1-adrenoceptors at different stimulation frequencies, which ultimately lead to a relatively modest increase in action potential duration and significant increase in [Ca2+]i transients. In particular, the model includes two subpopulations of the L-type Ca2+ channels, in caveolae and extracaveolae compartments, and their effects on the action potential and [Ca2+]i transients are investigated. The presented model can be used by researchers for the interpretation of experimental data and for the developments of mathematical models for other species or for pathological conditions. PMID:24586529
Rubart, M; Lopshire, J C; Fineberg, N S; Zipes, D P
2000-06-01
We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid-myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by approximately 6 and approximately 3 mV, respectively (P < 0.02), and prolonged action potential duration at 90% repolarization from 235+/-8 msec to 278+/-8 msec (1 Hz; P = 0.02). Rapid pacing-induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4-aminopyridine-sensitive transient outward K+ current, Ito, over the range of physiologic frequencies, resulting from a approximately 30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L-type Ca2+ currents, I(Ca.L), by 15% to 35 % between +10 and +60 mV; and (3) increases in peak density of the Ca2+-activated chloride current, I(Cl.Ca), by 30% to 120% between +30 and +50 mV. Frequency-dependent reduction in Ito combined with enhanced I(Ca.L) causes an increase in net inward current that may be responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward I(Ca.Cl).
Calderón, Juan C; Bolaños, Pura; Caputo, Carlo
2011-01-01
Abstract We used enzymatically dissociated flexor digitorum brevis (FDB) and soleus fibres loaded with the fast Ca2+ dye Magfluo-4 AM, and adhered to Laminin, to test whether repetitive stimulation induces progressive changes in the kinetics of Ca2+ release and reuptake in a fibre-type-dependent fashion. We applied a protocol of tetani of 350 ms, 100 Hz, every 4 s to reach a mean amplitude reduction of 25% of the first peak. Morphology type I (MT-I) and morphology type II (MT-II) fibres underwent a total of 96 and 52.8 tetani (P < 0.01 between groups), respectively. The MT-II fibres (n = 18) showed significant reductions of the amplitude (19%), an increase in rise time (8.5%) and a further reduction of the amplitude/rise time ratio (25.5%) of the first peak of the tetanic transient after 40 tetani, while MT-I fibres (n = 5) did not show any of these changes. However, both fibre types showed significant reductions in the maximum rate of rise of the first peak after 40 tetani. Two subpopulations among the MT-II fibres could be distinguished according to Ca2+ reuptake changes. Fast-fatigable MT-II fibres (fMT-II) showed an increase of 32.2% in the half-width value of the first peak, while for fatigue-resistant MT-II fibres (rMT-II), the increase amounted to 6.9%, both after 40 tetani. Significant and non-significant increases of 36.4% and 11.9% in the first time constant of decay (t1) values were seen after 40 tetani in fMT-II and rMT-II fibres, respectively. MT-I fibres did not show kinetic changes in any of the Ca2+ reuptake variables. All changes were reversed after an average recovery of 7.5 and 15.4 min for MT-I and MT-II fibres, respectively. Further experiments ruled out the possibility that the differences in the kinetic changes of the first peak of the Ca2+ transients between fibres MT-I and MT-II could be related to the inactivation of Ca2+ release mechanism. In conclusion, we established a model of enzymatically dissociated fibres, loaded with Magfluo-4 and adhered to Laminin, to study muscle fatigue and demonstrated fibre-type-dependent, fatigue-induced kinetic changes in both Ca2+ release and reuptake. PMID:21878526
Bergmann glia modulate cerebellar Purkinje cell bistability via Ca2+-dependent K+ uptake
Wang, Fushun; Xu, Qiwu; Wang, Weishan; Takano, Takahiro; Nedergaard, Maiken
2012-01-01
Recent studies have shown that cerebellar Bergmann glia display coordinated Ca2+ transients in live mice. However, the functional significance of Bergmann glial Ca2+ signaling remains poorly understood. Using transgenic mice that allow selective stimulation of glial cells, we report here that cytosolic Ca2+ regulates uptake of K+ by Bergmann glia, thus providing a powerful mechanism for control of Purkinje cell-membrane potential. The decline in extracellular K+ evoked by agonist-induced Ca2+ in Bergmann glia transiently increased spike activity of Purkinje cells in cerebellar slices as well as in live anesthetized mice. Thus, Bergmann glia play a previously unappreciated role in controlling the membrane potential and thereby the activity of adjacent Purkinje cells. PMID:22547829
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cha, Seho; Lim, Chunghun; Lee, Jae Young
2010-04-16
During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.
Regional business cycle synchronization through expectations
NASA Astrophysics Data System (ADS)
Onozaki, Tamotsu; Yanagita, Tatsuo; Kaizoji, Taisei; Toyabe, Kazutaka
2007-09-01
This paper provides an example in which regional business cycles may synchronize via producers’ expectations, even though there is no interregional trade, by means of a system of globally coupled, noninvertible maps. We concentrate on the dependence of the dynamics on a parameter η which denotes the inverse of price elasticity of demand. Simulation results show that several phases (the short transient, the complete asynchronous, the long transient and the intermediate transient) appear one after another as η increases. In the long transient phase, the intermittent clustering process with a long chaotic transient appears repeatedly.
Liu, W M; Chu, W M; Choudary, P V; Schmid, C W
1995-01-01
The abundance of Alu RNA is transiently increased by heat shock in human cell lines. This effect is specific to Alu repeats among Pol III transcribed genes, since the abundance of 7SL, 7SK, 5S and U6 RNAs is essentially unaffected by heat shock. The rapid induction of Alu expression precedes the heat shock induction of mRNAs for the ubiquitin and HSP 70 heat shock genes. Heat shock mimetics also transiently induce Alu expression indicating that increased Alu expression is a general cell-stress response. Cycloheximide treatment rapidly and transiently increases the abundance of Alu RNA. Again, compared with other genes transcribed by Pol III, this increase is specific to Alu. However, as distinguished from the cell stress response, cycloheximide does not induce expression of HSP 70 and ubiquitin mRNAs. Puromycin also increases Alu expression, suggesting that this response is generally caused by translational inhibition. The response of mammalian SINEs to cell stress and translational inhibition is not limited to SINEs which are Alu homologues. Heat shock and cycloheximide each transiently induce Pol III directed expression of B1 and B2 RNAs in mouse cells and C-element RNA in rabbit cells. Together, these three species exemplify the known SINE composition of placental mammals, suggesting that mammalian SINEs are similarly regulated and may serve a common function. Images PMID:7784180
Mitrovic, Katarina; Vukovic, Rade; Milenkovic, Tatjana; Todorovic, Sladjana; Radivojcevic, Jovana; Zdravkovic, Dragan
2016-02-01
Congenital hypothyroidism (CH) is the most frequent congenital endocrine disorder. The purpose of the present study was to determine the incidence of CH in Central Serbia from 1983 to 2013. Newborn screening for CH was based on measuring neonatal thyroid-stimulating hormone (TSH) using a 30 mU/l cutoff (CO) until 12/1987 (P1), 15 mU/l until 12/1997 (P2), 10 mU/l until 12/2006 (P3), and 9 mU/l thereafter (P4). During the study period, there were 1,547,122 live births screened for CH. Primary CH was detected in 434 newborns, with incidence of 1:3728. With gradual lowering of the CO, the incidences of CH increased from 1:5943 in P1 to 1:1872 in P4 (p < 0.001). Incidence of CH with ectopic and enlarged gland doubled (p < 0.001), while prevalence of athyreosis remained relatively constant. The most prominent finding was the increase in the transient CH from none in P1 to 35 % of all CH patients in P4. The overall incidence of CH in Central Serbia during study period nearly tripled, with a significant increase in almost all etiological categories, and was associated with lowering TSH cutoffs as well as other yet unidentified factors. Further studies are needed to identify other factors associated with increasing incidence of CH. Congenital hypothyroidism (CH) is the main cause of preventable mental retardation. Recent reports have indicated a progressive increase in the incidence of primary CH throughout the world, partially explained by lowering of the TSH cutoff values. During the study period associated with lowering of the TSH cutoffs, the overall incidence of CH in Serbia tripled, including transient CH, ectopy, and dyshormonogenesis, while prevalence of athyreosis remained stable during 30 years. Significant increase in the incidence of both permanent and transient CH was observed, associated with lowering of TSH cutoffs as well as other yet unidentified factors.
Terminal Transient Phase of Chaotic Transients
NASA Astrophysics Data System (ADS)
Lilienkamp, Thomas; Parlitz, Ulrich
2018-03-01
Transient chaos in spatially extended systems can be characterized by the length of the transient phase, which typically grows quickly with the system size (supertransients). For a large class of these systems, the chaotic phase terminates abruptly, without any obvious precursors in commonly used observables. Here we investigate transient spatiotemporal chaos in two different models of this class. By probing the state space using perturbed trajectories we show the existence of a "terminal transient phase," which occurs prior to the abrupt collapse of chaotic dynamics. During this phase the impact of perturbations is significantly different from the earlier transient and particular patterns of (non)susceptible regions in state space occur close to the chaotic trajectories. We therefore hypothesize that even without perturbations proper precursors for the collapse of chaotic transients exist, which might be highly relevant for coping with spatiotemporal chaos in cardiac arrhythmias or brain functionality, for example.
Analysis of flowpath dynamics in a steep unchannelled hollow in the Tanakami Mountains of Japan
NASA Astrophysics Data System (ADS)
Uchida, Taro; Asano, Yuko; Ohte, Nobuhito; Mizuyama, Takahisa
2003-02-01
Simultaneous measurements of runoff, soil pore water pressure, soil temperature, and water chemistry were taken to evaluate the spatial and temporal nature of flowpaths in a steep 0·1 ha unchannelled hollow in the Tanakami Mountains of central Japan. Tensiometers showed that a saturated area formed and a downward hydraulic gradient existed continuously in the area near a spring. The amplitude of the soil-bedrock interface temperature difference near the spring was smaller than that in the upper hollow, although soil depth near the spring was smaller than in the upper hollow. This suggests that, in the small perennially saturated area near the spring, water percolates through the vadose zone mixed with water emerging from the bedrock. During summer rainstorms, the soil-bedrock interface temperature increased as the ground became saturated. Silica and sodium concentrations in the transient saturated groundwater during these episodes were significantly lower than those in the perennial groundwater, suggesting that both rainwater and shallow soil water had important effects on the formation of transient saturated groundwater on the upper slope. In this case, the streamflow varied with the soil pore water pressure on the upper slope; the soil pore water pressure in the area near the spring remained nearly constant. Moreover, the spring water temperature was almost the same as the transient groundwater temperature on the upper slope. This indicates that the transient groundwater in the upper slope flowed to the spring via lateral preferential paths. The relative inflow of bedrock groundwater to the spring decreased as rainfall increased.
[Atomoxetine for treatment of children and adolescents with ADHD].
Resen, Katarina; Pagsberg, Anne Katrine; Jörgens, Gesche
2014-03-03
Atomoxetine reduces ADHD symptoms in children and adolescents significantly and is indicated for ADHD with co-morbid anxiety, depression and tics or with an increased risk of abuse. Number needed to treat is 3.4-5. Common adverse effects are stomach pain, decreased appetite and somnolence. Serious adverse effects include increased vascular tone, decreased growth rate and increased suicidal behaviour. In most cases adverse effects are mild to moderate and transient. Since atomoxetine was launched in 2006, 117 cases of toxic exposures have been reported in Denmark.
Uzumcu, Mehmet; Suzuki, Hiroetsu; Skinner, Michael K
2004-01-01
Vinclozolin is a systemic dicarboximide fungicide that is used on fruits, vegetables, ornamental plants, and turf grass. Vinclozolin and its metabolites are known to be endocrine disruptors and act as androgen receptor antagonists. The hypothesis tested in the current study is that transient embryonic exposure to an anti-androgenic endocrine disruptor at the time of testis determination alters testis development and subsequently influences adult spermatogenic capacity and male reproduction. The effects of vinclozolin on embryonic testicular cord formation in vitro were examined, as well as the effects of transient in utero vinclozolin exposure on postnatal testis development and function. Embryonic day 13 (E13, sperm-positive vaginal smear day = E0) gonads were cultured in the absence or presence of vinclozolin (50-500microM). Vinclozolin treated gonads had significantly fewer cords (P < 0.05) and the histology of the cords that formed were abnormal as compared to vehicle-treated organs. Pregnant rats were exposed to vinclozolin (100 mg/kg/day) between embryonic days 8 and 14 (E8-E14) of development. Testis morphology and function were analyzed from postnatal day (P) 0, pubertal P20, and adult P60. No significant effect of vinclozolin on testis histology or germ cell viability was observed in P0 testis. The pubertal P20 testis from vinclozolin exposed animals had significantly higher numbers of apoptotic germ cells (P < 0.01), but testis weight was not affected. The adult P60 sperm motility was significantly lower in vinclozolin exposed males (P < 0.01). In addition, apoptotic germ cell number in testis of vinclozolin exposed animals was higher in adult P60 animals. Observations demonstrate that vinclozolin can effect embryonic testicular cord formation in vitro and that transient in utero exposure to vinclozolin increases apoptotic germ cell numbers in the testis of pubertal and adult animals. This correlated to reduced sperm motility in the adult. In conclusion, transient exposure to vinclozolin during the time of testis differentiation (i.e. cord formation) alters testis development and function. Observations indicate that transient exposure to an anti-androgenic endocrine disruptor during embryonic development causes delayed effects later in adult life on spermatogenic capacity.
Lichtstein, D; Gati, I; Haver, E; Katz, U
1992-01-01
Digitalis-like compounds (DLC), constituents of animal tissues, are possible regulators of the Na+, K(+)-ATPase implicated in water and salt homeostasis. The distribution of DLC in the toad (Bufo viridis) was determined following methanol extraction and partial purification. DLC highest levels were found in the skin but it was also detected in the plasma and many internal organs. Short term (hours) exposure of the toad to hypertonic shock (1.5% NaCl) induced an increase in plasma osmolarity due to an increase in Na+ and Cl- levels. This treatment induced a transient, three fold, increase of DLC levels in the brain and transient reduction of its levels in the ventral skin. Acclimation of the toads to burrowing conditions for six weeks resulted in an increase in plasma osmolarity due to a large increase in plasma urea with a small increase in ion concentrations. Under these conditions DLC levels in the dorsal skin increased by 100% without alteration of its levels in the plasma, brain and ventral skin. DLC levels in the toad brain of control animals, showed a significant dependence on season, being highest in the summer and lowest in the winter. DLC levels in the skin peaked in May while the levels in the plasma were season independent. The changes in DLC levels induced by the short- as well as long-term perturbations in the animal environmental salinity together with the seasonal differences suggest that DLC in the toad is involved in water and salt homeostasis of these animals, but may also participate in other unknown functions.
Transient translational quiescence in primordial germ cells
Oulhen, Nathalie; Swartz, S. Zachary; Laird, Jessica; Mascaro, Alexandra
2017-01-01
Stem cells in animals often exhibit a slow cell cycle and/or low transcriptional activity referred to as quiescence. Here, we report that the translational activity in the primordial germ cells (PGCs) of the sea urchin embryo (Strongylocentrotus purpuratus) is quiescent. We measured new protein synthesis with O-propargyl-puromycin and L-homopropargylglycine Click-iT technologies, and determined that these cells synthesize protein at only 6% the level of their adjacent somatic cells. Knockdown of translation of the RNA-binding protein Nanos2 by morpholino antisense oligonucleotides, or knockout of the Nanos2 gene by CRISPR/Cas9 resulted in a significant, but partial, increase (47%) in general translation specifically in the PGCs. We found that the mRNA of the translation factor eEF1A is excluded from the PGCs in a Nanos2-dependent manner, a consequence of a Nanos/Pumilio response element (PRE) in its 3′UTR. In addition to eEF1A, the cytoplasmic pH of the PGCs appears to repress translation and simply increasing the pH also significantly restores translation selectively in the PGCs. We conclude that the PGCs of this sea urchin institute parallel pathways to quiesce translation thoroughly but transiently. PMID:28235822
Drug delivery across the blood-brain barrier using focused ultrasound
Burgess, Alison; Hynynen, Kullervo H.
2015-01-01
Introduction The presence of the blood-brain barrier (BBB) is a significant impediment to the delivery of therapeutic agents to the brain for treatment of brain diseases. Focused ultrasound (FUS) has been developed as a non-invasive method for transiently increasing the permeability of the BBB to promote drug delivery to targeted regions of the brain. Areas Covered The present review briefly compares the methods used to promote drug delivery to the brain and describes the benefits and limitations of FUS technology. We summarize the experimental data which shows that FUS, combined with intravascular microbubbles, increases therapeutic agent delivery into the brain leading to significant reductions in pathology in preclinical models of disease. The potential for translation of this technology to the clinic is also discussed. Expert Opinion The introduction of MRI guidance and intravascular administration of microbubbles to FUS treatments permits the consistent, transient, and targeted opening of the BBB. The development of feedback systems and real-time monitoring techniques improve the safety of BBB opening. Successful clinical translation of FUS has the potential to revolutionize the treatment of brain disease resulting in effective, less-invasive treatments without the need for expensive drug development. PMID:24650132
Drug delivery across the blood-brain barrier using focused ultrasound.
Burgess, Alison; Hynynen, Kullervo
2014-05-01
The presence of the blood-brain barrier (BBB) is a significant impediment to the delivery of therapeutic agents to the brain for treatment of brain diseases. Focused ultrasound (FUS) has been developed as a noninvasive method for transiently increasing the permeability of the BBB to promote drug delivery to targeted regions of the brain. The present review briefly compares the methods used to promote drug delivery to the brain and describes the benefits and limitations of FUS technology. We summarize the experimental data which shows that FUS, combined with intravascular microbubbles, increases therapeutic agent delivery into the brain leading to significant reductions in pathology in preclinical models of disease. The potential for translation of this technology to the clinic is also discussed. The introduction of magnetic resonance imaging guidance and intravascular administration of microbubbles to FUS treatments permits the consistent, transient and targeted opening of the BBB. The development of feedback systems and real-time monitoring techniques improve the safety of BBB opening. Successful clinical translation of FUS has the potential to revolutionize the treatment of brain disease resulting in effective, less-invasive treatments without the need for expensive drug development.
Wahab, Suzaily; Abdul Rahman, Abdul Hamid; Sidek, Dinsuhaimi; Zakaria, Mohd. Normani
2016-01-01
Objective Electrophysiological studies, which are mostly focused on afferent pathway, have proven that auditory processing deficits exist in patients with schizophrenia. Nevertheless, reports on the suppressive effect of efferent auditory pathway on cochlear outer hair cells among schizophrenia patients are limited. The present, case-control, study examined the contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) in patients with schizophrenia. Methods Participants were twenty-three healthy controls and sixteen schizophrenia patients with normal hearing, middle ear and cochlear outer hair cells function. Absolute non-linear and linear TEOAEs were measured in both ears by delivering clicks stimuli at 80 dB SPL and 60 dB SPL respectively. Subsequently, contralateral suppression was determined by subtracting the absolute TEOAEs response obtained at 60 dBpe SPL during the absence and presence of contralateral white noise delivered at 65 dB HL. No attention tasks were conducted during measurements. Results We found no significant difference in absolute TEOAEs responses at 80 dB SPL, in either diagnosis or ear groups (p>0.05). However, the overall contralateral suppression was significantly larger in schizophrenia patients (p<0.05). Specifically, patients with schizophrenia demonstrated significantly increased right ear contralateral suppression compared to healthy control (p<0.05). Conclusion The present findings suggest increased inhibitory effect of efferent auditory pathway especially on the right cochlear outer hair cells. Further studies to investigate increased suppressive effects are crucial to expand the current understanding of auditory hallucination mechanisms in schizophrenia patients. PMID:26766950
VanderWerf, Frans; Reits, Dik; Metselaar, Mick; De Zeeuw, Chris I
2012-03-01
To determine the functional recovery in patients with severe transient peripheral facial motor paralysis (Bell palsy). Prospective controlled trial. Academic medical center. Blink recovery was studied in 2 groups of severely affected Bell palsy patients during a follow-up period of 84 weeks. The patients in one group received prednisolone within the first week after the onset of symptoms. No medication was given to the other group. A control group of healthy subjects was also included. Simultaneous orbicularis oculi muscle activity and eyelid kinematics were recorded by surface electromyographic (EMG) recording and eyelid search coils, respectively. At the beginning of the paralysis, very little integrated orbicularis oculi muscle activity and eyelid movement was measured at the palsied side of the face. Thirteen weeks later, the integrated orbicularis oculi EMG and functional blink recovery gradually improved until 39 weeks. Beyond, only the integrated orbicularis oculi EMG slightly increased. At 84 weeks, the integrated orbicularis oculi EMG was significantly larger in the prednisolone group compared with the control group. The integrated EMG of the nonmedicated group recovered to normal values. Curiously enough, the functional blink recovery at the palsied side remained reduced to 64% compared with the healthy controls in the prednisolone-treated group and to 36% in the nonmedicated group. The authors demonstrate that prednisolone significantly increased the orbicularis oculi muscle activity and significantly improved functional blink recovery in severely affected Bell palsy patients. However, the increase of muscle activity was insufficient to restore functional blinking to normal values.
Zhang, Baihua; Li, Jianhua; Yue, Yong; Qian, Wei
2017-01-01
Using computational fluid dynamics (CFD) method, the feasibility of simulating transient airflow in a CT-based airway tree with more than 100 outlets for a whole respiratory period is studied, and the influence of truncations of terminal bronchi on CFD characteristics is investigated. After an airway model with 122 outlets is extracted from CT images, the transient airflow is simulated. Spatial and temporal variations of flow velocity, wall pressure, and wall shear stress are presented; the flow pattern and lobar distribution of air are gotten as well. All results are compared with those of a truncated model with 22 outlets. It is found that the flow pattern shows lobar heterogeneity that the near-wall air in the trachea is inhaled into the upper lobe while the center flow enters the other lobes, and the lobar distribution of air is significantly correlated with the outlet area ratio. The truncation decreases airflow to right and left upper lobes and increases the deviation of airflow distributions between inspiration and expiration. Simulating the transient airflow in an airway tree model with 122 bronchi using CFD is feasible. The model with more terminal bronchi decreases the difference between the lobar distributions at inspiration and at expiration. PMID:29333194
Transient effects of anesthetics on dendritic spines and filopodia in the living mouse cortex
Yang, Guang; Chang, Paul C.; Bekker, Alex; Blanck, Thomas; Gan, Wen-Biao
2013-01-01
Background Anesthetics are widely used to induce unconsciousness, pain relief and immobility during surgery. It remains unclear whether the use of anesthetics has significant and long lasting effects on synapse development and plasticity in the brain. To address this question, we examined the formation and elimination of dendritic spines, postsynaptic sites of excitatory synapses, in the developing mouse cortex during and after anesthetics exposure. Methods Transgenic mice expressing yellow fluorescence protein in layer 5 pyramidal neurons were used in this study. Mice at 1 month of age underwent ketamine-xylazine and isoflurane anesthesia over a period of hours. The elimination and formation rates of dendritic spines and filopodia, the precursors of spines, were followed over hours to days in the primary somatosensory cortex using transcranial two-photon microscopy. 4–5 animals were examined under each experimental condition. Student's t-test and Mann-Whitney U-test were used to analyze the data. Results Administration of either ketamine-xylazine or isoflurane rapidly altered dendritic filopodial dynamics but had no significant effects on spine dynamics. Ketamine-xylazine increased filopodial formation while isoflurane decreased filopodial elimination during 4 hours of anesthesia. Both effects were transient and disappeared within a day after the animals woke up. Conclusion Our studies suggest that exposure to anesthetics transiently affects the dynamics of dendritic filopodia but has no significant effect on dendritic spine development and plasticity in the cortex of 1-month-old mice. PMID:21768874
Rizopoulos, Theodoros; Papadaki-Petrou, Helen; Assimakopoulou, Martha
2018-06-15
The Transient Receptor Potential (TRP) family of selective and non-selective ion channels is well represented throughout the mammalian gastrointestinal track. Several members of the Transient Receptor Potential Vanilloid (TRPV) subfamily have been identified in contributing to modulation of mobility, secretion and sensitivity of the human intestine. Previous studies have focused on the detection of TRPV mRNA levels in colon tissue of patients with inflammatory bowel disease (IBD) whereas little information exists regarding TRPV channel expression in the colonic epithelium. The aim of this study was to evaluate the expression levels of TRPV1, TRPV2, TRPV3 and TRPV4 in mucosa epithelial cells of colonic biopsies from patients with ulcerative colitis (UC) in comparison to colonic resections from non-IBD patients (control group). Immunohistochemistry, using specific antibodies and quantitative analyses of TRPV-immunostained epithelial cells, was performed in semi-serial sections of the samples. TRPV1 expression was significantly decreased whereas TRPV4 expression was significantly increased in the colonic epithelium of UC patients compared to patients in the control group ( p < 0.05). No significant difference for TRPV2 and TRPV3 expression levels between UC and control specimens was detected ( p > 0.05). There was no correlation between TRPV channel expression and the clinical features of the disease ( p > 0.05). Further investigation is needed to clarify the role of TRPV channels in human bowel inflammatory response.
Relationship between hot flashes and ambulatory blood pressure: the Hilo women's health study.
Brown, Daniel E; Sievert, Lynnette L; Morrison, Lynn A; Rahberg, Nichole; Reza, Angela
2011-01-01
To examine ambulatory blood pressure (BP) differences between women who report hot flashes (HFs) and those who do not, and to observe whether an objectively measured HF is associated with transient changes in BP. HFs have been associated with elevated BP, but studies have not examined the relationship between objectively measured HFs and blood pressure during normal daily activities. A sample of 202 women in Hilo, Hawaii, aged 45 to 55 years, were asked to fill out a questionnaire that included demographic information and an inventory of symptoms. The women underwent simultaneous 24-hour monitoring of ambulatory BP and HFs, at the same time keeping a diary that included mood and HF reports. No significant difference was present in mean BP between women who reported having an HF during the last 2 weeks and those who did not. When measurements controlled for negative mood reports and posture, there was a highly significant elevation in Z scores of systolic BP when a measured, objective HF occurred within 10 minutes before a BP reading, and a significant elevation of Z scores of diastolic BP when a subjectively reported HF occurred within 10 minutes after a BP reading. These results suggest that objectively measured HFs precede transient elevations of systolic BP, but it is unclear if there is a causal relationship. These results also suggest that women experience subjective HFs within 10 minutes after a transient increase in diastolic BP. Again, the causal relationship is not understood.
NASA Astrophysics Data System (ADS)
Soga, Kouichi; Kotake, Toshihisa; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro; Hoson, Takayuki
Azuki bean (Vigna angularis Ohwi et Ohashi) seedlings were exposed to centrifugal hypergravity, and the changes in the orientation of cortical microtubules and the expression of genes cording γ-tubulin complex (VaTUBG and VaSpc98p) were examined. By 300 g treatment, the percentage of cells with transverse microtubules was decreased, while that with longitudinal microtubules was increased in epicotyls. Hypergravity increased the expression of VaTUBG and VaSpc98p transiently. Also, the expression of both genes was increased transiently by removal of hypergravity stimulus. Lanthanum and gadolinium ions, potential blockers of mechanosensitive calcium ion-permeable channels (mechanoreceptors), nullified reorientation of microtubules as well as up-regulation of expression of VaTUBG and VaSpc98p by hypergravity. These results suggest that mechanoreceptors on the plasma membrane may perceive the gravity signal, which leads to reorientation of cortical microtubules by transiently stimulating the formation of γ-tubulin complex.
Climate variability and vadose zone controls on damping of transient recharge
Corona, Claudia R.; Gurdak, Jason J.; Dickinson, Jesse; Ferré, T.P.A.; Maurer, Edwin P.
2018-01-01
Increasing demand on groundwater resources motivates understanding of the controls on recharge dynamics so model predictions under current and future climate may improve. Here we address questions about the nonlinear behavior of flux variability in the vadose zone that may explain previously reported teleconnections between global-scale climate variability and fluctuations in groundwater levels. We use hundreds of HYDRUS-1D simulations in a sensitivity analysis approach to evaluate the damping depth of transient recharge over a range of periodic boundary conditions and vadose zone geometries and hydraulic parameters that are representative of aquifer systems of the conterminous United States (U.S). Although the models were parameterized based on U.S. aquifers, findings from this study are applicable elsewhere that have mean recharge rates between 3.65 and 730 mm yr–1. We find that mean infiltration flux, period of time varying infiltration, and hydraulic conductivity are statistically significant predictors of damping depth. The resulting framework explains why some periodic infiltration fluxes associated with climate variability dampen with depth in the vadose zone, resulting in steady-state recharge, while other periodic surface fluxes do not dampen with depth, resulting in transient recharge. We find that transient recharge in response to the climate variability patterns could be detected at the depths of water levels in most U.S. aquifers. Our findings indicate that the damping behavior of transient infiltration fluxes is linear across soil layers for a range of texture combinations. The implications are that relatively simple, homogeneous models of the vadose zone may provide reasonable estimates of the damping depth of climate-varying transient recharge in some complex, layered vadose zone profiles.
Cho, Soyoun
2014-01-01
Synaptic vesicles release both neurotransmitter and protons during exocytosis, which may result in a transient acidification of the synaptic cleft that can block Ca2+ channels located close to the sites of exocytosis. Evidence for this effect has been reported for retinal ribbon-type synapses, but not for hair cell ribbon synapses. Here, we report evidence for proton release from bullfrog auditory hair cells when they are held at more physiological, in vivo–like holding potentials (Vh = −60 mV) that facilitate multivesicular release. During paired recordings of hair cells and afferent fibers, L-type voltage-gated Ca2+ currents showed a transient block, which was highly correlated with the EPSC amplitude (or the amount of glutamate release). This effect was masked at Vh = −90 mV due to the presence of a T-type Ca2+ current and blocked by strong pH buffering with HEPES or TABS. Increasing vesicular pH with internal methylamine in hair cells also abolished the transient block. High concentrations of intracellular Ca2+ buffer (10 mm BAPTA) greatly reduced exocytosis and abolished the transient block of the Ca2+ current. We estimate that this transient block is due to the rapid multivesicular release of ∼600–1300 H+ ions per synaptic ribbon. Finally, during a train of depolarizing pulses, paired pulse plasticity was significantly changed by using 40 mm HEPES in addition to bicarbonate buffer. We propose that this transient block of Ca2+ current leads to more efficient exocytosis per Ca2+ ion influx and it may contribute to spike adaptation at the auditory nerve. PMID:25429130
The calcium–frequency response in the rat ventricular myocyte: an experimental and modelling study
Gattoni, Sara; Røe, Åsmund Treu; Frisk, Michael; Louch, William E.; Niederer, Steven A.
2016-01-01
Key points In the majority of species, including humans, increased heart rate increases cardiac contractility. This change is known as the force–frequency response (FFR). The majority of mammals have a positive force–frequency relationship (FFR). In rat the FFR is controversial.We derive a species‐ and temperature‐specific data‐driven model of the rat ventricular myocyte.As a measure of the FFR, we test the effects of changes in frequency and extracellular calcium on the calcium–frequency response (CFR) in our model and three altered models.The results show a biphasic peak calcium–frequency response, due to biphasic behaviour of the ryanodine receptor and the combined effect of the rapid calmodulin buffer and the frequency‐dependent increase in diastolic calcium.Alterations to the model reveal that inclusion of Ca2+/calmodulin‐dependent protein kinase II (CAMKII)‐mediated L‐type channel and transient outward K+ current activity enhances the positive magnitude calcium–frequency response, and the absence of CAMKII‐mediated increase in activity of the sarco/endoplasmic reticulum Ca2+‐ATPase induces a negative magnitude calcium–frequency response. Abstract An increase in heart rate affects the strength of cardiac contraction by altering the Ca2+ transient as a response to physiological demands. This is described by the force–frequency response (FFR), a change in developed force with pacing frequency. The majority of mammals, including humans, have a positive FFR, and cardiac contraction strength increases with heart rate. However, the rat and mouse are exceptions, with the majority of studies reporting a negative FFR, while others report either a biphasic or a positive FFR. Understanding the differences in the FFR between humans and rats is fundamental to interpreting rat‐based experimental findings in the context of human physiology. We have developed a novel model of rat ventricular electrophysiology and calcium dynamics, derived predominantly from experimental data recorded under physiological conditions. As a measure of FFR, we tested the effects of changes in stimulation frequency and extracellular calcium concentration on the simulated Ca2+ transient characteristics and showed a biphasic peak calcium–frequency relationship, consistent with recent observations of a shift from negative to positive FFR when approaching the rat physiological frequency range. We tested the hypotheses that (1) inhibition of Ca2+/calmodulin‐dependent protein kinase II (CAMKII)‐mediated increase in sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) activity, (2) CAMKII modulation of SERCA, L‐type channel and transient outward K+ current activity and (3) Na+/K+ pump dynamics play a significant role in the rat FFR. The results reveal a major role for CAMKII modulation of SERCA in the peak Ca2+–frequency response, driven most significantly by the cytosolic calcium buffering system and changes in diastolic Ca2+. PMID:26916026
Hristov, Kiril L.; Parajuli, Shankar P.; Provence, Aaron
2016-01-01
In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability. Testosterone (100 nM) significantly increased the depolarization-induced whole cell outward currents in DSM cells. The selective pharmacological inhibition of the large-conductance voltage- and Ca2+-activated K+ (BK) channels with paxilline (1 μM) completely abolished this stimulatory effect of testosterone, suggesting a mechanism involving BK channels. At a holding potential of −20 mV, DSM cells exhibited transient BK currents (TBKCs). Testosterone (100 nM) significantly increased TBKC activity in DSM cells. In current-clamp mode, testosterone (100 nM) significantly hyperpolarized the DSM cell resting membrane potential and increased spontaneous transient hyperpolarizations. Testosterone (100 nM) rapidly increased the single BK channel open probability in inside-out excised membrane patches from DSM cells, clearly suggesting a direct BK channel activation via a nongenomic mechanism. Live-cell Ca2+ imaging showed that testosterone (100 nM) caused a decrease in global intracellular Ca2+ concentration, consistent with testosterone-induced membrane hyperpolarization. In conclusion, the data provide compelling mechanistic evidence that under physiological conditions, testosterone at nanomolar concentrations directly activates BK channels in DSM cells, independent from genomic testosterone receptors, and thus regulates DSM excitability. PMID:27605581
Wright, J; Harrison, S; McGeorge, M; Patterson, C; Russell, I; Russell, D; Small, N; Taylor, M; Walsh, M; Warren, E; Young, J
2006-01-01
Problem Rapid referral and management of patients with transient ischaemic attacks is a key component in the national strategy for stroke prevention. However, patients with transient ischaemic attacks are poorly identified and undertreated. Design and setting Before and after evaluation of quality improvement programme with controlled comparison in three primary care trusts reflecting diverse populations and organisational structures in an urban district in the North of England. Key measures for improvement The proportion of patients receiving antiplatelet drugs and safe driving advice on referral to a speciality clinic, and the numbers of referrals, adjusted for age, to the specialist clinic before and after the improvement programme. Strategies for change Interviews with patient and professionals to identify gaps and barriers to good practice; development of evidence based guidelines for the management of patients with transient ischaemic attacks; interactive multidisciplinary workshops for each primary care trust with feedback of individual audit results of referral practice; outreach visits to teams who were unable to attend the workshops; referral templates and desktop summaries to provide reminders of the guidelines to clinicians; incorporation of standards into professional contracts. Effects of change A significant improvement occurred in identification and referral of patients with transient ischaemic attacks to specialist clinics, with a 41% increase in referrals from trained practices compared with control practices. There were also significant improvements in the early treatment and safety advice provided to patients before referral. Lessons learnt A strategic approach to effective quality improvement across a diverse health community is feasible and achievable. Careful planning with patient and professional involvement to develop a tailored and multifaceted quality improvement programme to implement evidence based practice can work in very different primary care settings. Key components of the effectiveness of the model include contextual analysis, strong professional support, clear recommendations based on robust evidence, simplicity of adoption, good communication, and use of established networks and opinion leaders. PMID:16456203
Wright, J; Harrison, S; McGeorge, M; Patterson, C; Russell, I; Russell, D; Small, N; Taylor, M; Walsh, M; Warren, E; Young, J
2006-02-01
Rapid referral and management of patients with transient ischaemic attacks is a key component in the national strategy for stroke prevention. However, patients with transient ischaemic attacks are poorly identified and undertreated. Before and after evaluation of quality improvement programme with controlled comparison in three primary care trusts reflecting diverse populations and organisational structures in an urban district in the North of England. The proportion of patients receiving antiplatelet drugs and safe driving advice on referral to a specialty clinic, and the numbers of referrals, adjusted for age, to the specialist clinic before and after the improvement programme. Interviews with patient and professionals to identify gaps and barriers to good practice; development of evidence based guidelines for the management of patients with transient ischaemic attacks; interactive multidisciplinary workshops for each primary care trust with feedback of individual audit results of referral practice; outreach visits to teams who were unable to attend the workshops; referral templates and desktop summaries to provide reminders of the guidelines to clinicians; incorporation of standards into professional contracts. A significant improvement occurred in identification and referral of patients with transient ischaemic attacks to specialist clinics, with a 41% increase in referrals from trained practices compared with control practices. There were also significant improvements in the early treatment and safety advice provided to patients before referral. A strategic approach to effective quality improvement across a diverse health community is feasible and achievable. Careful planning with patient and professional involvement to develop a tailored and multifaceted quality improvement programme to implement evidence based practice can work in very different primary care settings. Key components of the effectiveness of the model include contextual analysis, strong professional support, clear recommendations based on robust evidence, simplicity of adoption, good communication, and use of established networks and opinion leaders.
Parametric Analysis of a Turbine Trip Event in a BWR Using a 3D Nodal Code
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gorzel, A.
2006-07-01
Two essential thermal hydraulics safety criteria concerning the reactor core are that even during operational transients there is no fuel melting and not-permissible cladding temperatures are avoided. A common concept for boiling water reactors is to establish a minimum critical power ratio (MCPR) for steady state operation. For this MCPR it is shown that only a very small number of fuel rods suffers a short-term dryout during the transient. It is known from experience that the limiting transient for the determination of the MCPR is the turbine trip with blocked bypass system. This fast transient was simulated for a Germanmore » BWR by use of the three-dimensional reactor analysis transient code SIMULATE-3K. The transient behaviour of the hot channels was used as input for the dryout calculation with the transient thermal hydraulics code FRANCESCA. By this way the maximum reduction of the CPR during the transient could be calculated. The fast increase in reactor power due to the pressure increase and to an increased core inlet flow is limited mainly by the Doppler effect, but automatically triggered operational measures also can contribute to the mitigation of the turbine trip. One very important method is the short-term fast reduction of the recirculation pump speed which is initiated e. g. by a pressure increase in front of the turbine. The large impacts of the starting time and of the rate of the pump speed reduction on the power progression and hence on the deterioration of CPR is presented. Another important procedure to limit the effects of the transient is the fast shutdown of the reactor that is caused when the reactor power reaches the limit value. It is shown that the SCRAM is not fast enough to reduce the first power maximum, but is able to prevent the appearance of a second - much smaller - maximum that would occur around one second after the first one in the absence of a SCRAM. (author)« less
NASA Technical Reports Server (NTRS)
Angelaki, D. E.; McHenry, M. Q.; Dickman, J. D.; Perachio, A. A.
2000-01-01
The effects of functional, reversible ablation and potential recruitment of the most irregular otolith afferents on the dynamics and sensitivity of the translational vestibuloocular reflexes (trVORs) were investigated in rhesus monkeys trained to fixate near and far targets. Translational motion stimuli consisted of either steady-state lateral and fore-aft sinusoidal oscillations or short-lasting transient lateral head displacements. Short-duration (usually <2 s) anodal (inhibitory) and cathodal (excitatory) currents (50-100 microA) were delivered bilaterally during motion. In the presence of anodal labyrinthine stimulation, trVOR sensitivity and its dependence on viewing distance were significantly decreased. In addition, anodal currents significantly increased phase lags. During transient motion, anodal stimulation resulted in significantly lower initial eye acceleration and more sluggish responses. Cathodal currents tended to have opposite effects. The main characteristics of these results were simulated by a simple model where both regularly and irregularly discharging afferents contribute to the trVORs. Anodal labyrinthine currents also were found to decrease eye velocity during long-duration, constant velocity rotations, although results were generally more variable compared with those during translational motion.
An ultrasound transient elastography system with coded excitation.
Diao, Xianfen; Zhu, Jing; He, Xiaonian; Chen, Xin; Zhang, Xinyu; Chen, Siping; Liu, Weixiang
2017-06-28
Ultrasound transient elastography technology has found its place in elastography because it is safe and easy to operate. However, it's application in deep tissue is limited. The aim of this study is to design an ultrasound transient elastography system with coded excitation to obtain greater detection depth. The ultrasound transient elastography system requires tissue vibration to be strictly synchronous with ultrasound detection. Therefore, an ultrasound transient elastography system with coded excitation was designed. A central component of this transient elastography system was an arbitrary waveform generator with multi-channel signals output function. This arbitrary waveform generator was used to produce the tissue vibration signal, the ultrasound detection signal and the synchronous triggering signal of the radio frequency data acquisition system. The arbitrary waveform generator can produce different forms of vibration waveform to induce different shear wave propagation in the tissue. Moreover, it can achieve either traditional pulse-echo detection or a phase-modulated or a frequency-modulated coded excitation. A 7-chip Barker code and traditional pulse-echo detection were programmed on the designed ultrasound transient elastography system to detect the shear wave in the phantom excited by the mechanical vibrator. Then an elasticity QA phantom and sixteen in vitro rat livers were used for performance evaluation of the two detection pulses. The elasticity QA phantom's results show that our system is effective, and the rat liver results show the detection depth can be increased more than 1 cm. In addition, the SNR (signal-to-noise ratio) is increased by 15 dB using the 7-chip Barker coded excitation. Applying 7-chip Barker coded excitation technique to the ultrasound transient elastography can increase the detection depth and SNR. Using coded excitation technology to assess the human liver, especially in obese patients, may be a good choice.
Transient Phenomena in Multiphase and Multicomponent Systems: Research Report
NASA Astrophysics Data System (ADS)
Zur Beurteilung von Stoffen in der Landwirtschaft, Senatskommission
2000-09-01
Due to the reinforced risk and safety-analysis of industrial plants in chemical and energy-engineering there has been increased demand in industry for more information on thermo- and fluiddynamic effects of non-equilibria during strong transients. Therefore, the 'Deutsche Forschungsgemeinschaft' initiated a special research program focusing on the study of transient phenomena in multiphase systems with one or several components. This book describes macroscopic as well as microscopic transient situations. A large part of the book deals with numerical methods for describing transients in two-phase mixtures. New developments in measuring techniques are also presented.
Transient Relay Function of Midline Thalamic Nuclei during Long-Term Memory Consolidation in Humans
ERIC Educational Resources Information Center
Thielen, Jan-Willem; Takashima, Atsuko; Rutters, Femke; Tendolkar, Indira; Fernández, Guillén
2015-01-01
To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a…
Cortical cholinergic signaling controls the detection of cues
Gritton, Howard J.; Howe, William M.; Mallory, Caitlin S.; Hetrick, Vaughn L.; Berke, Joshua D.; Sarter, Martin
2016-01-01
The cortical cholinergic input system has been described as a neuromodulator system that influences broadly defined behavioral and brain states. The discovery of phasic, trial-based increases in extracellular choline (transients), resulting from the hydrolysis of newly released acetylcholine (ACh), in the cortex of animals reporting the presence of cues suggests that ACh may have a more specialized role in cognitive processes. Here we expressed channelrhodopsin or halorhodopsin in basal forebrain cholinergic neurons of mice with optic fibers directed into this region and prefrontal cortex. Cholinergic transients, evoked in accordance with photostimulation parameters determined in vivo, were generated in mice performing a task necessitating the reporting of cue and noncue events. Generating cholinergic transients in conjunction with cues enhanced cue detection rates. Moreover, generating transients in noncued trials, where cholinergic transients normally are not observed, increased the number of invalid claims for cues. Enhancing hits and generating false alarms both scaled with stimulation intensity. Suppression of endogenous cholinergic activity during cued trials reduced hit rates. Cholinergic transients may be essential for synchronizing cortical neuronal output driven by salient cues and executing cue-guided responses. PMID:26787867
Aronson, Doron; Burger, Andrew J
2010-07-01
Worsening renal function (WRF) is an ominous complication in patients with acute heart failure syndrome (AHFS). Few data are available with regard to the clinical implications of transient versus persistent WRF in this setting. We studied 467 patients with AHFS and creatinine measurements at baseline and on days 2, 5, 14, and 30. WRF (>/= 0.5 mg/dL increase in serum creatinine above baseline at any time point) was defined as persistent when serum creatinine remained >/= 0.5 mg/dL above baseline throughout day 30, and transient when creatinine levels subsequently decreased to < 0.5 mg/dL above baseline. WRF occurred in 115 patients, and was transient in 39 patients (33.9%). The 6-month mortality rates were 17.3%, 20.5%, and 46.1% in patients without WRF, transient WRF, and persistent WRF, respectively. In a multivariable Cox model, compared with patients with stable renal function, the adjusted hazard ratio for mortality was 0.8 (95% CI 0.4-1.7; P = .58) in patients with transient WRF and 3.2 (95% CI 2.1-5.0; P < .0001) in patients with persistent WRF. Transient WRF is frequent among patients with AHFS. Whereas persistent WRF portends increased mortality, transient WRF appears to be associated with a better outcome as compared with persistent renal failure. Copyright 2010 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Girault, Frédéric; Schubnel, Alexandre; Pili, Éric
2017-09-01
In seismically active fault zones, various crustal fluids including gases are released at the surface. Radon-222, a radioactive gas naturally produced in rocks, is used in volcanic and tectonic contexts to illuminate crustal deformation or earthquake mechanisms. At some locations, intriguing radon signals have been recorded before, during, or after tectonic events, but such observations remain controversial, mainly because physical characterization of potential radon anomalies from the upper crust is lacking. Here we conducted several month-long deformation experiments under controlled dry upper crustal conditions with a triaxial cell to continuously monitor radon emission from crustal rocks affected by three main effects: a fluid pressure pulse, micro-crack closure, and differential stress increase to macroscopic failure. We found that these effects are systematically associated with a variety of radon signals that can be explained using a first-order advective model of radon transport. First, connection to a source of deep fluid pressure (a fluid pressure pulse) is associated with a large transient radon emission increase (factor of 3-7) compared with the background level. We reason that peak amplitude is governed by the accumulation time and the radon source term, and that peak duration is controlled by radioactive decay, permeability, and advective losses of radon. Second, increasing isostatic compression is first accompanied by an increase in radon emission followed by a decrease beyond a critical pressure representing the depth below which crack closure hampers radon emission (150-250 MPa, ca. 5.5-9.5 km depth in our experiments). Third, the increase of differential stress, and associated shear and volumetric deformation, systematically triggers significant radon peaks (ca. 25-350% above background level) before macroscopic failure, by connecting isolated cracks, which dramatically enhances permeability. The detection of transient radon signals before rupture indicates that connection of initially isolated cracks in crustal rocks may occur before rupture and potentially lead to radon transients measurable at the surface in tectonically active regions. This study offers thus an experimental and physical basis for understanding predicted or reported radon anomalies.
NASA Astrophysics Data System (ADS)
Schubnel, A.; Girault, F.; Pili, E.
2017-12-01
In seismically active fault zones, various crustal fluids including gases are released at the surface. Radon-222, a radioactive gas naturally produced in rocks, is used in volcanic and tectonic contexts to illuminate crustal deformation or earthquake mechanisms. At some locations, intriguing radon signals have been recorded before, during, or after tectonic events, but such observations remain controversial, mainly because physical characterization of potential radon anomalies from the upper crust is lacking. Here we conducted several month-long deformation experiments under controlled dry upper crustal conditions with a triaxial cell to continuously monitor radon emission from crustal rocks affected by three main effects: a fluid pressure pulse, micro-crack closure, and differential stress increase to macroscopic failure. We found that these effects are systematically associated with a variety of radon signals that can be explained using a first-order advective model of radon transport. First, connection to a source of deep fluid pressure (a fluid pressure pulse) is associated with a large transient radon emission increase (factor of 3-7) compared with the background level. We reason that peak amplitude is governed by the accumulation time and the radon source term, and that peak duration is controlled by radioactive decay, permeability, and advective losses of radon. Second, increasing isostatic compression is first accompanied by an increase in radon emission followed by a decrease beyond a critical pressure representing the depth below which crack closure hampers radon emission (150-250 MPa, ca. 5.5-9.5 km depth in our experiments). Third, the increase of differential stress, and associated shear and volumetric deformation, systematically triggers significant radon peaks (ca. 25-350% above background level) before macroscopic failure, by connecting isolated cracks, which dramatically enhances permeability. The detection of transient radon signals before rupture indicates that connection of initially isolated cracks in crustal rocks may occur before rupture and potentially lead to radon transients measurable at the surface in tectonically active regions. This study offers thus an experimental and physical basis for understanding predicted or reported radon anomalies.
Coronal disturbances and their terrestrial effects /Tutorial Lecture/
NASA Technical Reports Server (NTRS)
Rust, D. M.
1983-01-01
An assessment is undertaken of recent approaches to the prediction of the interplanetary consequences of coronal disturbances, with attention to the relationships of shocks and energetic particles to coronal transients, of proton events to gamma-ray and microwave bursts, of geomagnetic storms to filament eruptions, and of solar wind increases to the flare site magnetic field direction. A discussion is given concerning the novel phenomenon of transient coronal holes, which appear astride the long decay enhancements of 2-50 A X-ray emission following H-alpha filament eruptions. These voids in the corona are similar to long-lived coronal holes, which are the sources of high speed solar wind streams. The transient coronal holes may also be associated with transient solar wind speed increases.
Studies of Transient Meteor Activity
NASA Technical Reports Server (NTRS)
Jenniskens, Peter M. M.
2002-01-01
Meteoroids bombard Earth's atmosphere daily, but occasionally meteor rates increase to unusual high levels when Earth crosses the relatively fresh ejecta of comets. These transient events in meteor activity provide clues about the whereabouts of Earth-threatening long-period comets, the mechanisms of large-grain dust ejection from comets, and the particle composition and size distribution of the cometary ejecta. Observations of these transient events provide important insight in natural processes that determine the large grain dust environment of comets, in natural phenomena that were prevalent during the time of the origin of life, and in processes that determine the hazard of civilizations to large impacts and of man-made satellites to the periodic blizzard of small meteoroids. In this proposal, three tasks form a coherent program aimed at elucidating various aspects of meteor outbursts, with special reference to planetary astronomy and astrobiology. Task 1 was a ground-based effort to observe periods of transient meteor activity. This includes: (1) stereoscopic imaging of meteors during transient meteor events for measurements of particle size distribution, meteoroid orbital dispersions and fluxes; and (2) technical support for Global-MS-Net, a network of amateur-operated automatic counting stations for meteor reflections from commercial VHF radio and TV broadcasting stations, keeping a 24h vigil on the level of meteor activity for the detection of new meteor streams. Task 2 consisted of ground-based and satellite born spectroscopic observations of meteors and meteor trains during transient meteor events for measurements of elemental composition, the presence of organic matter in the meteoroids, and products generated by the interaction of the meteoroid with the atmosphere. Task 3 was an airborne effort to explore the 2000 Leonid meteor outbursts, which are anticipated to be the most significant of transient meteor activity events in the remainder of the agreement period. This includes technical support for a multi-instrument aircraft campaign, Leonid MAC.
Beniya, Atsushi; Hirata, Hirohito; Watanabe, Yoshihide
2016-11-17
Relaxation dynamics of hot metal clusters on oxide surfaces play a crucial role in a variety of physical and chemical processes. However, their transient mobility has not been investigated as much as other systems such as atoms and molecules on metal surfaces due to experimental difficulties. To study the role of the transient mobility of clusters on the oxide surface, we investigated the initial adsorption process of size-selected Pt clusters on a thin Al 2 O 3 film. Soft-landing the size-selected clusters while suppressing the thermal migration resulted in the transient migration controlling the initial adsorption states as an isolated and aggregated cluster, as revealed using scanning tunneling microscopy. We demonstrate that transient migration significantly contributes to the initial cluster adsorption process; the cross section for aggregation is seven times larger than the expected value from geometrical considerations, indicating that metal clusters are highly mobile during a energy dissipation process on the oxide surface.
Regulation of hematopoiesis in the suspended rat as a model for space flight
NASA Technical Reports Server (NTRS)
Dunn, C. D. R.; Johnson, P. C.
1984-01-01
A series of studies was completed in which a variety of routine hematological and other parameters were obtained from sequential sampling of control and suspended rats. These data showed that, during suspension, the rats failed to gain weight at the same rate as the controls, ate and drank significantly less, demonstrated a transient increase in peripheral hematocrit and RBC count, a transient decrease in MCH, suppressed reticulocyte counts and a progressive decrease in MCV but no change in RBC shape. Leukocyte counts were variably decreased but no significant changes in platelet numbers were noted. Post-suspension, evidence of anemia was present from a reduced RBC count, hemoglobin, hematocrit, and MCV. A leukocytosis was also noted. Efforts directed to the collection of data aimed at understanding changes in blood volume during suspension are also discussed. As part of these studies the following parameters were investigated; RBC survival, in vitro leukocyte reactivity to PHA, bone marrow and spleen cellularity and morphology, ferrokinetics, and the hematopoietic inductive microenvironment.
Cell and defect behavior in lithium-counterdoped solar cells
NASA Technical Reports Server (NTRS)
Weinberg, I.; Mehta, S.; Swartz, C. K.
1984-01-01
Some n(+)/p cells in which lithium is introduced as a counterdopant, by ion-implantation, into the cell's boron-doped p-region were studied. To determine if the cells radiation resistance could be significantly improved by lithium counterdoping. Defect behavior was related to cell performance using deep level transient spectroscopy. Results indicate a significantly increased radiation resistance for the lithium counterdoped cells when compared to the boron doped 1 ohm-cm control cell. The increased radiation resistance of the lithium counterdoped cells is due to the complexing of lithium with divacancies and boron. It is speculated that complexing with oxygen and single vacancies also contributes to the increased radiation resistance. Counterdoping silicon with lithium results in a different set of defects.
The Zwicky Transient Facility: Overview and Commissioning Activities
NASA Astrophysics Data System (ADS)
Graham, Matthew; Zwicky Transient Facility (ZTF) Project Team
2018-01-01
The Zwicky Transient Facility (ZTF) is the first of a new generation of LSST-scope sky surveys to be realized. It will employ a 47 square degree field-of-view camera mounted on the Samuel Oschin 48-inch Schmidt telescope at Palomar Observatory to scan more than 3750 square degrees an hour to a depth of 20.5 – 21 mag. This will lead to unprecedented discovery rates for transients – a young supernova less than 24 hours after its explosion each night as well as rarer and more exotic sources. Repeated imaging of the Northern sky (including the Galactic Plane) will produce a photometric variability catalog with nearly 300 observations each year, ideal for studies of variable stars, binaries, AGN, and asteroids. ZTF represents a significant increase in scale relative to previous surveys in terms of both data volume and data complexity. It will be the first survey to produce one million alerts a night and the first to have a trillion row data archive. We will present an overview of the survey and its challenges and describe recent commissioning activities.
Evidences of trapping in tungsten and implications for plasma-facing components
NASA Astrophysics Data System (ADS)
Longhurst, G. R.; Anderl, R. A.; Holland, D. F.
Trapping effects that include significant delays in permeation saturation, abrupt changes in permeation rate associated with temperature changes, and larger than expected inventories of hydrogen isotopes in the material, were seen in implantation-driven permeation experiments using 25- and 50-micron thick tungsten foils at temperatures of 638 to 825 K. Computer models that simulate permeation transients reproduce the steady-state permeation and reemission behavior of these experiments with expected values of material parameters. However, the transient time characteristics were not successfully simulated without the assumption of traps of substantial trap energy and concentration. An analytical model based on the assumptions of thermodynamic equilibrium between trapped hydrogen atoms and a comparatively low mobile atom concentration successfully accounts for the observed behavior. Using steady-state and transient permeation data from experiments at different temperatures, the effective trap binding energy may be inferred. We analyze a tungsten coated divertor plate design representative of those proposed for ITER and ARIES and consider the implications for tritium permeation and retention if the same trapping we observed was present in that tungsten. Inventory increases of several orders of magnitude may result.
Briones, Teresita L; Woods, Julie; Wadowska, Magdalena; Rogozinska, Magdalena
2006-04-03
In this study we examined whether expression of microtubule-associated protein 2 (MAP2) after transient global cerebral ischemia can be influenced by behavioral experience and if the changes are associated with functional improvement. Rats received either ischemia or sham surgery then assigned to: complex environment housing (EC) or social housing (SC) as controls for 14 days followed by water maze testing. Upregulation of MAP2 was seen in all ischemic animals with a significant overall increase evident in the EC housed rats. Behaviorally, all animals learned to perform the water maze task over time but the ischemia SC rats had the worst performance overall while all the EC housed animals demonstrated the best performance in general. Regression analysis showed that increase MAP2 expression was able to explain some of the variance in the behavioral parameters in the water maze suggesting that this cytoskeletal protein probably played a role in mediating enhanced functional outcomes.
The dynamic volume changes of polymerising polymethyl methacrylate bone cement.
Muller, Scott D; Green, Sarah M; McCaskie, Andrew W
2002-12-01
The Swedish hip register found an increased risk of early revision of vacuum-mixed cemented total hip replacements. The influence of cement mixing technique on the dynamic volume change in polymerising PMMA is not well understood and may be relevant to this observation. Applying Archimedes' principle, we have investigated the dynamic volume changes in polymerising cement and determined the influence of mixing technique. All specimens showed an overall volume reduction: hand-mixed 3.4% and vacuum-mixed 6.0%. Regression analysis of sectional porosity and volume reduction showed a highly significant relationship. Hand-mixed porous cement showed a transient volume increase before solidification. However, vacuum-mixed cement showed a progressive volume reduction throughout polymerisation. Transient expansion of porous cement occurs at the critical time of micro-interlock formation, possibly improving fixation. Conversely, progressive volume reduction of vacuum-mixed cement throughout the formation of interlock may damage fixation. Stable fixation of vacuum-mixed cement may depend on additional techniques to offset the altered volumetric behaviour of vacuum-mixed cement.
NASA Astrophysics Data System (ADS)
Russell, J. L.
2017-12-01
Floats deployed by oceanographers are giving us all ringside seats to the epic battle between the wind and the deep ocean around Antarctica which will determine the rate of global atmospheric warming over the next century. The poleward-shift and intensification of the Southern Hemisphere westerly winds has been shown to maintain the connection between the surface ocean and the atmosphere with the deep ocean even as the surface ocean warms. This "doorway" allows the vast deep ocean reservoir to play a significant role in the transient global climate response to increasing atmospheric greenhouse gases. Coupled climate and earth system models at low and high resolution all simulate poleward-shifted and intensified Southern Hemisphere surface westerly winds when subjected to an atmospheric carbon dioxide doubling. Comparisons of these simulations reveal how stratification, resolution and eddies affect the transient global climate response to increasing atmospheric greenhouse gases - and our collective fate.
Zhou, J; Zhang, H Y; Tang, X C
2001-11-09
The protective effects of huperzine A on transient global ischemia in gerbils were investigated. Five min of global ischemia in gerbils results in working memory impairments shown by increased escape latency in a water maze and reduced time spent in the target quadrant. These signs of dysfunction are accompanied by delayed degeneration of pyramidal hippocampal CA1 neurons and by decrease in acetylcholinesterase activity in the hippocampus. Subchronic oral administration of huperzine A (0.1 mg/kg, twice per day for 14 days) after ischemia significantly reduced the memory impairment, reduced neuronal degeneration in the CA1 region, and partially restored hippocampal choline acetyltransferase activity. The ability of huperzine A to attenuate memory deficits and neuronal damage after ischemia might be beneficial in cerebrovascular type dementia.
Gruen, Dieter M.; Young, Charles E.; Pellin, Michael J.
1989-01-01
A charged particle spectrometer for performing ultrasensitive quantitative analysis of selected atomic components removed from a sample. Significant improvements in performing energy and angular refocusing spectroscopy are accomplished by means of a two dimensional structure for generating predetermined electromagnetic field boundary conditions. Both resonance and non-resonance ionization of selected neutral atomic components allow accumulation of increased chemical information. A multiplexed operation between a SIMS mode and a neutral atomic component ionization mode with EARTOF analysis enables comparison of chemical information from secondary ions and neutral atomic components removed from the sample. An electronic system is described for switching high level signals, such as SIMS signals, directly to a transient recorder and through a charge amplifier to the transient recorder for a low level signal pulse counting mode, such as for a neutral atomic component ionization mode.
Photovoltaic effect and photopolarization in Pb [(Mg1/3Nb2/3) 0.68Ti0.32] O3 crystal
NASA Astrophysics Data System (ADS)
Makhort, A. S.; Chevrier, F.; Kundys, D.; Doudin, B.; Kundys, B.
2018-01-01
Ferroelectric materials are an alternative to semiconductor-based photovoltaics and offer the advantage of above bandgap photovoltage generation. However, there are few known compounds, and photovoltaic efficiencies remain low. Here, we report the discovery of a photovoltaic effect in undoped lead magnesium niobate-lead titanate crystal and a significant improvement in the photovoltaic response under suitable electric fields and temperatures. The photovoltaic effect is maximum near the electric-field-driven ferroelectric dipole reorientation, and increases threefold near the Curie temperature (Tc). Moreover, at ferroelectric saturation, the photovoltaic response exhibits clear remanent and transient effects. The transient-remanent combinations together with electric and thermal tuning possibilities indicate photoferroelectric crystals as emerging elements for photovoltaics and optoelectronics, relevant to all-optical information storage and beyond.
2010-01-01
Exposure to urban particulate matter has been associated with an increased risk of cardiovascular disease and thrombosis. We studied the effects of transient exposure to diesel particles on fibrin clot structure of 16 healthy individuals (age 21- 44). The subjects were randomly exposed to diesel exhaust and filtered air on two separate occasions. Blood samples were collected before exposure, and 2 and 6 hours after exposure. There were no significant changes on clot permeability, maximum turbidity, lag time, fibre diameter, fibre density and fibrinogen level between samples taken after diesel exhaust exposure and samples taken after filtered air exposure. These data show that there are no prothrombotic changes in fibrin clot structure in young, healthy individuals exposed to diesel exhaust. PMID:20565709
Sarcoplasmic reticulum buffering of myoplasmic calcium in bovine coronary artery smooth muscle.
Sturek, M; Kunda, K; Hu, Q
1992-01-01
1. We tested the hypothesis that the sarcoplasmic reticulum (SR) buffers (attenuates) the increase in averaged myoplasmic free [Ca2+] (Ca(im)) resulting from Ca2+ influx. 2. Fura-2 measurements of Ca(im) were obtained in single smooth muscle cells freshly dispersed from bovine coronary artery. 3. Caffeine (5 x 10(-3) M) elicited a transient increase in Ca(im) and depleted the SR Ca2+ store. In the continued presence of caffeine or 10(-5) M-ryanodine SR buffering of Ca(im) was inhibited. Subsequent exposure to high extracellular [K+] (greater than 30 mM, equimolar Na+ removal) elicited a 2-fold more rapid and 2-fold greater peak increase in Ca(im) than high K+ elicited when SR buffering of Ca(im) was normal. The augmented increase in Ca(im) was inhibited 35% by 10(-5) M-diltiazem, 65% by 2 x 10(-4) M-LaCl3, and 87% in Ca(2+)-free external solution. 4. When Ca(im) buffering capacity was increased by partially depleting the SR with a transient (1 min) exposure to caffeine, subsequent exposure to 80 nM-K+ solution increased Ca(im) almost 2-fold more slowly than 80 mM-K+ before depletion of Ca2+ from the SR. However, the influxing Ca2+ was sequestered by the SR and refilled it, as evident by the subsequent caffeine-induced Ca(im) transient being identical to the first. Increasing extracellular [K+] (thus, increasing depolarization and Na+ removal) caused proportional increases in Ca(im) and the subsequent caffeine-induced Ca(im) transients were proportionally larger, indicating a graded filling of the SR by Ca2+ influx. 5. Diltiazem (10(-5) M) inhibited the refilling of the SR achieved by 80 mM-K+, by 26%. Refilling was inhibited 76% by 80 mM-K+, Ca(2+)-free solution, indicating the fraction of refilling dependent on influx of Ca2+ through voltage-gated Ca2+ channels, leak channels, and other influx pathways. Mild depolarization with 35 mM-K+ (no Na+ removal) often caused no increase in Ca(im), but influx through voltage-gated Ca2+ channels occurred because the SR Ca2+ store was refilled. Also, 10(-5) M-diltiazem or 10(-6) M-TA3090 inhibited the refilling to levels attributable only to leak influx of Ca2+. 6. All data support our hypothesis that the SR significantly attenuates the amount of Ca2+ influx that accumulates to increase Ca(im).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1403813
Transient and sustained neural responses to death-related linguistic cues
Shi, Zhenhao
2013-01-01
Recent research showed that perception of death-related vs death-unrelated linguistic cues produced increased frontoparietal activity but decreased insular activity. This study investigated (i) whether the increased frontoparietal and decreased insular activities are, respectively, associated with transient trial-specific processes of death-related linguistic cues and sustained death-related thought during death-relevance judgments on linguistic cues and (ii) whether the neural activity underlying death-related thought can predict individuals’ dispositional death anxiety. Participants were presented with death-related/unrelated words, life-related/unrelated words, and negative-valence/neutral words in separate sessions. Participants were scanned using functional magnetic resonance imaging while performing death-relevance, life-relevance, and valence judgments on the words, respectively. The contrast of death-related vs death-unrelated words during death-relevance judgments revealed transient increased activity in the left inferior parietal lobule, the right frontal eye field, and the right superior parietal lobule. The contrast of death-relevance judgments vs life-relevance/valence judgments showed decreased activity in the bilateral insula. The sustained insular activity was correlated with dispositional death anxiety, but only in those with weak transient frontoparietal responses to death-related words. Our results dissociate the transient and sustained neural responses to death-related linguistic cues and suggest that the combination of the transient and sustained neural activities can predict dispositional death anxiety. PMID:22422804
Horikawa, Yo
2016-04-01
Metastable dynamical transient patterns in arrays of bidirectionally coupled neurons with self-coupling and asymmetric output were studied. First, an array of asymmetric sigmoidal neurons with symmetric inhibitory bidirectional coupling and self-coupling was considered and the bifurcations of its steady solutions were shown. Metastable dynamical transient spatially nonuniform states existed in the presence of a pair of spatially symmetric stable solutions as well as unstable spatially nonuniform solutions in a restricted range of the output gain of a neuron. The duration of the transients increased exponentially with the number of neurons up to the maximum number at which the spatially nonuniform steady solutions were stabilized. The range of the output gain for which they existed reduced as asymmetry in a sigmoidal output function of a neuron increased, while the existence range expanded as the strength of inhibitory self-coupling increased. Next, arrays of spiking neuron models with slow synaptic inhibitory bidirectional coupling and self-coupling were considered with computer simulation. In an array of Class 1 Hindmarsh-Rose type models, in which each neuron showed a graded firing rate, metastable dynamical transient firing patterns were observed in the presence of inhibitory self-coupling. This agreed with the condition for the existence of metastable dynamical transients in an array of sigmoidal neurons. In an array of Class 2 Bonhoeffer-van der Pol models, in which each neuron had a clear threshold between firing and resting, long-lasting transient firing patterns with bursting and irregular motion were observed. Copyright © 2016 Elsevier Ltd. All rights reserved.
LEE, JAE-CHUL; TAE, HYUN-JIN; CHO, GEUM-SIL; KIM, IN HYE; AHN, JI HYEON; PARK, JOON HA; CHEN, BAI HUI; CHO, JEONG-HWI; SHIN, BICH NA; CHO, JUN HWI; BAE, EUN JOO; PARK, JINSEU; KIM, YOUNG-MYEONG; CHOI, SOO YOUNG; WON, MOO-HO
2015-01-01
Pyramidal neurons in region I of hippocampus proper (CA1) are particularly vulnerable to excitotoxic processes following transient forebrain ischemia. Kynurenic acid (KYNA) is a small molecule derived from tryptophan when this amino acid is metabolized through the kynurenine pathway. In the present study, we examined the effects of ischemic preconditioning (IPC) on the immunoreactivity and protein levels of KYNA following 5 min of transient forebrain ischemia in gerbils. The animals were randomly assigned to 4 groups (sham-operated group, ischemia-operated group, IPC + sham-operated group and IPC + ischemia-operated group). IPC was induced by subjecting the gerbils to 2 min of ischemia followed by 1 day of recovery. In the ischemia-operated group, we observed a significant loss of pyramidal neurons in the CA1 stratum pyramidale (SP) at 5 days post-ischemia; however, in the IPC + ischemia-operated group, the pyramidal neurons were well protected. KYNA immunoreactivity in the SP of the ischemia-operated group was significantly altered following ischemia-reperfusion and was very low 5 days following ischemia-reperfusion. In the IPC + ischemia-operated group, however, KYNA immunoreactivity was constitutively detected in the SP of the CA1 region after the ischemic insult. We also found that the alteration pattern of the KYNA protein level in the CA1 region following ischemia was generally similar to the immunohistochemical changes observed. In brief, our findings demonstrated that IPC maintained and even increased KYNA immunoreactivity in the SP of the CA1 region following ischemia-reperfusion. The data from the present study thus indicate that the enhancement of KYNA expression by IPC may be necessary for neuronal survival following transient ischemic injury. PMID:25872573
Transient hyperprolactinemia in infertile women with luteal phase deficiency.
Huang, K E; Bonfiglio, T A; Muechler, E K
1991-10-01
This study was conducted to evaluate the prevalence of transient hyperprolactinemia in infertile women with luteal phase deficiency. One hundred fifty-one luteal phase deficiency patients and 11 controls had serum prolactin (PRL) measured daily for 3-4 days near ovulation. Thirty-three subjects (21.9%) had transient hyperprolactinemia, with PRL above 20 ng/mL for 1 or 2 days, and were studied further. The blood samples of these 33 subjects and of the controls were also analyzed for LH and FSH. Plasma progesterone was measured on the fourth, seventh, and tenth days after ovulation in both groups. The mean (+/- SD) of the mid-cycle integrated LH surge (125.0 +/- 23.0 mIU/mL; N = 26) and the sum of three plasma progesterone levels (23.8 +/- 4.5 ng/mL; N = 21) in the luteal phase deficiency women were significantly (P less than .001) lower than those of the controls (LH 158.7 +/- 13.8 mIU/mL; progesterone 33.8 +/- 6.5 ng/mL). All 33 luteal phase deficiency subjects with transient hyperprolactinemia were treated with bromocriptine at a dose ranging from 1.25-5 mg/day to maintain mid-cycle PRL levels between 5-15 ng/mL. Both the integrated LH surge and the sum of three progesterone levels increased significantly (P less than .05) during bromocriptine treatment, to 142.6 +/- 22.4 mIU/mL (N = 20) and 28.2 +/- 6.2 ng/mL (N = 18), respectively. Fourteen of the 33 patients conceived. The cumulative probability of conception was 31% for six cycles and 45% for 12 cycles of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
NASA Technical Reports Server (NTRS)
Han, J. C.; Ekkad, S. V.; Du, H.; Teng, S.
2000-01-01
Unsteady wake effect, with and without trailing edge ejection, on detailed heat transfer coefficient and film cooling effectiveness distributions is presented for a downstream film-cooled gas turbine blade. Tests were performed on a five-blade linear cascade at an exit Reynolds number of 5.3 x 10(exp 5). Upstream unsteady wakes were simulated using a spoke-wheel type wake generator. Coolant blowing ratio was varied from 0.4 to 1.2; air and CO2 were used as coolants to simulate different density ratios. Surface heat transfer and film effectiveness distributions were obtained using a transient liquid crystal technique; coolant temperature profiles were determined with a cold wire technique. Results show that Nusselt numbers for a film cooled blade are much higher compared to a blade without film injection. Unsteady wake slightly enhances Nusselt numbers but significantly reduces film effectiveness versus no wake cases. Nusselt numbers increase only slic,htly but film cooling, effectiveness increases significantly with increasing, blowing ratio. Higher density coolant (CO2) provides higher effectiveness at higher blowing ratios (M = 1.2) whereas lower density coolant (Air) provides higher 0 effectiveness at lower blowing ratios (M = 0.8). Trailing edge ejection generally has more effect on film effectiveness than on the heat transfer, typically reducing film effectiveness and enhancing heat transfer. Similar data is also presented for a film cooled cylindrical leading edge model.
Interaction of calcitonin gene related peptide (CGRP) and substance P (SP) in human skin.
Schlereth, Tanja; Schukraft, Jonas; Krämer-Best, Heidrun H; Geber, Christian; Ackermann, Tatiana; Birklein, Frank
2016-10-01
Calcitonin gene related peptide (CGRP) and substance P (SP) are neuropeptides that are simultaneously released from nociceptive C-fibers. CGRP is a potent vasodilator, inducing a long-lasting increase in superficial skin blood flow, whereas SP induces only a brief vasodilation but a significant plasma extravasation. CGRP and SP may play important roles in the pathophysiology of various pain states but little is known about their interaction. Different concentrations of SP (ranging from 10 -5 M to 10 -9 M) were applied to the volar forearm of 24 healthy subjects via dermal microdialysis. SP was applied either alone or in combination with CGRP10 -9 M and CGRP 10 -6 M. As expected, SP induced a transient increase in skin blood flow that decayed shortly after application. This transient blood flow peak was blunted with co-application of CGRP 10 -9 M and inhibited with co-application of CGRP10 -6 M. SP alone induced plasma protein extravasation (PPE). However, when CGRP10 -6 M was added, the PPE significantly increased. Our results demonstrate a complex interaction of the neuropeptides CGRP and SP. CGRP10 -6 M prevented SP-induced early vasodilation but augmented SP-induced PPE. These interactions might explain why vascular symptoms in chronic pain can differ strikingly between individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.
Hiemstra, Jessica A.; Gutiérrez‐Aguilar, Manuel; Marshall, Kurt D.; McCommis, Kyle S.; Zgoda, Pamela J.; Cruz‐Rivera, Noelany; Jenkins, Nathan T.; Krenz, Maike; Domeier, Timothy L.; Baines, Christopher P.; Emter, Craig A.
2014-01-01
Abstract We recently developed a clinically relevant mini‐swine model of heart failure with preserved ejection fraction (HFpEF), in which diastolic dysfunction was associated with increased mitochondrial permeability transition (MPT). Early diastolic function is ATP and Ca2+‐dependent, thus, we hypothesized chronic low doses of cyclosporine (CsA) would preserve mitochondrial function via inhibition of MPT and subsequently maintain normal cardiomyocyte Ca2+ handling and contractile characteristics. Left ventricular cardiomyocytes were isolated from aortic‐banded Yucatan mini‐swine divided into three groups; control nonbanded (CON), HFpEF nontreated (HF), and HFpEF treated with CsA (HF‐CsA). CsA mitigated the deterioration of mitochondrial function observed in HF animals, including functional uncoupling of Complex I‐dependent mitochondrial respiration and increased susceptibility to MPT. Attenuation of mitochondrial dysfunction in the HF‐CsA group was not associated with commensurate improvement in cardiomyocyte Ca2+ handling or contractility. Ca2+ transient amplitude was reduced and transient time to peak and recovery (tau) prolonged in HF and HF‐CsA groups compared to CON. Alterations in Ca2+ transient parameters observed in the HF and HF‐CsA groups were associated with decreased cardiomyocyte shortening and shortening rate. Cellular function was consistent with impaired in vivo systolic and diastolic whole heart function. A significant systemic hypertensive response to CsA was observed in HF‐CsA animals, and may have played a role in the accelerated the development of heart failure at both the whole heart and cellular levels. Given the significant detriment to cardiac function observed in response to CsA, our findings suggest chronic CsA treatment is not a viable therapeutic option for HFpEF. PMID:24963034
Juffermans, L J M; Dijkmans, P A; Musters, R J P; Visser, C A; Kamp, O
2006-10-01
In the present study, we addressed the interactions among ultrasound, microbubbles, and living cells as well as consequent arising bioeffects. We specifically investigated whether hydrogen peroxide (H(2)O(2)) is involved in transient permeabilization of cell membranes in vitro after ultrasound exposure at low diagnostic power, in the presence of stable oscillating microbubbles, by measuring the generation of H(2)O(2) and Ca(2+) influx. Ultrasound, in the absence or presence of SonoVue microbubbles, was applied to H9c2 cells at 1.8 MHz with a mechanical index (MI) of 0.1 or 0.5 during 10 s. This was repeated every minute, for a total of five times. The production of H(2)O(2) was measured intracellularly with CM-H(2)DCFDA. Cell membrane permeability was assessed by measuring real-time changes in intracellular Ca(2+) concentration with fluo-4 using live-cell fluorescence microscopy. Ultrasound, in the presence of microbubbles, caused a significant increase in intracellular H(2)O(2) at MI 0.1 of 50% and MI 0.5 of 110% compared with control (P < 0.001). Furthermore, we found increases in intracellular Ca(2+) levels at both MI 0.1 and MI 0.5 in the presence of microbubbles, which was not detected in the absence of extracellular Ca(2+). In addition, in the presence of catalase, Ca(2+) influx immediately following ultrasound exposure was completely blocked at MI 0.1 (P < 0.01) and reduced by 50% at MI 0.5 (P < 0.001). Finally, cell viability was not significantly affected, not even 24 h later. These results implicate a role for H(2)O(2) in transient permeabilization of cell membranes induced by ultrasound-exposed microbubbles.
Krieger, Patrik
2009-11-01
In spines on basal dendrites of layer 2/3 pyramidal neurons in somatosensory barrel cortex, calcium transients evoked by back-propagating action potentials (bAPs) were investigated (i) along the length of the basal dendrite, (ii) with postnatal development and (iii) with sensory deprivation during postnatal development. Layer 2/3 pyramidal neurons were investigated at three different ages. At all ages [postnatal day (P)8, P14, P21] the bAP-evoked calcium transient amplitude increased with distance from the soma with a peak at around 50 microm, followed by a gradual decline in amplitude. The effect of sensory deprivation on the bAP-evoked calcium was investigated using two different protocols. When all whiskers on one side of the rat snout were trimmed daily from P8 to P20-24 there was no difference in the bAP-evoked calcium transient between cells in the contralateral hemisphere, lacking sensory input from the whisker, and cells in the ipsilateral barrel cortex, with intact whisker activation. When, however, only the D-row whiskers on one side were trimmed the distribution of bAP-evoked calcium transients in spines was shifted towards larger amplitudes in cells located in the deprived D-column. In conclusion, (i) the bAP-evoked calcium transient gradient along the dendrite length is established at P8, (ii) the calcium transient increases in amplitude with age and (iii) this increase is enhanced in layer 2/3 pyramidal neurons located in a sensory-deprived barrel column that is bordered by non-deprived barrel columns.
Zhang, Liying; Hu, Xiquan; Luo, Jing; Li, Lili; Chen, Xingyong; Huang, Ruxun; Pei, Zhong
2013-04-08
Physical exercise improves functional recovery after stroke through a complex mechanism that is not fully understood. Transient focal cerebral ischemia induces autophagy, apoptosis and neurogenesis in the peri-infarct region. This study is aimed to examine the effects of physical exercise on autophagy, apoptosis and neurogenesis in the peri-infarct region in a rat model of transient middle cerebral artery occlusion (MCAO). We found that autophagosomes, as labeled by microtubule-associated protein 1A light chain 3-II (LC3-II), were evident in the peri-infarct region at 3 days after 90-minute MCAO. Moreover, 44.6% of LC3-positive cells were also stained with TUNEL. The number of LC3 positive cells was significantly lower in physical exercise group than in control group at 14 and 21 days after MCAO. Suppression of autophagosomes by physical exercise was positively associated with improvement of neurological function. In addition, physical exercise significantly decreased the number of TUNEL-positive cells and increased the numbers of Ki67-positive, a proliferative marker, and insulin-like growth factor-1 (IGF-1) positive cells at 7, 14, and 21 days after MCAO. The present results demonstrate that physical exercise enhances neurological function possibly by reduction of autophagosome accumulation, attenuation of apoptosis and enhancement of neurogenesis in the peri-infarct region after transient MCAO in rats.
NASA Astrophysics Data System (ADS)
Reddy, C. D.; Prajapati, S. K.; Sunil, P. S.; Arora, S. K.
2012-02-01
Throughout the world, the tsunami generation potential of some large under-sea earthquakes significantly contributes to regional seismic hazard, which gives rise to significant risk in the near-shore provinces where human settlements are in sizeable population, often referred to as coastal seismic risk. In this context, we show from the pertinent GPS data that the transient stresses generated by the viscoelastic relaxation process taking place in the mantle is capable of rupturing major faults by stress transfer from the mantle through the lower crust including triggering additional rupture on the other major faults. We also infer that postseismic relaxation at relatively large depths can push some of the fault segments to reactivation causing failure sequences. As an illustration to these effects, we consider in detail the earthquake sequence comprising six events, starting from the main event of Mw = 7.5, on 10 August 2009 and tapering off to a small earthquake of Mw = 4.5 on 2 February 2011 over a period of eighteen months in the intensely seismic Andaman Islands between India and Myanmar. The persisting transient stresses, spatio-temporal seismic pattern, modeled Coulomb stress changes, and the southward migration of earthquake activity has increased the probability of moderate earthquakes recurring in the northern Andaman region, particularly closer to or somewhat south of Diglipur.
Mulholland, Patrick J; Spencer, Kathryn B; Hu, Wei; Kroener, Sven; Chandler, L Judson
2015-06-01
Chronic alcohol-induced cognitive impairments and maladaptive plasticity of glutamatergic synapses are well-documented. However, it is unknown if prolonged alcohol exposure affects dendritic signaling that may underlie hippocampal dysfunction in alcoholics. Back-propagation of action potentials (bAPs) into apical dendrites of hippocampal neurons provides distance-dependent signals that modulate dendritic and synaptic plasticity. The amplitude of bAPs decreases with distance from the soma that is thought to reflect an increase in the density of Kv4.2 channels toward distal dendrites. The aim of this study was to quantify changes in hippocampal Kv4.2 channel function and expression using electrophysiology, Ca(2+) imaging, and western blot analyses in a well-characterized in vitro model of chronic alcohol exposure. Chronic alcohol exposure significantly decreased expression of Kv4.2 channels and KChIP3 in hippocampus. This reduction was associated with an attenuation of macroscopic A-type K(+) currents in CA1 neurons. Chronic alcohol exposure increased bAP-evoked Ca(2+) transients in the distal apical dendrites of CA1 pyramidal neurons. The enhanced bAP-evoked Ca(2+) transients induced by chronic alcohol exposure were not related to synaptic targeting of N-methyl-D-aspartate (NMDA) receptors or morphological adaptations in apical dendritic arborization. These data suggest that chronic alcohol-induced decreases in Kv4.2 channel function possibly mediated by a downregulation of KChIP3 drive the elevated bAP-associated Ca(2+) transients in distal apical dendrites. Alcohol-induced enhancement of bAPs may affect metaplasticity and signal integration in apical dendrites of hippocampal neurons leading to alterations in hippocampal function.
Abdominal pain and the neurotrophic system in ulcerative colitis.
Deberry, Jennifer J; Bielefeldt, Klaus; Davis, Brian M; Szigethy, Eva M; Hartman, Douglas J; Coates, Matthew D
2014-12-01
We undertook a study to test the hypothesis that inflammation alters peripheral sensory mechanisms, thereby contributing to chronic abdominal pain in ulcerative colitis (UC). Patients with UC and healthy individuals rated abdominal pain using a visual analog scale and completed surveys describing anxiety or depression (Hospital Anxiety and Depression Score) and gastrointestinal symptoms (Rome III questionnaire). Patient age, sex, and severity of inflammation were determined. Rectal biopsies were processed using immunohistochemical techniques to assess nerve fiber density and real-time PCR to determine transcript expression of neurotrophins (nerve growth factor, glial cell-derived neurotrophic factor, artemin, neurturin), ion channels (transient receptor potential vanilloid type 1, transient receptor potential ankyrin 1) and inflammatory mediators (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-10, IL-17). A total of 77 patients with UC (27 female, 50 male) and 21 controls (10 female, 11 male) were enrolled. Patients with UC with pain had significantly higher depression scores than controls and patients with UC without pain (P < 0.05). There was no correlation between any of the inflammatory markers and pain scores. Visual analog scale pain scores significantly correlated with younger age, higher depression scores, increased expression of neurturin and decreased expression of transient receptor potential ankyrin 1 in the mucosa. Mucosal nerve fiber density did not correlate with any measures of inflammation or pain. Only higher depression scores independently predicted pain in UC (r > 0.5). We did not observe changes in mucosal innervation and did not see a significant relationship between nerve fiber density, inflammatory mediators, neurotrophic factors, or mucosal ion channel expression and pain. In contrast, the importance of depression as the only independent predictor of pain ratings mirrors functional disorders, where central processes significantly contribute to symptom development and/or perpetuation.
Zarski, Jean-Pierre; Sturm, Nathalie; Guechot, Jérôme; Paris, Adeline; Zafrani, Elie-Serge; Asselah, Tarik; Boisson, Renée-Claude; Bosson, Jean-Luc; Guyader, Dominique; Renversez, Jean-Charles; Bronowicki, Jean-Pierre; Gelineau, Marie-Christine; Tran, Albert; Trocme, Candice; De Ledinghen, Victor; Lasnier, Elisabeth; Poujol-Robert, Armelle; Ziegler, Frédéric; Bourliere, Marc; Voitot, Hélène; Larrey, Dominique; Rosenthal-Allieri, Maria Alessandra; Fouchard Hubert, Isabelle; Bailly, François; Vaubourdolle, Michel
2012-01-01
Blood tests and transient elastography (Fibroscan™) have been developed as alternatives to liver biopsy. This ANRS HCEP-23 study compared the diagnostic accuracy of nine blood tests and transient elastography (Fibroscan™) to assess liver fibrosis, vs. liver biopsy, in untreated patients with chronic hepatitis C (CHC). This was a multicentre prospective independent study in 19 French University hospitals of consecutive adult patients having simultaneous liver biopsy, biochemical blood tests (performed in a centralized laboratory) and Fibroscan™. Two experienced pathologists independently reviewed the liver biopsies (mean length=25±8.4 mm). Performance was assessed using ROC curves corrected by Obuchowski's method. Fibroscan™ was not interpretable in 113 (22%) patients. In the 382 patients having both blood tests and interpretable Fibroscan™, Fibroscan™ performed similarly to the best blood tests for the diagnosis of significant fibrosis and cirrhosis. Obuchowski's measure showed Fibrometer® (0.86), Fibrotest® (0.84), Hepascore® (0.84), and interpretable Fibroscan™ (0.84) to be the most accurate tests. The combination of Fibrotest®, Fibrometer®, or Hepascore® with Fibroscan™ or Apri increases the percentage of well classified patients from 70-73% to 80-83% for significant fibrosis, but for cirrhosis a combination offers no improvement. For the 436 patients having all the blood tests, AUROC's ranged from 0.82 (Fibrometer®) to 0.75 (Hyaluronate) for significant fibrosis, and from 0.89 (Fibrometer® and Hepascore®) to 0.83 (FIB-4) for cirrhosis. Contrarily to blood tests, performance of Fibroscan™ was reduced due to uninterpretable results. Fibrotest®, interpretable Fibroscan™, Fibrometer®, and Hepascore® perform best and similarly for diagnosis of significant fibrosis and cirrhosis. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Transient loads analysis for space flight applications
NASA Technical Reports Server (NTRS)
Thampi, S. K.; Vidyasagar, N. S.; Ganesan, N.
1992-01-01
A significant part of the flight readiness verification process involves transient analysis of the coupled Shuttle-payload system to determine the low frequency transient loads. This paper describes a methodology for transient loads analysis and its implementation for the Spacelab Life Sciences Mission. The analysis is carried out using two major software tools - NASTRAN and an external FORTRAN code called EZTRAN. This approach is adopted to overcome some of the limitations of NASTRAN's standard transient analysis capabilities. The method uses Data Recovery Matrices (DRM) to improve computational efficiency. The mode acceleration method is fully implemented in the DRM formulation to recover accurate displacements, stresses, and forces. The advantages of the method are demonstrated through a numerical example.
[Transient enlargement of craniopharyngioma cysts after stereotactic radiotherapy and radiosurgery].
Mazerkina, N A; Savateev, A N; Gorelyshev, S K; Konovalov, A N; Trunin, Yu Yu; Golanov, A V; Medvedeva, O A; Kalinin, P L; Kutin, M A; Astafieva, L I; Krasnova, T S; Ozerova, V I; Serova, N K; Butenko, E I; Strunina, Yu V
Stereotactic radiotherapy/radiosurgery (RT/ES) is an effective technique for treating craniopharyngiomas (CPs). However, enlargement of the cystic part of the tumor occurs in some cases after irradiation. The enlargement may be transient and not require treatment or be a true relapse requiring treatment. In this study, we performed a retrospective analysis of 79 pediatric patients who underwent stereotactic RT or RS after resection of craniopharyngioma. Five-year relapse-free survival after complex treatment of CP was 86%. In the early period after irradiation, 3.5 months (2.7-9.4) on average, enlargement of the cystic component of the tumor was detected in 10 (12.7%) patients; in 9 (11.4%) of them, the enlargement was transient and did not require treatment; in one case, the patient underwent surgery due to reduced visual acuity. In 8 (10.1%) patients, an increase in the residual tumor (a solid component of the tumor in 2 cases and a cystic component of the tumor in 6 cases) occurred in the long-term period after irradiation - after 26.3 months (16.6-48.9) and did not decrease during follow-up in none of the cases, i.e. continued growth of the tumor was diagnosed. A statistical analysis revealed that differences in the terms of transient enlargement and true continued growth were statistically significant (p<0.01). Enlargement of a craniopharyngioma cyst in the early period (up to 1 year) after RT/RS is usually transient and does not require surgical treatment (except cases where worsening of neurological symptoms occurs, or occlusive hydrocephalus develops).
Thrombogenic potential of transcatheter aortic valve implantation with trivial paravalvular leakage
Siegel, Rolland
2014-01-01
Background Significant paravalvular leakage after transcatheter aortic valve implantation (TAVI) correlates with increased morbidity and mortality, but adverse consequences of trivial paravalvular leakage have stimulated few investigations. Using a unique method distinctly different from other diagnostic approaches, we previously reported elevated backflow velocities of short duration (transients) in mechanical valve closure. In this study, similar transients were found in a transcatheter valve paravalvular leakage avatar. Methods Paravalvular leakage rate (zero to 58 mL/second) and aortic valve incompetence (volumetric back flow/forward flow; zero to 32%) were made adjustable using a mock transcatheter aortic valve device and tested in quasi-steady and pulsatile flow test systems. Projected dynamic valve area (PDVA) from the back illuminated mock transcatheter aortic valve device was measured and regional backflow velocities were derived by dividing volumetric flow rate by the PDVA over the open and closing valve phase and the total closed valve area derived from backflow leakage. Results Aortic incompetence from 1-32% generated negative backflow transients from 8 to 267 meters/second, a range not dissimilar to that measured in mechanical valves with zero paravalvular leakage. Optimal paravalvular leakage was identified; not too small generating high backflow transients, not too large considering volume overload and cardiac energy loss caused by defective valve behavior and fluid motion. Conclusions Thrombogenic potential of transcatheter aortic valves with trivial aortic incompetence and high magnitude regional backflow velocity transients was comparable to mechanical valves. This may have relevance to stroke rate, asymptomatic microembolic episodes and indications for anticoagulation therapy after transcatheter valve insertion. PMID:25333018
Wang, Mei; Agarwal, Sachin; Mayevsky, Avraham; Joshi, Shailendra
2014-01-01
The neuroprotective benefit of intra-operative anesthetics is widely described and routinely aimed to invoke electroencephalographic (EEG) silence in anticipation of transient cerebral ischemia. Previous rat survival studies have questioned an additional benefit from achieving EEG silence during transient global cerebral hypoperfusion. Surgical preparation on twelve New Zealand white rabbits under ketamine–propofol anesthesia, included placement of skull screws for bilateral EEG monitoring, skull shaving for laser Doppler probes, and a 5 mm diameter right temporal craniotomy for the NADH probe. Transient global cerebral hypoperfusion was achieved with bilateral internal carotid artery occlusion and pharmacologically induced systemic hypotension. All animals acted as controls, and had cerebral hypoperfusion under baseline propofol anesthesia with an active EEG. Thereafter, animals were randomized to receive bolus injection of intracarotid (3–5 mg) or intravenous (10–20 mg) 1% propofol to create EEG silence for 1–2 min. The data collected at baseline, peak hypoperfusion, and 5 and 10 min post hypoperfusion was analyzed by repeated measures ANOVA with post hoc Bonferroni–Dunn test. Eleven of the twelve rabbits completed the protocol. Hemodynamics and cerebral blood flow changes were comparable in all the animals. Compared to controls, the increase in NADH during ischemia was unaffected by EEG silence with either intravenous or intraarterial propofol. We failed to observe any significant additional attenuation of the elevation in NADH levels with propofol induced EEG silence during transient global cerebral hypoperfusion. This is consistent with previous rat survival studies showing that EEG silence was not required for full neuroprotective effects of pentothal anesthesia. PMID:21570061
Transient Performance Improvement Circuit (TPIC)s for DC-DC converter applications
NASA Astrophysics Data System (ADS)
Lim, Sungkeun
Gordon Moore famously predicted the exponential increase in transistor integration and computing power that has been witnessed in recent decades [1]. In the near future, it is expected that more than one billion transistors will be integrated per chip, and advanced microprocessors will require clock speeds in excess of several GHz. The increasing number of transistors and high clock speeds will necessitate the consumption of more power. By 2014, it is expected that the maximum power consumption of the microprocessor will reach approximately 150W, and the maximum load current will be around 150A. Today's trend in power and thermal management is to reduce supply voltage as low as possible to reduce delivered power. It is anticipated that the Intel cores will operate on 0.8V of supply voltage by 2014 [2]. A significant challenge in Voltage Regulator Module (VRM) development for next generation microprocessors is to regulate the supply voltage within a certain tolerance band during high slew rate load transitions, since the required supply voltage tolerance band will be much narrower than the current requirement. If VR output impedance is maintained at a constant value from DC to high frequency, large output voltage spikes can be avoided during load cur- rent transients. Based on this, the Adaptive Voltage Position (AVP) concept was developed to achieve constant VR output impedance to improve transient response performance [3]. However, the VR output impedance can not be made constant over the entire frequency range with AVP design, because the AVP design makes the VR output impedance constant only at low frequencies. To make the output impedance constant at high frequencies, many bulk capacitors and ceramic capacitors are required. The tight supply voltage tolerance for the next generation of microprocessors during high slew rate load transitions requires fast transient response power supplies. A VRM can not follow the high slew rate load current transients, because of the slow inductor current slew rate which is determined by the input voltage, output voltage, and the inductance. The remaining inductor current in the power delivery path will charge the output capacitors and develop a voltage across the ESR. As a result, large output voltage spikes occur during load current transients. Due to their limited control bandwidth, traditional VRs can not sufficiently respond rapidly to certain load transients. As a result, a large output voltage spike can occur during load transients, hence requiring a large amount of bulk capacitance to decouple the VR from the load [2]. If the remaining inductor current is removed from the power stage or the inductor current slew rate is changed, the output voltage spikes can be clamped, allowing the output capacitance to be reduced. A new design methodology for a Transient Performance Improvement Circuit(TPIC) based on controlling the output impedance of a regulator is presented. The TPIC works in parallel with a voltage regulator (VR)'s ceramic capacitors to achieve faster voltage regulation without the need for a large bulk capacitance, and can serve as a replacement for bulk capacitors. The specific function of the TPIC is to mimic the behavior of the bulk capacitance in a traditional VRM by sinking and sourcing large currents during transients, allowing the VR to respond quickly to current transients without the need for a large bulk capacitance. This will allow fast transient response without the need for a large bulk capacitor. The main challenge in applying the TPIC is creating a design which will not interfere with VR operation. A TPIC for a 4 Switch Buck-Boost (4SBB) converter is presented which functions by con- trolling the inductor current slew rate during load current transients. By increasing the inductor current slew rate, the remaining inductor current can be removed from the 4SBB power delivery path and the output voltage spike can be clamped. A second TPIC is presented which is designed to improve the performance of an LDO regulator during output current transients. A TPIC for a LDO regulator is proposed to reduce the over voltage spike settling time. During a load current step down transient, the only current discharging path is a light load current. However, it takes a long time to discharge the current charged in the output capacitors with the light load current. The proposed TPIC will make an additional current discharging path to reduce the long settling time. By reducing the settling time, the load current transient frequency of the LDO regulator can be increased. A Ripple Cancellation Circuit (RCC) is proposed to reduce the output voltage ripple. The RCC has a very similar concept with the TPIC which is sinking or injecting additional current to the power stage to compensate the inductor ripple current. The proposed TPICs and RCC have been implemented with a 0.6m CMOS process. A single-phase VR, a 4SBB converter, and a LDO regulator have been utilized with the proposed TPIC to evaluate its performance. The theoretical analysis will be confirmed by Cadence simulation results and experimental results.
Transiently enhanced LPS-induced fever following hyperthermic stress in rabbits
NASA Astrophysics Data System (ADS)
Shibata, Masaaki; Uno, Tadashi; Riedel, Walter; Nishimaki, Michiyo; Watanabe, Kaori
2005-11-01
Hyperthermia has been shown to induce an enhanced febrile response to the bacterial-derived endotoxin lipopolysaccharide (LPS). The aim of the present study was to test the hypothesis that the enhanced LPS-induced fever seen in heat stressed (HS) animals is caused by leakage of intestinal bacterial LPS into the circulation. Male rabbits were rendered transiently hyperthermic (a maximum rectal temperature of 43°C) and divided into three groups. They were then allowed to recover in a room at 24°C for 1, 2 or 3 days post-HS. One day after injection with LPS, the post-HS rabbits exhibited significantly higher fevers than the controls, though this was not seen in rabbits at either 2 or 3 days post-HS. The plasma levels of endogenous LPS were significantly increased during the HS as compared to those seen in normothermic rabbits prior to HS. LPS fevers were not induced in these animals. One day post-HS, rabbits that had been pretreated with oral antibiotics exhibited significantly attenuated LPS levels. When challenged with human recombinant interleukin-1β instead of LPS, the 1-day post-HS rabbits did not respond with enhanced fevers. The plasma levels of TNFα increased similarly during LPS-induced fevers in both the control and 1-day post-HS rabbits, while the plasma levels of corticosterone and the osmolality of the 1-day post-HS rabbits showed no significant differences to those seen prior to the HS. These results suggest that the enhanced fever in the 1-day post-HS rabbits is LPS specific, and may be caused by increased leakage of intestinal endotoxin into blood circulation.
Increased radiation resistance in lithium-counterdoped silicon solar cells
NASA Technical Reports Server (NTRS)
Weinberg, I.; Swartz, C. K.; Mehta, S.
1984-01-01
Lithium-counterdoped n(+)p silicon solar cells are found to exhibit significantly increased radiation resistance to 1-MeV electron irradiation when compared to boron-doped n(+)p silicon solar cells. In addition to improved radiation resistance, considerable damage recovery by annealing is observed in the counterdoped cells at T less than or equal to 100 C. Deep level transient spectroscopy measurements are used to identify the defect whose removal results in the low-temperature aneal. It is suggested that the increased radiation resistance of the counterdoped cells is primarily due to interaction of the lithium with interstitial oxygen.
Nociceptive Neuropeptide Increases and Periorbital Allodynia in a Model of Traumatic Brain Injury
Elliott, Melanie B.; Oshinsky, Michael L.; Amenta, Peter S.; Awe, Olatilewa O.; Jallo, Jack I.
2014-01-01
Objective This study tests the hypothesis that injury to the somatosensory cortex is associated with periorbital allodynia and increases in nociceptive neuropeptides in the brainstem in a mouse model of controlled cortical impact (CCI) injury. Methods Male C57BL/6 mice received either CCI or craniotomy-only followed by weekly periorbital von Frey (mechanical) sensory testing for up to 28 days post-injury. Mice receiving an incision only and naïve mice were included as control groups. Changes in calcitonin gene-related peptide (CGRP) and substance P (SP) within the brainstem were determined using enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Activation of ionized calcium-binding adaptor molecule-1–labeled macrophages/microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes were evaluated using immunohistochemistry because of their potential involvement in nociceptor sensitization. Results Incision-only control mice showed no changes from baseline periorbital von Frey mechanical thresholds. CCI significantly reduced mean periorbital von Frey thresholds (periorbital allodynia) compared with baseline and craniotomy-only at each endpoint, analysis of variance P < .0001. Craniotomy significantly reduced periorbital threshold at 14 days but not 7, 21, or 28 days compared with baseline threshold, P < .01. CCI significantly increased SP immunoreactivity in the brainstem at 7 and 14 days but not 28 days compared with craniotomy-only and controls, P < .001. CGRP levels in brainstem tissues were significantly increased in CCI groups compared with controls (incision-only and naïve mice) or craniotomy-only mice at each endpoint examined, P < .0001. There was a significant correlation between CGRP and periorbital allodynia (P < .0001, r = −0.65) but not for SP (r = 0.20). CCI significantly increased the number of macrophage/microglia in the injured cortex at each endpoint up to 28 days, although cell numbers declined over weeks post-injury, P < .001. GFAP+ immunoreactivity was significantly increased at 7 but not 14 or 28 days after CCI, P < .001. Craniotomy resulted in transient periorbital allodynia accompanied by transient increases in SP, CGRP, and GFAP immunoreactivity compared with control mice. There was no increase in the number of macrophage/microglia cells compared with controls after craniotomy. Conclusion Injury to the somatosensory cortex results in persistent periorbital allodynia and increases in brainstem nociceptive neuropeptides. Findings suggest that persistent allodynia and increased neuropeptides are maintained by mechanisms other than activation of macrophage/microglia or astrocyte in the injured somatosensory cortex. PMID:22568499
Effects of CO2/HCO3- in perilymph on the endocochlear potential in guinea pigs.
Nimura, Yoshitsugu; Mori, Yoshiaki; Inui, Takaki; Sohma, Yoshiro; Takenaka, Hiroshi; Kubota, Takahiro
2007-02-01
The effect of CO(2)/HCO(3)(-) on the endocochlear potential (EP) was examined by using both ion-selective and conventional microelectrodes and the endolymphatic or perilymphatic perfusion technique. The main findings were as follows: (i) A decrease in the EP from approximately +75 to approximately +35 mV was produced by perilymphatic perfusion with CO(2)/HCO(3)(-)-free solution, which decrease was accompanied by an increase in the endolymphatic pH (DeltapH(e), approximately 0.4). (ii) Perilymphatic perfusion with a solution containing 20 mM NH(4)Cl produced a decrease in the EP (DeltaEP, approximately 20 mV) with an increase in the pH(e) (DeltapH(e), approximately 0.2), whereas switching the perfusion solution from the NH(4)Cl solution to a 5% CO(2)/25 mM HCO(3)(-) solution produced a gradual increase in the EP to the control level with the concomitant recovery of the pH(e). (iii) The perfusion with a solution of high or low HCO(3)(-) with a constant CO(2) level within 10 min produced no significant changes in the EP. (iv) Perfusion of the perilymph with 10 microg/ml nifedipine suppressed the transient asphyxia-induced decrease in EP slightly, but not significantly. (v) By contrast, the administration of 1 microg/ml nifedipine via the endolymph inhibited significantly the reduction in the EP induced by transient asphyxia or perilymphatic perfusion with CO(2)/HCO(3)(-)-free or 20 mM NH(4)Cl solution. These findings suggest that the effect of CO(2) removal from perilymphatic perfusion solution on the EP may be mediated by an increase in cytosolic Ca(2+) concentration induced by an elevation of cytosolic pH in endolymphatic surface cells.
Yin, Dechun; Chen, Mu; Yang, Na; Wu, Adonis Z; Xu, Dongzhu; Tsai, Wei-Chung; Yuan, Yuan; Tian, Zhipeng; Chan, Yi-Hsin; Shen, Changyu; Chen, Zhenhui; Lin, Shien-Fong; Weiss, James N; Chen, Peng-Sheng; Everett, Thomas H
2018-05-01
Apamin-sensitive small conductance calcium-activated K current (I KAS ) is up-regulated during ventricular pacing and masks short-term cardiac memory (CM). The purpose of this study was to determine the role of I KAS in long-term CM. CM was created with 3-5 weeks of ventricular pacing and defined by a flat or inverted T wave off pacing. Epicardial optical mapping was performed in both paced and normal ventricles. Action potential duration (APD 80 ) was determined during right atrial pacing. Ventricular stability was tested before and after I KAS blockade. Four paced hearts and 4 normal hearts were used for western blotting and histology. There were no significant differences in either echocardiographic parameters or fibrosis levels between groups. Apamin induced more APD 80 prolongation in CM than in normal ventricles (mean [95% confidence interval]: 9.6% [8.8%-10.5%] vs 3.1% [1.9%-4.3%]; P <.001). Apamin significantly lengthened APD 80 in the CM model at late activation sites, indicating significant I KAS up-regulation at those sites. The CM model also had altered Ca 2+ handling, with the 50% Ca 2+ transient duration and amplitude increased at distal sites compared to a proximal site (near the pacing site). After apamin, the CM model had increased ventricular fibrillation (VF) inducibility (paced vs control: 33/40 (82.5%) vs 7/20 (35%); P <.001) and longer VF durations (124 vs 26 seconds; P <.001). Chronic ventricular pacing increases Ca 2+ transients at late activation sites, which activates I KAS to maintain repolarization reserve. I KAS blockade increases VF vulnerability in chronically paced rabbit ventricles. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Lin, Yun; Zhang, Jian-Cheng; Fu, Jun; Chen, Fang; Wang, Jie; Wu, Zhi-Lin; Yuan, Shi-Ying
2013-02-01
Hyperforin, a lipophilic constituent of medicinal herb St John's wort, has been identified as the main active ingredient of St John's wort extract for antidepressant action by experimental and clinical studies. Hyperforin is currently known to activate transient receptor potential canonical (subtype) 6 (TRPC6) channel, increase the phosphorylated CREB (p-CREB), and has N-methyl-D-aspartate receptor-antagonistic effect that convert potential neuroprotective effects in vitro. However, the protective effects of hyperforin on ischemic stroke in vivo remain controversial and its neuroprotective mechanisms are still unclear. This study was designed to examine the effects of intracerebroventricular (i.c.v.) injection of hyperforin on transient focal cerebral ischemia in rats. Hyperforin, when applied immediately after middle cerebral artery occlusion (MCAO) onset, significantly reduced infarct volumes and apoptotic cells, and also increased neurologic scores at 24 hours after reperfusion accompanied by elevated TRPC6 and p-CREB activity and decreased SBDP145 activity. When MEK or CaMKIV activity was specifically inhibited, the neuroprotective effect of hyperforin was attenuated, and we observed a correlated decrease in CREB activity. In conclusion, our results clearly showed that i.c.v. injection of hyperforin immediately after MCAO onset blocked calpain-mediated TRPC6 channels degradation, and then to stimulate the Ras/MEK/ERK and CaMKIV pathways that converge on CREB activation, contributed to neuroprotection.
Lin, Yun; Zhang, Jian-Cheng; Fu, Jun; Chen, Fang; Wang, Jie; Wu, Zhi-Lin; Yuan, Shi-Ying
2013-01-01
Hyperforin, a lipophilic constituent of medicinal herb St John's wort, has been identified as the main active ingredient of St John's wort extract for antidepressant action by experimental and clinical studies. Hyperforin is currently known to activate transient receptor potential canonical (subtype) 6 (TRPC6) channel, increase the phosphorylated CREB (p-CREB), and has N-methyl-𝒟-aspartate receptor-antagonistic effect that convert potential neuroprotective effects in vitro. However, the protective effects of hyperforin on ischemic stroke in vivo remain controversial and its neuroprotective mechanisms are still unclear. This study was designed to examine the effects of intracerebroventricular (ICV) injection of hyperforin on transient focal cerebral ischemia in rats. Hyperforin, when applied immediately after middle cerebral artery occlusion (MCAO) onset, significantly reduced infarct volumes and apoptotic cells, and also increased neurologic scores at 24 hours after reperfusion accompanied by elevated TRPC6 and p-CREB activity and decreased SBDP145 activity. When MEK or CaMKIV activity was specifically inhibited, the neuroprotective effect of hyperforin was attenuated, and we observed a correlated decrease in CREB activity. In conclusion, our results clearly showed that ICV injection of hyperforin immediately after MCAO onset blocked calpain-mediated TRPC6 channels degradation, and then to stimulate the Ras/MEK/ERK and CaMKIV pathways that converge on CREB activation, contributed to neuroprotection. PMID:23149561
Transient myocardial tissue and function changes during a marathon in less fit marathon runners.
Gaudreault, Valerie; Tizon-Marcos, Helena; Poirier, Paul; Pibarot, Philippe; Gilbert, Philippe; Amyot, Marc; Rodés-Cabau, Josep; Després, Jean-Pierre; Bertrand, Olivier; Larose, Eric
2013-10-01
Although regular physical activity improves health, strenuous exercise might transiently increase cardiac risk. Training and fitness might provide protection. We prospectively studied 20 recreational marathon runners without known cardiovascular disease or symptoms: at peak training before, immediately after, and 3 months after a 42.2-km marathon. Changes in global/segmental myocardial function, edema, resting perfusion, and fibrosis were measured. At peak training, runners exercised 8.1 ± 2.3 hours and 62 ± 18 km per week with mean maximal oxygen consumption (VO2max) of 53.2 ± 8.3 mL/kg/min. In response to the marathon, global left ventricular and right ventricular ejection fraction decreased in half of the runners; these runners had poorer peak training distance, training time, and fitness level. Change in global left ventricular ejection fraction was associated with VO2max. Overall, 36% of segments developed edema, 53% decreased function, and 59% decreased perfusion. Significant agreement was observed between segment decreasing function, decreasing perfusion, and developing edema. Myocardial changes were reversible at 3 months. Completing a marathon leads to localized myocardial edema, diminished perfusion, and decreased function occurring more extensively in less trained and fit runners. Although reversible, these changes might contribute to the transient increase in cardiac risk reported during sustained vigorous exercise. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Caradu, Caroline; Guy, Alexandre; James, Chloé; Reynaud, Annabel; Gadeau, Alain-Pierre; Renault, Marie-Ange
2018-04-01
Hedgehog (Hh) signalling has been shown to be re-activated in ischaemic tissues and participate in ischaemia-induced angiogenesis. Sonic Hedgehog (Shh) is upregulated by more than 80-fold in the ischaemic skeletal muscle, however its specific role in ischaemia-induced angiogenesis has not yet been fully investigated. The purpose of the present study was to investigate the role of endogenous Shh in ischaemia-induced angiogenesis. To this aim, we used inducible Shh knock-out (KO) mice and unexpectedly found that capillary density was significantly increased in re-generating muscle of Shh deficient mice 5 days after hind limb ischaemia was induced, demonstrating that endogenous Shh does not promote angiogenesis but more likely limits it. Myosin and MyoD expression were equivalent in Shh deficient mice and control mice, indicating that endogenous Shh is not required for ischaemia-induced myogenesis. Additionally, we observed a significant increase in macrophage infiltration in the ischaemic muscle of Shh deficient mice. Our data indicate that this was due to an increase in chemokine expression by myoblasts in the setting of impaired Hh signalling, using tissue specific Smoothened conditional KO mice. The increased macrophage infiltration in mice deficient for Hh signalling in myocytes was associated with increased VEGFA expression and a transiently increased angiogenesis, demonstrating that Shh limits inflammation and angiogenesis indirectly by signalling to myocytes. Although ectopic administration of Shh has previously been shown to promote ischaemia-induced angiogenesis, the present study reveals that endogenous Shh does not promote ischaemia-induced angiogenesis. On the contrary, the absence of Shh leads to aberrant ischaemic tissue inflammation and a transiently increased angiogenesis.
Two-Flux Method for Transient Radiative Transfer in a Semitransparent Layer
NASA Technical Reports Server (NTRS)
Siegel, Robert
1996-01-01
The two-flux method was used to obtain transient solutions for a plane layer including internal reflections and scattering. The layer was initially at uniform temperature, and was heated or cooled by external radiation and convection. The two-flux equations were examined as a means for evaluating the radiative flux gradient in the transient energy equation. Comparisons of transient temperature distributions using the two-flux method were made with results where the radiative flux gradient was evaluated from the exact radiative transfer equations. Good agreement was obtained for optical thicknesses from 0.5 to 5 and for refractive indices of 1 and 2. Illustrative results obtained with the two-flux method demonstrate the effect of isotropic scattering coupled with changing the refractive index. For small absorption with large scattering the maximum layer temperature is increased when the refractive index is increased. For larger absorption the effect is opposite, and the maximum temperature decreases with increased refractive index .
Sun, Hao; Li, De-Pei; Chen, Shao-Rui; Hittelman, Walter N; Pan, Hui-Lin
2009-12-01
The arterial baroreceptor is critically involved in the autonomic regulation of homoeostasis. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed on both somatic and visceral sensory neurons. Here, we examined the TRPV1 innervation of baroreceptive pathways and its functional significance in the baroreflex. Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, was used to ablate TRPV1-expressing afferent neurons and fibers in adult rats. Immunofluorescence labeling revealed that TRPV1 immunoreactivity was present on nerve fibers and terminals in the adventitia of the ascending aorta and aortic arch, the nodose ganglion neurons, and afferent fibers in the solitary tract of the brainstem. RTX treatment eliminated TRPV1 immunoreactivities in the aorta, nodose ganglion, and solitary tract. Renal sympathetic nerve activity, blood pressure, and heart rate were recorded in anesthetized rats. The baroreflex was triggered by lowering and raising blood pressure through intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Inhibition of sympathetic nerve activity and heart rate by the phenylephrine-induced increase in blood pressure was largely impaired in RTX-treated rats. The maximum gain of the baroreflex function was significantly lower in RTX-treated than vehicle-treated rats. Furthermore, blocking of TRPV1 receptors significantly blunted the baroreflex and decreased the maximum gain of baroreflex function in the high blood pressure range. Our findings provide important new information that TRPV1 is expressed along the entire baroreceptive afferent pathway. TRPV1 receptors expressed on baroreceptive nerve endings can function as mechanoreceptors to detect the increase in blood pressure and maintain the homoeostasis.
Sun, Hao; Li, De-Pei; Chen, Shao-Rui; Hittelman, Walter N.
2009-01-01
The arterial baroreceptor is critically involved in the autonomic regulation of homoeostasis. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed on both somatic and visceral sensory neurons. Here, we examined the TRPV1 innervation of baroreceptive pathways and its functional significance in the baroreflex. Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, was used to ablate TRPV1-expressing afferent neurons and fibers in adult rats. Immunofluorescence labeling revealed that TRPV1 immunoreactivity was present on nerve fibers and terminals in the adventitia of the ascending aorta and aortic arch, the nodose ganglion neurons, and afferent fibers in the solitary tract of the brainstem. RTX treatment eliminated TRPV1 immunoreactivities in the aorta, nodose ganglion, and solitary tract. Renal sympathetic nerve activity, blood pressure, and heart rate were recorded in anesthetized rats. The baroreflex was triggered by lowering and raising blood pressure through intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Inhibition of sympathetic nerve activity and heart rate by the phenylephrine-induced increase in blood pressure was largely impaired in RTX-treated rats. The maximum gain of the baroreflex function was significantly lower in RTX-treated than vehicle-treated rats. Furthermore, blocking of TRPV1 receptors significantly blunted the baroreflex and decreased the maximum gain of baroreflex function in the high blood pressure range. Our findings provide important new information that TRPV1 is expressed along the entire baroreceptive afferent pathway. TRPV1 receptors expressed on baroreceptive nerve endings can function as mechanoreceptors to detect the increase in blood pressure and maintain the homoeostasis. PMID:19726694
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang Man; Shi Wenjie; Fei Xiaowei
2008-02-01
The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on ion channels has been widely studied in several cell models, but less is known about their modulatory mechanisms. In this report, the effect of mefenamic acid on voltage-activated transient outward K{sup +} current (I{sub A}) in cultured rat cerebellar granule cells was investigated. At a concentration of 5 {mu}M to 100 {mu}M, mefenamic acid reversibly inhibited I{sub A} in a dose-dependent manner. However, mefenamic acid at a concentration of 1 {mu}M significantly increased the amplitude of I{sub A} to 113 {+-} 1.5% of the control. At more than 10 {mu}M, mefenamic acidmore » inhibited the amplitude of I{sub A} without any effect on activation or inactivation. In addition, a higher concentration of mefenamic acid induced a significant acceleration of recovery from inactivation with an increase of the peak amplitude elicited by the second test pulse. Intracellular application of mefenamic acid could significantly increase the amplitude of I{sub A}, but had no effect on the inhibition induced by extracellular mefenamic acid, implying that mefenamic acid may exert its effect from both inside and outside the ion channel. Furthermore, the activation of current induced by intracellular application of mefenamic acid was mimicked by other cyclooxygenase inhibitors and arachidonic acid. Our data demonstrate that mefenamic acid is able to bi-directionally modulate I{sub A} channels in neurons at different concentrations and by different methods of application, and two different mechanisms may be involved.« less
Park, Seung Min; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich-Na; Cho, Jeong Hwi; Kim, In Hye; Park, Joon Ha; Won, Moo-Ho; Ahn, Ji Hyeon; Tae, Hyun-Jin; Shin, Myoung Cheol; Park, Chan Woo; Cho, Jun Hwi; Lee, Hui Young
2016-01-01
Objective(s): The alteration of glucose transporters is closely related with the pathogenesis of brain edema. We compared neuronal damage/death in the hippocampus between adult and young gerbils following transient cerebral ischemia/reperfusion and changes of glucose transporter-1(GLUT-1)-immunoreactive microvessels in their ischemic hippocampal CA1 region. Materials and Methods: Transient cerebral ischemia was developed by 5-min occlusion of both common carotid arteries. Neuronal damage was examined by cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining and changes in GLUT-1 expression was carried out by immunohistochemistry. Results: About 90% of pyramidal neurons only in the adult CA1 region were damaged after ischemia/reperfusion; in the young, about 53 % of pyramidal neurons were damaged from 7 days after ischemia/reperfusion. The density of GLUT-1-immunoreactive microvessels was significantly higher in the young sham-group than that in the adult sham-group. In the ischemia-operated-groups, the density of GLUT-1-immunoreactive microvessels was significantly decreased in the adult and young at 1 and 4 days post-ischemia, respectively, thereafter, the density of GLUT-1-immunoreactive microvessels was gradually increased in both groups after ischemia/reperfusion. Conclusion: CA1 pyramidal neurons of the young gerbil were damaged much later than that in the adult and that GLUT-1-immunoreactive microvessels were significantly decreased later in the young. These data indicate that GLUT-1 might differently contribute to neuronal damage according to age after ischemic insults. PMID:27403259
Capasso, Raffaele; Aviello, Gabriella; Borrelli, Francesca; Romano, Barbara; Ferro, Matteo; Castaldo, Luigi; Montanaro, Vittorino; Altieri, Vincenzo; Izzo, Angelo A
2011-04-01
To evaluate the effect of a Cannabis sativa extract enriched in cannabidiol (CBD) botanic drug substance (BDS) and pure CBD, on bladder contractility in vitro. Cannabis based-medicines, including CBD-enriched extracts, have been shown to reduce urinary urgency, incontinence episodes, frequency, and nocturia in patients with multiple sclerosis. Strips were cut from male Wistar rats and the human bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation, acetylcholine, KCl, and α,β-methylene adenosine triphosphate. CBD BDS significantly reduced the contractions induced by acetylcholine, but not those induced with electrical field stimulation, KCl, or α,β-methylene adenosine triphosphate in the isolated rat bladder. The inhibitory effect of CBD BDS was not significantly modified by the cannabinoid or opioid receptor antagonists or by modulators of calcium levels, but it was increased by ruthenium red and capsazepine, 2 transient receptor potential vanilloid type-1 blockers. In humans, CBD BDS and pure CBD significantly reduced acetylcholine-induced contractions, an effect that was not changed by the transient receptor potential vanilloid type-1 blockers. Our data have suggested that CBD BDS reduces cholinergic-mediated contractility and that this effect is modulated by transient receptor potential vanilloid type-1 in rats but not in humans. CBD is the chemical ingredient of CBD BDS responsible for such activity. If confirmed in vivo, such results could provide a pharmacologic basis to explain, at least in part, the efficacy of Cannabis medicines in reducing incontinence episodes in patients with multiple sclerosis. Copyright © 2011 Elsevier Inc. All rights reserved.
The Relation between Hot Flashes and Ambulatory Blood Pressure: The Hilo Women’s Health Study
Brown, Daniel E.; Sievert, Lynnette L.; Morrison, Lynn A.; Rahberg, Nichole; Reza, Angela
2011-01-01
Objectives Hot flashes (HFs) have been associated with elevated blood pressure, but studies have not examined the relationship between objectively measured HFs and blood pressure during normal daily activities. The objectives of this study are to examine ambulatory blood pressure (BP) differences between women who report HFs and those who do not, and to observe whether an objectively measured HF is associated with transient changes in BP. Methods A sample of 202 women in Hilo, Hawaii aged 45–55 years were asked to fill out a questionnaire that included demographic information and an inventory of symptoms. The women underwent simultaneous 24-hour monitoring of ambulatory BP and HFs, while keeping a diary that included mood and HF reports. Results No significant difference was present in mean BP between women who reported having a HF during the past 2 weeks and those who did not. When measurements controlled for negative mood reports and posture, there was a highly significant elevation in Z scores of systolic BP when a measured, objective HF occurred within 10 minutes preceding a BP reading, and a significant elevation of Z scores of diastolic BP when a subjectively reported HF occurred within 10 minutes after a BP reading. Conclusions These results suggest that objectively measured HFs precede transient elevations of systolic BP, but it is unclear if there is a causal relationship. These results also suggest that women experience subjective HFs within 10 minutes after a transient increase in diastolic BP. Again, the causal relationship is not understood. PMID:21183716
Baker, Salah A; Drumm, Bernard T; Saur, Dieter; Hennig, Grant W; Ward, Sean M; Sanders, Kenton M
2016-06-15
Interstitial cells of Cajal at the level of the deep muscular plexus (ICC-DMP) in the small intestine generate spontaneous Ca(2+) transients that consist of localized Ca(2+) events and limited propagating Ca(2+) waves. Ca(2+) transients in ICC-DMP display variable characteristics: from discrete, highly localized Ca(2+) transients to regionalized Ca(2+) waves with variable rates of occurrence, amplitude, duration and spatial spread. Ca(2+) transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells. Ca(2+) transients in ICC-DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s). Functional intracellular Ca(2+) stores are essential for spontaneous Ca(2+) transients, and the sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump is necessary for maintenance of spontaneity. Ca(2+) release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3 Rs). Release from these channels is interdependent. ICC express transcripts of multiple RyRs and InsP3 Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC-DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC-DMP are mediated by activation of Ca(2+) -activated Cl(-) channels; thus, Ca(2+) signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca(2+) transients in ICC-DMP within intact jejunal muscles expressing a genetically encoded Ca(2+) indicator (GCaMP3) selectively in ICC. ICC-DMP displayed spontaneous Ca(2+) transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca(2+) transients was highly variable, and it was determined that firing was stochastic in nature. Ca(2+) transients were tabulated in multiple cells within fields of view, and no correlation was found between the events in adjacent cells. TTX (1 μm) significantly increased the occurrence of Ca(2+) transients, suggesting that ICC-DMP contributes to the tonic inhibition conveyed by ongoing activity of inhibitory motor neurons. Ca(2+) transients were minimally affected after 12 min in Ca(2+) free solution, indicating these events do not depend immediately upon Ca(2+) influx. However, inhibitors of sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump and blockers of inositol triphosphate receptor (InsP3 R) and ryanodine receptor (RyR) channels blocked ICC Ca(2+) transients. These data suggest an interdependence between RyR and InsP3 R in the generation of Ca(2+) transients. Itpr1 and Ryr2 were the dominant transcripts expressed by ICC. These findings provide the first high-resolution recording of the subcellular Ca(2+) dynamics that control the behaviour of ICC-DMP in situ. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Baker, Salah A.; Drumm, Bernard T.; Saur, Dieter; Hennig, Grant W.; Ward, Sean M.
2016-01-01
Key points Interstitial cells of Cajal at the level of the deep muscular plexus (ICC‐DMP) in the small intestine generate spontaneous Ca2+ transients that consist of localized Ca2+ events and limited propagating Ca2+ waves.Ca2+ transients in ICC‐DMP display variable characteristics: from discrete, highly localized Ca2+ transients to regionalized Ca2+ waves with variable rates of occurrence, amplitude, duration and spatial spread.Ca2+ transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells.Ca2+ transients in ICC‐DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s).Functional intracellular Ca2+ stores are essential for spontaneous Ca2+ transients, and the sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) pump is necessary for maintenance of spontaneity.Ca2+ release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3Rs). Release from these channels is interdependent.ICC express transcripts of multiple RyRs and InsP3Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Abstract Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC‐DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC‐DMP are mediated by activation of Ca2+‐activated Cl− channels; thus, Ca2+ signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca2+ transients in ICC‐DMP within intact jejunal muscles expressing a genetically encoded Ca2+ indicator (GCaMP3) selectively in ICC. ICC‐DMP displayed spontaneous Ca2+ transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca2+ transients was highly variable, and it was determined that firing was stochastic in nature. Ca2+ transients were tabulated in multiple cells within fields of view, and no correlation was found between the events in adjacent cells. TTX (1 μm) significantly increased the occurrence of Ca2+ transients, suggesting that ICC‐DMP contributes to the tonic inhibition conveyed by ongoing activity of inhibitory motor neurons. Ca2+ transients were minimally affected after 12 min in Ca2+ free solution, indicating these events do not depend immediately upon Ca2+ influx. However, inhibitors of sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) pump and blockers of inositol triphosphate receptor (InsP3R) and ryanodine receptor (RyR) channels blocked ICC Ca2+ transients. These data suggest an interdependence between RyR and InsP3R in the generation of Ca2+ transients. Itpr1 and Ryr2 were the dominant transcripts expressed by ICC. These findings provide the first high‐resolution recording of the subcellular Ca2+ dynamics that control the behaviour of ICC‐DMP in situ. PMID:26824875
Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sood, Shilpa; Choudhary, Shambhunath; Wang, Hwa-Chain Robert, E-mail: hcrwang@utk.edu
Highlights: •Triclocarban exposure induces breast epithelial cell carcinogenesis. •Triclocarban induces the Erk–Nox pathway, ROS elevation, and DNA damage. •Physiological doses of triclocarban induce cellular carcinogenesis. •Non-cytotoxic curcumin blocks triclocarban-induced carcinogenesis and pathways. -- Abstract: More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens and co-carcinogens. To identify co-carcinogens with abilities to induce cellular pre-malignancy, we studied the activity of triclocarban (TCC), an antimicrobial agent commonly used in household and personal care products. Here, we demonstrated, for the first time, that chronic exposure to TCC at physiologically-achievable nanomolar concentrations resulted in progressive carcinogenesis ofmore » human breast cells from non-cancerous to pre-malignant. Pre-malignant carcinogenesis was measured by increasingly-acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth and increased cell proliferation, without acquisition of cellular tumorigenicity. Long-term TCC exposure also induced constitutive activation of the Erk–Nox pathway and increases of reactive oxygen species (ROS) in cells. A single TCC exposure induced transient induction of the Erk–Nox pathway, ROS elevation, increased cell proliferation, and DNA damage in not only non-cancerous breast cells but also breast cancer cells. Using these constitutively- and transiently-induced changes as endpoints, we revealed that non-cytotoxic curcumin was effective in intervention of TCC-induced cellular pre-malignancy. Our results lead us to suggest that the co-carcinogenic potential of TCC should be seriously considered in epidemiological studies to reveal the significance of TCC in the development of sporadic breast cancer. Using TCC-induced transient and constitutive endpoints as targets will likely help identify non-cytotoxic preventive agents, such as curcumin, effective in suppressing TCC-induced cellular pre-malignancy.« less
Identification of noise artifacts in searches for long-duration gravitational-wave transients
NASA Astrophysics Data System (ADS)
Prestegard, Tanner; Thrane, Eric; Christensen, Nelson L.; Coughlin, Michael W.; Hubbert, Ben; Kandhasamy, Shivaraj; MacAyeal, Evan; Mandic, Vuk
2012-05-01
We present an algorithm for the identification of transient noise artifacts (glitches) in cross-correlation searches for long gravitational-wave (GW) transients lasting seconds to weeks. The algorithm utilizes the auto-power in each detector as a discriminator between well-behaved stationary noise (possibly including a GW signal) and non-stationary noise transients. We test the algorithm with both Monte Carlo noise and time-shifted data from the LIGO S5 science run and find that it removes a significant fraction of glitches while keeping the vast majority (99.6%) of the data. We show that this cleaned data can be used to observe GW signals at a significantly lower amplitude than can otherwise be achieved. Using an accretion disk instability signal model, we estimate that the algorithm is accidentally triggered at a rate of less than 10-5% by realistic signals, and less than 3% even for exceptionally loud signals. We conclude that the algorithm is a safe and effective method for cleaning the cross-correlation data used in searches for long GW transients.
Investigations of an Environmentally Induced Long Duration Hall Thruster Start Transient (PREPRINT)
2006-02-06
Hall thruster start transient is produced by exposure of the thruster to ambient laboratory atmosphere. This behavior was first observed during operation of a cluster of four 200 W BHT-200 Hall effect thrusters where large anode discharge fluctuations, visible as increased anode current and a diffuse plume structure, occurred in an apparently random manner. During operation of a single thruster, the start transient appears as a quickly rising and later smoothly decaying elevated anode current with a diffuse plume that persists for less than 500 seconds. The start transient
Singh, Lovedeep; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh
2017-08-15
Reactive oxygen species are the reactive molecules that are derived from molecular oxygen and play an important role as redox signaling molecules to confer cardioprotection. Various scientists have demonstrated the key role of redox signaling in cardioprotection by showing a transient increase in their levels during remote ischemic preconditioning (RIPC) phase. The transient increase in reactive oxygen species levels during remote preconditioning phase may take place either through activation of K ATP channels or through increased nitric oxide (NO) production. A transient increase in reactive oxygen species during preconditioning may also increase the expression of heat shock proteins (HSP), the level of antioxidant enzymes and decrease the expression of inflammatory genes (Egr-1) during ischemia-reperfusion phase to confer cardioprotection. The present review describes the role of redox signaling in RIPC-induced cardioprotective effect with possible mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.
Šimůnek, Jirka; Nimmo, John R.
2005-01-01
A modified version of the Hydrus software package that can directly or inversely simulate water flow in a transient centrifugal field is presented. The inverse solver for parameter estimation of the soil hydraulic parameters is then applied to multirotation transient flow experiments in a centrifuge. Using time‐variable water contents measured at a sequence of several rotation speeds, soil hydraulic properties were successfully estimated by numerical inversion of transient experiments. The inverse method was then evaluated by comparing estimated soil hydraulic properties with those determined independently using an equilibrium analysis. The optimized soil hydraulic properties compared well with those determined using equilibrium analysis and steady state experiment. Multirotation experiments in a centrifuge not only offer significant time savings by accelerating time but also provide significantly more information for the parameter estimation procedure compared to multistep outflow experiments in a gravitational field.
Changes in serotonin receptors in different brain regions after light exposure of dark-reared rats.
Murphy, S; Uzbekov, M G; Rose, S P
1980-05-01
Male rats dark-reared from birth until 50 days of age and then exposed to light for 3 h show significant increases in specific [3H]serotonin (5-[3H]HT) binding to P2 membranes from visual and motor cortex and superior colliculus (25, 65 and 23% respectively) as compared with normal and dark-reared littermates. These increases are transient and return to normal levels after 7 days. The role of 5-HT as a transmitter in the visual system is discussed.
Herzog, D.C.
1992-01-01
Geomagnetic storms are large and sometimes rapid fluctuations in the Earth's magnetic field that are related to disturbances on the Sun's surface. Although it is not widely recognized, these transient magnetic disturbances can be a significant hazard to people and property. Many of us know that the intensity of the auroral lights increases during magnetic storms, but few people realize that these storms can also cause massive power outages, interrupt radio communications and satellite operations, increase corrosion in oil and gas pipelines, and lead to spuriously high rejection rates in the manufacture of sensitive electronic equipment.
Radhakishun, Nalini; Blokhuis, Charlotte; van Vliet, Mariska; von Rosenstiel, Ines; Weijer, Olivier; Heymans, Martijn; Beijnen, Jos; Brandjes, Dees; Diamant, Michaela
2014-08-01
The radical change of lifestyle during Ramadan fast has shown to affect cardiometabolic risk variables in adults. In youth, however, no studies are available. We aimed to evaluate the effect of Ramadan fast on Body Mass Index (BMI) and the cardiometabolic profile of obese adolescents. A prospective cohort study was conducted. We measured weight, height, body composition, blood pressure, heart rate, glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, triglycerides, and high sensitivity C-reactive protein (hs-CRP) levels before, during the last week of and at 6 weeks after Ramadan. Twenty-five obese adolescents were included. BMI and glucose metabolism did not change after Ramadan or at 6 week after cessation of Ramadan. At the end of Ramadan, a significant decrease in body fat percentage was observed, while significant increases in heart rate, total cholesterol, LDL cholesterol, HDL cholesterol, and hs-CRP were found (all P < 0.05). Six weeks after Ramadan, all parameters returned to baseline levels. In this sample of 25 ethnic obese adolescents transient cardiometabolic changes were observed during Ramadan fasting. Since most of these changes were reversible within 6 weeks, there seems no harm or benefit for obese adolescents to participate in Ramadan.
NASA Astrophysics Data System (ADS)
Tan, Jie; Li, Fenghui; Sun, Huiling; Gao, Fei; Yan, Jingping; Gai, Chunlei; Chen, Aihua; Wang, Qingyin
2015-04-01
Grading procedure in routine sea cucumber hatchery production is thought to affect juvenile sea cucumber immunological response. The present study investigated the impact of a 3-min mechanical perturbation mimicking the grading procedure on neuroendocrine and immune parameters of the sea cucumber Apostichopus japonicus. During the application of stress, concentrations of noradrenaline and dopamine in coelomic fluid increased significantly, indicating that the mechanical perturbation resulted in a transient state of stress in sea cucumbers. Coelomocytes concentration in coelomic fluid increased transiently after the beginning of stressing, and reached the maximum in 1 h. Whereas, coelomocytes phagocytosis at 3 min, superoxide anion production from 3 min to 0.5 h, acid phosphatase activity at 0.5 h, and phenoloxidase activity from 3 min to 0.5 h were all significantly down-regulated. All of the immune parameters recovered to baseline levels after the experiment was conducted for 8 h, and an immunostimulation occurred after the stress considering the phagocytosis and acid phosphatase activity. The results suggested that, as in other marine invertebrates, neuroendocrine/immune connections exist in sea cucumber A. japonicus. Mechanical stress can elicit a profound influence on sea cucumber neuroendocrine system. Neuroendocrine messengers act in turn to modulate the immunity functions. Therefore, these effects should be considered for developing better husbandry procedures.
Revealing transient strain in geodetic data with Gaussian process regression
NASA Astrophysics Data System (ADS)
Hines, T. T.; Hetland, E. A.
2018-03-01
Transient strain derived from global navigation satellite system (GNSS) data can be used to detect and understand geophysical processes such as slow slip events and post-seismic deformation. Here we propose using Gaussian process regression (GPR) as a tool for estimating transient strain from GNSS data. GPR is a non-parametric, Bayesian method for interpolating scattered data. In our approach, we assume a stochastic prior model for transient displacements. The prior describes how much we expect transient displacements to covary spatially and temporally. A posterior estimate of transient strain is obtained by differentiating the posterior transient displacements, which are formed by conditioning the prior with the GNSS data. As a demonstration, we use GPR to detect transient strain resulting from slow slip events in the Pacific Northwest. Maximum likelihood methods are used to constrain a prior model for transient displacements in this region. The temporal covariance of our prior model is described by a compact Wendland covariance function, which significantly reduces the computational burden that can be associated with GPR. Our results reveal the spatial and temporal evolution of strain from slow slip events. We verify that the transient strain estimated with GPR is in fact geophysical signal by comparing it to the seismic tremor that is associated with Pacific Northwest slow slip events.
Okazaki, Y; Azuma, K; Nishizaki, Y
2000-02-01
A pulse of blue light induced both a transient increase in activity of apoplastic K+ and membrane depolarization in laminar pulvinus of Phaseolus vulgaris L. This shows that blue-light-induced net efflux of K+ from motor cells is closely related to membrane depolarization.
Arzola, Lucas; Chen, Junxing; Rattanaporn, Kittipong; Maclean, James M; McDonald, Karen A
2011-01-01
Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin), CMG2-Fc. This chimeric fusion protein, designed to protect against the deadly anthrax toxins, is composed of the von Willebrand factor A (VWA) domain of human capillary morphogenesis 2 (CMG2), an effective anthrax toxin receptor, and the Fc region of human immunoglobulin G (IgG). We evaluated, in N. benthamiana intact plants and detached leaves, the expression of CMG2-Fc under the control of the constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine different viral suppressors of post-transcriptional gene silencing (PTGS): p1, p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc expression was higher on intact plants than detached leaves. Maximum expression was observed with p1 co-expression at 3.5 days post-infiltration (DPI), with a level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble protein, a ten-fold increase in expression when compared to absence of suppression. Co-expression with the p25 PTGS suppressor also significantly increased the CMG2-Fc expression level after just 3.5 DPI.
Transient cosmic ray increase associated with a geomagnetic storm
NASA Technical Reports Server (NTRS)
Kudo, S.; Wada, M.; Tanskanen, P.; Kodama, M.
1985-01-01
On the basis of worldwide network data of cosmic ray nucleonic components, the transient cosmic ray increase due to the depression of cosmic ray cutoff rigidity during a severe geomagnetic storm was investigated in terms of the longitudinal dependence. Multiple correlation analysis among isotropic and diurnal terms of cosmic ray intensity variations and Dst term of the geomagnetic field is applied to each of various station's data. It is shown that the amplitude of the transient cosmic ray increase associated with Dst depends on the local time of the station, and that its maximum phase is found in the evening sector. This fact is consistent with the theoretical estimation based on the azimuthally asymmetric ring current model for the magnetic DS field.
Heterogeneous CPA sensitivity of spontaneous excitation in smooth muscle of the rabbit urethra.
Hashitani, Hikaru; Yanai, Yoshimasa; Kohri, Kenjiro; Suzuki, Hikaru
2006-06-01
1. To investigate the role of intracellular Ca stores in generating spontaneous excitation of the urethra, the effects of cyclopiazonic acid (CPA) on spontaneous contractions, transient increases in intracellular calcium concentration ([Ca2+]i; Ca transients) and depolarizations were examined in smooth muscles of the rabbit urethra. 2. In about 90% of circular smooth muscle (CSM) preparations, CPA (10 microM) increased the amplitude of spontaneous contractions by about 180% and reduced their frequency to some 25% of control values (CPA-resistant), while it readily abolished the contractions in the remaining preparations. 3. In about 70% of CSM preparations, CPA prevented the generation of spontaneous depolarizations termed slow waves, but increased their amplitude and duration in the remainder. CPA also prevented the generation of spontaneous Ca transients in about 40% of CSM preparations, while increasing their amplitude and duration in the remaining preparations. In CPA-resistant preparations that had been exposed to nicardipine (1 microM), subsequent CPA invariably abolished residual spontaneous depolarizations or Ca transients. CPA abolished caffeine-induced Ca transients in Ca-free solutions, suggesting that it effectively depleted intracellular Ca stores. 4. Longitudinal smooth muscles generated spontaneous action potentials, which had a shape distinct from that of slow waves in CSM. Spontaneous action potentials were abolished by nicardipine but not CPA. 5. Transmural nerve stimulation increased the frequency of Ca transients to give a sustained rise in [Ca2+]i, but inhibited their generation after blocking alpha-adrenoceptors with phentolamine (1 microM). These nerve-evoked responses were preserved in preparations that had been exposed to CPA. Similarly, both in control and CPA-treated CSM preparations, spontaneous Ca transients were accelerated by noradrenaline (NAd, 1 microM) and were suppressed by 3-morpholino-sydnonimine (SIN-1, 10 microM), a nitric oxide (NO) donor. 6. In conclusion, CSM of the urethra generates spontaneous activity, which depends on Ca release from intracellular Ca stores. However, after blocking this primary pacemaking mechanism, L-type Ca channel-dependent action potentials may drive CSM. Irrespective of the origin of pacemaking, neurally-released NAd and NO are capable of modulating spontaneous excitation.
What can He II 304 Å tell us about transient seismic emission from solar flares?
NASA Astrophysics Data System (ADS)
Lindsey, C.; Donea, A. C.
2017-10-01
After neary 20 years since their discovery by Kosovichev and Zharkova, the mechanics of the release of seismic transients into the solar interior from some flares remain a mystery. Seismically emissive flares invariably show the signatures of intense chromosphere heating consistent with pressure variations sufficient to drive seismic transients commensurate with helioseismic observations-under certain conditions. Magnetic observations show the signatures of apparent magnetic changes, suggesting Lorentz-force transients that could likewise drive seismic transients-similarly subject to certain conditions. But, the diagnostic signatures of both of these prospective drivers are apparent over vast regions from which no significant seismic emission emanates. What distinguishes the source regions of transient seismic emission from the much vaster regions that show the signatures of both transient heating and magnetic variations but are acoustically unproductive? Observations of acoustically active flares in He II 304 Å by the Atomospheric Imaging Assembly (AIA) aboard the Solar Dynamics Observatory (SDO) offer a promising new resource with which to address this question.
Total Dose Effects on Error Rates in Linear Bipolar Systems
NASA Technical Reports Server (NTRS)
Buchner, Stephen; McMorrow, Dale; Bernard, Muriel; Roche, Nicholas; Dusseau, Laurent
2007-01-01
The shapes of single event transients in linear bipolar circuits are distorted by exposure to total ionizing dose radiation. Some transients become broader and others become narrower. Such distortions may affect SET system error rates in a radiation environment. If the transients are broadened by TID, the error rate could increase during the course of a mission, a possibility that has implications for hardness assurance.
Sakashita, Y.; Kanai, M.; Sugimoto, T.; Taki, S.; Takamori, M.
1997-01-01
OBJECTIVE—Previous reports about changes in cerebral blood flow (CBF) in transient global amnesia disclosed decreased flow in some parts of the brain. However, CBF analyses in most reports were qualitative but not quantitative. The purpose of this study was to determine changes in CBF in transient global amnesia. METHODS—The CBF was measured and the vasoreactive response to acetazolamide was evaluated in six patients with transient global amnesia using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT). The CBF was measured during an attack in two patients and soon after an attack in the other four. About one month later, CBF was re-evaluated in each patient. RESULTS—Two patients examined during an attack and one patient examined five hours after an attack had increased blood flow in the occipital cortex and cerebellum. Three patients examined at six to 10 hours after an attack had decreased blood flow in the thalamus, cerebellum, or putamen. These abnormalities of blood flow almost disappeared in all patients one month after onset. The vasodilatory response to acetazolamide, which was evaluated initially using SPECT, was poor in areas of increased blood flow. By the second evaluation of CBF with acetazolamide, the vasodilatory response had returned to normal. CONCLUSIONS—In a patient with transient global amnesia, CBF increased in the vertebrobasilar territory during the attack and decreased afterwards. The vasodilatory response to acetazolamide may be impaired in the parts of the brain with increased blood flow. It is suggested that transient global amnesia is distinct from migraine but may share the same underlying mechanism. PMID:9408101
Roles of calcium and pH in activation of eggs of the medaka fish, Oryzias latipes
1983-01-01
Unfertilized eggs of the medaka fish (Oryzias latipes) were injected with pH-buffered calcium buffers. Medaka egg activation is accompanied by a transient increase in cytoplasmic free calcium (Gilkey, J. C., L. F. Jaffe, E. B. Ridgway, and G. T. Reynolds, 1978, J. Cell Biol., 76:448-466). The calcium buffer injections demonstrated that (a) the threshold free calcium required to elicit the calcium transient and activate the egg is between 1.7 and 5.1 microM at pH 7.0, well below the 30 microM reached during the transient, and (b) buffers which hold free calcium below threshold prevent activation of the buffered region in subsequently fertilized eggs. Therefore an increase in free calcium is necessary and sufficient to elicit the calcium transient, and the calcium transient is necessary to activate the egg. Further, these results are additional proof that the calcium transient is initiated and propagated through the cytoplasm by a mechanism of calcium- stimulated calcium release. Finally, a normal calcium transient must propagate through the entire cytoplasm to ensure normal development. Unfertilized eggs were injected with pH buffers to produce short-term, localized changes in cytoplasmic pH. The eggs were then fertilized at various times after injection. In other experiments, unfertilized and fertilized eggs were exposed to media containing either NH4Cl or CO2 to produce longer term, global changes in cytoplasmic pH. These treatments neither activated the eggs nor interfered with the normal development of fertilized eggs, suggesting that even if a natural change in cytoplasmic pH is induced by activation, it has no role in medaka egg development. The injected pH buffers altered the rate of propagation of the calcium transient through the cytoplasm, suggesting that the threshold free calcium required to trigger calcium-stimulated calcium release might be pH dependent. The results of injection of pH-buffered calcium buffers support this conjecture: for a tenfold increase in hydrogen ion concentration, free calcium must also be raised tenfold to elicit the calcium transient. PMID:6411737
The calcium-frequency response in the rat ventricular myocyte: an experimental and modelling study.
Gattoni, Sara; Røe, Åsmund Treu; Frisk, Michael; Louch, William E; Niederer, Steven A; Smith, Nicolas P
2016-08-01
In the majority of species, including humans, increased heart rate increases cardiac contractility. This change is known as the force-frequency response (FFR). The majority of mammals have a positive force-frequency relationship (FFR). In rat the FFR is controversial. We derive a species- and temperature-specific data-driven model of the rat ventricular myocyte. As a measure of the FFR, we test the effects of changes in frequency and extracellular calcium on the calcium-frequency response (CFR) in our model and three altered models. The results show a biphasic peak calcium-frequency response, due to biphasic behaviour of the ryanodine receptor and the combined effect of the rapid calmodulin buffer and the frequency-dependent increase in diastolic calcium. Alterations to the model reveal that inclusion of Ca(2+) /calmodulin-dependent protein kinase II (CAMKII)-mediated L-type channel and transient outward K(+) current activity enhances the positive magnitude calcium-frequency response, and the absence of CAMKII-mediated increase in activity of the sarco/endoplasmic reticulum Ca(2+) -ATPase induces a negative magnitude calcium-frequency response. An increase in heart rate affects the strength of cardiac contraction by altering the Ca(2+) transient as a response to physiological demands. This is described by the force-frequency response (FFR), a change in developed force with pacing frequency. The majority of mammals, including humans, have a positive FFR, and cardiac contraction strength increases with heart rate. However, the rat and mouse are exceptions, with the majority of studies reporting a negative FFR, while others report either a biphasic or a positive FFR. Understanding the differences in the FFR between humans and rats is fundamental to interpreting rat-based experimental findings in the context of human physiology. We have developed a novel model of rat ventricular electrophysiology and calcium dynamics, derived predominantly from experimental data recorded under physiological conditions. As a measure of FFR, we tested the effects of changes in stimulation frequency and extracellular calcium concentration on the simulated Ca(2+) transient characteristics and showed a biphasic peak calcium-frequency relationship, consistent with recent observations of a shift from negative to positive FFR when approaching the rat physiological frequency range. We tested the hypotheses that (1) inhibition of Ca(2+) /calmodulin-dependent protein kinase II (CAMKII)-mediated increase in sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) activity, (2) CAMKII modulation of SERCA, L-type channel and transient outward K(+) current activity and (3) Na(+) /K(+) pump dynamics play a significant role in the rat FFR. The results reveal a major role for CAMKII modulation of SERCA in the peak Ca(2+) -frequency response, driven most significantly by the cytosolic calcium buffering system and changes in diastolic Ca(2+) . © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Transient rheology of crystallizing andesitic magmas
NASA Astrophysics Data System (ADS)
de Biasi, L. J.; Chevrel, M. O.; Hanson, J. B.; Cimarelli, C.; Lavallée, Y.; Dingwell, D. B.
2012-04-01
The viscosity of magma strongly influences its rheological behaviour, which is a key determinant of magma transport processes and volcanic eruptions. Understanding the factors controlling the viscosity of magma is important to our assessment of hazards posed by active volcanoes. In nature, magmas span a very wide range in viscosity (10-1 to 1014 Pa s), depending on chemical composition (including volatile content), temperature, and importantly, crystal fraction, which further induces a complex strain rate dependence (i.e. non-Newtonian rheology). Here, we present results of transient viscosities of a crystallizing andesitic melt (57 wt.% SiO2) from Tungurahua volcano (Ecuador). We followed the experimental method developed by Vona et al. (2011) for the concentric cylinder apparatus, but optimized its implementation by leaving the spindle in situ before quenching the experimental products, to preserve the complete developed texture of the sample. The viscosity is investigated under super-liquidus (1400 ° C) and sub-liquidus temperatures (1162 and 1167 ° C). For each temperature increment, thermal equilibrium is achieved over a period of days while the spindle constantly stirs the magma. Simultaneous monitoring of the torque is used to calculate the apparent viscosity of the transient suspension. To get a better understanding of the nucleation and crystal growth processes that are involved at sub-liquidus conditions, further time-step experiments were carried out, where the samples were quenched at various equilibration stages. The mineralogical assemblage, as well as the crystal fraction, distribution and preferential alignment were then quantitatively analyzed. At temperatures below the liquidus, the suspension shows a progressive, but irregular increase of the relative shear viscosity. First, the viscosity slightly increases, possibly due to the crystallization of small, equant oxides and the formation of plagioclase nuclei. After some time (1.5-2.5 days), crystallization of large, tabular plagioclase begins, inducing a significantly stronger increase in apparent viscosity until thermo-chemical equilibration is achieved. After continued stirring the apparent viscosity slightly decreases, likely due to increasing crystal alignment. The analysis of pre-equilibrium quenched samples indicates that crystals nucleate and grow preferentially in proximity to both the spindle and the crucible wall. Furthermore, decreasing the stirring rate (aka strain rate) results in an increase in the apparent viscosity, which evidences the non-Newtonian characteristics of the magmatic suspension. In conclusion, these experiments indicate that natural andesitic magmas undergo significant rheological changes at the onset of crystallization. The observed thermo-chemical variations elucidate a transient viscosity, which deserves consideration into all problems of magma transport. Reference: Vona, A., Romano, C., Dingwell, D.B., Giordano, D. 2011. The rheology of crystal-bearing basaltic magmas from Stromboli and Etna. Geochim. Cosmochim. Acta, 75, 3214-3236.
Sekhar, Ashok; Kay, Lewis E
2013-08-06
The importance of dynamics to biomolecular function is becoming increasingly clear. A description of the structure-function relationship must, therefore, include the role of motion, requiring a shift in paradigm from focus on a single static 3D picture to one where a given biomolecule is considered in terms of an ensemble of interconverting conformers, each with potentially diverse activities. In this Perspective, we describe how recent developments in solution NMR spectroscopy facilitate atomic resolution studies of sparsely populated, transiently formed biomolecular conformations that exchange with the native state. Examples of how this methodology is applied to protein folding and misfolding, ligand binding, and molecular recognition are provided as a means of illustrating both the power of the new techniques and the significant roles that conformationally excited protein states play in biology.
Gruen, D.M.; Young, C.E.; Pellin, M.J.
1989-12-26
A charged particle spectrometer is described for performing ultrasensitive quantitative analysis of selected atomic components removed from a sample. Significant improvements in performing energy and angular refocusing spectroscopy are accomplished by means of a two dimensional structure for generating predetermined electromagnetic field boundary conditions. Both resonance and non-resonance ionization of selected neutral atomic components allow accumulation of increased chemical information. A multiplexed operation between a SIMS mode and a neutral atomic component ionization mode with EARTOF analysis enables comparison of chemical information from secondary ions and neutral atomic components removed from the sample. An electronic system is described for switching high level signals, such as SIMS signals, directly to a transient recorder and through a charge amplifier to the transient recorder for a low level signal pulse counting mode, such as for a neutral atomic component ionization mode. 12 figs.
Improved pump turbine transient behaviour prediction using a Thoma number-dependent hillchart model
NASA Astrophysics Data System (ADS)
Manderla, M.; Kiniger, K.; Koutnik, J.
2014-03-01
Water hammer phenomena are important issues for high head hydro power plants. Especially, if several reversible pump-turbines are connected to the same waterways there may be strong interactions between the hydraulic machines. The prediction and coverage of all relevant load cases is challenging and difficult using classical simulation models. On the basis of a recent pump-storage project, dynamic measurements motivate an improved modeling approach making use of the Thoma number dependency of the actual turbine behaviour. The proposed approach is validated for several transient scenarios and turns out to increase correlation between measurement and simulation results significantly. By applying a fully automated simulation procedure broad operating ranges can be covered which provides a consistent insight into critical load case scenarios. This finally allows the optimization of the closing strategy and hence the overall power plant performance.
Rodriguez, Michelle E; Poindexter, Brian J; Bick, Roger J; Dasgupta, Amitava
2008-12-01
We studied the potential cardiac effects of two alcohol extracts of commercially available hawthorn using rat cardiomyocytes and measuring calcium transients by real-time fluorescence spectrophotometry. One preparation was a blend of hawthorn flowers, leaves, and berries (extract #1), and the other (extract #2) was from a "berries-only" preparation. Fluorescent images and calcium transients were acquired concurrently. Addition of extract #1 resulted in the initiation of robust calcium transients and eventual calcium overload, while addition of extract #2 caused increased calcium sparking, initiation of calcium transients, and an increased beating rate but no calcium overload. To identify the mechanisms of increased calcium influx, adult rat cardiomyocytes were challenged with 10 microM ouabain, a Na(+),K(+)-ATPase inhibitor, and the calcium channel blocker nifedipine. The findings revealed that equal volumes of the two readily available hawthorn preparations demonstrated markedly different effects on isolated adult rat cardiomyocytes, suggesting important implications for patients who are using these preparations to supplement or even replace their prescribed cardiac medications as to which preparation(s) to use, and potential dire consequences, particularly in cardiac patients. Our study indicates that the mechanism of cardiac activity of hawthorn is via the Na(+),K(+)-ATPase and intracellular calcium concentrations are influenced.
Transient electronic anisotropy in overdoped NaF e1 -xC oxAs superconductors
NASA Astrophysics Data System (ADS)
Liu, Shenghua; Zhang, Chunfeng; Deng, Qiang; Wen, Hai-hu; Li, Jian-xin; Chia, Elbert E. M.; Wang, Xiaoyong; Xiao, Min
2018-01-01
By combining polarized pump-probe spectroscopic and Laue x-ray diffraction measurements, we have observed nonequivalent transient optical responses with the probe beam polarized along the x and y axes in overdoped NaF e1 -xC oxAs superconductors. Such transient anisotropic behavior has been uncovered in the tetragonal phase with the doping level and temperature range far from the borders of static nematic phases. The measured transient anisotropy can be well explained as a result of nematic fluctuation driven by an orbital order with energy splitting of the dx z- and dy z-dominant bands. In addition, the doping level dependence and the pressure effect of the crossover temperature show significant differences between the transient nematic fluctuation and static nematic phase, implying spin and orbital orders may play different roles in static and transient nematic behaviors.
Rajendra, Yashas; Hougland, Maria D; Alam, Riazul; Morehead, Teresa A; Barnard, Gavin C
2015-05-01
Transient gene expression (TGE) is a rapid method for the production of recombinant proteins in mammalian cells. While the volumetric productivity of TGE has improved significantly over the past decade, most methods involve extensive cell line engineering and plasmid vector optimization in addition to long fed batch cultures lasting up to 21 days. Our colleagues have recently reported the development of a CHO K1SV GS-KO host cell line. By creating a bi-allelic glutamine synthetase knock out of the original CHOK1SV host cell line, they were able to improve the efficiency of generating high producing stable CHO lines for drug product manufacturing. We developed a TGE method using the same CHO K1SV GS-KO host cell line without any further cell line engineering. We also refrained from performing plasmid vector engineering. Our objective was to setup a TGE process to mimic protein quality attributes obtained from stable CHO cell line. Polyethyleneimine (PEI)-mediated transfections were performed at high cell density (4 × 10(6) cells/mL) followed by immediate growth arrest at 32 °C for 7 days. Optimizing DNA and PEI concentrations proved to be important. Interestingly, found the direct transfection method (where DNA and PEI were added sequentially) to be superior to the more common indirect method (where DNA and PEI are first pre-complexed). Moreover, the addition of a single feed solution and a polar solvent (N,N dimethylacetamide) significantly increased product titers. The scalability of process from 2 mL to 2 L was demonstrated using multiple proteins and multiple expression volumes. Using this simple, short, 7-day TGE process, we were able to successfully produce 54 unique proteins in a fraction of the time that would have been required to produce the respective stable CHO cell lines. The list of 54 unique proteins includes mAbs, bispecific antibodies, and Fc-fusion proteins. Antibody titers of up to 350 mg/L were achieved with the simple 7-day process. Titers were increased to 1 g/L by extending the culture to 16 days. We also present two case studies comparing product quality of material generated by transient HEK293, transient CHO K1SV GS-KO, and stable CHO K1SV KO pool. Protein from transient CHO was more representative of stable CHO protein compared to protein produced from HEK293. © 2014 Wiley Periodicals, Inc.
Hakimizadeh, Elham; Shamsizadeh, Ali; Roohbakhsh, Ali; Arababadi, Mohammad Kazemi; Hajizadeh, Mohammad R; Shariati, Mehdi; Rahmani, Mohammad R; Allahtavakoli, Mohammad
2017-08-01
Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke. © 2017 Société Française de Pharmacologie et de Thérapeutique.
Sheibley, Rich W.; Duff, John H.; Tesoriero, Anthony J.
2014-01-01
We used mass load budgets, transient storage modeling, and nutrient spiraling metrics to characterize nitrate (NO3−), ammonium (NH4+), and inorganic phosphorus (SRP) demand in seven agricultural streams across the United States and to identify in-stream services that may control these conditions. Retention of one or all nutrients was observed in all but one stream, but demand for all nutrients was low relative to the mass in transport. Transient storage metrics (As/A, Fmed200, Tstr, and qs) correlated with NO3− retention but not NH4+ or SRP retention, suggesting in-stream services associated with transient storage and stream water residence time could influence reach-scale NO3− demand. However, because the fraction of median reach-scale travel time due to transient storage (Fmed200) was ≤1.2% across the sites, only a relatively small demand for NO3− could be generated by transient storage. In contrast, net uptake of nutrients from the water column calculated from nutrient spiraling metrics were not significant at any site because uptake lengths calculated from background nutrient concentrations were statistically insignificant and therefore much longer than the study reaches. These results suggest that low transient storage coupled with high surface water NO3− inputs have resulted in uptake efficiencies that are not sufficient to offset groundwater inputs of N. Nutrient retention has been linked to physical and hydrogeologic elements that drive flow through transient storage areas where residence time and biotic contact are maximized; however, our findings indicate that similar mechanisms are unable to generate a significant nutrient demand in these streams relative to the loads.
Alempijevic, Tamara; Zec, Simon; Nikolic, Vladimir; Veljkovic, Aleksandar; Stojanovic, Zoran; Matovic, Vera; Milosavljevic, Tomica
2017-01-31
Accurate clinical assessment of liver fibrosis is essential and the aim of our study was to compare and combine hemodynamic Doppler ultrasonography, liver stiffness by transient elastography, and non-invasive serum biomarkers with the degree of fibrosis confirmed by liver biopsy, and thereby to determine the value of combining non-invasive method in the prediction significant liver fibrosis. We included 102 patients with chronic liver disease of various etiology. Each patient was evaluated using Doppler ultrasonography measurements of the velocity and flow pattern at portal trunk, hepatic and splenic artery, serum fibrosis biomarkers, and transient elastography. These parameters were then input into a multilayer perceptron artificial neural network with two hidden layers, and used to create models for predicting significant fibrosis. According to METAVIR score, clinically significant fibrosis (≥F2) was detected in 57.8% of patients. A model based only on Doppler parameters (hepatic artery diameter, hepatic artery systolic and diastolic velocity, splenic artery systolic velocity and splenic artery Resistance Index), predicted significant liver fibrosis with a sensitivity and specificity of75.0% and 60.0%. The addition of unrelated non-invasive tests improved the diagnostic accuracy of Doppler examination. The best model for prediction of significant fibrosis was obtained by combining Doppler parameters, non-invasive markers (APRI, ASPRI, and FIB-4) and transient elastography, with a sensitivity and specificity of 88.9% and 100%. Doppler parameters alone predict the presence of ≥F2 fibrosis with fair accuracy. Better prediction rates are achieved by combining Doppler variables with non-invasive markers and liver stiffness by transient elastography.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Roar Skartlien; Espen Sollum; Andreas Akselsen
2012-07-01
A 3D lattice Boltzmann model for two-phase flow with amphiphilic surfactant was used to investigate the evolution of emulsion morphology and shear stress in starting shear flow. The interfacial contributions were analyzed for low and high volume fractions and varying surfactant activity. A transient viscoelastic contribution to the emulsion rheology under constant strain rate conditions was attributed to the interfacial stress. For droplet volume fractions below 0.3 and an average capillary number of about 0.25, highly elliptical droplets formed. Consistent with affine deformation models, gradual elongation of the droplets increased the shear stress at early times and reduced it atmore » later times. Lower interfacial tension with increased surfactant activity counterbalanced the effect of increased interfacial area, and the net shear stress did not change significantly. For higher volume fractions, co-continuous phases with a complex topology were formed. The surfactant decreased the interfacial shear stress due mainly to advection of surfactant to higher curvature areas. Our results are in qualitative agreement with experimental data for polymer blends in terms of transient interfacial stresses and limited enhancement of the emulsion viscosity at larger volume fractions where the phases are co-continuous.« less
The alkaloid matrine of the root of Sophora flavescens prevents arrhythmogenic effect of ouabain.
Zhou, Yuhong; Wu, Yun; Deng, Lin; Chen, Lanlan; Zhao, Dandan; Lv, Lifang; Chen, Xu; Man, Jinyu; Wang, Yansong; Shan, Hongli; Lu, Yanjie
2014-06-15
Matrine, a alkaloid of the root of Sophora flavescens, has multiple protective effects on the cardiovascular system including cardiac arrhythmias. However, the molecular and ionic mechanisms of matrine have not been well investigated. Our study aimed at to shed a light on the issue to investigate the antiarrhythmic effects of matrine by using ouabain to construct an arrhythmic model of cardiomyocytes. In this experiment, matrine significantly and dose-dependently increased the doses of ouabain required to induce cardiac arrhythmias and decreased the duration of arrhythmias in guinea pigs. In cardiomyocytes of guinea pigs, ouabain 10 μM prolonged action potential duration by 80% (p<0.05) and increased L-type Ca(2+) currents and Ca(2+) transients induced by KCl (p<0.05). Matrine 100 μM shortened the prolongation of APD and prevented the increase of L-type Ca(2+) currents and Ca(2+) transients induced by ouabain. Taken together, these findings provide the first evidence that matrine possessed arrhythmogenic effect of ouabain by inhibiting of L-type Ca(2+) currents and Ca(2+) overload in guinea pigs. Copyright © 2014 Elsevier GmbH. All rights reserved.
NASA Technical Reports Server (NTRS)
Jefferies, K. S.; Tew, R. C.
1974-01-01
A digital computer study was made of reactor thermal transients during startup of the Brayton power conversion loop of a 60-kWe reactor Brayton power system. A startup procedure requiring the least Brayton system complication was tried first; this procedure caused violations of design limits on key reactor variables. Several modifications of this procedure were then found which caused no design limit violations. These modifications involved: (1) using a slower rate of increase in gas flow; (2) increasing the initial reactor power level to make the reactor respond faster; and (3) appropriate reactor control drum manipulation during the startup transient.
NASA Astrophysics Data System (ADS)
Feng, L.; Vaulin, R.; Hewitt, J. N.; Remillard, R.; Kaplan, D. L.; Murphy, Tara; Kudryavtseva, N.; Hancock, P.; Bernardi, G.; Bowman, J. D.; Briggs, F.; Cappallo, R. J.; Deshpande, A. A.; Gaensler, B. M.; Greenhill, L. J.; Hazelton, B. J.; Johnston-Hollitt, M.; Lonsdale, C. J.; McWhirter, S. R.; Mitchell, D. A.; Morales, M. F.; Morgan, E.; Oberoi, D.; Ord, S. M.; Prabu, T.; Udaya Shankar, N.; Srivani, K. S.; Subrahmanyan, R.; Tingay, S. J.; Wayth, R. B.; Webster, R. L.; Williams, A.; Williams, C. L.
2017-03-01
Many astronomical sources produce transient phenomena at radio frequencies, but the transient sky at low frequencies (<300 MHz) remains relatively unexplored. Blind surveys with new wide-field radio instruments are setting increasingly stringent limits on the transient surface density on various timescales. Although many of these instruments are limited by classical confusion noise from an ensemble of faint, unresolved sources, one can in principle detect transients below the classical confusion limit to the extent that the classical confusion noise is independent of time. We develop a technique for detecting radio transients that is based on temporal matched filters applied directly to time series of images, rather than relying on source-finding algorithms applied to individual images. This technique has well-defined statistical properties and is applicable to variable and transient searches for both confusion-limited and non-confusion-limited instruments. Using the Murchison Widefield Array as an example, we demonstrate that the technique works well on real data despite the presence of classical confusion noise, sidelobe confusion noise, and other systematic errors. We searched for transients lasting between 2 minutes and 3 months. We found no transients and set improved upper limits on the transient surface density at 182 MHz for flux densities between ˜20 and 200 mJy, providing the best limits to date for hour- and month-long transients.
NASA Astrophysics Data System (ADS)
Tanisawa, Hidekazu; Kato, Fumiki; Koui, Kenichi; Sato, Shinji; Watanabe, Kinuyo; Takahashi, Hiroki; Murakami, Yoshinori; Sato, Hiroshi
2018-04-01
In this paper, we demonstrate a mounting technology that improves the tolerance to transient power loss by adding a heat capacity near the device. Silicon carbide (SiC) power devices can operate at high temperatures, up to 250 °C, at which silicon (Si) power devices cannot. Therefore, it is possible to allow a large temperature difference between the device and ambient air. Thus, the size of a power converter equipped with an SiC power module is reduced by simplifying the cooling system. The temperature of the power module is important not only in the steady state, but in transient loads as well. Therefore, we developed the Al-bump flip-chip mounting technology to increase heat capacity near the device. With this proposed structure, the heat capacity per device increased by 1.7% compared with the total heat capacity of the conventional structure using wire bonding. The reduction in transient thermal impedance is observed from 0.003 to 3 s, and we confirmed that the transient thermal impedance is reduced very efficiently by 15% at the maximum, compared with the conventional structure.
Transient risk factors for acute traumatic hand injuries: a case‐crossover study in Hong Kong
Chow, C Y; Lee, H; Lau, J; Yu, I T S
2007-01-01
Objectives To identify the remediable transient risk factors of occupational hand injuries in Hong Kong in order to guide the development of prevention strategies. Methods The case‐crossover study design was adopted. Study subjects were workers with acute hand injuries presenting to the government Occupational Medicine Unit for compensation claims within 90 days from the date of injury. Detailed information on exposures to specific transient factors during the 60 minutes prior to the occurrence of the injury, during the same time interval on the day prior to the injury, as well as the usual exposure during the past work‐month was obtained through telephone interviews. Both matched‐pair interval approach and usual frequency approach were adopted to assess the associations between transient exposures in the workplace and the short‐term risk of sustaining a hand injury. Results A total of 196 injured workers were interviewed. The results of the matched‐pair interval analysis matched well with the results obtained using the usual frequency analysis. Seven significant transient risk factors were identified: using malfunctioning equipment/materials, using a different work method, performing an unusual work task, working overtime, feeling ill, being distracted and rushing, with odds ratios ranging from 10.5 to 26.0 in the matched‐pair interval analysis and relative risks ranging between 8.0 and 28.3 with the usual frequency analysis. Wearing gloves was found to have an insignificant protective effect on the occurrence of hand injury in both analyses. Conclusions Using the case‐crossover study design for acute occupational hand injuries, seven transient risk factors that were mostly modifiable were identified. It is suggested that workers and their employers should increase their awareness of these risk factors, and efforts should be made to avoid exposures to these factors by means of engineering and administrative controls supplemented by safety education and training. PMID:16973734
Ng, Lih Chyuan; Kyle, Barry D; Lennox, Alison R; Shen, Xiao-Ming; Hatton, William J; Hume, Joseph R
2008-01-01
Previous studies have shown that, in acutely dispersed canine pulmonary artery smooth muscle cells (PASMCs), depletion of both functionally independent inositol 1,4,5-trisphosphate (IP(3))- and ryanodine-sensitive Ca(2+) stores activates capacitative Ca(2+) entry (CCE). The present study aimed to determine if cell culture modifies intracellular Ca(2+) stores and alters Ca(2+) entry pathways caused by store depletion and hypoxia in canine PASMCs. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured in fura 2-loaded cells. Mn(2+) quench of fura 2 signal was performed to study divalent cation entry, and the effects of hypoxia were examined under oxygen tension of 15-18 mmHg. In acutely isolated PASMCs, depletion of IP(3)-sensitive Ca(2+) stores with cyclopiazonic acid (CPA) did not affect initial caffeine-induced intracellular Ca(2+) transients but abolished 5-HT-induced Ca(2+) transients. In contrast, CPA significantly reduced caffeine- and 5-HT-induced Ca(2+) transients in cultured PASMCs. In cultured PASMCs, store depletion or hypoxia caused a transient followed by a sustained rise in [Ca(2+)](i). The transient rise in [Ca(2+)](i) was partially inhibited by nifedipine, whereas the nifedipine-insensitive transient rise in [Ca(2+)](i) was inhibited by KB-R7943, a selective inhibitor of reverse mode Na(+)/Ca(2+) exchanger (NCX). The nifedipine-insensitive sustained rise in [Ca(2+)](i) was inhibited by SKF-96365, Ni(2+), La(3+), and Gd(3+). In addition, store depletion or hypoxia increased the rate of Mn(2+) quench of fura 2 fluorescence that was also inhibited by these blockers, exhibiting pharmacological properties characteristic of CCE. We conclude that cell culture of canine PASMCs reorganizes IP(3) and ryanodine receptors into a common intracellular Ca(2+) compartment, and depletion of this store or hypoxia activates voltage-operated Ca(2+) entry, reverse mode NCX, and CCE.
Kim, D J; Kim, D I; Lee, S K; Suh, S H; Lee, Y J; Kim, J; Chung, T S; Lee, J E
2006-04-01
The goal of thrombolytic therapy in patients with acute ischemic stroke is early recanalization, but this may result in delayed reperfusion injury. The purpose of this study was to evaluate the neuroprotective effect of agmatine in a transient ischemic cat model by using MR perfusion imaging and histopathologic analyses. One-hour temporary occlusion of the left middle cerebral artery of cats was performed in the control ischemia group (n = 10), and 100 mg/kg of agmatine was intravenously injected immediately after recanalization in the agmatine-treated group (n = 15). MR imaging was performed at 1, 24, and 48 hours after recanalization, and the perfusion patterns were investigated. Terminal-deoxynucleotidyl transferase mediated nick and end-labeling (TUNEL) and hematoxylin-eosin (H&E) stainings were performed at the corresponding sections. In the control ischemia group, the number of TUNEL-positive cells was significantly increased in the areas with reperfusion hyperemia (P < .05). In the agmatine-treated group, no significant increase in the number of TUNEL-positive cells was noted in the areas of reperfusion hyperemia. The difference in the number of TUNEL-positive cells between the control ischemia and agmatine-treated group in the areas of reperfusion hyperemia was significant (P < .05). The total number of TUNEL-positive cells and the area of severe ischemic neuronal damage on H&E stain were also significantly attenuated in the agmatine-treated cats compared with the control ischemia cats (P < .05). Our results suggest that agmatine has neuroprotective effects against reperfusion injury and ischemia.
Hockey, J S; Wu, C; Fry, C H
2000-09-01
To determine the important cellular site(s) of action of a brief exposure to NaCN (chosen to reduce mitochondrial respiration and hence mimic cellular hypoxia) on the mechanical properties and regulation of intracellular [Ca2+] in human detrusor smooth muscle. Using muscle samples obtained from patients with stable and unstable bladders, to determine whether the unstable bladder is associated with changes in the functional properties of detrusor muscle under these circumstances. Materials and methods Experiments were conducted in vitro on muscle strips or isolated cells. Isometric tension was recorded in muscle strips during electrical stimulation or exposure to agonists. Intracellular [Ca2+] and [H+] were measured by epifluorescence microscopy, and cell autofluorescence measured as an index of mitochondrial function. There were no differences in the responses to electrical stimulation and varying concentrations of carbachol in muscle strips from stable and unstable bladders. NaCN (2 mmol/L) reduced the contraction induced by carbachol (10 micromol/L) by a mean (SD) of 43 (16)% and 56 (15)% in the two groups; the reduction in the unstable was significantly less than in the stable group. NaCN similarly reduced the response to 10 mmol/L caffeine, but had no effect on the KCl-induced contraction. NaCN significantly increased the resting sarcoplasmic [Ca2+] and attenuated the calcium transients evoked by carbachol and caffeine, but again had no effect on the KCl-induced transient. The reduction of the carbachol calcium transient was also less in cells from unstable bladders than in those from stable bladders. There was no effect of NaCN on intracellular pH, except for a brief, transient alkalosis. NaCN reduces both the contraction and Ca-transient to carbachol by reducing Ca2+ accumulation by intracellular stores, because the carbachol- and caffeine-evoked responses were similar. Any effect on transmembrane Ca2+ flux was minimal because there was no effect on KCl-induced responses. The greater resilience of tissue from unstable bladders to acute cellular hypoxia may reflect some adaptation acquired in vivo.
Liu, Z Gerald; Vasys, Victoria N; Kittelson, David B
2007-09-15
The effects of fuel sulfur content and primary dilution on PM number emissions were investigated during transient operations of an old and a modern diesel engine. Emissions were also studied during steady-state operations in order to confirm consistency with previous findings. Testing methods were concurrent with those implemented by the EPA to regulate PM mass emissions, including the use of the Federal Transient Testing Procedure-Heavy Duty cycle to simulate transient conditions and the use of a Critical Flow Venturi-Constant Volume System to provide primary dilution. Steady-state results were found to be consistent with previous studies in that nuclei-mode particulate emissions were largely reduced when lower-sulfur content fuel was used in the newer engine, while the nuclei-mode PM emissions from the older engine were much less affected by fuel sulfur content. The transient results, however, show that the total number of nuclei-mode PM emissions from both engines increases with fuel sulfur content, although this effect is only seen under the higher primary dilution ratios with the older engine. Transient results further show that higher primary dilution ratios increase total nuclei-mode PM number emissions in both engines.
Time Domain Astronomy with Fermi GBM in the Multi-messenger Era
NASA Astrophysics Data System (ADS)
Wilson-Hodge, Colleen A.; Fermi GBM team, GBM-LIGO team
2018-01-01
As the Multi-Messenger era begins with detections of gravitational waves with LIGO/Virgo and neutrinos with IceCube, the Fermi Gamma-ray Burst Monitor (GBM) provides context observations of gamma-ray transients between 8 keV and 40 MeV. Fermi GBM has a wide field of view, high uptime, and both in-orbit triggering and high time resolution continuous data enabling offline searches for weaker transients. GBM detects numerous gamma-ray bursts (GRBs), soft gamma-ray repeaters, X-ray bursters, solar flares and terrestrial gamma-ray flashes. Longer timescale transients, predominantly in our galaxy so far, are detected using the Earth occultation technique and epoch-folding for periodic sources. The GBM team has developed two ground-based searches to enhance detections of faint transients, especially short GRBs. The targeted search uses the time and location of an event detected with another instrument to coherently search the GBM data, increasing the sensitivity to a transient. The untargeted search agnostically searches the GBM data for all directions and times to find weaker transients. This search finds about 80 short GRBs per year, adding to the 40 per year triggered on-orbit. With its large field of view, high duty cycle and increasingly sophisticated detection methods, Fermi GBM is expected to have a major role in the Multi-Messenger era.
Van der Lubbe, Rob H J; Blom, Jorian H G; De Kleine, Elian; Bohlmeijer, Ernst T
2017-02-01
We examined whether sustained vs. transient spatial attention differentially affect the processing of electrical nociceptive stimuli. Cued nociceptive stimuli of a relevant intensity (low or high) on the left or right forearm required a foot pedal press. The cued side varied trial wise in the transient attention condition, while it remained constant during a series of trials in the sustained attention condition. The orienting phase preceding the nociceptive stimuli was examined by focusing on lateralized EEG activity. ERPs were computed to examine the influence of spatial attention on the processing of the nociceptive stimuli. Results for the orienting phase showed increased ipsilateral alpha and beta power above somatosensory areas in both the transient and the sustained attention conditions, which may reflect inhibition of ipsilateral and/or disinhibition of contralateral somatosensory areas. Cued nociceptive stimuli evoked a larger N130 than uncued stimuli, both in the transient and the sustained attention conditions. Support for increased efficiency of spatial attention in the sustained attention condition was obtained for the N180 and the P540 component. We concluded that spatial attention is more efficient in the case of sustained than in the case of transient spatial attention. Copyright © 2016 Elsevier B.V. All rights reserved.
Vázquez-León, Priscila; Martínez-Mota, Lucía; Quevedo-Corona, Lucía; Miranda-Páez, Abraham
2017-09-01
Stress can be experienced with or without adverse effects, of which anxiety and depression are two of the most important due to the frequent comorbidity with alcohol abuse in humans. Historically, stress has been considered a cause of drug use, particularly alcohol abuse due to its anxiolytic effects. In the present work we exposed male Wistar rats to two different stress conditions: single housing (social isolation, SI), and chronic mild stress (CMS). We compared both stressed groups to group-housed rats and rats without CMS (GH) to allow the determination of a clear behavioral response profile related to their respective endocrine stress response and alcohol intake pattern. We found that SI and CMS, to a greater extent, induced short-lasting increased sucrose consumption, a transient increase in serum corticosterone level, high latency/immobility, and low burying behavior in the defensive burying behavior (DBB) test, and a transient increase in alcohol intake. Thus, the main conclusion was that stress caused by both SI and CMS induced immobility in the DBB test and, subsequently, induced a transient increased voluntary ethanol intake in Wistar rats with a free-choice home-cage drinking paradigm. Copyright © 2017 Elsevier Inc. All rights reserved.
Intellectual Deficits After Transient Tyrosinemia in the Term Neonate
ERIC Educational Resources Information Center
Mamunes, Peter; And Others
1976-01-01
In order to determine if prolonged significant transient neonatal tyrosinemia is injurious to the developing central nervous system, 15 term infants who had suffered from this disorder (involving high blood levels of the amino acid tyrosine) were evaluated. (Author/DB)
NASA Astrophysics Data System (ADS)
Climente-Alarcon, V.; Antonino-Daviu, J.; Riera-Guasp, M.; Pons-Llinares, J.; Roger-Folch, J.; Jover-Rodriguez, P.; Arkkio, A.
2011-02-01
The present work is focused on the diagnosis of mixed eccentricity faults in induction motors via the study of currents demanded by the machine. Unlike traditional methods, based on the analysis of stationary currents (Motor Current Signature Analysis (MCSA)), this work provides new findings regarding the diagnosis approach proposed by the authors in recent years, which is mainly focused on the fault diagnosis based on the analysis of transient quantities, such as startup or plug stopping currents (Transient Motor Current Signature Analysis (TMCSA)), using suitable time-frequency decomposition (TFD) tools. The main novelty of this work is to prove the usefulness of tracking the transient evolution of high-order eccentricity-related harmonics in order to diagnose the condition of the machine, complementing the information obtained with the low-order components, whose transient evolution was well characterised in previous works. Tracking of high-order eccentricity-related harmonics during the transient, through their associated patterns in the time-frequency plane, may significantly increase the reliability of the diagnosis, since the set of fault-related patterns arising after application of the corresponding TFD tool is very unlikely to be caused by other faults or phenomena. Although there are different TFD tools which could be suitable for the transient extraction of these harmonics, this paper makes use of a Wigner-Ville distribution (WVD)-based algorithm in order to carry out the time-frequency decomposition of the startup current signal, since this is a tool showing an excellent trade-off between frequency resolution at both high and low frequencies. Several simulation results obtained with a finite element-based model and experimental results show the validity of this fault diagnosis approach under several faulty and operating conditions. Also, additional signals corresponding to the coexistence of the eccentricity and other non-fault related phenomena making difficult the diagnosis (fluctuating load torque) are included in the paper. Finally, a comparison with an alternative TFD tool - the discrete wavelet transform (DWT) - applied in previous papers, is also carried out in the contribution. The results are promising regarding the usefulness of the methodology for the reliable diagnosis of eccentricities and for their discrimination against other phenomena.
Metabolic studies of transient tyrosinemia in premature infants
NASA Technical Reports Server (NTRS)
Fernbach, S. A.; Summons, R. E.; Pereira, W. E.; Duffield, A. M.
1975-01-01
The recently developed technique of gas chromatography-mass spectrometry supported by computer has considerably improved the analysis of physiologic fluids. This study attempted to demonstrate the value of this system in the investigation of metabolite patterns in urine in two metabolic problems of prematurity, transient tyrosinemia and late metabolic acidosis. Serial 24-hr urine specimens were analyzed in 9 infants. Transient tyrosinemia, characterized by 5- 10-fold increases over basal excretion of tyrosine, p-hydroxyphenyllactate, and p-hydroxyphenylpyruvate in urine, was noted in five of the infants. Late metabolic acidosis was seen in four infants, but bore no relation to transient tyrosinemia.
Apparent dispersion in transient groundwater flow
Goode, Daniel J.; Konikow, Leonard F.
1990-01-01
This paper investigates the effects of large-scale temporal velocity fluctuations, particularly changes in the direction of flow, on solute spreading in a two-dimensional aquifer. Relations for apparent longitudinal and transverse dispersivity are developed through an analytical solution for dispersion in a fluctuating, quasi-steady uniform flow field, in which storativity is zero. For transient flow, spatial moments are evaluated from numerical solutions. Ignored or unknown transients in the direction of flow primarily act to increase the apparent transverse dispersivity because the longitudinal dispersivity is acting in a direction that is not the assumed flow direction. This increase is a function of the angle between the transient flow vector and the assumed steady state flow direction and the ratio of transverse to longitudinal dispersivity. The maximum effect on transverse dispersivity occurs if storativity is assumed to be zero, such that the flow field responds instantly to boundary condition changes.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Volkov, M. S.; Gusev, Yu. P., E-mail: GusevYP@mpei.ru; Monakov, Yu. V.
The insertion of current-limiting reactors into electrical equipment operating at a voltage of 110 and 220 kV produces a change in the parameters of the transient recovery voltages at the contacts of the circuit breakers for disconnecting short circuits, which could be the reason for the increase in the duration of the short circuit, damage to the electrical equipment and losses in the power system. The results of mathematical modeling of the transients, caused by tripping of the short circuit in a reactive electric power transmission line are presented, and data are given on the negative effect of a current-limitingmore » resistor on the rate of increase and peak value of the transient recovery voltages. Methods of ensuring the standard requirements imposed on the parameters of the transient recovery voltages when using current-limiting reactors in the high-voltage electrical equipment of power plants and substations are proposed and analyzed.« less
Persistent and transient cost efficiency—an application to the Swiss hydropower sector
Filippini, Massimo; Geissmann, Thomas; Greene, William H.
2017-11-27
Electricity prices on the European market have decreased significantly over the past few years, resulting in a deterioration of Swiss hydropower firms’ competitiveness and profitability. One option to improve the sector’s competitiveness is to increase cost efficiency. The goal of this study is to quantify the level of persistent and transient cost efficiency of individual firms by applying the generalized true random effects (GTRE) model introduced by Colombi et al. (Journal of Productivity Analysis 42(2): 123–136, 2014) and Filippini and Greene (Journal of Productivity Analysis 45(2): 187–196, 2016). Applying this newly developed GTRE model to a total cost function, themore » level of cost efficiency of 65 Swiss hydropower firms is analyzed for the period between 2000 and 2013. A true random effects specification is estimated as a benchmark for the transient level of cost efficiency. The results show the presence of both transient as well as persistent cost inefficiencies. The GTREM predicts the aggregate level of cost inefficiency to amount to 21.8% (8.0% transient, 13.8% persistent) on average between 2000 and 2013. These two components differ in interpretation and implication. From an individual firm’s perspective, the two types of cost inefficiencies might require a firm’s management to respond with different improvement strategies. The existing level of persistent inefficiency could prevent the hydropower firms from adjusting their production processes to new market environments. From a regulatory point of view, the results of this study could be used in the scope and determination of the amount of financial support given to struggling firms.« less
Free radicals mediate postshock contractile impairment in cardiomyocytes.
Tsai, Min-Shan; Sun, Shijie; Tang, Wanchun; Ristagno, Giuseppe; Chen, Wen-Jone; Weil, Max Harry
2008-12-01
Previous studies demonstrated myocardial dysfunction after electrical shock and indicated it may be related to free radicals. Whether the free radicals are generated after electrical shock has not been documented at the cellular level. This study was to investigate whether electrical shock generates intracellular free radicals inside cardiomyocytes and to evaluate whether reducing intracellular free radicals by pretreatment of ascorbic acid would reduce the contractile dysfunction after electrical shock. Randomized prospective animal study. University affiliated research laboratory. Sprague-Dawley rats. Cardiomyocytes isolated from adult male rats were divided into four groups: (1) electrical shock alone; (2) electrical shock pretreated with ascorbic acid; (3) pretreated with ascorbic acid alone; and (4) control. Ascorbic acid (0.2 mM) was administrated in the perfusate of the ascorbic acid + electrical shock and ascorbic acid groups. A 2-J electrical shock was delivered to the electrical shock and ascorbic acid + electrical shock groups. DCFH-DA-loaded cardiomyocytes showed increased intracellular free radicals after electrical shock. The contractions and Ca2+ transients were recorded optically with fura-2 loading. Within 4 mins after electrical shock in the electrical shock group, the length shortening decreased from 8.4% +/- 2.5% to 5.6% +/- 3.4% (p = 0.000) and the Ca2+ transient decreased from 1.15 +/- 0.13 au to 1.08 +/- 0.1 au (p = 0.038). Compared with control, a significant difference in length shortening (p = 0.001) but not Ca2+ transient (p = 0.052) was noted. In the presence of ascorbic acid, electrical shock did not affect length shortening and Ca2+ transient. Electrical shock generates free radicals inside the cardiomyocyte, and causes contractile impairment and associated decrease of Ca transient. Administering ascorbic acid may improve such damage by eliminating free radicals.
Persistent and transient cost efficiency—an application to the Swiss hydropower sector
DOE Office of Scientific and Technical Information (OSTI.GOV)
Filippini, Massimo; Geissmann, Thomas; Greene, William H.
Electricity prices on the European market have decreased significantly over the past few years, resulting in a deterioration of Swiss hydropower firms’ competitiveness and profitability. One option to improve the sector’s competitiveness is to increase cost efficiency. The goal of this study is to quantify the level of persistent and transient cost efficiency of individual firms by applying the generalized true random effects (GTRE) model introduced by Colombi et al. (Journal of Productivity Analysis 42(2): 123–136, 2014) and Filippini and Greene (Journal of Productivity Analysis 45(2): 187–196, 2016). Applying this newly developed GTRE model to a total cost function, themore » level of cost efficiency of 65 Swiss hydropower firms is analyzed for the period between 2000 and 2013. A true random effects specification is estimated as a benchmark for the transient level of cost efficiency. The results show the presence of both transient as well as persistent cost inefficiencies. The GTREM predicts the aggregate level of cost inefficiency to amount to 21.8% (8.0% transient, 13.8% persistent) on average between 2000 and 2013. These two components differ in interpretation and implication. From an individual firm’s perspective, the two types of cost inefficiencies might require a firm’s management to respond with different improvement strategies. The existing level of persistent inefficiency could prevent the hydropower firms from adjusting their production processes to new market environments. From a regulatory point of view, the results of this study could be used in the scope and determination of the amount of financial support given to struggling firms.« less
WATCHDOG: A COMPREHENSIVE ALL-SKY DATABASE OF GALACTIC BLACK HOLE X-RAY BINARIES
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tetarenko, B. E.; Sivakoff, G. R.; Heinke, C. O.
With the advent of more sensitive all-sky instruments, the transient universe is being probed in greater depth than ever before. Taking advantage of available resources, we have established a comprehensive database of black hole (and black hole candidate) X-ray binary (BHXB) activity between 1996 and 2015 as revealed by all-sky instruments, scanning surveys, and select narrow-field X-ray instruments on board the INTErnational Gamma-Ray Astrophysics Laboratory, Monitor of All-Sky X-ray Image, Rossi X-ray Timing Explorer, and Swift telescopes; the Whole-sky Alberta Time-resolved Comprehensive black-Hole Database Of the Galaxy or WATCHDOG. Over the past two decades, we have detected 132 transient outbursts, trackedmore » and classified behavior occurring in 47 transient and 10 persistently accreting BHs, and performed a statistical study on a number of outburst properties across the Galactic population. We find that outbursts undergone by BHXBs that do not reach the thermally dominant accretion state make up a substantial fraction (∼40%) of the Galactic transient BHXB outburst sample over the past ∼20 years. Our findings suggest that this “hard-only” behavior, observed in transient and persistently accreting BHXBs, is neither a rare nor recent phenomenon and may be indicative of an underlying physical process, relatively common among binary BHs, involving the mass-transfer rate onto the BH remaining at a low level rather than increasing as the outburst evolves. We discuss how the larger number of these “hard-only” outbursts and detected outbursts in general have significant implications for both the luminosity function and mass-transfer history of the Galactic BHXB population.« less
VizieR Online Data Catalog: WATCHDOG: an all-sky database of Galactic BHXBs (Tetarenko+, 2016)
NASA Astrophysics Data System (ADS)
Tetarenko, B. E.; Sivakoff, G. R.; Heinke, C. O.; Gladstone, J. C.
2016-03-01
With the advent of more sensitive all-sky instruments, the transient universe is being probed in greater depth than ever before. Taking advantage of available resources, we have established a comprehensive database of black hole (and black hole candidate) X-ray binary (BHXB) activity between 1996 and 2015 as revealed by all-sky instruments, scanning surveys, and select narrow-field X-ray instruments on board the INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL), Monitor of All-Sky X-ray Image (MAXI), Rossi X-ray Timing Explorer (RXTE), and Swift telescopes; the Whole-sky Alberta Time-resolved Comprehensive black-Hole Database Of the Galaxy or WATCHDOG. Over the past two decades, we have detected 132 transient outbursts, tracked and classified behavior occurring in 47 transient and 10 persistently accreting BHs, and performed a statistical study on a number of outburst properties across the Galactic population. We find that outbursts undergone by BHXBs that do not reach the thermally dominant accretion state make up a substantial fraction (~40%) of the Galactic transient BHXB outburst sample over the past ~20 years. Our findings suggest that this "hard-only" behavior, observed in transient and persistently accreting BHXBs, is neither a rare nor recent phenomenon and may be indicative of an underlying physical process, relatively common among binary BHs, involving the mass-transfer rate onto the BH remaining at a low level rather than increasing as the outburst evolves. We discuss how the larger number of these "hard-only" outbursts and detected outbursts in general have significant implications for both the luminosity function and mass-transfer history of the Galactic BHXB population. (9 data files).
WATCHDOG: A Comprehensive All-sky Database of Galactic Black Hole X-ray Binaries
NASA Astrophysics Data System (ADS)
Tetarenko, B. E.; Sivakoff, G. R.; Heinke, C. O.; Gladstone, J. C.
2016-02-01
With the advent of more sensitive all-sky instruments, the transient universe is being probed in greater depth than ever before. Taking advantage of available resources, we have established a comprehensive database of black hole (and black hole candidate) X-ray binary (BHXB) activity between 1996 and 2015 as revealed by all-sky instruments, scanning surveys, and select narrow-field X-ray instruments on board the INTErnational Gamma-Ray Astrophysics Laboratory, Monitor of All-Sky X-ray Image, Rossi X-ray Timing Explorer, and Swift telescopes; the Whole-sky Alberta Time-resolved Comprehensive black-Hole Database Of the Galaxy or WATCHDOG. Over the past two decades, we have detected 132 transient outbursts, tracked and classified behavior occurring in 47 transient and 10 persistently accreting BHs, and performed a statistical study on a number of outburst properties across the Galactic population. We find that outbursts undergone by BHXBs that do not reach the thermally dominant accretion state make up a substantial fraction (∼40%) of the Galactic transient BHXB outburst sample over the past ∼20 years. Our findings suggest that this “hard-only” behavior, observed in transient and persistently accreting BHXBs, is neither a rare nor recent phenomenon and may be indicative of an underlying physical process, relatively common among binary BHs, involving the mass-transfer rate onto the BH remaining at a low level rather than increasing as the outburst evolves. We discuss how the larger number of these “hard-only” outbursts and detected outbursts in general have significant implications for both the luminosity function and mass-transfer history of the Galactic BHXB population.
Guo, Huijun; Liu, Yunchuan; Li, Xiao; Yan, Zhihui; Xie, Yongdun; Xiong, Hongchun; Zhao, Linshu; Gu, Jiayu; Zhao, Shirong; Liu, Luxiang
2017-05-08
Transient starch provides carbon and energy for plant growth, and its synthesis is regulated by the joint action of a series of enzymes. Starch synthesis IV (SSIV) is one of the important starch synthase isoforms, but its impact on wheat starch synthesis has not yet been reported due to the lack of mutant lines. Using the TILLING approach, we identified 54 mutations in the wheat gene TaSSIVb-D, with a mutation density of 1/165 Kb. Among these, three missense mutations and one nonsense mutation were predicted to have severe impacts on protein function. In the mutants, TaSSIVb-D was significantly down-regulated without compensatory increases in the homoeologous genes TaSSIVb-A and TaSSIVb-B. Altered expression of TaSSIVb-D affected granule number per chloroplast; compared with wild type, the number of chloroplasts containing 0-2 granules was significantly increased, while the number containing 3-4 granules was decreased. Photosynthesis was affected accordingly; the maximum quantum yield and yield of PSII were significantly reduced in the nonsense mutant at the heading stage. These results indicate that TaSSIVb-D plays an important role in the formation of transient starch granules in wheat, which in turn impact the efficiency of photosynthesis. The mutagenized population created in this study allows the efficient identification of novel alleles of target genes and could be used as a resource for wheat functional genomics.
Kirilly, Eszter; Molnar, Eszter; Balogh, Brigitta; Kantor, Sandor; Hansson, Stefan R; Palkovits, Miklos; Bagdy, Gyorgy
2008-09-01
The recreational drug ecstasy [3,4-methylenedioxymethamphetamine (MDMA)], has been found to selectively damage brain serotonin neurons in experimental animals, and probably in human MDMA users, but detailed morphometric analyses and parallel functional measures during damage and recovery are missing. Since there is evidence that serotonin regulates sleep, we have compared serotonergic markers parallel with detailed analysis of sleep patterns at three time-points within 180 d after a single dose of 15 mg/kg MDMA in male Dark Agouti rats. At 7 d and 21 d after MDMA treatment, significant(30-40%), widespread reductions in serotonin transporter (5-HTT) density were detected in the cerebral cortex, hippocampus, most parts of the hypothalamus, and some of the brainstem nuclei. With the exception of the hippocampus, general recovery was observed in the brain 180 d after treatment. Transient increases followed by decreases were detected in 5-HTT mRNA expression of dorsal and median raphe nuclei at 7 d and 21 d after the treatment. Significant reductions in rapid eye movement (REM) sleep latency, increases in delta power spectra in non-rapid eye movement sleep and increased fragmentation of sleep were also detected, but all these alterations disappeared by the 180th day. The present data provide evidence for long-term, albeit, except for the hippocampus, transient changes in the terminal and cellular regions of the serotonergic system after this drug. Reduced REM latency and increased sleep fragmentation are the most characteristic alterations of sleep consistently described in depression using EEG sleep polygraphy.
So, Rosa Q; McConnell, George C; Grill, Warren M
2017-03-01
Methamphetamine-induced circling is used to quantify the behavioral effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in hemiparkinsonian rats. We observed a frequency-dependent transient effect of DBS on circling, and quantified this effect to determine its neuronal basis. High frequency STN DBS (75-260Hz) resulted in transient circling contralateral to the lesion at the onset of stimulation, which was not sustained after the first several seconds of stimulation. Following the transient behavioral change, DBS resulted in a frequency-dependent steady-state reduction in pathological ipsilateral circling, but no change in overall movement. Recordings from single neurons in globus pallidus externa (GPe) and substantia nigra pars reticulata (SNr) revealed that high frequency, but not low frequency, STN DBS elicited transient changes in both firing rate and neuronal oscillatory power at the stimulation frequency in a subpopulation of GPe and SNr neurons. These transient changes were not sustained, and most neurons exhibited a different response during the steady-state phase of DBS. During the steady-state, DBS produced elevated neuronal oscillatory power at the stimulus frequency in a majority of GPe and SNr neurons, and the increase was more pronounced during high frequency DBS than during low frequency DBS. Changes in oscillatory power during both transient and steady-state DBS were highly correlated with changes in firing rates. These results suggest that distinct neural mechanisms were responsible for transient and sustained behavioral responses to STN DBS. The transient contralateral turning behavior following the onset of high frequency DBS was paralleled by transient changes in firing rate and oscillatory power in the GPe and SNr, while steady-state suppression of ipsilateral turning was paralleled by sustained increased synchronization of basal ganglia neurons to the stimulus pulses. Our analysis of distinct frequency-dependent transient and steady-state responses to DBS lays the foundation for future mechanistic studies of the immediate and persistent effects of DBS. Copyright © 2016 Elsevier B.V. All rights reserved.
Transitions to Mild Cognitive Impairments, Dementia, and Death: Findings from the Nun Study
Tyas, Suzanne L.; Salazar, Juan Carlos; Snowdon, David A.; Desrosiers, Mark F.; Riley, Kathryn P.; Mendiondo, Marta S.; Kryscio, Richard J.
2007-01-01
The potential of early interventions for dementia has increased interest in cognitive impairments less severe than dementia. However, predictors of the trajectory from intact cognition to dementia have not yet been clearly identified. The purpose of this study was to determine whether known risk factors for dementia increased the risk of mild cognitive impairments or progression from mild cognitive impairments to dementia. A polytomous logistic regression model was used, with parameters governing transitions within transient states (intact cognition, mild cognitive impairments, global impairment) estimated separately from parameters governing the transition from transient to absorbing state (dementia or death). Analyses were based on seven annual examinations (1991–2002) of 470 Nun Study participants aged ≥75 years at baseline and living in the United States. Odds of developing dementia increased with age primarily for those with low educational levels. In these women, presence of an apolipoprotein E gene *E4 allele increased the odds more than fourfold by age 95 years. Age, education, and the apolipoprotein E gene were all significantly associated with mild cognitive impairments. Only age, however, was associated with progression to dementia. Thus, risk factors for dementia may operate primarily by predisposing individuals to develop mild cognitive impairments; subsequent progression to dementia then depends on only time and competing mortality. PMID:17431012
Transitions to mild cognitive impairments, dementia, and death: findings from the Nun Study.
Tyas, Suzanne L; Salazar, Juan Carlos; Snowdon, David A; Desrosiers, Mark F; Riley, Kathryn P; Mendiondo, Marta S; Kryscio, Richard J
2007-06-01
The potential of early interventions for dementia has increased interest in cognitive impairments less severe than dementia. However, predictors of the trajectory from intact cognition to dementia have not yet been clearly identified. The purpose of this study was to determine whether known risk factors for dementia increased the risk of mild cognitive impairments or progression from mild cognitive impairments to dementia. A polytomous logistic regression model was used, with parameters governing transitions within transient states (intact cognition, mild cognitive impairments, global impairment) estimated separately from parameters governing the transition from transient to absorbing state (dementia or death). Analyses were based on seven annual examinations (1991-2002) of 470 Nun Study participants aged > or = 75 years at baseline and living in the United States. Odds of developing dementia increased with age primarily for those with low educational levels. In these women, presence of an apolipoprotein E gene *E4 allele increased the odds more than fourfold by age 95 years. Age, education, and the apolipoprotein E gene were all significantly associated with mild cognitive impairments. Only age, however, was associated with progression to dementia. Thus, risk factors for dementia may operate primarily by predisposing individuals to develop mild cognitive impairments; subsequent progression to dementia then depends on only time and competing mortality.
Sulfur driven nucleation mode formation in diesel exhaust under transient driving conditions.
Karjalainen, Panu; Rönkkö, Topi; Pirjola, Liisa; Heikkilä, Juha; Happonen, Matti; Arnold, Frank; Rothe, Dieter; Bielaczyc, Piotr; Keskinen, Jorma
2014-02-18
Sulfur driven diesel exhaust nucleation particle formation processes were studied in an aerosol laboratory, on engine dynamometers, and on the road. All test engines were equipped with a combination of a diesel oxidation catalyst (DOC) and a partial diesel particulate filter (pDPF). At steady operating conditions, the formation of semivolatile nucleation particles directly depended on SO2 conversion in the catalyst. The nucleation particle emission was most significant after a rapid increase in engine load and exhaust gas temperature. Results indicate that the nucleation particle formation at transient driving conditions does not require compounds such as hydrocarbons or sulfated hydrocarbons, however, it cannot be explained only by the nucleation of sulfuric acid. A real-world exhaust study with a heavy duty diesel truck showed that the nucleation particle formation occurs even with ultralow sulfur diesel fuel, even at downhill driving conditions, and that nucleation particles can contribute 60% of total particle number emissions. In general, due to sulfur storage and release within the exhaust aftertreatment systems and transients in driving, emissions of nucleation particles can even be the dominant part of modern diesel vehicle exhaust particulate number emissions.
Challenges in investigating transient rash illness in nursery children.
Paranthaman, K; Pooransingh, S; McCarthy, N; Saunders, P; Haworth, E
2010-06-01
In October 2007, the Thames Valley Health Protection Unit (TVHPU) was notified by a parent that her child developed a transient rash after eating lunch at a nursery in Oxfordshire. An initial investigation undertaken by TVHPU was escalated when similar incidents were reported in nurseries in other parts of England. A detailed epidemiological and food tracing investigation was conducted to ascertain the aetiology. Investigations revealed 11 incidents affecting 164 children between July and November 2007 in six nurseries operated by two companies. The symptoms included a transient rash around the mouth and hands of children who ate meals prepared on site by the nurseries. Consumption of the lunch main course appeared to be a strong aetiological factor. Expert opinion pointed to biogenic amines (e.g. histamine) as a possible cause for the symptoms displayed, but there was insufficient evidence to support testing of food samples. The incident highlighted significant gaps in reporting of unexplained symptoms among children in nurseries, indicating that such incidents do not always come to the attention of public health authorities. Timely notification to HPUs will enable prompt investigation, increase the likelihood of identifying the cause and inform appropriate responses to prevent future incidents.
Currie, Yaleaka; Moch, John; Underwood, Joshua; Kharabsheh, Hamzah; Quesenberry, Amy; Miyagi, Risa; Thomas, Carolyn; Boney, Melanie; Woods, Samantha; Chen, Ming-Shun; Zhu, Lieceng
2014-02-01
Heat stress exerts a profound impact on the resistance of plants to parasites. In this research, we investigated the impact of an acute transient heat stress on the resistance of the wheat line 'Molly,' which contains the R gene H13, to an avirulent Hessian fly (Mayetiola destructor (Say)) population. We found that a significant portion of Molly seedlings stressed at 40 degrees C for 6 h during or after the initial Hessian fly larval attack became susceptible to otherwise avirulent insects, whereas unstressed control plants remained 100% resistant. Specifically, 77.8, 73.3, 83.3, and 46.7% of plants heat stressed at 0, 6,12, and 24 h, respectively, after the initial larval attack became susceptible. Biochemical analysis revealed that heat stress caused a transient decrease in 12-oxo-phytodienoic acid, but an increase in salicylic acid accumulation in Molly plants. The change in phytohormones after heat stress and Hessian fly infestation was not observed in 'Newton,' a near-isogenic but Hessian fly susceptible wheat line. Instead, heat stress caused a relatively prolonged reduction in palmitoleic acid. The role of phytohormones in heat-induced loss of wheat resistance was discussed.
Assessment of the stability of a multimachine power system by the transient energy margin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stanton, S.E.
1982-01-01
This reasearch develops a tool for the direct assessment of the transient stability of a multimachine electric power system that is subject to a large disturbance. The tool is the Transient Energy Margin. The transient of interest is the first swing (or inertial) transient. The Transient Energy Margin is computed by evaluating an energy function using the relevant unstable equilibrium point and the system states at the instant the disturbance is removed. In evaluating the function, a significant portion of the fault kinetic energy is identified as not contributing to system instability. The resulting energy value is a measure ofmore » the margin-of-safety for the disturbed system. A distinction is proposed between assessing system stability and assessing system security. The Transient Energy Margin is used first to assess the stability of the system. This profile ranks various distrubances to display the strengths and weaknesses of the system. A modified Transient Energy Margin is then proposed as an assessment of security; the transient energy margin profile is repeated to evaluate the system response in terms of the local minimum energy conditions approached by the critical trajectories. Both techniques are applied to a practical, 17 generator test system.« less
Wang, Y. M.; Zhang, G. Y.; Wang, Y.; Hu, M.; Zhou, J. J.; Sawyer, A.; Cao, Q.; Wang, Y.; Zheng, G.; Lee, V. W. S.; Harris, D. C. H.
2017-01-01
Summary Regulatory T cells (Tregs) have been recognized as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. The loss of Tregs or their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of Tregs in the chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of Tregs in a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2‐interacting mediator (Bim) knock‐out mice by transient depleting Tregs. Bim is a pro‐apoptotic member of the B cell lymphoma 2 (Bcl‐2) family. Bim knock‐out (Bim–/–) mice fail to delete autoreactive T cells in thymus, leading to chronic spontaneous autoimmune kidney disease. We found that Treg depletion in Bim–/– mice exacerbated the kidney injury with increased proteinuria, impaired kidney function, weight loss and greater histological injury compared with wild‐type mice. There was a significant increase in interstitial infiltrate of inflammatory cells, antibody deposition and tubular damage. Furthermore, the serum levels of cytokines interleukin (IL)−2, IL‐4, IL‐6, IL‐10, IL‐17α, interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α were increased significantly after Treg depletion in Bim–/– mice. This study demonstrates that transient depletion of Tregs leads to enhanced self‐reactive T effector cell function followed by exacerbation of kidney disease in the chronic spontaneous kidney disease model of Bim‐deficient mice. PMID:28152566
Tween-20 transiently changes the surface morphology of PK-15 cells and improves PCV2 infection.
Hua, Tao; Zhang, Xuehua; Tang, Bo; Chang, Chen; Liu, Guoyang; Feng, Lei; Yu, Yang; Zhang, Daohua; Hou, Jibo
2018-04-24
Low concentrations of nonionic surfactants can change the physical properties of cell membranes, and thus and in turn increase drug permeability. Porcine circovirus 2 (PCV2) is an extremely slow-growing virus, and PCV2 infection of PK-15 cells yields very low viral titers. The present study investigates the effect of various nonionic surfactants, namely, Tween-20, Tween-28, Tween-40, Tween-80, Brij-30, Brij-35, NP-40, and Triton X-100 on PCV2 infection and yield in PK-15 cells. Significantly increased PCV2 infection was observed in cells treated with Tween-20 compared to those treated with Tween-28, Tween-40, Brij-30, Brij-35, NP-40, and Triton X-100 (p < 0.01). Furthermore, 24 h incubation with 0.03% Tween-20 has shown to induce significant cellular morphologic changes (cell membrane underwent slight intumescence and bulged into a balloon, and the number of microvilli decreased), as well as to increase caspase-3 activity and to decrease cell viability in PCV2-infected PK-15 cells cmpared to control group; all these changes were restored to normal after Tween-20 has been washed out from the plate. Our data demonstrate that Tween-20 transiently changes the surface morphology of PK-15 cells and improves PCV2 infection. The findings of the present study may be utilized in the development of a PCV2 vaccine.
An analytical study of thermal barrier coated first stage blades in a JT9D engine
NASA Technical Reports Server (NTRS)
Sevcik, W. R.; Stoner, B. L.
1978-01-01
Steady state and transient heat transfer and structural calculations were completed to determine the coating and base alloy temperatures and strains. Results indicate potential for increased turbine life using thin durable thermal barrier coatings on turbine airfoils due to a significant reduction in blade average and maximum temperatures, and alloy strain range. An intepretation of the analytical results is compared to the experimental engine test data.
Etiological evaluation of primary congenital hypothyroidism cases.
Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz
2017-06-01
Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007-June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism.
NASA Astrophysics Data System (ADS)
Raos, B. J.; Simpson, M. C.; Doyle, C. S.; Murray, A. F.; Graham, E. S.; Unsworth, C. P.
2018-06-01
Objective. Recent literature suggests that astrocytes form organized functional networks and communicate through transient changes in cytosolic Ca2+. Traditional techniques to investigate network activity, such as pharmacological blocking or genetic knockout, are difficult to restrict to individual cells. The objective of this work is to develop cell-patterning techniques to physically manipulate astrocytic interactions to enable the study of Ca2+ in astrocytic networks. Approach. We investigate how an in vitro cell-patterning platform that utilizes geometric patterns of parylene-C on SiO2 can be used to physically isolate single astrocytes and small astrocytic networks. Main results. We report that single astrocytes are effectively isolated on 75 × 75 µm square parylene nodes, whereas multi-cellular astrocytic networks are isolated on larger nodes, with the mean number of astrocytes per cluster increasing as a function of node size. Additionally, we report that astrocytes in small multi-cellular clusters exhibit spatio-temporal clustering of Ca2+ transients. Finally, we report that the frequency and regularity of Ca2+ transients was positively correlated with astrocyte connectivity. Significance. The significance of this work is to demonstrate how patterning hNT astrocytes replicates spatio-temporal clustering of Ca2+ signalling that is observed in vivo but not in dissociated in vitro cultures. We therefore highlight the importance of the structure of astrocytic networks in determining ensemble Ca2+ behaviour.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Young-Hoon; Department of Neurosurgery, Seoul National University College of Medicine, Seoul; Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.kr
2013-01-01
Purpose: We evaluated the prognostic factors for hearing outcomes after stereotactic radiosurgery (SRS) for unilateral sporadic intracanalicular vestibular schwannomas (IC-VSs) as a clinical homogeneous group of VSs. Methods and Materials: Sixty consecutive patients with unilateral sporadic IC-VSs, defined as tumors in the internal acoustic canal, and serviceable hearing (Gardner-Roberson grade 1 or 2) were treated with SRS as an initial treatment. The mean tumor volume was 0.34 {+-} 0.03 cm{sup 3} (range, 0.03-1.00 cm{sup 3}), and the mean marginal dose was 12.2 {+-} 0.1 Gy (range, 11.5-13.0 Gy). The median follow-up duration was 62 months (range, 36-141 months). Results: Themore » actuarial rates of serviceable hearing preservation were 70%, 63%, and 55% at 1, 2, and 5 years after SRS, respectively. In multivariate analysis, transient volume expansion of {>=}20% from initial tumor size was a statistically significant risk factor for loss of serviceable hearing and hearing deterioration (increase of pure tone average {>=}20 dB) (odds ratio = 7.638; 95% confidence interval, 2.317-25.181; P=.001 and odds ratio = 3.507; 95% confidence interval, 1.228-10.018; P=.019, respectively). The cochlear radiation dose did not reach statistical significance. Conclusions: Transient volume expansion after SRS for VSs seems to be correlated with hearing deterioration when defined properly in a clinically homogeneous group of patients.« less
Thermal-Hydraulic Transient Analysis of a Packed Particle Bed Reactor Fuel Element
1990-06-01
long fuel elements, arranged to form a core , were analyzed for an up-power transient from 0 MWt to approximately 18 MWt. The simple model significantly...VARIATIONS IN FUEL ELEMENT GEOMETRY ............. 60 4.4 VARIATIONS IN THE MANNER OF TRANSIENT CONTROL ..... 62 4.5 CORE REPRESENTATION BY MULTIPLE FUEL ...the HTGR , however, the PBR packs small fuel particles between inner and outer retention elements, designated as frits. The PBR is appropriate for a
The Transient High-Energy Sky and Early Universe Surveyor (THESEUS)
NASA Astrophysics Data System (ADS)
Amati, L.
2016-10-01
THESEUS is a mission concept by a large international collaboration aimed at exploiting GRBs for investigating the early universe and at vastly increasing the discovery space of the high energy transient phenomena over the entire cosmic history.
Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis
Yüksel, Melih; Power, Jeffrey J.; Ribbe, Jan; Volkmann, Thorsten; Maier, Berenike
2016-01-01
In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off. PMID:27375604
Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis.
Yüksel, Melih; Power, Jeffrey J; Ribbe, Jan; Volkmann, Thorsten; Maier, Berenike
2016-01-01
In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off.
Flow path oscillations in transient ground-water simulations of large peatland systems
Reeve, A.S.; Evensen, R.; Glaser, P.H.; Siegel, D.I.; Rosenberry, D.
2006-01-01
Transient numerical simulations of the Glacial Lake Agassiz Peatland near the Red Lakes in Northern Minnesota were constructed to evaluate observed reversals in vertical ground-water flow. Seasonal weather changes were introduced to a ground-water flow model by varying evapotranspiration and recharge over time. Vertical hydraulic reversals, driven by changes in recharge and evapotranspiration were produced in the simulated peat layer. These simulations indicate that the high specific storage associated with the peat is an important control on hydraulic reversals. Seasonally driven vertical flow is on the order of centimeters in the deep peat, suggesting that seasonal vertical advective fluxes are not significant and that ground-water flow into the deep peat likely occurs on decadal or longer time scales. Particles tracked within the ground-water flow model oscillate over time, suggesting that seasonal flow reversals will enhance vertical mixing in the peat column. The amplitude of flow path oscillations increased with increasing peat storativity, with amplitudes of about 5 cm occurring when peat specific storativity was set to about 0.05 m-1. ?? 2005 Elsevier B.V. All rights reserved.
Pfleger, B; Bonds, A B
1995-01-01
The influence of GABAA receptors on orientation selectivity of cat complex cells was tested by iontophoresis of the GABAA receptor blockers bicuculline and N-methyl-bicuculline while stimulating with drifting sinusoidal gratings. Reduction of orientation tuning was markedly less than reported in previous studies that used drifting bars as visual stimuli. Only 3/31 cells lost orientation selectivity, with an average increase in bandwidth of 33%, as opposed to half the cells losing selectivity and a bandwidth increase for the remainder of 47% as reported previously. Infusion of GABAA blockers revealed a prominent stimulus onset transient response, lasting about 120 ms, that showed a broadening of orientation selectivity comparable to that found using drifting bars under similar circumstances. We believe that drifting gratings emphasize a steady-state response component that retains, in the presence of GABAA blockers, significant orientation selectivity. Because the onset transient is initially unselective for orientation, we suggest that the steady-state, orientation-selective response component develops from an alternate inhibitory mechanism, possibly mediated by GABAB receptors.
Sensitization of TRPV1 by protein kinase C in rats with mono-iodoacetate-induced joint pain.
Koda, K; Hyakkoku, K; Ogawa, K; Takasu, K; Imai, S; Sakurai, Y; Fujita, M; Ono, H; Yamamoto, M; Fukuda, I; Yamane, S; Morita, A; Asaki, T; Kanemasa, T; Sakaguchi, G; Morioka, Y
2016-07-01
To assess the functional changes of Transient receptor potential vanilloid 1 (TRPV1) receptor and to clarify its mechanism in a rat mono-iodoacetate (MIA)-induced joint pain model (MIA rats), which has joint degeneration with cartilage loss similar to osteoarthritis. Sensitization of TRPV1 in MIA rats was assessed by transient spontaneous pain behavior induced by capsaicin injection in knee joints and electrophysiological changes of dorsal root ganglion (DRG) neurons innervating knee joints in response to capsaicin. Mechanisms of TRPV1 sensitization were analyzed by a newly developed sandwich enzyme-linked immunosorbent assay that detects phosphorylated TRPV1, followed by functional and expression analyses of protein kinase C (PKC) in vivo and in vitro, which involves TRPV1 phosphorylation. Pain-related behavior induced by intra-articular injection of capsaicin was significantly increased in MIA rats compared with sham rats. In addition, capsaicin sensitivity, evaluated by capsaicin-induced inward currents, was significantly increased in DRG neurons of MIA rats. Protein levels of TRPV1 remained unchanged, but phosphorylated TRPV1 at Ser800 increased in DRG neurons of MIA rats. Phosphorylated-PKCɛ (p-PKCɛ) increased and co-localized with TRPV1 in DRG neurons of MIA rats. Capsaicin-induced pain-related behavior in MIA rats was inhibited by intra-articular pretreatment of the PKC inhibitor bisindolylmaleimide I. In addition, intra-articular injection of the PKC activator phorbol 12-myristate 13-acetate increased capsaicin-induced pain-related behavior in normal rats. TRPV1 was sensitized at the knee joint and at DRG neurons of MIA rats through PKC activation. Thus, TRPV1 sensitization might be involved in chronic pain caused by osteoarthritis. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Amarasekera, Dilru C; Resende, Arthur F; Waisbourd, Michael; Puri, Sanjeev; Moster, Marlene R; Hark, Lisa A; Katz, L Jay; Fudemberg, Scott J; Mantravadi, Anand V
2018-01-01
This study evaluates two rapid electrophysiological glaucoma diagnostic tests that may add a functional perspective to glaucoma diagnosis. This study aimed to determine the ability of two office-based electrophysiological diagnostic tests, steady-state pattern electroretinogram and short-duration transient visual evoked potentials, to discern between glaucomatous and healthy eyes. This is a cross-sectional study in a hospital setting. Forty-one patients with glaucoma and 41 healthy volunteers participated in the study. Steady-state pattern electroretinogram and short-duration transient visual evoked potential testing was conducted in glaucomatous and healthy eyes. A 64-bar-size stimulus with both a low-contrast and high-contrast setting was used to compare steady-state pattern electroretinogram parameters in both groups. A low-contrast and high-contrast checkerboard stimulus was used to measure short-duration transient visual evoked potential parameters in both groups. Steady-state pattern electroretinogram parameters compared were MagnitudeD, MagnitudeD/Magnitude ratio, and the signal-to-noise ratio. Short-duration transient visual evoked potential parameters compared were amplitude and latency. MagnitudeD was significantly lower in glaucoma patients when using a low-contrast (P = 0.001) and high-contrast (P < 0.001) 64-bar-size steady-state pattern electroretinogram stimulus. MagnitudeD/Magnitude ratio and SNR were significantly lower in the glaucoma group when using a high-contrast 64-bar-size stimulus (P < 0.001 and P = 0.010, respectively). Short-duration transient visual evoked potential amplitude and latency were not significantly different between the two groups. Steady-state pattern electroretinogram was effectively able to discern between glaucomatous and healthy eyes. Steady-state pattern electroretinogram may thus have a role as a clinically useful electrophysiological diagnostic tool. © 2017 Royal Australian and New Zealand College of Ophthalmologists.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hai Bo; Yang Zhenhua; Shangguan Lei
2012-05-01
Purpose: Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explored the potential of transient activation of Wnt/{beta}-catenin signaling in preventing radiation damage to salivary glands in a preclinical model. Methods and Materials: Wnt reporter transgenic mice were exposed to 15 Gy single-dose radiation in the head and neck area to evaluate the effects of radiation on Wnt activity in salivary glands. Transient Wnt1 overexpression in basal epithelia was induced in inducible Wnt1 transgenic mice before together with, after,more » or without local radiation, and then saliva flow rate, histology, apoptosis, proliferation, stem cell activity, and mRNA expression were evaluated. Results: Radiation damage did not significantly affect activity of Wnt/{beta}-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated the Wnt/{beta}-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of the Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects, mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis, likely due to extensive induction of mitosis and up-regulation of proapoptosis gene PUMA while that after radiation might miss the critical treatment window. Conclusion: These results suggest that concurrent transient activation of the Wnt/{beta}-catenin pathway could prevent radiation-induced salivary gland dysfunction.« less
Huber, P; Jöchle, K; Debus, J
1998-10-01
Monitoring the generation of cavitation is of great interest for diagnostic and therapeutic use of ultrasound in medicine, since cavitation is considered to play a major role in nonthermal ultrasound interactions with tissue. Important parameters are the number of cavitation events and the energy released during the bubble collapse. This energy is correlated to the maximum bubble radius which is related to the cavitation lifespan. The aim of this study was therefore to investigate the influence of the acoustic pressure amplitude and the pulse repetition frequency (PRF) in the field of a lithotripter (Lithostar, Siemens) on the number, size and lifespan of transient cavitation bubbles in water. We used scattered laser light recorded by a photodiode and stroboscopic photographs to monitor the cavitation activity. We found that PRF (range 0.5-5 Hz) had no influence on the cavitation bubble lifespan and size, whereas lifespan and size increased with the acoustic pressure amplitude. In contrast, the number of cavitation events strongly increased with PRF, whereas the pressure amplitude had no significant influence on the number of cavitation events. Thus, by varying the pressure amplitude and PRF, it might be possible to deliver a defined relative number of cavitations at a defined relative energy level in a defined volume. This seems to be relevant to further studies that address the biological effects of transient cavitation occurring in the fields of lithotripters.
Hashitani, Hikaru; Suzuki, Hikaru
2007-01-01
Interstitial cells of Cajal-like cells (ICC-LCs) in the urethra may act as electrical pacemakers of spontaneous contractions. However, their properties in situ and their interaction with neighbouring urethral smooth muscle cells (USMCs) remain to be elucidated. To further explore the physiological role of ICC-LCs, spontaneous changes in [Ca2+]i (Ca2+ transients) were visualized in fluo-4 loaded preparations of rabbit urethral smooth muscle. ICC-LCs were sparsely distributed, rather than forming an extensive network. Ca2+ transients in ICC-LCs had a lower frequency and a longer half-width than those of USMCs. ICC-LCs often exhibited Ca2+ transients synchronously with each other, but did not often show a close temporal relationship with Ca2+ transients in USMCs. Nicardipine (1 μm) suppressed Ca2+ transients in USMCs but not in ICC-LCs. Ca2+ transients in ICC-LCs were abolished by cyclopiazonic acid (10 μm), ryanodine (50 μm) and caffeine (10 mm) or by removing extracellular Ca2+, and inhibited by 2-aminoethoxydiphenyl borate (50 μm) and 3-morpholino-sydnonimine (SIN-1; 10 μm), but facilitated by increasing extracellular Ca2+ or phenylephrine (1–10 μm). These results indicated that Ca2+ transients in urethral ICC-LCs in situ rely on both Ca2+ release from intracellular Ca2+ stores and Ca2+ influx through non-L-type Ca2+ channel pathways. ICC-LCs may not act as a coordinated pacemaker electrical network as do ICC in the gastrointestinal (GI) tract. Rather they may randomly increase excitability of USMCs to maintain the tone of urethral smooth muscles. PMID:17615099
Adam S. Ward; Robert A. Payn; Michael N. Gooseff; Brian L. McGlynn; Kenneth E. Bencala; Christa A. Kellecher; Steven M. Wondzell; Thorsten Wagener
2013-01-01
The accumulation of discharge along a stream valley is frequently assumed to be the primary control on solute transport processes. Relationships of both increasing and decreasing transient storage, and decreased gross losses of stream water have been reported with increasing discharge; however, we have yet to validate these relationships with extensive field study. We...
Risk factors for postoperative hypocalcemia.
Docimo, Giovanni; Ruggiero, Roberto; Casalino, Giuseppina; Del Genio, Gianmattia; Docimo, Ludovico; Tolone, Salvatore
2017-06-01
Hypocalcaemia is one of the most common complications after thyroidectomy; however, it is still unclear what preoperative factors could predict this event. The aim of this study was to evaluate the role of risk factors for hypocalcaemia after total thyroidectomy (TT). Consecutive patients who underwent total thyroidectomyat our institution between January 2014 and January 2016 were enrolled. The clinical and pathologic characteristics and surgical details of normocalcemic and hypocalcemic patients were compared. Univariate and multivariate analyses to estimate risk ratio were assessed. A total of 328 patients underwent TT; histology revealed benign and malignant disease in 83 and 17% of cases, respectively. Central-compartment neck dissection (CCND) was performed in 36 subjects (10.9%). Parathyroid glands were observed in 23% (76) of specimens. Laboratory asymptomatic hypocalcaemia was observed in 92 (28%) patients; symptomatic hypocalcaemia occurred in 26 (7.9%). Transient hypocalcaemia has been observed in 48 (14.6%) patients; permanent hypocalcaemia occurred in two subjects (0.6%). On univariate analysis, malignant pathology (p < 0.001), CCND (p < 0.05), female gender (p < 0.001), presence of at least two parathyroid glands in specimens (p < 0.002), and operative time longer than 120 min (p < 0.05) were factors that significantly increased the risk of developing asymptomatic and transient hypocalcaemia. After logistic regression analysis, malignant pathology (p < 0.000; p < 0.001) and CCND (p < 0.005; p = 0.013) were the significant factors that affected the development of symptomatic and transient hypocalcaemia. The presence of malignant pathology and CCND was found to be significant risks factors for postoperative hypocalcaemia. In patients in whom this pathological features are present, attention should be paid to rapidly start an adequate therapy.
VO2 Off Transient Kinetics in Extreme Intensity Swimming.
Sousa, Ana; Figueiredo, Pedro; Keskinen, Kari L; Rodríguez, Ferran A; Machado, Leandro; Vilas-Boas, João P; Fernandes, Ricardo J
2011-01-01
Inconsistencies about dynamic asymmetry between the on- and off- transient responses in oxygen uptake are found in the literature. Therefore, the purpose of this study was to characterize the oxygen uptake off-transient kinetics during a maximal 200-m front crawl effort, as examining the degree to which the on/off regularity of the oxygen uptake kinetics response was preserved. Eight high level male swimmers performed a 200-m front crawl at maximal speed during which oxygen uptake was directly measured through breath-by-breath oxymetry (averaged every 5 s). This apparatus was connected to the swimmer by a low hydrodynamic resistance respiratory snorkel and valve system. The on- and off-transient phases were symmetrical in shape (mirror image) once they were adequately fitted by a single-exponential regression models, and no slow component for the oxygen uptake response was developed. Mean (± SD) peak oxygen uptake was 69.0 (± 6.3) mL·kg(-1)·min(-1), significantly correlated with time constant of the off- transient period (r = 0.76, p < 0.05) but not with any of the other oxygen off-transient kinetic parameters studied. A direct relationship between time constant of the off-transient period and mean swimming speed of the 200-m (r = 0.77, p < 0.05), and with the amplitude of the fast component of the effort period (r = 0.72, p < 0.05) were observed. The mean amplitude and time constant of the off-transient period values were significantly greater than the respective on- transient. In conclusion, although an asymmetry between the on- and off kinetic parameters was verified, both the 200-m effort and the respectively recovery period were better characterized by a single exponential regression model. Key pointsThe VO2 slow component was not observed in the recovery period of swimming extreme efforts;The on and off transient periods were better fitted by a single exponential function, and so, these effort and recovery periods of swimming extreme efforts are symmetrical;The rate of VO2 decline during the recovery period may be due to not only the magnitude of oxygen debt but also the VO2peak obtained during the effort period.
M.I.T. studies of transient X-ray phenomena. [astronomical observations
NASA Technical Reports Server (NTRS)
Canizares, C. R.
1976-01-01
A variety of transient X-ray phenomena have been studied. Data from the OSO-7 satellite reveal both long and short time-scale transients. Extensive observations have been made of the Lupus X-ray Nova (3U1543-47) and GX339-4(MX 1658-48) which may represent a very different type of transient source. A unique, intense X-ray flare lasting ten minutes was also recorded, and the X-ray emission from the active galaxy Cen A was found to vary significantly over a period of several days. In a recent balloon flight the Crab pulsar, NP0532, was observed to exhibit a transient pulsed component distinct from the usual main pulse and interpulse. A sounding-rocket experiment detected an ultrasoft transient X-ray source tentatively associated with SS Cygni, and preliminary results from SAS-3 show a very hard spectrum for the new source A0535 + 26. On the other hand, extensive OSO-7 null observations of both Type I and II supernovae and of the flaring radio star Algol make it unlikely that these types of objects are potent transient X-ray emitters.
Chowdhury, H H; Popoff, M R; Zorec, R
1999-12-01
1. We measured membrane capacitance (Cm) in cultured rat melanotrophs pretreated with Clostridium spiroforme toxin (CST), which specifically depolymerizes cortical filamentous actin (F-actin). Phalloidin staining confirmed that CST treatment depolymerised the F-actin. 2. In control cells, cytosol dialysis with 1 microM Ca2+i increased Cm by 23 +/- 4 % (n = 11) relative to the resting Cm 400 s after the start of patch rupture. In CST-treated cells the increase in Cm was 32 +/- 5 % (n = 15), not significantly different from controls. The rate of Cm increase was affected transiently by CST treatment, peaking at 1 min after patch rupture. The maximal rate of Cm increase was 4.27 +/- 0.85 fF s-1 (n = 12; measured 200 s after the start of patch rupture) in controls and 8.0 +/- 1.35 fF s-1 (n = 23; measured 75 s after the start of patch rupture) in CST-treated cells (P < 0.01). 3. In control cells cytosol dialysis with 0 microM Ca2+i decreased Cm by 9 +/- 3 % (n = 7), in CST-treated cells Cm increased by 11 +/- 3 % (n = 7) relative to resting Cm 400 s after the start of cytosol dialysis. The rate of change in Cm remained constant (controls: -1 to -2 fF s-1; CST treatment: 1-2 fF s-1). 4. Transient and sustained effects of CST treatment on changes in Cm at high or low [Ca2+]i, respectively, suggest a distinct role of cytoskeleton in Ca2+-dependent and Ca2+-independent changes in Cm. Transient enhancement of the rate of Cm by CST is consistent with a barrier role of cytoskeleton in regulated exocytosis. The sustained effect of CST on Ca2+-independent changes in Cm suggests cytoskeletal involvement in endocytosis.
Chowdhury, Helena H; Popoff, Michel R; Zorec, Robert
1999-01-01
We measured membrane capacitance (Cm) in cultured rat melanotrophs pretreated with Clostridium spiroforme toxin (CST), which specifically depolymerises cortical filamentous actin (F-actin). Phalloidin staining confirmed that CST treatment depolymerised the F-actin. In control cells, cytosol dialysis with 1 μm Ci2+ increased Cm by 23 ± 4% (n = 11) relative to the resting Cm 400 s after the start of patch rupture. In CST-treated cells the increase in Cm was 32 ± 5% (n = 15), not significantly different from controls. The rate of Cm increase was affected transiently by CST treatment, peaking at 1 min after patch rupture. The maximal rate of Cm increase was 4.27 ± 0.85 fF s−1 (n = 12; measured 200 s after the start of patch rupture) in controls and 8.0 ± 1.35 fF s−1 (n = 23; measured 75 s after the start of patch rupture) in CST-treated cells (P < 0.01). In control cells cytosol dialysis with 0 μm Ci2+ decreased Cm by 9 ± 3% (n = 7), in CST-treated cells Cm increased by 11 ± 3% (n = 7) relative to resting Cm 400 s after the start of cytosol dialysis. The rate of change in Cm remained constant (controls: -1 to -2 fF s−1; CST treatment: 1-2 fF s−1). Transient and sustained effects of CST treatment on changes in Cm at high or low [Ca2+]i, respectively, suggest a distinct role of cytoskeleton in Ca2+-dependent and Ca2+-independent changes in Cm. Transient enhancement of the rate of Cm by CST is consistent with a barrier role of cytoskeleton in regulated exocytosis. The sustained effect of CST on Ca2+-independent changes in Cm suggests cytoskeletal involvement in endocytosis. PMID:10581310
Casadaban, Leigh C; Parvinian, Ahmad; Couture, Patrick M; Minocha, Jeet; Knuttinen, M Grace; Bui, James T; Gaba, Ron C
2014-12-01
The purpose of this article is to characterize the temporal evolution and clinical impact of laboratory liver function parameters after transjugular intrahepatic portosystemic shunt (TIPS) creation. In this single-institution retrospective study, 157 patients (98 men and 59 women; median age, 55 years) underwent TIPS between 2000 and 2012 and had 1-month hepatobiliary laboratory follow-up. Medical record review was used to compare baseline, peak, and low bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and international normalized ratio (INR) levels within 30 days after TIPS in surviving and dying patients to assess laboratory responses to shunt creation. TIPSs were created with a hemodynamic success rate of 98%, with median pressure gradient reduction of 13 mm Hg. Ninety-day mortality was 21%. Hepatobiliary laboratory values showed significant increases in the days after TIPS compared with baseline levels (bilirubin, 1.6 vs 3.5 mg/dL; AST, 49 vs 149 U/L; ALT, 26 vs 90 U/L; alkaline phosphatase, 97 vs 177 U/L; and INR, 1.5 vs 2.0; p<0.05 in all cases). Patients surviving to 90 days experienced statistically significant but transient laboratory value elevations-up to twofold over baseline-within days of TIPS, whereas patients dying within 90 days experienced three-to fourfold increases over a longer period that did not return to baseline. Differences in laboratory evolution were statistically significant in surviving versus dying patients. TIPS results in acute transient elevation of hepatobiliary enzymes, which may be more pronounced in patients with early mortality. An exaggerated laboratory elevation in excess of threefold greater than baseline or a prolonged increase exceeding 1 week may herald poorer clinical outcome.
Zorzon, M; Antonutti, L; Masè, G; Biasutti, E; Vitrani, B; Cazzato, G
1995-09-01
The purpose of the present study was to make an attempt to ascertain the etiology of transient global amnesia (TGA), which is still disputed more than 30 years after the first description of this clinical entity. In a case-control study, we compared the prevalence of vascular risk factors in 64 TGA patients with 64 first-ever transient ischemic attack (TIA) control subjects and 108 normal community-based control subjects matched for age and sex. We prospectively studied the vascular events and mortality rates of the TGA cases and of the TIA control subjects. Then we compared the outcome of the two groups using actuarial analysis based on survival curves. We did not find evidence of an increased risk of TGA associated with any vascular risk factor. In contrast to TIA control subjects, no TGA patient suffered stroke, myocardial infarction, or TIA during the follow-up period. Migraine was more common in TGA patients than in both normal and TIA control subjects. In three patients (4.5%), the TGA was eventually considered to be of epileptic origin. The results of our case-control and longitudinal studies point to the conclusion that TGA and TIA do not share the same etiology. Since half of our patients had a precipitating event in their history, it is reasonable to hypothesize that spreading depression may play a role in TGA. The significant positive association between migraine and TGA may support this hypothesis. Epilepsy may mimic TGA in a minority of cases.
Damping of transient energy growth of three-dimensional perturbations in hydromagnetic pipe flow
NASA Astrophysics Data System (ADS)
Åkerstedt, Hans O.
1995-05-01
The stability of infinitesimal three-dimensional perturbations in hydromagnetic pipe flow where the applied magnetic field is in the streamwise direction is considered. The study is limited to the case of small magnetic Reynolds numbers and the main objective of the paper is to study the transient evolution of the kinetic energy. A general effect of the magnetic field is to increase the damping of the eigenvalues of the individual perturbation modes. For the case of infinitely long perturbations, which in the non-magnetic case has been found to have the largest transient growth, the magnetic field perturbations are decoupled from the flow and there is no effect on the stability properties of the flow. For shorter waves, and for moderate values of the interaction parameter ( I = RmA2 ≈ 1-3) the hydromagnetic damping effect on the transient energy growth is, however, substantial, especially for small azimuthal mode numbers n. (Here Rm is the magnetic Reynolds number and A is the Alfvén number.) This parameter range has been found in experiments to give significantly higher transitional Reynolds numbers (Fraim and Heiser, 1968). Since the hydromagnetic damping effect is weak for long waves and large for shorter waves, the implications of the results to ordinary pipe flow is that the energy growth found for short waves may be more crucial as a mechanism for transition than the corresponding growth for longer waves.
Focused ultrasound-mediated drug delivery through the blood-brain barrier
Burgess, Alison; Shah, Kairavi; Hough, Olivia; Hynynen, Kullervo
2015-01-01
Despite recent advances in blood-brain barrier (BBB) research, it remains a significant hurdle for the pharmaceutical treatment of brain diseases. Focused ultrasound (FUS) is one method to transiently increase permeability of the BBB to promote drug delivery to specific brain regions. An introduction to the BBB and a brief overview of the methods which can be used to circumvent the BBB to promote drug delivery is provided. In particular, we discuss the advantages and limitations of FUS technology and the efficacy of FUS-mediated drug delivery in models of disease. MRI for targeting and evaluating FUS treatments, combined with administration of microbubbles, allows for transient, reproducible BBB opening. The integration of a real-time acoustic feedback controller has improved treatment safety. Successful clinical translation of FUS has the potential to transform the treatment of brain disease worldwide without requiring the development of new pharmaceutical agents. PMID:25936845
Docetaxel in combination with epirubicin in metastatic breast cancer: pharmacokinetic interactions.
Ceruti, M; Tagini, V; Recalenda, V; Arpicco, S; Cattel, L; Airoldi, M; Bumma, C
1999-01-01
Epirubicin (75 mg/m2) and docetaxel (75 mg/m2) were administered to 16 patients affected by metastatic breast cancer following two different schedules: (1) docetaxel as infusion administered 1 h after epirubicin administration (schedule A); and (2) docetaxel as infusion immediately (10 min) after the end of epirubicin i.v. bolus administration (schedule B). Experimental non-compartmental analyses such as AUC and Css, were affected very little by the drug combination, irrespective of whether the administration of docetaxel was immediately after the epirubicin bolus (10 min) or delayed (1 h). However, serum levels showed evidence of transient drug interaction: in schedule A, docetaxel infusion was associated with a transient increase of plasma epirubicin in correspondence with Cssmax of docetaxel. Bi-compartmental analysis showed a significant difference in epirubicin clearance between protocols A and B. It is suggested that polysorbate 80, used in minimal amounts to formulate docetaxel, may interfere with epirubicin plasma level.
Behaviour of Lyapunov exponents near crisis points in the dissipative standard map
NASA Astrophysics Data System (ADS)
Pompe, B.; Leven, R. W.
1988-11-01
We numerically study the behaviour of the largest Lyapunov characteristic exponent λ1 in dependence on a control parameter in the 2D standard map with dissipation. In order to investigate the system's motion in parameter intervals slightly above crisis points we introduce "partial" Lyapunov exponents which characterize the average exponential divergence of nearby orbits on a semi-attractor at a boundary crisis and on distinct parts of a "large" chaotic attractor near an interior crisis. In the former case we find no significant difference between λ1 in the pre-crisis regime and the partial Lyapunov exponent describing transient chaotic motions slightly above the crisis. For the latter case we give a quantitative description of the drastic increase of λ1. Moreover, a formula which connects the critical exponent of a chaotic transient above a boundary crisis with a pointwise dimension is derived.
Fast-responding property of electromagnetically induced transparency in Rydberg atoms
NASA Astrophysics Data System (ADS)
Zhang, Qi; Bai, Zhengyang; Huang, Guoxiang
2018-04-01
We investigate the transient optical response property of an electromagnetically induced transparency (EIT) in a cold Rydberg atomic gas. We show that both the transient behavior and the steady-state EIT spectrum of the system depend strongly on Rydberg interaction. Especially, the response speed of the Rydberg-EIT can be five times faster (and even higher) than the conventional EIT without the Rydberg interaction. For comparison, two different theoretical approaches (i.e., two-atom model and many-atom model) are considered, revealing that Rydberg blockade effect plays a significant role for increasing the response speed of the Rydberg-EIT. The fast-responding Rydberg-EIT by using the strong, tunable Rydberg interaction uncovered here is not only helpful for enhancing the understanding of the many-body dynamics of Rydberg atoms but also useful for practical applications in quantum information processing by using Rydberg atoms.
A numerical study of transient heat and mass transfer in crystal growth
NASA Technical Reports Server (NTRS)
Han, Samuel Bang-Moo
1987-01-01
A numerical analysis of transient heat and solute transport across a rectangular cavity is performed. Five nonlinear partial differential equations which govern the conservation of mass, momentum, energy and solute concentration related to crystal growth in solution, are simultaneously integrated by a numerical method based on the SIMPLE algorithm. Numerical results showed that the flow, temperature and solute fields are dependent on thermal and solutal Grashoff number, Prandtl number, Schmidt number and aspect ratio. The average Nusselt and Sherwood numbers evaluated at the center of the cavity decrease markedly when the solutal buoyancy force acts in the opposite direction to the thermal buoyancy force. When the solutal and thermal buoyancy forces act in the same direction, however, Sherwood number increases significantly and yet Nusselt number decreases. Overall effects of convection on the crystal growth are seen to be an enhancement of growth rate as expected but with highly nonuniform spatial growth variations.
Valentino, Francesco; Beccari, Mario; Villano, Marianna; Tandoi, Valter; Majone, Mauro
2017-05-25
A pure culture of the filamentous bacterium Thiothrix, strain CT3, was aerobically cultured in a chemostat under continuous acetate feeding at three different culture residence times (RT 6, 12 or 22 d) and the same volumetric organic load rate (OLR 0.12gCOD/L/d). Cells cultured at decreasing RT in the chemostat had an increasing transient response to acetate spikes in batch tests. The maximum specific acetate removal rate increased from 25 to 185mgCOD/gCOD/h, corresponding to a 1.8 to 8.1 fold higher respective steady-state rate in the chemostat. The transient response was mainly due to acetate storage in the form of poly(3-hydroxybutyrate) (PHB), whereas no growth response was observed at any RT. Interestingly, even though the storage rate also decreased as the RT increased, the storage yield increased from 0.41 to 0.50 COD/COD. This finding does not support the traditional view that storage plays a more important role as the transient response increases. The transient response of the steady-state cells was much lower than in cells cultured under periodic feeding (at 6 d RT, from 82 to 247mgCOD/gCOD/h), with the latter cells showing both storage and growth responses. On the other hand, even though steady-state cells had no growth response and their storage rate was also less, steady-state cells showed a higher storage yield than cells cultured under dynamic feeding. This suggests that in Thiothrix strain CT3, the growth response is triggered by periodic feeding, whereas the storage response is a constitutive mechanism, independent from previous acclimation to transient conditions. Copyright © 2016 Elsevier B.V. All rights reserved.
Arzola, Lucas; Chen, Junxing; Rattanaporn, Kittipong; Maclean, James M.; McDonald, Karen A.
2011-01-01
Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin), CMG2-Fc. This chimeric fusion protein, designed to protect against the deadly anthrax toxins, is composed of the von Willebrand factor A (VWA) domain of human capillary morphogenesis 2 (CMG2), an effective anthrax toxin receptor, and the Fc region of human immunoglobulin G (IgG). We evaluated, in N. benthamiana intact plants and detached leaves, the expression of CMG2-Fc under the control of the constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine different viral suppressors of post-transcriptional gene silencing (PTGS): p1, p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc expression was higher on intact plants than detached leaves. Maximum expression was observed with p1 co-expression at 3.5 days post-infiltration (DPI), with a level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble protein, a ten-fold increase in expression when compared to absence of suppression. Co-expression with the p25 PTGS suppressor also significantly increased the CMG2-Fc expression level after just 3.5 DPI. PMID:21954339
Transient ST segment depression during Holter monitoring: how to avoid false positive findings.
Völler, H; Andresen, D; Brüggemann, T; Jereczek, M; Becker, B; Schröder, R
1992-09-01
To increase the specificity of 24-hour Holter monitoring in detecting transient myocardial ischemia, we separated genuine ST deviations from those dependent on artifacts by adding a detailed shape analysis of real-time printouts to the usual criteria of significant ST segment depression. We screened 116 apparently healthy subjects; 31 had to be excluded, because of pathologic findings in preliminary examinations. The remaining 85 (49 women and 36 men; mean age, 43.1 years) underwent Holter monitoring for assessment of the extent, frequency, and duration of episodes of horizontal and descending ST segment depression of at least 0.1 mV that persisted for at least 60 msec after the J point and that were at least 1 minute apart. On the basis of these criteria, six subjects (7.1%) showed 24 episodes of horizontal or descending ST segment depression with a mean of 0.2 mV (range, 0.15 to 0.25 mV), a frequency of four episodes per 24 hours (one to nine), and a duration of 12.2 minutes (range 3-range 41 minutes). Supplementary criteria--e.g., sudden onset of ST segment depression, identical orientation of PQ and ST segments, or simultaneous increase in R and P wave amplitude--made it possible to identify ST changes caused by artifacts in four volunteers. In only two subjects (2.4%) could true silent ischemia not be differentiated from false positive results. Thus consideration of only the extent, frequency, and duration of episodes does not permit a differentiation between true silent ischemia and false positive results. A supplementary shape analysis increases the specificity of ST segment analysis in detecting transient myocardial ischemia during 24-hour Holter monitoring.
Buvinic, Sonja; Almarza, Gonzalo; Bustamante, Mario; Casas, Mariana; López, Javiera; Riquelme, Manuel; Sáez, Juan Carlos; Huidobro-Toro, Juan Pablo; Jaimovich, Enrique
2009-01-01
ATP released from cells is known to activate plasma membrane P2X (ionotropic) or P2Y (metabotropic) receptors. In skeletal muscle cells, depolarizing stimuli induce both a fast calcium signal associated with contraction and a slow signal that regulates gene expression. Here we show that nucleotides released to the extracellular medium by electrical stimulation are partly involved in the fast component and are largely responsible for the slow signals. In rat skeletal myotubes, a tetanic stimulus (45 Hz, 400 1-ms pulses) rapidly increased extracellular levels of ATP, ADP, and AMP after 15 s to 3 min. Exogenous ATP induced an increase in intracellular free Ca2+ concentration, with an EC50 value of 7.8 ± 3.1 μm. Exogenous ADP, UTP, and UDP also promoted calcium transients. Both fast and slow calcium signals evoked by tetanic stimulation were inhibited by either 100 μm suramin or 2 units/ml apyrase. Apyrase also reduced fast and slow calcium signals evoked by tetanus (45 Hz, 400 0.3-ms pulses) in isolated mouse adult skeletal fibers. A likely candidate for the ATP release pathway is the pannexin-1 hemichannel; its blockers inhibited both calcium transients and ATP release. The dihydropyridine receptor co-precipitated with both the P2Y2 receptor and pannexin-1. As reported previously for electrical stimulation, 500 μm ATP significantly increased mRNA expression for both c-fos and interleukin 6. Our results suggest that nucleotides released during skeletal muscle activity through pannexin-1 hemichannels act through P2X and P2Y receptors to modulate both Ca2+ homeostasis and muscle physiology. PMID:19822518
Saegusa, Noriko; Garg, Vivek
2013-01-01
The contribution of transient outward current (Ito) to changes in ventricular action potential (AP) repolarization induced by acidosis is unresolved, as is the indirect effect of these changes on calcium handling. To address this issue we measured intracellular pH (pHi), Ito, L-type calcium current (ICa,L), and calcium transients (CaTs) in rabbit ventricular myocytes. Intracellular acidosis [pHi 6.75 with extracellular pH (pHo) 7.4] reduced Ito by ∼50% in myocytes with both high (epicardial) and low (papillary muscle) Ito densities, with little effect on steady-state inactivation and activation. Of the two candidate α-subunits underlying Ito, human (h)Kv4.3 and hKv1.4, only hKv4.3 current was reduced by intracellular acidosis. Extracellular acidosis (pHo 6.5) shifted Ito inactivation toward less negative potentials but had negligible effect on peak current at +60 mV when initiated from −80 mV. The effects of low pHi-induced inhibition of Ito on AP repolarization were much greater in epicardial than papillary muscle myocytes and included slowing of phase 1, attenuation of the notch, and elevation of the plateau. Low pHi increased AP duration in both cell types, with the greatest lengthening occurring in epicardial myocytes. The changes in epicardial AP repolarization induced by intracellular acidosis reduced peak ICa,L, increased net calcium influx via ICa,L, and increased CaT amplitude. In summary, in contrast to low pHo, intracellular acidosis has a marked inhibitory effect on ventricular Ito, perhaps mediated by Kv4.3. By altering the trajectory of the AP repolarization, low pHi has a significant indirect effect on calcium handling, especially evident in epicardial cells. PMID:23585132
Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak
Sankaranarayanan, Rajiv; Li, Yatong; Greensmith, David J.; Eisner, David A.
2016-01-01
Key points Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay.In the presence of β‐adrenergic stimulation, RyR‐mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase.Two forms of Ca leak have been studied, Ca‐sensitising (induced by caffeine) and non‐sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient.Only Ca‐sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine.Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. Abstract In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca‐sensitising and non‐sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo‐3 in voltage‐clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non‐sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l−1) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the biphasic decay was replaced by slow decay. We conclude that, in the presence of adrenergic stimulation, Ca leak can produce biphasic decay; the slow phase results from the leak opposing Ca uptake by SERCA. The degree of leak determines whether decay of Ca waves, biphasic or monophasic, occurs. PMID:26537441
Aldosterone Upregulates Transient Receptor Potential Melastatin 7 (TRPM7)*
Valinsky, William C.; Jolly, Anna; Miquel, Perrine
2016-01-01
Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed Mg2+-permeable ion channel fused to a C-terminal α-kinase domain. Recently, aldosterone was shown to increase intracellular Mg2+ levels and alter inflammatory signaling in TRPM7-expressing HEK293 cells. This study was undertaken to assess whether these effects were related to an aldosterone-mediated increase of TRPM7 current and/or plasma membrane localization. Using HEK293 cells stably expressing WT-TRPM7, we found that 18-h application of aldosterone significantly increased TRPM7 current and TRPM7 plasma membrane protein expression by 48% and 34%, respectively. The aldosterone-mediated increase of TRPM7 current was inhibited by eplerenone, a mineralocorticoid receptor (MR) blocker, and GSK-650394, an inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1). SGK1 blockade also prevented the aldosterone-induced increase of TRPM7 plasma membrane protein. It was further determined that K1648R-TRPM7, the phosphotransferase-inactive TRPM7 mutant, was unresponsive to aldosterone. Therefore, chronic aldosterone treatment increases the plasma membrane expression of TRPM7, which is associated with an increase of TRPM7 current. This process occurs via an MR-dependent, genomic signaling cascade involving SGK1 and a functioning TRPM7 α-kinase domain. We suggest that this mechanism may be of general relevance when interpreting the effects of aldosterone because the MR receptor is found in multiple tissues, and TRPM7 and SGK1 are ubiquitously expressed. PMID:27466368
Coincidental match of numerical simulation and physics
NASA Astrophysics Data System (ADS)
Pierre, B.; Gudmundsson, J. S.
2010-08-01
Consequences of rapid pressure transients in pipelines range from increased fatigue to leakages and to complete ruptures of pipeline. Therefore, accurate predictions of rapid pressure transients in pipelines using numerical simulations are critical. State of the art modelling of pressure transient in general, and water hammer in particular include unsteady friction in addition to the steady frictional pressure drop, and numerical simulations rely on the method of characteristics. Comparison of rapid pressure transient calculations by the method of characteristics and a selected high resolution finite volume method highlights issues related to modelling of pressure waves and illustrates that matches between numerical simulations and physics are purely coincidental.
Design and calibration of a novel transient radiative heat flux meter for a spacecraft thermal test
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sheng, Chunchen; Hu, Peng, E-mail: hupeng@ustc.edu.cn; Cheng, Xiaofang
2016-06-15
Radiative heat flux measurement is significantly important for a spacecraft thermal test. To satisfy the requirements of both high accuracy and fast response, a novel transient radiative heat flux meter was developed. Its thermal receiver consists of a central thermal receiver and two thermal guarded annular plates, which ensure the temperature distribution of the central thermal receiver to be uniform enough for reasonably applying lumped heat capacity method in a transient radiative heat flux measurement. This novel transient radiative heat flux meter design can also take accurate measurements regardless of spacecraft surface temperature and incident radiation spectrum. The measurement principlemore » was elaborated and the coefficients were calibrated. Experimental results from testing a blackbody furnace and an Xenon lamp show that this novel transient radiative heat flux meter can be used to measure transient radiative heat flux up to 1400 W/m{sup 2} with high accuracy and the response time of less than 10 s.« less
Optimization of startup and shutdown operation of simulated moving bed chromatographic processes.
Li, Suzhou; Kawajiri, Yoshiaki; Raisch, Jörg; Seidel-Morgenstern, Andreas
2011-06-24
This paper presents new multistage optimal startup and shutdown strategies for simulated moving bed (SMB) chromatographic processes. The proposed concept allows to adjust transient operating conditions stage-wise, and provides capability to improve transient performance and to fulfill product quality specifications simultaneously. A specially tailored decomposition algorithm is developed to ensure computational tractability of the resulting dynamic optimization problems. By examining the transient operation of a literature separation example characterized by nonlinear competitive isotherm, the feasibility of the solution approach is demonstrated, and the performance of the conventional and multistage optimal transient regimes is evaluated systematically. The quantitative results clearly show that the optimal operating policies not only allow to significantly reduce both duration of the transient phase and desorbent consumption, but also enable on-spec production even during startup and shutdown periods. With the aid of the developed transient procedures, short-term separation campaigns with small batch sizes can be performed more flexibly and efficiently by SMB chromatography. Copyright © 2011 Elsevier B.V. All rights reserved.
Sensitivity analysis of reactive ecological dynamics.
Verdy, Ariane; Caswell, Hal
2008-08-01
Ecological systems with asymptotically stable equilibria may exhibit significant transient dynamics following perturbations. In some cases, these transient dynamics include the possibility of excursions away from the equilibrium before the eventual return; systems that exhibit such amplification of perturbations are called reactive. Reactivity is a common property of ecological systems, and the amplification can be large and long-lasting. The transient response of a reactive ecosystem depends on the parameters of the underlying model. To investigate this dependence, we develop sensitivity analyses for indices of transient dynamics (reactivity, the amplification envelope, and the optimal perturbation) in both continuous- and discrete-time models written in matrix form. The sensitivity calculations require expressions, some of them new, for the derivatives of equilibria, eigenvalues, singular values, and singular vectors, obtained using matrix calculus. Sensitivity analysis provides a quantitative framework for investigating the mechanisms leading to transient growth. We apply the methodology to a predator-prey model and a size-structured food web model. The results suggest predator-driven and prey-driven mechanisms for transient amplification resulting from multispecies interactions.
Mattos, A Z; Mattos, A A
Many different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. A systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. Eight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. In conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.
Production of high transient heat and particle fluxes in a linear plasma device
NASA Astrophysics Data System (ADS)
De Temmerman, G.; Zielinski, J. J.; van der Meiden, H.; Melissen, W.; Rapp, J.
2010-08-01
We report on the generation of high transient heat and particle fluxes in a linear plasma device by pulsed operation of the plasma source. A capacitor bank is discharged into the source to transiently increase the discharge current up to 1.7 kA, allowing peak densities and temperature of 70×1020 m-3 and 6 eV corresponding to a surface power density of about 400 MW m-2.
Impaired mitochondria and intracellular calcium transients in the salivary glands of obese rats.
Ittichaicharoen, Jitjiroj; Apaijai, Nattayaporn; Tanajak, Pongpan; Sa-Nguanmoo, Piangkwan; Chattipakorn, Nipon; Chattipakorn, Siriporn C
2017-04-01
Long-term consumption of a high-fat diet (HFD) causes not only obese-insulin resistance, but is also associated with mitochondrial dysfunction in several organs. However, the effect of obese-insulin resistance on salivary glands has not been investigated. We hypothesized that obese-insulin resistance induced by HFD impaired salivary gland function by reducing salivation, increasing inflammation, and fibrosis, as well as impairing mitochondrial function and calcium transient signaling. Male Wistar rats (200-220 g) were fed either a ND or an HFD (n = 8/group) for 16 weeks. At the end of week 16, salivary flow rates, metabolic parameters, and plasma oxidative stress were determined. Rats were then sacrificed and submandibular glands were removed to determine inflammation, fibrosis, apoptosis, mitochondrial function and dynamics, and intracellular calcium transient signaling. Long-term consumption of an HFD caused obese-insulin resistance and increased oxidative stress, fibrosis, inflammation, and apoptosis in the salivary glands. In addition, impaired mitochondrial function, as indicated by increased mitochondrial reactive oxygen species, mitochondrial membrane depolarization, and mitochondrial swelling in salivary glands and impaired intracellular calcium regulation, as indicated by a reduced intracellular calcium transient rising rate, decay rates, and amplitude of salivary acinar cells, were observed in HFD-fed rats. However, salivary flow rate and level of aquaporin 5 protein were not different between both groups. Although HFD consumption did not affect salivation, it caused obese-insulin resistance, leading to pathophysiological alteration of salivary glands, including impaired intracellular calcium transients, increased oxidative stress and inflammation, and salivary mitochondrial dysfunction.
Jin, Jinshan; Guo, Lei; VonTungeln, Linda; Vanlandingham, Michelle; Cerniglia, Carl E; Chen, Huizhong
2018-05-28
The use of smokeless tobacco products (STPs) can cause many serious health problems. The oral microbiota plays important roles in oral and systemic health, and the disruption in the oral microbial population is linked to periodontal disease and other health problems. To assess the impact of smokeless tobacco on oral microbiota in vivo, high-throughput sequencing was used to examine the oral microbiota present in Syrian Golden hamster cheek pouches. Sixteen hamsters were divided into four groups and treated with the STP Grizzly snuff (0, 2.5, 25, or 250 mg) twice daily for 4 weeks. After 0, 1, 2, 3, and 4 weeks of treatment, bacterial genomic DNA was extracted from oral swabs sampled from the cheek pouches of the hamsters. The oral bacterial communities present in different hamster groups were characterized by sequencing the hypervariable regions V1-V2 and V4 of 16S rRNA using the Illumina MiSeq platform. Fifteen phyla, 27 classes, 59 orders, 123 families, and 250 genera were identified from 4,962,673 sequence reads from the cheek pouch samples. The bacterial diversity and taxonomic abundances for the different treatment groups were compared to the non-treated hamsters. Bacterial diversity was significantly decreased after 4 weeks of exposure to 2.5 mg, and significantly increased by exposure to 250 mg STP. Treatment with 250 mg STP significantly increased Firmicutes, transiently increased Cyanobacteria and TM7, and decreased Bacteroidetes and Fusobacteria compared to the control group. At the genus level, 4 weeks of administration of 250 mg STP significantly increased Granulicatella, Streptococcus, Oribacterium, Anaerococcus, Acidaminococcus, Actinomyces, Eubacterium, Negativicoccus, and Staphylococcus, and decreased Bacteroides, Buleidia, Dialister, and Leptotrichia, and transiently decreased Arcanobacterium compared to the control group. For the first time, an animal model was used for evaluating the effects of STP on oral microbiota by metagenomic sequencing. Our results provide a view of the shift of the oral microbiota in response to STP exposure in Syrian Golden hamster. Our findings indicate that the use of smokeless tobacco significantly disrupts the oral microbiota. Published by Elsevier Ltd.
Saffer, D.M.; Bekins, B.A.
1998-01-01
Down-hole geochemical anomalies encountered in active accretionary systems can be used to constrain the timing, rates, and localization of fluid flow. Here we combine a coupled flow and solute transport model with a kinetic model for smectite dehydration to better understand and quantify fluid flow in the Nankai accretionary complex offshore of Japan. Compaction of sediments and clay dehydration provide fluid sources which drive the model flow system. We explicitly include the consolidation rate of underthrust sediments in our calculations to evaluate the impact that variations in this unknown quantity have on pressure and chloride distribution. Sensitivity analysis of steady state pressure solutions constrains bulk and flow conduit permeabilities. Steady state simulations with 30% smectite in the incoming sedimentary sequence result in minimum chloride concentrations at site 808 of 550 mM, but measured chlorinity is as low as 447 mM. We simulate the transient effects of hydrofracture or a strain event by assuming an instantaneous permeability increase of 3-4 orders of magnitude along a flow conduit (in this case the de??collement), using steady state results as initial conditions. Transient results with an increase in de??collement permeability from 10-16 m2 to 10-13 m2 and 20% smectite reproduce the observed chloride profile at site 808 after 80-160 kyr. Modeled chloride concentrations are highly sensitive to the consolidation rate of underthrust sediments, such that rapid compaction of underthrust material leads to increased freshening. Pressures within the de??collement during transient simulations rise rapidly to a significant fraction of lithostatic and remain high for at least 160 kyr, providing a mechanism for maintaining high permeability. Flow rates at the deformation front for transient simulations are in good agreement with direct measurements, but steady state flow rates are 2-3 orders of magnitude smaller than observed. Fluid budget calculations indicate that nearly 71% of the incoming water in the sediments leaves the accretionary wedge via diffuse flow out the seafloor, 0-5% escapes by focused flow along the de??collement, and roughly 1% is subducted. Copyright 1998 by the American Geophysical Union.
Long, S Alice; Rieck, Mary; Sanda, Srinath; Bollyky, Jennifer B; Samuels, Peter L; Goland, Robin; Ahmann, Andrew; Rabinovitch, Alex; Aggarwal, Sudeepta; Phippard, Deborah; Turka, Laurence A; Ehlers, Mario R; Bianchine, Peter J; Boyle, Karen D; Adah, Steven A; Bluestone, Jeffrey A; Buckner, Jane H; Greenbaum, Carla J
2012-09-01
Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy.
Tong, Jie; Sun, Lijun; Zhu, Bin; Fan, Yun; Ma, Xingfeng; Yu, Liyin; Zhang, Jianbao
2017-10-01
Pulsed electromagnetic fields (PEMF) can be used to treat bone-related diseases, but the underlying mechanism remains unclear, especially the process by which PEMFs initiate biological effects. In this study, we demonstrated the effects of PEMF on proliferation and differentiation of osteoblasts using the model of calcium transients induced by high extracellular calcium. Our results showed that PEMF can increase both the percentage of responding cells and amplitude of intracellular calcium transients induced by high extracellular calcium stimulation. Compared with corresponding extracellular calcium levels, PEMF stimulation increased proliferation and differentiation of osteoblasts and related gene expressions, such as insulin-like growth factor 1 (IGF-1), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), which can be completely abolished by BAPTA-AM. Moreover, PEMF did not affect proliferation and differentiation of osteoblasts if no intracellular calcium transient was present in osteoblasts during PEMF exposure. Our results revealed that PEMF affects osteoblast proliferation and differentiation through enhanced intracellular calcium transients, which provided a cue to treat bone-related diseases with PEMF. Bioelectromagnetics. 38:541-549, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Suslova, A.; El-Atwani, O.; Sagapuram, D.; Harilal, S. S.; Hassanein, A.
2014-11-01
Tungsten has been chosen as the main candidate for plasma facing components (PFCs) due to its superior properties under extreme operating conditions in future nuclear fusion reactors such as ITER. One of the serious issues for PFCs is the high heat load during transient events such as ELMs and disruption in the reactor. Recrystallization and grain size growth in PFC materials caused by transients are undesirable changes in the material, since the isotropic microstructure developed after recrystallization exhibits a higher ductile-to-brittle transition temperature which increases with the grain size, a lower thermal shock fatigue resistance, a lower mechanical strength, and an increased surface roughening. The current work was focused on careful determination of the threshold parameters for surface recrystallization, grain growth rate, and thermal shock fatigue resistance under ELM-like transient heat events. Transient heat loads were simulated using long pulse laser beams for two different grades of ultrafine-grained tungsten. It was observed that cold rolled tungsten demonstrated better power handling capabilities and higher thermal stress fatigue resistance compared to severely deformed tungsten. Higher recrystallization threshold, slower grain growth, and lower degree of surface roughening were observed in the cold rolled tungsten.
The SED Machine: A Robotic Spectrograph for Fast Transient Classification
NASA Astrophysics Data System (ADS)
Blagorodnova, Nadejda; Neill, James D.; Walters, Richard; Kulkarni, Shrinivas R.; Fremling, Christoffer; Ben-Ami, Sagi; Dekany, Richard G.; Fucik, Jason R.; Konidaris, Nick; Nash, Reston; Ngeow, Chow-Choong; Ofek, Eran O.; O’ Sullivan, Donal; Quimby, Robert; Ritter, Andreas; Vyhmeister, Karl E.
2018-03-01
Current time domain facilities are finding several hundreds of transient astronomical events a year. The discovery rate is expected to increase in the future as soon as new surveys such as the Zwicky Transient Facility (ZTF) and the Large Synoptic Sky Survey (LSST) come online. Presently, the rate at which transients are classified is approximately one order or magnitude lower than the discovery rate, leading to an increasing “follow-up drought”. Existing telescopes with moderate aperture can help address this deficit when equipped with spectrographs optimized for spectral classification. Here, we provide an overview of the design, operations and first results of the Spectral Energy Distribution Machine (SEDM), operating on the Palomar 60-inch telescope (P60). The instrument is optimized for classification and high observing efficiency. It combines a low-resolution (R ∼ 100) integral field unit (IFU) spectrograph with “Rainbow Camera” (RC), a multi-band field acquisition camera which also serves as multi-band (ugri) photometer. The SEDM was commissioned during the operation of the intermediate Palomar Transient Factory (iPTF) and has already lived up to its promise. The success of the SEDM demonstrates the value of spectrographs optimized for spectral classification.
Suslova, A.; El-Atwani, O.; Sagapuram, D.; Harilal, S. S.; Hassanein, A.
2014-01-01
Tungsten has been chosen as the main candidate for plasma facing components (PFCs) due to its superior properties under extreme operating conditions in future nuclear fusion reactors such as ITER. One of the serious issues for PFCs is the high heat load during transient events such as ELMs and disruption in the reactor. Recrystallization and grain size growth in PFC materials caused by transients are undesirable changes in the material, since the isotropic microstructure developed after recrystallization exhibits a higher ductile-to-brittle transition temperature which increases with the grain size, a lower thermal shock fatigue resistance, a lower mechanical strength, and an increased surface roughening. The current work was focused on careful determination of the threshold parameters for surface recrystallization, grain growth rate, and thermal shock fatigue resistance under ELM-like transient heat events. Transient heat loads were simulated using long pulse laser beams for two different grades of ultrafine-grained tungsten. It was observed that cold rolled tungsten demonstrated better power handling capabilities and higher thermal stress fatigue resistance compared to severely deformed tungsten. Higher recrystallization threshold, slower grain growth, and lower degree of surface roughening were observed in the cold rolled tungsten. PMID:25366885
Suslova, A; El-Atwani, O; Sagapuram, D; Harilal, S S; Hassanein, A
2014-11-04
Tungsten has been chosen as the main candidate for plasma facing components (PFCs) due to its superior properties under extreme operating conditions in future nuclear fusion reactors such as ITER. One of the serious issues for PFCs is the high heat load during transient events such as ELMs and disruption in the reactor. Recrystallization and grain size growth in PFC materials caused by transients are undesirable changes in the material, since the isotropic microstructure developed after recrystallization exhibits a higher ductile-to-brittle transition temperature which increases with the grain size, a lower thermal shock fatigue resistance, a lower mechanical strength, and an increased surface roughening. The current work was focused on careful determination of the threshold parameters for surface recrystallization, grain growth rate, and thermal shock fatigue resistance under ELM-like transient heat events. Transient heat loads were simulated using long pulse laser beams for two different grades of ultrafine-grained tungsten. It was observed that cold rolled tungsten demonstrated better power handling capabilities and higher thermal stress fatigue resistance compared to severely deformed tungsten. Higher recrystallization threshold, slower grain growth, and lower degree of surface roughening were observed in the cold rolled tungsten.
Single event induced transients in I/O devices - A characterization
NASA Technical Reports Server (NTRS)
Newberry, D. M.; Kaye, D. H.; Soli, G. A.
1990-01-01
The results of single-event upset (SEU) testing performed to evaluate the parametric transients, i.e., amplitude and duration, in several I/O devices, and the impact of these transients are discussed. The failure rate of these devices is dependent on the susceptibility of interconnected devices to the resulting transient change in the output of the I/O device. This failure rate, which is a function of the susceptibility of the interconnected device as well as the SEU response of the I/O device itself, may be significantly different from an upset rate calculated without taking these factors into account. The impact at the system level is discussed by way of an example.
Zhao, Jun Hui; Thomson, Douglas J; Pilapil, Matt; Pillai, Rajesh G; Rahman, G M Aminur; Freund, Michael S
2010-04-02
Dynamic resistive memory devices based on a conjugated polymer composite (PPy(0)DBS(-)Li(+) (PPy: polypyrrole; DBS(-): dodecylbenzenesulfonate)), with field-driven ion migration, have been demonstrated. In this work the dynamics of these systems has been investigated and it has been concluded that increasing the applied field can dramatically increase the rate at which information can be 'written' into these devices. A conductance model using space charge limited current coupled with an electric field induced ion reconfiguration has been successfully utilized to interpret the experimentally observed transient conducting behaviors. The memory devices use the rising and falling transient current states for the storage of digital states. The magnitude of these transient currents is controlled by the magnitude and width of the write/read pulse. For the 500 nm length devices used in this work an increase in 'write' potential from 2.5 to 5.5 V decreased the time required to create a transient conductance state that can be converted into the digital signal by 50 times. This work suggests that the scaling of these devices will be favorable and that 'write' times for the conjugated polymer composite memory devices will decrease rapidly as ion driving fields increase with decreasing device size.
Tuor, Ursula I; Qiao, Min
2017-04-01
To determine whether cumulative brain damage produced adjacent to a minor stroke that is followed by a mild transient ischemia is detectable with MRI and histology, and whether acute or chronic recovery between insults influences this damage. A minor photothrombotic (PT) stroke was followed acutely (1-2 days) or chronically (7 days) by a mild transient middle cerebral artery occlusion (tMCAO). MRI was performed after each insult, followed by final histology. The initial PT produced small hyperintense T 2 and DW infarct lesions and peri-lesion regions of scattered necrosis and modestly increased T 2 . Following tMCAO, in a slice and a region adjacent to the PT, a region of T 2 augmentation was observed when recovery between insults was acute but not chronic. Within the PT slice, a modest region of exacerbated T 2 change proximate to the PT was also observed in the chronic group. Corresponding histological changes within regions of augmented T 2 included increased vacuolation and cell death. Within regions adjacent to an experimental minor stroke, a recurrence of a mild transient cerebral ischemia augmented T 2 above increases produced by tMCAO alone, reflecting increased damage in this region. Exacerbation appeared broader with acute versus chronic recovery between insults.
Effects of urban stream burial on nitrogen uptake and ...
Urbanization has resulted in extensive burial and channelization of headwater streams, yet little is known about impacts on stream ecosystem functions critical for reducing downstream nitrogen pollution. To characterize the biogeochemical impact of stream burial, we measured NO3- uptake, using 15N-NO3- isotope tracer releases, and whole stream metabolism, during four seasons in three paired buried and open streams reaches within the Baltimore Ecosystem Study Long-term Ecological Research Network. Stream burial increased NO3- uptake lengths, by a factor of 7.5 (p < 0.01) and decreased nitrate uptake velocity and areal nitrate uptake rate by factors of 8.2 (p = 0.01) and 9.6 (p < 0.001), respectively. Stream burial decreased gross primary productivity by a factor of 9.2 (p < 0.05) and decreased ecosystem respiration by a factor of 4.2 (p = 0.06). From statistical analysis of Excitation Emissions Matrices (EEMs), buried streams were also found to have significantly less labile dissolved organic matter. Furthermore, buried streams had significantly lower transient storage and water temperatures. Overall, differences in NO3- uptake and metabolism were primarily explained by decreased transient storage and light availability in buried streams. We estimate that stream burial increases daily watershed nitrate export by as much as 500% due to decreased in-stream retention and may considerably decrease carbon export via decreased primary production. These results
Silva, Darizy Flavia; de Almeida, Monica Moura; Chaves, Cinthia Guedes; Braz, Ana Letícia; Gomes, Maria Aparecida; Pinho-da-Silva, Leidiane; Pesquero, Jorge Luiz; Andrade, Viviane Aguiar; Leite, Maria de Fátima; de Albuquerque, José George Ferreira; Araujo, Islania Giselia Albuquerque; Nunes, Xirley Pereira; Barbosa-Filho, José Maria; Cruz, Jader dos Santos; Correia, Nadja de Azevedo; de Medeiros, Isac Almeida
2015-01-01
In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the understanding of the role of these thermosensitive TRP channels in vascular tissue. Thus, message and protein levels of TRPM8 were measured by semi-quantitative PCR and western blotting in superior mesenteric arteries from 12 week-old Spague-Dawley (SD) rats. Isometric tension recordings evaluated the relaxant response in mesenteric rings were also performed. Additionally, the intracellular Ca2+ changes in mesenteric artery myocytes were measured using confocal microscopy. Using PCR and western blotting, both TRPM8 channel mRNA and protein expression was measured in SD rat mesenteric artery. Rotundifolone and menthol induced relaxation in the isolated superior mesenteric artery from SD rats and improved the relaxant response induced by cool temperatures. Also, this monoterpene induced an increase in transient intracellular Ca2+. These responses were significantly attenuated by pretreatment with capsazepine or BCTC, both TRPM8 channels blockers. The response induced by rotundifolone was not significantly attenuated by ruthenium red, a non-selective TRP channels blocker, or following capsaicin-mediated desensitization of TRPV1. Our findings suggest that rotundifolone induces relaxation by activating TRPM8 channels in rat superior mesenteric artery, more selectively than menthol, the classic TRPM8 agonist, and TRPM8 channels participates in vasodilatory pathways in isolated rat mesenteric arteries.
NASA Astrophysics Data System (ADS)
Zhang, H.; Yu, W.
2015-08-01
Episodic jets are usually observed in the intermediate state of black hole transients during their X-ray outbursts. Here we report the discovery of a strong positive correlation between the peak radio power of the episodic jet Pjet and the corresponding peak X-ray luminosity Lx of the soft state (in Eddington units) in a complete sample of the outbursts of black hole transients observed during the RXTE era of which data are available, which follows the relation log Pjet = (2.2 ± 0.3) + (1.6 ± 0.2) × log Lx. The transient ultraluminous X-ray source in M31 and HLX-1 in EXO 243-49 fall on the relation if they contain stellar-mass black hole and either stellar-mass black hole or intermediate-mass black hole, respectively. Besides, a significant correlation between the peak power of the episodic jet and the rate of increase of the X-ray luminosity dLx/dt during the rising phase of those outbursts is also found, following log Pjet = (2.0 ± 0.4) + (0.7 ± 0.2) × log dLx/dt. In GX 339-4 and H 1743-322 in which data for two outbursts are available, measurements of the peak radio power of the episodic jet and the X-ray peak luminosity (and its rate of change) shows similar positive correlations between outbursts, which demonstrate the dominant role of accretion over black hole spin in generating episodic jet power. On the other hand, no significant difference is seen among the systems with different measured black hole spin in current sample. This implies that the power of the episodic jet is strongly affected by non-stationary accretion instead of black hole spin characterized primarily by the rate of change of the mass accretion rate.
Prior, Peter L; Hachinski, Vladimir; Unsworth, Karen; Chan, Richard; Mytka, Sharon; O'Callaghan, Christina; Suskin, Neville
2011-11-01
Comprehensive cardiac rehabilitation (CCR), which integrates structured lifestyle interventions and medications, reduces morbidity and mortality among cardiac patients. CCR has not typically been used with cerebrovascular populations, despite important commonalities with heart patients. We tested feasibility and effectiveness of 6-month outpatient CCR for secondary prevention after transient ischemic attack or mild, nondisabling stroke. This article presents risk factors. A future article will discuss psychological outcomes. Consecutive consenting subjects having sustained a transient ischemic attack or mild, nondisabling stroke within the previous 12 months (mean, 11.5 weeks; event-to-CCR entry) with ≥1 vascular risk factor, were recruited from a stroke prevention clinic providing usual care. We measured 6-month CCR outcomes following a prospective cohort design. Of 110 subjects recruited from January 2005 to April 2006, 100 subjects (mean age, 64.9 years; 46 women) entered and 80 subjects completed CCR. We obtained favorable, significant intake-to-exit changes in: aerobic capacity (+31.4%; P<0.001), total cholesterol (-0.30 mmol/L; P=0.008), total cholesterol/high-density lipoprotein (-11.6%; P<0.001), triglycerides (-0.27 mmol/L; P=0.003), waist circumference (-2.44 cm; P<0.001), body mass index (-0.53 kg/m(2); P=0.003), and body weight (-1.43 kg; P=0.001). Low-density lipoprotein (-0.24 mmol/L), high-density lipoprotein (+0.06 mmol/L), systolic (-3.21 mm Hg) and diastolic (-2.34 mm Hg) blood pressure changed favorably, but nonsignificantly. A significant shift toward nonsmoking occurred (P=0.008). Compared with intake, 11 more individuals (25.6% increase) finished CCR in the lowest-mortality risk category of the Duke Treadmill Score (P<0.001). CCR is feasible and effective for secondary prevention after transient ischemic attack or mild, nondisabling stroke, offering a promising model for vascular protection across chronic disease entities. We know of no similar previous investigation, and are now conducting a randomized trial.
Viscoelasticity, postseismic slip, fault interactions, and the recurrence of large earthquakes
Michael, A.J.
2005-01-01
The Brownian Passage Time (BPT) model for earthquake recurrence is modified to include transient deformation due to either viscoelasticity or deep post seismic slip. Both of these processes act to increase the rate of loading on the seismogenic fault for some time after a large event. To approximate these effects, a decaying exponential term is added to the BPT model's uniform loading term. The resulting interevent time distributions remain approximately lognormal, but the balance between the level of noise (e.g., unknown fault interactions) and the coefficient of variability of the interevent time distribution changes depending on the shape of the loading function. For a given level of noise in the loading process, transient deformation has the effect of increasing the coefficient of variability of earthquake interevent times. Conversely, the level of noise needed to achieve a given level of variability is reduced when transient deformation is included. Using less noise would then increase the effect of known fault interactions modeled as stress or strain steps because they would be larger with respect to the noise. If we only seek to estimate the shape of the interevent time distribution from observed earthquake occurrences, then the use of a transient deformation model will not dramatically change the results of a probability study because a similar shaped distribution can be achieved with either uniform or transient loading functions. However, if the goal is to estimate earthquake probabilities based on our increasing understanding of the seismogenic process, including earthquake interactions, then including transient deformation is important to obtain accurate results. For example, a loading curve based on the 1906 earthquake, paleoseismic observations of prior events, and observations of recent deformation in the San Francisco Bay region produces a 40% greater variability in earthquake recurrence than a uniform loading model with the same noise level.
Sodium entry through endothelial store-operated calcium entry channels: regulation by Orai1
Xu, Ningyong; Cioffi, Donna L.; Alexeyev, Mikhail; Rich, Thomas C.
2014-01-01
Orai1 interacts with transient receptor potential protein of the canonical subfamily (TRPC4) and contributes to calcium selectivity of the endothelial cell store-operated calcium entry current (ISOC). Orai1 silencing increases sodium permeability and decreases membrane-associated calcium, although it is not known whether Orai1 is an important determinant of cytosolic sodium transitions. We test the hypothesis that, upon activation of store-operated calcium entry channels, Orai1 is a critical determinant of cytosolic sodium transitions. Activation of store-operated calcium entry channels transiently increased cytosolic calcium and sodium, characteristic of release from an intracellular store. The sodium response occurred more abruptly and returned to baseline more rapidly than did the transient calcium rise. Extracellular choline substitution for sodium did not inhibit the response, although 2-aminoethoxydiphenyl borate and YM-58483 reduced it by ∼50%. After this transient response, cytosolic sodium continued to increase due to influx through activated store-operated calcium entry channels. The magnitude of this sustained increase in cytosolic sodium was greater when experiments were conducted in low extracellular calcium and when Orai1 expression was silenced; these two interventions were not additive, suggesting a common mechanism. 2-Aminoethoxydiphenyl borate and YM-58483 inhibited the sustained increase in cytosolic sodium, only in the presence of Orai1. These studies demonstrate that sodium permeates activated store-operated calcium entry channels, resulting in an increase in cytosolic sodium; the magnitude of this response is determined by Orai1. PMID:25428882
Fang, Shona C; Rosen, Raymond C; Vita, Joseph A; Ganz, Peter; Kupelian, Varant
2015-01-01
Erectile dysfunction (ED) is associated with cardiovascular disease (CVD); however, the association between change in ED status over time and future underlying CVD risk is unclear. The aim of this study was to investigate the association between change in ED status and Framingham CVD risk, as well change in Framingham risk. We studied 965 men free of CVD in the Boston Area Community Health (BACH) Survey, a longitudinal cohort study with three assessments. ED was assessed with the five-item International Index of Erectile Function at BACH I (2002-2005) and BACH II (2007-2010) and classified as no ED/transient ED/persistent ED. CVD risk was assessed with 10-year Framingham CVD risk algorithm at BACH I and BACH III (2010-2012). Linear regression models controlled for baseline age, socio-demographic and lifestyle factors, as well as baseline Framingham risk. Models were also stratified by age (≥/< 50 years). Framingham CVD risk and change in Framingham CVD risk were the main outcome measures. Transient and persistent ED was significantly associated with increased Framingham risk and change in risk over time in univariate and age-adjusted models. In younger men, persistent ED was associated with a Framingham risk that was 1.58 percentage points higher (95% confidence interval [CI]: 0.11, 3.06) and in older men, a Framingham risk that was 2.54 percentage points higher (95% CI: -1.5, 6.59), compared with those without ED. Change in Framingham risk over time was also associated with transient and persistent ED in men <50 years, but not in older men. Data suggest that even after taking into account other CVD risk factors, transient and persistent ED is associated with Framingham CVD risk and a greater increase in Framingham risk over time, particularly in younger men. Findings further support clinical assessment of CVD risk in men presenting with ED, especially those under 50 years. © 2014 International Society for Sexual Medicine.
Transient cerebral hypoperfusion assisted intraarterial cationic liposome delivery to brain tissue
Joshi, Shailendra; Singh-Moon, Rajinder P.; Wang, Mei; Chaudhuri, Durba B.; Holcomb, Mark; Straubinger, Ninfa L.; Bruce, Jeffrey N.; Bigio, Irving J.; Straubinger, Robert M.
2014-01-01
Object Transient cerebral hypoperfusion (TCH) has empirically been used to assist intraarterial (IA) drug delivery to brain tumors. Transient (< 3 min) reduction of cerebral blood flow (CBF) occurs during many neuro- and cardiovascular interventions and has recently been used to better target IA drugs to brain tumors. In the present experiments, we assessed whether the effectiveness of IA delivery of cationic liposomes could be improved by TCH. Methods Cationic liposomes composed of 1:1 DOTAP:PC (dioleoyl-trimethylammonium-propane:phosphatidylcholine) were administered to three groups of Sprague Dawley rats. In the first group, we tested the effect of blood flow reduction on IA delivery of cationic liposomes. In the second group, we compared TCH-assisted IA liposomal delivery vs. intravenous (IV) administration of the same dose. In the third group, we assessed retention of cationic liposomes in brain four hours after TCH assisted delivery. The liposomes contained a near infrared dye, DilC18(7), whose concentration could be measured in vivo by diffuse reflectance spectroscopy. Results IA injections of cationic liposomes during TCH increased their delivery approximately four-fold compared to injections during normal blood flow. Optical pharmacokinetic measurements revealed that relative to IV injections, IA injection of cationic liposomes during TCH produced tissue concentrations that were 100-fold greater. The cationic liposomes were retained in the brain tissue four hours after a single IA injection. There was no gross impairment of neurological functions in surviving animals. Conclusions Transient reduction in CBF significantly increased IA delivery of cationic liposomes in the brain. High concentrations of liposomes could be delivered to brain tissue after IA injections with concurrent TCH while none could be detected after IV injection. IA-TCH injections were well tolerated and cationic liposomes were retained for at least 4 hours after IA administration. These results should encourage development of cationic liposomal formulations of chemotherapeutic drugs and their IA delivery during TCH. PMID:24664370
Predicting permanent and transient protein-protein interfaces.
La, David; Kong, Misun; Hoffman, William; Choi, Youn Im; Kihara, Daisuke
2013-05-01
Protein-protein interactions (PPIs) are involved in diverse functions in a cell. To optimize functional roles of interactions, proteins interact with a spectrum of binding affinities. Interactions are conventionally classified into permanent and transient, where the former denotes tight binding between proteins that result in strong complexes, whereas the latter compose of relatively weak interactions that can dissociate after binding to regulate functional activity at specific time point. Knowing the type of interactions has significant implications for understanding the nature and function of PPIs. In this study, we constructed amino acid substitution models that capture mutation patterns at permanent and transient type of protein interfaces, which were found to be different with statistical significance. Using the substitution models, we developed a novel computational method that predicts permanent and transient protein binding interfaces (PBIs) in protein surfaces. Without knowledge of the interacting partner, the method uses a single query protein structure and a multiple sequence alignment of the sequence family. Using a large dataset of permanent and transient proteins, we show that our method, BindML+, performs very well in protein interface classification. A very high area under the curve (AUC) value of 0.957 was observed when predicted protein binding sites were classified. Remarkably, near prefect accuracy was achieved with an AUC of 0.991 when actual binding sites were classified. The developed method will be also useful for protein design of permanent and transient PBIs. Copyright © 2013 Wiley Periodicals, Inc.
Abnormal Transient Pupillary Light Reflex in Individuals with Autism Spectrum Disorders
ERIC Educational Resources Information Center
Fan, Xiaofei; Miles, Judith H.; Takahashi, Nicole; Yao, Gang
2009-01-01
Computerized binocular infrared pupillography was used to measure the transient pupillary light reflex (PLR) in both children with autism spectrum disorders (ASDs) and children with typical development. We found that participants with ASDs showed significantly longer PLR latency, smaller constriction amplitude and lower constriction velocity than…
Systemic effects of an intraosseous injection of 2% lidocaine with 1:100,000 epinephrine.
Chamberlain, T M; Davis, R D; Murchison, D F; Hansen, S R; Richardson, B W
2000-01-01
The effect of a mandibular intraosseous injection of 2% lidocaine with 1:100,000 epinephrine on the heart rate and blood pressure of 20 volunteer patients was examined. Changes in blood pressure from preoperative levels were minimal and did not vary significantly at any time of measurement. The only statistically significant change in heart rate occurred immediately after the intraosseous injection (an increase of 12 beats per minute). In young healthy adults, the intraosseous injection of 1.5 mL of 2% lidocaine with 1:100,000 epinephrine resulted in a slight transient elevation in heart rate but had no significant effect on systolic or diastolic blood pressure.
Analysis of Spontaneous and Nerve-Evoked Calcium Transients in Intact Extraocular Muscles in Vitro
Feng, Cheng-Yuan; Hennig, Grant W.; Corrigan, Robert D.; Smith, Terence K.; von Bartheld, Christopher S.
2012-01-01
Extraocular muscles (EOMs) have unique calcium handling properties, yet little is known about the dynamics of calcium events underlying ultrafast and tonic contractions in myofibers of intact EOMs. Superior oblique EOMs of juvenile chickens were dissected with their nerve attached, maintained in oxygenated Krebs buffer, and loaded with fluo-4. Spontaneous and nerve stimulation-evoked calcium transients were recorded and, following calcium imaging, some EOMs were double-labeled with rhodamine-conjugated alpha-bungarotoxin (rhBTX) to identify EOM myofiber types. EOMs showed two main types of spontaneous calcium transients, one slow type (calcium waves with 1/2max duration of 2–12 s, velocity of 25–50 μm/s) and two fast “flash-like” types (Type 1, 30–90 ms; Type 2, 90–150 ms 1/2max duration). Single pulse nerve stimulation evoked fast calcium transients identical to the fast (Type 1) calcium transients. Calcium waves were accompanied by a local myofiber contraction that followed the calcium transient wavefront. The magnitude of calcium-wave induced myofiber contraction far exceeded those of movement induced by nerve stimulation and associated fast calcium transients. Tetrodotoxin eliminated nerve-evoked transients, but not spontaneous transients. Alpha-bungarotoxin eliminated both spontaneous and nerve-evoked fast calcium transients, but not calcium waves, and caffeine increased wave activity. Calcium waves were observed in myofibers lacking spontaneous or evoked fast transients, suggestive of multiply-innervated myofibers, and this was confirmed by double-labeling with rhBTX. We propose that the abundant spontaneous calcium transients and calcium waves with localized contractions that do not depend on innervation may contribute to intrinsic generation of tonic functions of EOMs. PMID:22579493
Xu, Qinyu; Sheng, Li; Bao, Han; Chen, Xiaoyu; Guo, Canjie; Li, Hai; Ma, Xiong; Qiu, Dekai; Hua, Jing
2017-03-01
Transient elastography (TE) can reliably stage liver fibrosis via liver stiffness measurement (LSM) in chronic liver disease. However, the accuracy of TE for assessment of liver fibrosis in patients with autoimmune hepatitis (AIH) is still limited. We evaluate TE in staging liver fibrosis in AIH patients and compare with other noninvasive diagnostic tools. A total of 100 patients with biopsy-proven AIH were included. The correlation between LSM and fibrosis stage was analyzed using Spearman correlation test. The optimal cut-off values of LSM were calculated for predicting individual fibrosis stages using receiver-operating characteristic curve. The diagnostic accuracy of LSM for severe fibrosis was compared with those of serum biochemical scores. Median LSM in AIH patients was higher than that of healthy controls (11.2 ± 8.2 kPa vs 4.3 ± 1.4 kPa, P < 0.01). LSM had significant correlation with fibrosis (r = 0.752, P < 0.01) and increased progressively with increasing fibrosis stages in AIH patients. AUROC values of LSM for stages F ≥ 2, F ≥ 3, and F4 were 0.878 (95%CI: 0.789-0.967), 0.883 (0.820-0.946), and 0.914 (0.852-0.976), respectively. The optimal cut-off values of LSM for fibrosis stages F ≥ 2, F ≥ 3, and F4 were 6.45, 8.75, and 12.50 kPa, respectively. LSM was superior to APRI score and FIB-4 score in detecting severe fibrosis (F ≥ 3). Serum ALT levels had minor effect on LSM values. Transient elastography is an accurate and reliable noninvasive tool in assessing liver fibrosis in AIH. Hepatic inflammatory activity had no significant effect on LSM determination. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
The Effects of Space Radiation on Linear Integrated Circuit
NASA Technical Reports Server (NTRS)
Johnston, A.
2000-01-01
Permanent and transient effects are discussed that are induced in linear integrated circuits by space radiation. Recent developments include enhanced damage at low dose rate, increased damage from protons due to displacement effects, and transients in digital comparators that can cause circuit malfunctions.
Transient analysis of a solid oxide fuel cell stack with crossflow configuration
NASA Astrophysics Data System (ADS)
Yuan, P.; Liu, S. F.
2018-05-01
This study investigates the transient response of the cell temperature and current density of a solid oxide fuel cell having 6 stacks with crossflow configuration. A commercial software repeatedly solves the governing equations of each stack, and get the convergent results of the whole SOFC stack. The preliminary results indicate that the average current density of each stack is similar to others, so the power output between different stacks are uniform. Moreover, the average cell temperature among stacks is different, and the central stacks have higher temperature due to its harder heat dissipation. For the operating control, the cell temperature difference among stacks is worth to concern because the temperature difference will be over 10 °C in the analysis case. The increasing of the inlet flow rate of the fuel and air will short the transient state, increase the average current density, and drop the cell temperature difference among the stacks. Therefore, the inlet flow rate is an important factor for transient performance of a SOFC stack.
von Bornstädt, Daniel; Houben, Thijs; Seidel, Jessica L; Zheng, Yi; Dilekoz, Ergin; Qin, Tao; Sandow, Nora; Kura, Sreekanth; Eikermann-Haerter, Katharina; Endres, Matthias; Boas, David A; Moskowitz, Michael A; Lo, Eng H; Dreier, Jens P; Woitzik, Johannes; Sakadžić, Sava; Ayata, Cenk
2015-03-04
Peri-infarct depolarizations (PIDs) are seemingly spontaneous spreading depression-like waves that negatively impact tissue outcome in both experimental and human stroke. Factors triggering PIDs are unknown. Here, we show that somatosensory activation of peri-infarct cortex triggers PIDs when the activated cortex is within a critical range of ischemia. We show that the mechanism involves increased oxygen utilization within the activated cortex, worsening the supply-demand mismatch. We support the concept by clinical data showing that mismatch predisposes stroke patients to PIDs as well. Conversely, transient worsening of mismatch by episodic hypoxemia or hypotension also reproducibly triggers PIDs. Therefore, PIDs are triggered upon supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. Based on the data, we propose that minimizing sensory stimulation and hypoxic or hypotensive transients in stroke and brain injury would reduce PID incidence and their adverse impact on outcome. Copyright © 2015 Elsevier Inc. All rights reserved.
von Bornstädt, Daniel; Houben, Thijs; Seidel, Jessica; Zheng, Yi; Dilekoz, Ergin; Qin, Tao; Sandow, Nora; Kura, Sreekanth; Eikermann-Haerter, Katharina; Endres, Matthias; Boas, David A.; Moskowitz, Michael A.; Lo, Eng H.; Dreier, Jens P.; Woitzik, Johannes; Sakadžić, Sava; Ayata, Cenk
2015-01-01
SUMMARY Peri-infarct depolarizations (PIDs) are seemingly spontaneous spreading depression-like waves that negatively impact tissue outcome in both experimental and human stroke. Factors triggering PIDs are unknown. Here, we show that somatosensory activation of peri-infarct cortex triggers PIDs when the activated cortex is within a critical range of ischemia. We show that the mechanism involves increased oxygen utilization within the activated cortex, worsening the supply-demand mismatch. We support the concept by clinical data showing that mismatch predisposes to PIDs in human stroke as well. Conversely, transient worsening of mismatch by episodic hypoxemia or hypotension also reproducibly triggers PIDs. Therefore, PIDs are triggered upon supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. Based on the data, we propose that minimizing sensory stimulation and hypoxic or hypotensive transients in stroke and brain injury would reduce PID incidence and their adverse impact on outcome. PMID:25741731
Leganés, Francisco; Forchhammer, Karl; Fernández-Piñas, Francisca
2009-01-01
A Ca2+ signal is required for the process of heterocyst differentiation in the filamentous diazotrophic cyanobacterium Anabaena sp. PCC 7120. This paper presents evidence that a transient increase in intracellular free Ca2+ is also involved in acclimation to nitrogen starvation in the unicellular non-diazotrophic cyanobacterium Synechococcus elongatus PCC 7942. The Ca2+ transient was triggered in response to nitrogen step-down or the addition of 2-oxoglutarate (2-OG), or its analogues 2,2-difluoropentanedioic acid (DFPA) and 2-methylenepentanedioic acid (2-MPA), to cells growing with combined nitrogen, suggesting that an increase in intracellular 2-OG levels precedes the Ca2+ transient. The signalling protein P(II) and the transcriptional regulator NtcA appear to be needed to trigger the signal. Suppression of the Ca2+ transient by the intracellular Ca2+ chelator N,N'-[1,2-ethanediylbis(oxy-2,1-phenylene)]bis[N-[2-[(acetyloxy)methoxy]-2-oxoethyl
Elhamdani, Abdeladim; Azizi, Fouad; Artalejo, Cristina R
2006-03-15
Transient fusion ("kiss-and-run") is accepted as a mode of transmitter release both in central neurons and neuroendocrine cells, but the prevalence of this mechanism compared with full fusion is still in doubt. Using a novel double patch-clamp method (whole cell/cell attached), permitting the recording of unitary capacitance events while stimulating under a variety of conditions including action potentials, we show that transient fusion is the predominant (>90%) mode of secretion in calf adrenal chromaffin cells. Raising intracellular Ca2+ concentration ([Ca]i) from 10 to 200 microM increases the incidence of full fusion events at the expense of transient fusion. Blocking rapid endocytosis that normally terminates transient fusion events also promotes full fusion events. Thus, [Ca]i controls the transition between transient and full fusion, each of which is coupled to different modes of endocytosis.
Dynamic simulation of coronal mass ejections
NASA Technical Reports Server (NTRS)
Steinolfson, R. S.; Wu, S. T.
1980-01-01
A model is developed for the formation and propagation through the lower corona of the loop-like coronal transients in which mass is ejected from near the solar surface to the outer corona. It is assumed that the initial state for the transient is a coronal streamer. The initial state for the streamer is a polytropic, hydrodynamic solution to the steady-state radial equation of motion coupled with a force-free dipole magnetic field. The numerical solution of the complete time-dependent equations then gradually approaches a stationary coronal streamer configuration. The streamer configuration becomes the initial state for the coronal transient. The streamer and transient simulations are performed completely independent of each other. The transient is created by a sudden increase in the pressure at the base of the closed-field region in the streamer configuration. Both coronal streamers and coronal transients are calculated for values of the plasma beta (the ratio of thermal to magnetic pressure) varying from 0.1 to 100.
Transient chaos - a resolution of breakdown of quantum-classical correspondence in optomechanics.
Wang, Guanglei; Lai, Ying-Cheng; Grebogi, Celso
2016-10-17
Recently, the phenomenon of quantum-classical correspondence breakdown was uncovered in optomechanics, where in the classical regime the system exhibits chaos but in the corresponding quantum regime the motion is regular - there appears to be no signature of classical chaos whatsoever in the corresponding quantum system, generating a paradox. We find that transient chaos, besides being a physically meaningful phenomenon by itself, provides a resolution. Using the method of quantum state diffusion to simulate the system dynamics subject to continuous homodyne detection, we uncover transient chaos associated with quantum trajectories. The transient behavior is consistent with chaos in the classical limit, while the long term evolution of the quantum system is regular. Transient chaos thus serves as a bridge for the quantum-classical transition (QCT). Strikingly, as the system transitions from the quantum to the classical regime, the average chaotic transient lifetime increases dramatically (faster than the Ehrenfest time characterizing the QCT for isolated quantum systems). We develop a physical theory to explain the scaling law.
Transient chaos - a resolution of breakdown of quantum-classical correspondence in optomechanics
Wang, Guanglei; Lai, Ying-Cheng; Grebogi, Celso
2016-01-01
Recently, the phenomenon of quantum-classical correspondence breakdown was uncovered in optomechanics, where in the classical regime the system exhibits chaos but in the corresponding quantum regime the motion is regular - there appears to be no signature of classical chaos whatsoever in the corresponding quantum system, generating a paradox. We find that transient chaos, besides being a physically meaningful phenomenon by itself, provides a resolution. Using the method of quantum state diffusion to simulate the system dynamics subject to continuous homodyne detection, we uncover transient chaos associated with quantum trajectories. The transient behavior is consistent with chaos in the classical limit, while the long term evolution of the quantum system is regular. Transient chaos thus serves as a bridge for the quantum-classical transition (QCT). Strikingly, as the system transitions from the quantum to the classical regime, the average chaotic transient lifetime increases dramatically (faster than the Ehrenfest time characterizing the QCT for isolated quantum systems). We develop a physical theory to explain the scaling law. PMID:27748418
Hierarchical Cluster Formation in Concentrated Monoclonal Antibody Formulations
NASA Astrophysics Data System (ADS)
Godfrin, P. Douglas; Zarzar, Jonathan; Zarraga, Isidro Dan; Porcar, Lionel; Falus, Peter; Wagner, Norman; Liu, Yun
Reversible cluster formation has been identified as an underlying cause of large solution viscosities observed in some concentrated monoclonal antibody (mAb) formulations. As high solution viscosity prevents the use of subcutaneous injection as a delivery method for some mAbs, a fundamental understanding of the interactions responsible for high viscosities in concentrated mAb solutions is of significant relevance to mAb applications in human health care as well as of intellectual interest. Here, we present a detailed investigation of a well-studied IgG1 based mAb to relate the short time dynamics and microstructure to significant viscosity changes over a range of pharmaceutically relevant physiochemical conditions. Using a combination of experimental techniques, it is found that upon adding Na2SO4, these antibodies dimerize in solution. Proteins form strongly bounded reversible dimers at dilute concentrations that, when concentrated, interact with each other to form loosely bounded, large, transient clusters. The combined effect of forming strongly bounded dimers and a large transient network is a significant increase in the solution viscosity. Strongly bounded, reversible dimers may exist in many IgG1 based mAb systems such that these results contribute to a more comprehensive understanding of the physical mechanisms producing high viscosities in concentrated protein solutions.
Costal-Oliveira, Fernanda; Guerra-Duarte, Clara; Oliveira, Maira Souza; Castro, Karen Larissa Pereira de; Lopes-de-Sousa, Leticia; Lara, Aline; Gomes, Enéas Ricardo de Morais; Bonilla, Cesar; Guatimosim, Sílvia; Melo, Marília Martins; Chávez-Olórtegui, Carlos
2017-01-01
Hadruroides lunatus is the most abundant scorpion species in the Peruvian central coast, where most of the accidents involving humans are registered. In spite of its prevalence, there are only very few studies on H. lunatus envenomation. The aim of the present study was to analyze the cardiorespiratory alterations caused by H. lunatus envenomation in rodents. Wistar rats injected with H. lunatus scorpion venom were submitted to electrocardiography. After euthanasia, rat lungs were collected and histopathologically analyzed. Mouse cardiomyocytes were used to perform immunofluorescence and calcium transient assays. Data were analyzed by ANOVA or Student's t-test. The significance level was set at p < 0.05. It was observed that H. lunatus venom increased heart rate and caused arrhythmia, thereby impairing the heart functioning. Lungs of envenomed animals showed significant alterations, such as diffuse hemorrhage. In addition, immunofluorescence showed that H. lunatus venom was capable of binding to cardiomyocytes. Furthermore, mouse ventricular cardiomyocytes incubated with H. lunatus venom showed a significant decrease in calcium transient, confirming that H. lunatus venom exerts a toxic effect on heart. Our results showed that H. lunatus venom is capable of inducing cardiorespiratory alterations, a typical systemic effect of scorpionism, stressing the importance of medical monitoring in envenomation cases.
VOEventNet: An Open Source of Transient Alerts for Astronomers.
NASA Astrophysics Data System (ADS)
Drake, Andrew J.; Williams, R.; Graham, M. J.; Mahabal, A.; Djorgovski, S. G.; White, R. R.; Vestrand, W. T.; Bloom, J.
2007-12-01
Event based astronomy is acquiring an increasingly important role in astronomy as large time-domain surveys such as Palomar Transient Factory (PTF), Pan-STARRs, SkyMapper and Allan Telescope Array (ATA) surveys come online. These surveys are expected to discover thousands of transients each year ranging from near earth asteroids to distant SNe. Although the primary instruments for of these surveys are in place, in order to fully utilize these event discovery streams, automated alerting and follow-up is a necessity. For the past two years the VOEventNet network has been globally distributing information about transient astronomical events using the VOEvent format, a Virtual Observatory standard. Events messages are openly distributed so that follow-up can utilize the most appropriate resources available in order to characterize the nature of the transients. Since its inception VOEventNet has broadcast more than 3500 SDSSSS Supernova candidates, 3300 GRB alert and follow-up notices from GCN, 700 OGLE microlensing event candidates, and 4300 newly discovered asteroid and optical transient candidates from the Palomar Quest survey. Additional transient event streams are expected this season including optical transients from the Catalina Sky Survey. VOEventNet astronomical transient events streams are available to all astronomers via traditional HTML tables, RSS news-feeds, real-time publication (via Jabber and TCP), and Google Sky mashups. VOEventNet currently carries out optical transient event follow-up with the Palomar 60 and 200in (Caltech), Faulkes Telescopes North and South (LCOGTN), RAPTOR (LANL), and PARITEL (UCB; CfA).
NASA Astrophysics Data System (ADS)
Hernandez, D.; Holt, W. E.; Bennett, R. A.; Dimitrova, L.; Haines, A. J.
2006-12-01
We are continuing work on developing and refining a tool for recognizing strain rate transients as well as for quantifying the magnitude and style of their temporal and spatial variations. We determined time-averaged velocity values in 0.05 year epochs using time-varying velocity estimates for continuous GPS station data from the Southern California Integrated GPS Network (SCIGN) for the time period between October 1999 and February 2004 [Li et al., 2005]. A self-consistent model velocity gradient tensor field solution is determined for each epoch by fitting bi-cubic Bessel interpolation to the GPS velocity vectors and we determine model dilatation strain rates, shear strain rates, and the rotation rates. Departures of the time dependent model strain rate and velocity fields from a master solution, obtained from a time-averaged solution for the period 1999-2004, with imposed plate motion constraints and Quaternary fault data, are evaluated in order to best characterize the time dependent strain rate field. A particular problem in determining the transient strain rate fields is the level of smoothing or damping that is applied. Our current approach is to choose a damping that both maximizes the departure of the transient strain rate field from the long-term master solution and achieves a reduced chi-squared value between model and observed GPS velocities of around 1.0 for all time epochs. We observe several noteworthy time-dependent changes. First, in the Eastern California Shear Zone (ECSZ) region, immediately following the October 1999 Hector Mine earthquake, there occurs a significant spatial increase of relatively high shear strain rate, which encompasses a significant portion of the ECSZ. Second, also following the Hector Mine event, there is a strain rate corridor that extends through the Pinto Mt. fault connecting the ECSZ to the San Andreas fault segment in the Salton Trough region. As this signal slowly decays, shear strain rates on segments of the San Andreas fault, just east of Palm Springs, and the San Jacinto fault increase during 2001-2004. During this period shear strain rates increase by roughly 20 nanostrain per year on the San Andreas fault and 20-30 nanostrain per year on the San Jacinto fault (over a zone approximately 20 km wide). Lastly, a further investigation into this strain rate recovery reveals a power law flow mechanism during the first six months after the earthquake for the Anza segment, after which strain rates appear to reach a steady state for the remainder of the data. Moreover, seismicity rates increase along these segments following the period of shear strain rate increase. These results quantify the spatial coverage of the strain rate changes and provide some bounds on their magnitude and confidence, as well as constraints on the associated regional rheology and interseismic cycle strain rate pattern. The compiled epoch solution "movies" may be viewed at the additional resources site.
Zhu, Lian; Xu, Zhi-Liang
2017-07-01
To investigate the effect of high-fat diet on the expression of transient receptor potential vanilloid 1 (TRPV1) in the respiratory system and the dorsal root ganglion (DRG) of mice, as well as its effect on the excitability of sensory neurons. A total of 20 C57BL/6 mice were randomly divided into normal-diet (ND) group and high-fat diet (HFD) group, with 10 mice in each group. The mice were given corresponding diets and body weights were monitored. After 7 weeks of feeding, lung tissue, bronchial tissue, and DRG at thoracic segments 3-4 were collected and immunohistochemical staining was performed. A patch clamp was used to measure the number of action potentials and TRPV1 current intensity in the DRG. After 7 weeks of feeding, the HFD group had significantly greater mean weight gain than the ND group (6.4±2.6 g vs 2.3±0.5 g; P<0.001). The HFD group had significantly higher expression of TRPV1 in the bronchus, pulmonary alveoli, and DRG than the ND group (P<0.05). Compared with the ND group, the HFD group had significant increases in the TRPV1 current intensity and number of action potentials in the DRG (P<0.05). High-fat diet induces a significant increase in body weight and leads to high expression of TRPV1 and high excitability in the respiratory system and the peripheral sensory neurons. This suggests that TRPV1 may be an important factor in the physiopathological mechanisms of bronchial hyperresponsiveness.
Berge, Jerica M; Tate, Allan; Trofholz, Amanda; Fertig, Angela; Crow, Scott; Neumark-Sztainer, Dianne; Miner, Michael
2018-01-16
Although prior research suggests that stress may play a role in parent's use of food-related parenting practices, it is unclear whether certain types of stress (e.g., transient, chronic) result in different food-related parenting practices. Identifying whether and how transient (i.e., momentary; parent/child conflict) and chronic (i.e., long-term; unemployment >6 months) sources of stress are related to parent food-related parenting practices is important with regard to childhood obesity. This is particularly important within racially/ethnically diverse parents who may be more likely to experience both types of stress and who have higher levels of obesity and related health problems. The current study examined the association between transient and chronic stressors and food-related parenting practices in a racially/ethnically diverse and immigrant sample. The current study is a cross-sectional, mixed-methods study using ecological momentary assessment (EMA). Parents (mean age = 35; 95% mothers) of children ages 5-7 years old (n = 61) from six racial/ethnic groups (African American, American Indian, Hispanic, Hmong, Somali, White) participated in this ten-day in-home observation with families. Transient stressors, specifically interpersonal conflicts, had significant within-day effects on engaging in more unhealthful food-related parenting practices the same evening with across-day effects weakening by day three. In contrast, financial transient stressors had stronger across-day effects. Chronic stressors, including stressful life events were not consistently associated with more unhealthful food-related parenting practices. Transient sources of stress were significantly associated with food-related parenting practices in racially/ethnically diverse and immigrant households. Chronic stressors were not consistently associated with food-related parenting practices. Future research and interventions may want to assess for transient sources of stress in parents and target these momentary factors in order to promote healthful food-related parenting practices.
Effect of substance P on cardiovascular and respiratory function in subjects.
Fuller, R W; Maxwell, D L; Dixon, C M; McGregor, G P; Barnes, V F; Bloom, S R; Barnes, P J
1987-04-01
The effect of substance P (SP), administered both intravenously and by inhalation, has been studied in normal and asthmatic humans. Intravenous infusion of SP (0.2-3.3 pmol X kg-1 X min-1) achieving a plasma concentration of SP between 5 and 25 pM produced vasodilatation (mean +/- SD), maximal increase in skin temperature (0.9 +/- 0.3 degree C) (P less than 0.05), and fall in diastolic blood pressure (8.5 +/- 2.9 mmHg) (P less than 0.05) associated with an increase in heart rate (15 +/- 10 beats/min) (P less than 0.05). All subjects had a fall in Vp30 (airflow at 70% of forced vital capacity measured from total lung capacity after a forced partial expiratory flow maneuver) at low infusion rate (P less than 0.05) and a significant rise at the highest infusion rate (P less than 0.05). Ventilation at rest and when stimulated by transient hypoxia increased (mean increase in resting ventilation 0.73 +/- 0.4 l/min and mean percent increase in transient ventilatory hypoxic response 41 +/- 27%). There was a small nonsignificant increase in plasma norepinephrine but no change in epinephrine or histamine. Inhaled SP, up to 0.7 mumol, caused a small nonsignificant fall in airway function in asthmatic subjects. SP has demonstrable effects on vascular smooth muscle and control of ventilation but at the doses studied had little effect on airway function.
NASA Technical Reports Server (NTRS)
Stevens, N. J.; Klinect, V. W.; Gore, J. V.
1977-01-01
The environmental charging of satellite surfaces during geomagnetic substorms is the apparent cause of a significant number of anomalous events occurring on geosynchronous satellites since the early 1970's. Electromagnetic pulses produced in connection with the differential charging of insulators can couple into the spacecraft harness and cause electronic switching anomalies. An investigation conducted to determine the response of the spacecraft surfaces to substorm particle fluxes makes use of a harness transient detector. The harness transient detector, called the Transient Event Counter (TEC) was built and integrated into the Canadian-American Communications Technology Satellite (CTS). A description of the TEC and its operational characteristics is given and the obtained data are discussed. The data show that the satellite surfaces appear to be charged to the point that discharges occur and that the discharge-induced transients couple into the wire harnesses.
Ding, Ruoting; Jiang, Hui; Sun, Baihui; Wu, Xiaoliang; Li, Wei; Zhu, Siyuan; Liao, Congrui; Zhong, Zhaoming; Chen, Jianting
2016-12-01
Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs), a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund's adjuvant (CFA) in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P<0.05). After intravenous injection of AOPPs-modified rat serum albumin (AOPPs-RSA) in Sprague-Dawley rats, the paw mechanical thresholds, measured by the electronic von Frey system, significantly declined. Immunofluorescence staining indicated that AOPPs increased expressions of NADPH oxidase 1 (Nox1), NADPH oxidase 4 (Nox4), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in the dorsal root ganglia (DRG) tissues. In-vitro studies were performed on primary DRG neurons which were obtained from both thoracic and lumbar DRG of rats. Results indicated that AOPPs triggered reactive oxygen species (ROS) production in DRG neurons, which were significantly abolished by ROS scavenger N-acetyl-l-cysteine (NAC) and small-interfering RNA (siRNA) silencing of Nox1 or Nox4. The expressions of Nox1, Nox4, TRPV1 and CGRP were significantly increased in AOPPs-induced DRG neurons. And relevant siRNA or inhibitors notably suppressed the expressions of these proteins and the calcium influxes in AOPPs-induced DRG neurons. In conclusion, AOPPs increased significantly in CFA-induced hyperalgesia rats and they activated Nox1/Nox4-ROS to sensitize TRPV1-dependent Ca2+ influx and CGRP release which led to inducing mechanical hyperalgesia. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Martin, Katie L; Hill, Grace A; Klein, Rob R; Arnett, Deborah G; Burd, Randy; Limesand, Kirsten H
2012-01-01
Treatment of head and neck cancer with radiation often results in damage to surrounding normal tissues such as salivary glands. Permanent loss of function in the salivary glands often leads patients to discontinue treatment due to incapacitating side effects. It has previously been shown that IGF-1 suppresses radiation-induced apoptosis and enhances G2/M arrest leading to preservation of salivary gland function. In an effort to recapitulate the effects of IGF-1, as well as increase the likelihood of translating these findings to the clinic, the small molecule therapeutic Roscovitine, is being tested. Roscovitine is a cyclin-dependent kinase inhibitor that acts to transiently inhibit cell cycle progression and allow for DNA repair in damaged tissues. Treatment with Roscovitine prior to irradiation induced a significant increase in the percentage of cells in the G(2)/M phase, as demonstrated by flow cytometry. In contrast, mice treated with radiation exhibit no differences in the percentage of cells in G(2)/M when compared to unirradiated controls. Similar to previous studies utilizing IGF-1, pretreatment with Roscovitine leads to a significant up-regulation of p21 expression and a significant decrease in the number of PCNA positive cells. Radiation treatment leads to a significant increase in activated caspase-3 positive salivary acinar cells, which is suppressed by pretreatment with Roscovitine. Administration of Roscovitine prior to targeted head and neck irradiation preserves normal tissue function in mouse parotid salivary glands, both acutely and chronically, as measured by salivary output. These studies suggest that induction of transient G(2)/M cell cycle arrest by Roscovitine allows for suppression of apoptosis, thus preserving normal salivary function following targeted head and neck irradiation. This could have an important clinical impact by preventing the negative side effects of radiation therapy in surrounding normal tissues.
Noel, Gary J; Goodman, Daniel B; Chien, Shuchean; Solanki, Bhavna; Padmanabhan, Mukund; Natarajan, Jaya
2004-05-01
A clinical trial was conducted in healthy volunteers using both periodic and continuous ECG recordings to assess the effect of increasing doses of levofloxacin on the QT and QTc interval. Periodic and continuous ECGs were recorded before and after subjects were dosed with placebo and increasing doses of levofloxacin (500 mg, 1000 mg, 1500 mg) that included doses twice the maximum recommended dose of 750 mg in a double-blind, randomized, four-period, four-sequence crossover trial. Mean heart rate (HR) and the QT and QTc interval after dosing with levofloxacin and placebo were compared, and HR-QT interval relationships defined by linear regression analysis were calculated. After single doses of 1000 and 1500 mg of levofloxacin, HR increased significantly, as measured by periodic and continuous ECG recordings. This transient increase occurred at times of peak plasma concentration and was without symptoms. Mean QT intervals after placebo and mean intervals after levofloxacin were indistinguishable. Using periodic ECG recordings, single doses of 1500 mg were associated with small increases in QTc that were statistically significant. In contrast, an effect on QTc was shown only using the Bazett formula with data obtained from continuous ECG recordings. Together with the finding that levofloxacin does not influence HR-QT relationships, these findings suggest that levofloxacin has little effect on prolonging ventricular repolarization and that small increases in HR associated with high doses of levofloxacin contribute to the drug's apparent effect on QTc. Single doses of 1000 or 1500 mg of levofloxacin transiently increase HR without affecting the uncorrected QT interval. Differences in mean QTc after levofloxacin compared to placebo vary depending on the correction formula used and whether the data analyzed are from periodic or continuous ECG recordings. This work suggests that using continuous ECG recordings in assessing QT/QTc effects of drugs may be of value, particularly with drugs that might influence HR.
RISPERIDONE VERSUS HALOPERIDOL IN ACUTE AND TRANSIENT PSYCHOTIC DISORDER
Chaudhuri, Bijoy Pratim; Bhagabati, Dipesh; Medhi, Dipanjali
2000-01-01
The mechanism of action of a relatively new antipsychotic drug-Risperidone differs from conventional antipsychotics like Haloperidol. We compared low dosages of Risperidone with near equivalent dosages of Haloperidol in first episode drug naive Acute and Transient Psychotic disorder. A single blind randomised four-week study protocol was employed. Highly significant and comparable efficacy as assessed by Brief Psychiatric Rating Scale and Global Assessment of Functioning Scale was seen at the end of the Study protocol in both the groups. Risperidone had significantly, an early onset of action on some of the positive as well as negative symptoms with less incidence of Extrapyramidal Symptoms in comparison to Haloperidol. We conclude that Risperidone may represent a potential useful first line agent in the treatment of Acute and Transient Psychotic Disorder. PMID:21407958
Transient acidosis while retrieving a fear-related memory enhances its lability
Du, Jianyang; Price, Margaret P; Taugher, Rebecca J; Grigsby, Daniel; Ash, Jamison J; Stark, Austin C; Hossain Saad, Md Zubayer; Singh, Kritika; Mandal, Juthika; Wemmie, John A; Welsh, Michael J
2017-01-01
Attenuating the strength of fearful memories could benefit people disabled by memories of past trauma. Pavlovian conditioning experiments indicate that a retrieval cue can return a conditioned aversive memory to a labile state. However, means to enhance retrieval and render a memory more labile are unknown. We hypothesized that augmenting synaptic signaling during retrieval would increase memory lability. To enhance synaptic transmission, mice inhaled CO2 to induce an acidosis and activate acid sensing ion channels. Transient acidification increased the retrieval-induced lability of an aversive memory. The labile memory could then be weakened by an extinction protocol or strengthened by reconditioning. Coupling CO2 inhalation to retrieval increased activation of amygdala neurons bearing the memory trace and increased the synaptic exchange from Ca2+-impermeable to Ca2+-permeable AMPA receptors. The results suggest that transient acidosis during retrieval renders the memory of an aversive event more labile and suggest a strategy to modify debilitating memories. DOI: http://dx.doi.org/10.7554/eLife.22564.001 PMID:28650315
NASA Astrophysics Data System (ADS)
Li, Huanhuan; Chen, Diyi; Zhang, Hao; Wang, Feifei; Ba, Duoduo
2016-12-01
In order to study the nonlinear dynamic behaviors of a hydro-turbine governing system in the process of sudden load increase transient, we establish a novel nonlinear dynamic model of the hydro-turbine governing system which considers the elastic water-hammer model of the penstock and the second-order model of the generator. The six nonlinear dynamic transfer coefficients of the hydro-turbine are innovatively proposed by utilizing internal characteristics and analyzing the change laws of the characteristic parameters of the hydro-turbine governing system. Moreover, from the point of view of engineering, the nonlinear dynamic behaviors of the above system are exhaustively investigated based on bifurcation diagrams and time waveforms. More importantly, all of the above analyses supply theoretical basis for allowing a hydropower station to maintain a stable operation in the process of sudden load increase transient.
Park, Mi Sung; Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Shin, Seung Hwan; Kang, Wonseok; Moon, Chansoo; Han, Kwang-Hyub
2015-02-01
Liver stiffness (LS) measurement using transient elastography and the FibroTest (FT) are alternatives to liver biopsy (LB) in assessing liver fibrosis. We investigated the prognostic role of the combined use of LS and FT in predicting liver-related events (LREs) in patients with chronic hepatitis B (CHB). Consecutive patients with CHB who underwent LB, along with LS and FT on the same day were recruited. LRE was defined as hepatic decompensation, hepatocellular carcinoma (HCC) or liver-related death. A total of 151 patients (86 male) were analyzed. During follow-up (median 59.9 months), overall 18 (11.9%) patients experienced LREs. The areas under receiver-operating characteristic curves of LS, FT, LS + FT and LS × FT in predicting LRE were 0.701, 0.668, 0.702 and 0.741 respectively. After adjusting for age and histological fibrosis staging, significant variables in univariate analysis (both P < 0.05), LS + FT and LS × FT were independent predictors of LREs with hazard ratios (HRs) of 1.080 and 1.126 (all P < 0.05) respectively. When subjects were divided into three groups according to quartile stratification (low quartile, interquartile and high quartile) using LS + FT and LS × FT, cumulative LRE development rate significantly increased with a corresponding increase in value among three groups respectively (log-rank test, all P < 0.05). The combined use of LS and FT significantly predicted forthcoming LRE development, but with only a slight additional benefit compared to LS or FT alone. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Kim, Jiwan; Hepat, Rahul; Lee, Daeweon; Kim, Yonggyun
2013-09-01
Parasitization by an endoparasitoid wasp, Cotesia plutellae, inhibits a larva-to-pupa metamorphosis of the diamondback moth, Plutella xylostella. This study tested an inhibitory effect of C. plutellae bracovirus (CpBV) on the metamorphosis of P. xylostella. Parasitized P. xylostella exhibited significantly reduced prothoracic gland (PTG) development at the last instar compared to nonparasitized larvae. Expression of the ecdysone receptor (EcR) was markedly suppressed during the last instar larvae parasitized by C. plutellae. By contrast, expression of the insulin receptor (InR) significantly increased in the parasitized larvae. Microinjection of CpBV significantly inhibited the larva-to-pupa metamorphosis of nonparasitized larvae in a dose-dependent manner. Injection of CpBV also inhibited the expression of the EcR and increased the expression of the InR. Individual CpBV segments were transiently expressed in its encoded genes in nonparasitized larvae and screened to determine antimetamorphic viral gene(s). Out of 21 CpBV segments, two viral segments (CpBV-S22 and CpBV-S27) were proved to inhibit larva-to-pupa metamorphosis by transient expression assay. RNA interference of each gene encoded in the viral segments was applied to determine antimetamorphic gene(s). Protein tyrosine phosphatase, early expressed gene, and four hypothetical genes were selected to be associated with the antimetamorphic activity of CpBV. These results suggest that antimetamorphosis of P. xylostella parasitized by C. plutellae is induced by inhibiting PTG development and subsequent ecdysteroid signaling with viral factors of CpBV. Copyright © 2013 Elsevier Inc. All rights reserved.
Creep Behavior of High-Strength Concrete Subjected to Elevated Temperatures.
Yoon, Minho; Kim, Gyuyong; Kim, Youngsun; Lee, Taegyu; Choe, Gyeongcheol; Hwang, Euichul; Nam, Jeongsoo
2017-07-11
Strain is generated in concrete subjected to elevated temperatures owing to the influence of factors such as thermal expansion and design load. Such strains resulting from elevated temperatures and load can significantly influence the stability of a structure during and after a fire. In addition, the lower the water-to-binder (W-B) ratio and the smaller the quantity of aggregates in high-strength concrete, the more likely it is for unstable strain to occur. Hence, in this study, the compressive strength, elastic modulus, and creep behavior were evaluated at target temperatures of 100, 200, 300, 500, and 800 °C for high-strength concretes with W-B ratios of 30%, 26%, and 23%. The loading conditions were set as non-loading and 0.33f cu . It was found that as the compressive strength of the concrete increased, the mechanical characteristics deteriorated and transient creep increased. Furthermore, when the point at which creep strain occurred at elevated temperatures after the occurrence of transient creep was considered, greater shrinkage strain occurred as the compressive strength of the concrete increased. At a heating temperature of 800 °C, the 80 and 100 MPa test specimens showed creep failure within a shrinkage strain range similar to the strain at the maximum load.
Creep Behavior of High-Strength Concrete Subjected to Elevated Temperatures
Yoon, Minho; Kim, Gyuyong; Kim, Youngsun; Lee, Taegyu; Choe, Gyeongcheol; Hwang, Euichul; Nam, Jeongsoo
2017-01-01
Strain is generated in concrete subjected to elevated temperatures owing to the influence of factors such as thermal expansion and design load. Such strains resulting from elevated temperatures and load can significantly influence the stability of a structure during and after a fire. In addition, the lower the water-to-binder (W–B) ratio and the smaller the quantity of aggregates in high-strength concrete, the more likely it is for unstable strain to occur. Hence, in this study, the compressive strength, elastic modulus, and creep behavior were evaluated at target temperatures of 100, 200, 300, 500, and 800 °C for high-strength concretes with W–B ratios of 30%, 26%, and 23%. The loading conditions were set as non-loading and 0.33fcu. It was found that as the compressive strength of the concrete increased, the mechanical characteristics deteriorated and transient creep increased. Furthermore, when the point at which creep strain occurred at elevated temperatures after the occurrence of transient creep was considered, greater shrinkage strain occurred as the compressive strength of the concrete increased. At a heating temperature of 800 °C, the 80 and 100 MPa test specimens showed creep failure within a shrinkage strain range similar to the strain at the maximum load. PMID:28773144
Im, Doo Soon; Jeon, Jeong Wook; Lee, Jin Soo; Won, Seok Joon; Cho, Sung Ig; Lee, Yong Beom; Gwag, Byoung Joo
2012-05-21
Excess activation of ionotropic glutamate receptors and iron is believed to contribute to free radical production and neuronal death following hypoxic ischemia. We examined the possibility that both NMDA receptor activation and iron overload determine spatial and temporal patterns of free radical production after transient middle cerebral artery occlusion (tMCAO) in male Sprague-Dawley rats. Mitochondrial free radical (MFR) levels were maximally increased in neurons in the core at 1 h and 24 h after tMCAO. Early MFR production was blocked by administration of MK-801, an NMDA receptor antagonist, but not deferoxamine, an iron chelator. Neither MK-801 nor deferoxamine attenuated late MFR production in the core. Increased MFRs were observed in penumbral neurons within 6 h and gradually increased over 24 h after tMCAO. Slowly-evolving MFRs in the core and penumbra were accompanied by iron overload. Deferoxamine blocked iron overload but reduced MFR production only in the penumbra. Combined MK-801/deferoxamine reduced late MFR production in both core and penumbra in an additive manner. Combination therapy significantly ameliorated infarction compared with monotherapy. These findings suggest that the NMDA receptor activation and iron overload mediate late MFR production and infarction after tMCAO. Copyright © 2012 Elsevier B.V. All rights reserved.
Rinaldi, Luca; Valente, Giovanna; Piai, Guido
2016-01-01
Background Liver transplanted patients need close surveillance for early signs of graft disease. Objectives Transient elastography can safely be repeated over time, offering serial liver stiffness measurement values. Serial stiffness measurements were compared to single baseline stiffness measurements in predicting the appearance of liver-related clinical events and guiding subsequent clinical decisions. Methods One hundred and sixty liver transplanted patients were observed for three years in our real-life practice. Results Liver stiffness measurements were stable in 75% of patients, decreased in 4% of patients, and increased in 21% of patients. The pattern of increased stiffness measurements was associated with both HCV-RNA positive status and the presence of an active biliary complication of liver transplantation and was more predictive of a clinically significant event resulting from any disease of the transplanted liver when compared to a stable pattern or to a single liver stiffness measurement. The procedures that were consequently performed were often diagnostic for unexpected situations, both in HCV-RNA positive and HCV-RNA negative patients. Conclusions The pattern of longitudinally increased liver stiffness measurements efficiently supported clinical decisions for individualized management strategies. Repeated transient elastography in real-life clinical practice appears to have a practical role in monitoring liver transplanted patients. PMID:28123442
Response and adaptation of Beagle dogs to hypergravity
NASA Technical Reports Server (NTRS)
Oyama, J.
1975-01-01
Eight male Beagle dogs, five months old, were centrifuged continuously for three months at progressively increasing loads. Heart rate and deep body temperature were monitored continuously by implant biotelemetry. Initially, centrifuged dogs showed transient decreases in heart rate and body temperature along with changes in their diurnal rhythm patterns. Compared with normal gravity controls, exposed dogs showed a slower growth rate and a reduced amount of body fat. Blood protein, total lipids, cholesterol, calcium, packed cell volume, red blood cell count, and hemoglobin were also decreased significantly. Absolute weights of the leg bones of centrifuged dogs were significantly greater than controls. Photon absorptiometry revealed significant density increases in selective regions of the femur and humerus of centrifuged dogs. In spite of the various changes noted, results from this and other studies affirm the view that dogs can tolerate and adapt to sustained loads as high as 2.5 g without serious impairment of their body structure and function.
Mizuta, Kentaro; Mizuta, Fumiko; Xu, Dingbang; Masaki, Eiji; Panettieri, Reynold A; Emala, Charles W
2011-12-01
γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system, and exerts its actions via both ionotropic (GABA(A)) and metabotropic (GABA(B)) receptors. Although the functional expression of GABA(B) receptors coupled to the G(i) protein was reported for airway smooth muscle, the role of GABA(B) receptors in airway responsiveness remains unclear. We investigated whether G(i)-coupled GABA(B) receptors cross-regulate phospholipase C (PLC), an enzyme classically regulated by G(q)-coupled receptors in human airway smooth muscle cells. Both the GABA(B)-selective agonist baclofen and the endogenous ligand GABA significantly increased the synthesis of inositol phosphate, whereas GABA(A) receptor agonists, muscimol, and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol exerted no effect. The baclofen-induced synthesis of inositol phosphate and transient increases in [Ca(2+)](i) were blocked by CGP35348 and CGP55845 (selective GABA(B) antagonists), pertussis toxin (PTX, which inactivates the G(i) protein), gallein (a G(βγ) signaling inhibitor), U73122 (an inhibitor of PLC-β), and xestospongin C, an inositol 1,4,5-triphosphate receptor blocker. Baclofen also potentiated the bradykinin-induced synthesis of inositol phosphate and transient increases in [Ca(2+)](i), which were blocked by CGP35348 or PTX. Moreover, baclofen potentiated the substance P-induced contraction of airway smooth muscle in isolated guinea pig tracheal rings. In conclusion, the stimulation of GABA(B) receptors in human airway smooth muscle cells rapidly mobilizes intracellular Ca(2+) stores by the synthesis of inositol phosphate via the activation of PLC-β, which is stimulated by G(βγ) protein liberated from G(i) proteins coupled to GABA(B) receptors. Furthermore, crosstalk between GABA(B) receptors and G(q)-coupled receptors potentiates the synthesis of inositol phosphate, transient increases in [Ca(2+)](i), and smooth muscle contraction through G(i) proteins.
Mizuta, Kentaro; Mizuta, Fumiko; Xu, Dingbang; Masaki, Eiji; Panettieri, Reynold A.
2011-01-01
γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system, and exerts its actions via both ionotropic (GABAA) and metabotropic (GABAB) receptors. Although the functional expression of GABAB receptors coupled to the Gi protein was reported for airway smooth muscle, the role of GABAB receptors in airway responsiveness remains unclear. We investigated whether Gi-coupled GABAB receptors cross-regulate phospholipase C (PLC), an enzyme classically regulated by Gq-coupled receptors in human airway smooth muscle cells. Both the GABAB-selective agonist baclofen and the endogenous ligand GABA significantly increased the synthesis of inositol phosphate, whereas GABAA receptor agonists, muscimol, and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol exerted no effect. The baclofen-induced synthesis of inositol phosphate and transient increases in [Ca2+]i were blocked by CGP35348 and CGP55845 (selective GABAB antagonists), pertussis toxin (PTX, which inactivates the Gi protein), gallein (a Gβγ signaling inhibitor), U73122 (an inhibitor of PLC-β), and xestospongin C, an inositol 1,4,5-triphosphate receptor blocker. Baclofen also potentiated the bradykinin-induced synthesis of inositol phosphate and transient increases in [Ca2+]i, which were blocked by CGP35348 or PTX. Moreover, baclofen potentiated the substance P–induced contraction of airway smooth muscle in isolated guinea pig tracheal rings. In conclusion, the stimulation of GABAB receptors in human airway smooth muscle cells rapidly mobilizes intracellular Ca2+ stores by the synthesis of inositol phosphate via the activation of PLC-β, which is stimulated by Gβγ protein liberated from Gi proteins coupled to GABAB receptors. Furthermore, crosstalk between GABAB receptors and Gq-coupled receptors potentiates the synthesis of inositol phosphate, transient increases in [Ca2+]i, and smooth muscle contraction through Gi proteins. PMID:21719794
Fernandes, Vítor S.; Xin, Wenkuan
2015-01-01
Hydrogen sulfide (H2S) is a key signaling molecule regulating important physiological processes, including smooth muscle function. However, the mechanisms underlying H2S-induced detrusor smooth muscle (DSM) contractions are not well understood. This study investigates the cellular and tissue mechanisms by which H2S regulates DSM contractility, excitatory neurotransmission, and large-conductance voltage- and Ca2+-activated K+ (BK) channels in freshly isolated guinea pig DSM. We used a multidisciplinary experimental approach including isometric DSM tension recordings, colorimetric ACh measurement, Ca2+ imaging, and patch-clamp electrophysiology. In isolated DSM strips, the novel slow release H2S donor, P-(4-methoxyphenyl)-p-4-morpholinylphosphinodithioic acid morpholine salt (GYY4137), significantly increased the spontaneous phasic and nerve-evoked DSM contractions. The blockade of neuronal voltage-gated Na+ channels or muscarinic ACh receptors with tetrodotoxin or atropine, respectively, reduced the stimulatory effect of GYY4137 on DSM contractility. GYY4137 increased ACh release from bladder nerves, which was inhibited upon blockade of L-type voltage-gated Ca2+ channels with nifedipine. Furthermore, GYY4137 increased the amplitude of the Ca2+ transients and basal Ca2+ levels in isolated DSM strips. GYY4137 reduced the DSM relaxation induced by the BK channel opener, NS11021. In freshly isolated DSM cells, GYY4137 decreased the amplitude and frequency of transient BK currents recorded in a perforated whole cell configuration and reduced the single BK channel open probability measured in excised inside-out patches. GYY4137 inhibited spontaneous transient hyperpolarizations and depolarized the DSM cell membrane potential. Our results reveal the novel findings that H2S increases spontaneous phasic and nerve-evoked DSM contractions by activating ACh release from bladder nerves in combination with a direct inhibition of DSM BK channels. PMID:25948731
Hemodynamic effects of sodium bicarbonate administration.
Katheria, A C; Brown, M K; Hassan, K; Poeltler, D M; Patel, D A; Brown, V K; Sauberan, J B
2017-05-01
To describe the hemodynamic changes that occur with sodium bicarbonate (NaHCO 3 ) administration in premature neonates. This retrospective study included premature neonates 23 to 31+6 weeks of gestational age who underwent continuous cardiac and cerebral monitoring as participants in prospective trials at our institution, and who received NaHCO 3 infused over 30 min in the first 24 h of life. Blood pressure (BP), heart rate, cardiac output (CO), SpO 2 and cerebral oximetry (StO 2 ) were captured every 2 s. A baseline was established for all continuous data and averaged over the 10 min before NaHCO 3 administration. Baseline was compared with measurements over 10 min epochs until 80 min after administration. Arterial blood gases before and within 1 h of administration were also compared. Significance was set at P<0.05. A total of 36 subjects received NaHCO 3 (1.3±0.3 mEq kg -1 ) in the first 24 h (14±8.5 h) of life. NaHCO 3 administration increased pH (7.23 vs 7.28, P<0.01) and decreased base deficit (-8.9 vs -6.8, P<0.01) and PaCO 2 (45 vs 43 mm Hg, P<0.05). There was a transient but significant (P<0.05) decrease in systemic BP coinciding with an increase in cerebral oxygenation without an increase in oxygen extraction. CO did not change. Early postnatal NaHCO 3 administration does not acutely improve CO but does cause transient fluctuations in cerebral and cardiovascular hemodynamics in extremely premature infants.
Wang, Y M; Zhang, G Y; Wang, Y; Hu, M; Zhou, J J; Sawyer, A; Cao, Q; Wang, Y; Zheng, G; Lee, V W S; Harris, D C H; Alexander, S I
2017-05-01
Regulatory T cells (T regs ) have been recognized as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. The loss of T regs or their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of T regs in the chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of T regs in a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2-interacting mediator (Bim) knock-out mice by transient depleting T regs . Bim is a pro-apoptotic member of the B cell lymphoma 2 (Bcl-2) family. Bim knock-out (Bim -/- ) mice fail to delete autoreactive T cells in thymus, leading to chronic spontaneous autoimmune kidney disease. We found that T reg depletion in Bim -/- mice exacerbated the kidney injury with increased proteinuria, impaired kidney function, weight loss and greater histological injury compared with wild-type mice. There was a significant increase in interstitial infiltrate of inflammatory cells, antibody deposition and tubular damage. Furthermore, the serum levels of cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17α, interferon (IFN)-γ and tumour necrosis factor (TNF)-α were increased significantly after T reg depletion in Bim -/- mice. This study demonstrates that transient depletion of T regs leads to enhanced self-reactive T effector cell function followed by exacerbation of kidney disease in the chronic spontaneous kidney disease model of Bim-deficient mice. © 2017 British Society for Immunology.
Zou, Weiying; Lin, Hua; Liu, Wenwen; Yang, Bei; Wu, Lei; Duan, Limin; Ling, Ping; Zhu, Lingyan; Dai, Qun; Zhao, Lintong; Zou, Ting; Zhang, Dalei
2016-04-01
To investigate the effects of moxibustion on visceral hyperalgesia (VH) and bone marrow cell transient receptor potential vanilloid type 1 (TRPV1) and heat shock protein (HSP) 70 expression in a rat model of VH. Mechanical colorectal distension was performed to induce VH in neonatal Sprague-Dawley rats. Eight-week-old VH rats were treated with moxibustion at acupuncture point BL25 or an ipsilateral non-acupuncture point. Abdominal withdrawal reflex (AWR) scoring and pain threshold pressure assessment were performed before and after moxibustion treatment for 7 consecutive days. The expression of TRPV1 and HSP70 in bone marrow cells was quantified by real-time quantitative PCR. The expression of TRPV1 and HSP70 in bone marrow cells was increased in rats with VH. Moxibustion at BL25 significantly decreased AWR scores and increased pain threshold pressure in rats with VH. Furthermore, moxibustion at BL25 significantly inhibited the VH-induced increase in the expression of TRPV1 and HSP70 in bone marrow cells. The up-regulation of TRPV1 and HSP70 expression in bone marrow cells may be involved in visceral pain development and the analgesic effect of moxibustion on VH may be mediated through down-regulation of TRPV1 and HSP70 expression in bone marrow cells. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Junghaenel, Doerte U; Cohen, Jules; Schneider, Stefan; Neerukonda, Anu R; Broderick, Joan E
2015-09-01
The goal of this study was to characterize changes in daily fatigue in women undergoing chemotherapy for breast cancer. We examined whether there are subgroups of patients with distinct fatigue trajectories and explored potential psychosocial and biomedical predictors of these subgroups. Participants were 77 women with breast cancer receiving adjuvant chemotherapy with AC-T (2-week cycle) and TC or TCH (3-week cycle) regimens. They completed 28 daily ratings online using an adapted version of the Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue instrument. Both regimens followed an "inverted-U-shaped" fatigue pattern over approximately 2 weeks. Growth mixture modeling identified three patient subgroups with distinct trajectories. Fatigue scores in the "low fatigue" group (23 %) increased following the infusion and quickly abated. The "transient fatigue" (27 %) group had a very pronounced increase. Patients in the "high fatigue" (50 %) group reported consistently elevated fatigue with a relatively small increase. Demographic and medical variables were not associated with fatigue trajectory. Patients in the "high fatigue" group reported significantly poorer physical, emotional, and social functioning, poorer general health, and more depressed mood than patients in the "low fatigue" group. The "transient fatigue" group reported significantly better physical and social functioning than the "high fatigue" group, but emotional distress and depression similar to the "high fatigue" group. The identification of patient subgroups with distinct fatigue trajectories during chemotherapy is an essential step for developing preventative strategies and tailored interventions. Our results suggest that different trajectories are associated with patients' psychosocial and general health.
Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study.
Tomida, Ileana; Azuara-Blanco, Augusto; House, Heather; Flint, Maggie; Pertwee, Roger G; Robson, Philip J
2006-10-01
The purpose of this study was to assess the effect on intraocular pressure (IOP) and the safety and tolerability of oromucosal administration of a low dose of delta-9-tetrahydrocannabinol (Delta-9-THC) and cannabidiol (CBD). A randomized, double-masked, placebo-controlled, 4 way crossover study was conducted at a single center, using cannabis-based medicinal extract of Delta-9-THC and CBD. Six patients with ocular hypertension or early primary open angle glaucoma received a single sublingual dose at 8 AM of 5 mg Delta-9-THC, 20 mg CBD, 40 mg CBD, or placebo. Main outcome measure was IOP. Secondary outcomes included visual acuity, vital signs, and psychotropic effects. Two hours after sublingual administration of 5 mg Delta-9-THC, the IOP was significantly lower than after placebo (23.5 mm Hg vs. 27.3 mm Hg, P=0.026). The IOP returned to baseline level after the 4-hour IOP measurement. CBD administration did not reduce the IOP at any time. However, the higher dose of CBD (40 mg) produced a transient elevation of IOP at 4 hours after administration, from 23.2 to 25.9 mm Hg (P=0.028). Vital signs and visual acuity were not significantly changed. One patient experienced a transient and mild paniclike reaction after Delta-9-THC administration. A single 5 mg sublingual dose of Delta-9-THC reduced the IOP temporarily and was well tolerated by most patients. Sublingual administration of 20 mg CBD did not reduce IOP, whereas 40 mg CBD produced a transient increase IOP rise.
Alawi, Khadija M.; Aubdool, Aisah A.; Liang, Lihuan; Wilde, Elena; Vepa, Abhinav; Psefteli, Maria-Paraskevi; Brain, Susan D.; Keeble, Julie E.
2015-01-01
Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β-adrenoceptor antagonist propranolol, the mixed α-/β-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.—Alawi, K. M., Aubdool, A. A., Liang, L., Wilde, E., Vepa, A., Psefteli, M.-P., Brain, S. D., Keeble, J. E. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature. PMID:26136480
Ha Park, Joon; Yoo, Ki-Yeon; Hye Kim, In; Cho, Jeong-Hwi; Lee, Jae-Chul; Hyeon Ahn, Ji; Jin Tae, Hyun; Chun Yan, Bing; Won Kim, Dae; Kyu Park, Ok; Kwon, Seung-Hae; Her, Song; Su Kim, Jin; Hoon Choi, Jung; Hyun Lee, Choong; Koo Hwang, In; Youl Cho, Jae; Hwi Cho, Jun; Kwon, Young-Guen; Ryoo, Sungwoo; Kim, Young-Myeong; Won, Moo-Ho; Jun Kang, Il
2016-12-01
Hydroquinone (HQ), a major benzene metabolite, occurs naturally in various plants and is manufactured for commercial use. Although HQ displays various biological effects, its neuroprotective effects following ischemic insults have not been investigated. In this study, we first examined neuroprotective effects of HQ in a rat model of transient focal cerebral ischemia. Animals were subjected to transient middle cerebral artery occlusion for 120 min. HQ (50 or 100 mg/kg) or vehicle was intraperitoneally administered once at 30 min after ischemia-reperfusion. Neuroprotection by treatment with 100 mg/kg of HQ was shown using evaluation of neurological deficits, positron-emission tomography (PET) and 2,3,5-triphenyltetrazoliumchloride (TTC) staining. In addition, HQ treatment significantly attenuated ischemia-induced Evans blue dye extravasation from blood vessels and significantly increased immunoreactivities of SMI-71 (an endothelial BBB marker) and glucose transporter-1 (GLUT-1, an endothelial cell marker) in ischemic cortex compared to the vehicle-treated ischemia-operated group. Confocal microscopy and western blot analysis also showed that HQ treatment maintained expressions of tight junction proteins (zonula occludens-1 and occludin) in the ischemic cortex. Post-treatment with HQ protected neurons from transient focal cerebral ischemic injury and the neuroprotective effect of HQ might be closely associated with prevention of BBB disruption via maintaining SMI-71 and GLUT-1 expressions as well as prevention of the degradation of zonula occludens-1 and occludin proteins. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Effect of indacaterol on arterial blood gases in patients suffering from acute exacerbation of COPD.
Rogliani, Paola; Ora, Josuel; Ciaprini, Chiara; Senis, Lucia; Stirpe, Emanuele; Cazzola, Mario
2014-02-01
The administration of β2-agonists to patients with airways obstruction often results in transient decrease in PaO2 despite concomitant bronchodilation. This effect is potentially dangerous for patients suffering from acute exacerbation of COPD (AECOPD). In this study, we investigated the effect of indacaterol 150 μg and 300 μg on the arterial blood gas tensions of hospitalised patients with AECOPD. We explored the acute effects on arterial blood gases and spirometry of two doses of indacaterol Breezhaler (150 and 300 μg) in 12 patients hospitalised because of an AECOPD in 2 non-consecutive days under open-label, randomized, crossover conditions, with blind evaluation. Blood specimens were taken just before the inhalation and at 15, 30, 60, 120, 240 and 360 min after inhalation of each treatment, and spirometry was performed at the same time points. Both doses of indacaterol did not cause significant changes in blood gases, although some patients with relatively well-preserved PaO2 presented transient episodes of oxygen desaturation that normalize spontaneously in a very short time. Moreover, they induced a significant mean increase in FEV1 and FVC, although the improvement caused by indacaterol 300 μg was larger. Indacaterol up to 300 μg is a potent bronchodilator that may induce small, transient decrease in PaO2 mainly in patients with relatively well-preserved PaO2. There appeared to be no clinical consequences of these PaO2 abnormalities in patients suffering from AECOPD. Copyright © 2013. Published by Elsevier Ltd.
NASA Astrophysics Data System (ADS)
Hadjiyska, Elena Ivanova
2009-06-01
Optical transients have been studied in isolated cases, but never mapped into a comprehensive data base in the past. These events vary in duration and signature, yet they are united under the umbrella of time varying observables and represent a significant portion of the dynamical processes in the universe. The Transient Optical Sky Survey (TOSS) System is a dedicated, ground-based system of small optical telescopes, observing nightly at fixed Declination while gathering 90 sec exposures and thus creating a repeated partial map of the sky. Presented here is a brief overview of some of the signatures of transient events and a description of the TOSS system along with the data acquired during the 2008-2009 observing campaign, potentially producing over 100,000 light curves.
Sepsis in the Pediatric Cardiac Intensive Care Unit
Wheeler, Derek S.; Jeffries, Howard E.; Zimmerman, Jerry J.; Wong, Hector R.; Carcillo, Joseph A.
2012-01-01
The survival rate for children with congenital heart disease (CHD) has increased significantly coincident with improved techniques in cardiothoracic surgery, cardiopulmonary bypass, and myocardial protection, and post-operative care. Cardiopulmonary bypass, likely in combination with ischemia-reperfusion injury, hypothermia, and surgical trauma, elicits a complex, systemic inflammatory response that is characterized by activation of the complement cascade, release of endotoxin, activation of leukocytes and the vascular endothelium, and release of pro-inflammatory cytokines. This complex inflammatory state causes a transient immunosuppressed state, which may increase the risk of hospital-acquired infection in these children. Postoperative sepsis occurs in nearly 3% of children undergoing cardiac surgery and significantly increases length of stay in the pediatric cardiac intensive care unit as well as the risk for mortality. Herein, we review the epidemiology, pathobiology, and management of sepsis in the pediatric cardiac intensive care unit. PMID:22337571
Cheloni, Daniele; D'Agostino, Nicola; Selvaggi, Giulio; Avallone, Antonio; Fornaro, Gianfranco; Giuliani, Roberta; Reale, Diego; Sansosti, Eugenio; Tizzani, Pietro
2017-04-12
In actively deforming regions, crustal deformation is accommodated by earthquakes and through a variety of transient aseismic phenomena. Here, we study the 2010-2014 Pollino (Southern Italy) swarm sequence (main shock M W 5.1) located within the Pollino seismic gap, by analysing the surface deformation derived from Global Positioning System and Synthetic Aperture Radar data. Inversions of geodetic time series show that a transient slip, with the same mechanism of the main shock, started about 3-4 months before the main shock and lasted almost one year, evolving through time with acceleration phases that correlate with the rate of seismicity. The moment released by the transient slip is equivalent to M W 5.5, significantly larger than the seismic moment release revealing therefore that a significant fraction of the overall deformation is released aseismically. Our findings suggest that crustal deformation in the Pollino gap is accommodated by infrequent "large" earthquakes (M W ≥ 6.5) and by aseismic episodes releasing a significant fraction of the accrued strain. Lower strain rates, relative to the adjacent Southern Apennines, and a mixed seismic/aseismic strain release are in favour of a longer recurrence for large magnitude earthquakes in the Pollino gap.
Digital implementation of the TF30-P-3 turbofan engine control
NASA Technical Reports Server (NTRS)
Cwynar, D. S.; Batterton, P. G.
1975-01-01
The standard hydromechanical control modes for TF30-P-3 engine were implemented on a digital process control computer. Programming methods are described, and a method is presented to solve stability problems associated with fast response dynamic loops contained within the exhaust nozzle control. A modification of the exhaust nozzle control to provide for either velocity or position servoactuation systems is discussed. Transient response of the digital control was evaluated by tests on a real time hybrid simulation of the TF30-P-3 engine. It is shown that the deadtime produced by the calculation time delay between sampling and final output is more significant to transient response than the effects associated with sampling rate alone. For the main fuel control, extended update and calculation times resulted in a lengthened transient response to throttle bursts from idle to intermediate with an increase in high pressure compressor stall margin. Extremely long update intervals of 250 msec could be achieved without instability. Update extension for the exhaust nozzle control resulted in a delayed response of the afterburner light-off detector and exhaust nozzle overshoot with resulting fan oversuppression. Long update times of 150 msec caused failure of the control due to a false indication by the blowout detector.
NASA Astrophysics Data System (ADS)
Mailen, Russell W.; Dickey, Michael D.; Genzer, Jan; Zikry, Mohammed
2017-11-01
Shape memory polymer (SMP) sheets patterned with black ink hinges change shape in response to external stimuli, such as absorbed thermal energy from an infrared (IR) light. The geometry of these hinges, including size, orientation, and location, and the applied thermal loads significantly influence the final folded shape of the sheet, but these variables have not been fully investigated. We perform a systematic study on SMP sheets to fundamentally understand the effects of single and double hinge geometries, hinge orientation and spacing, initial temperature, heat flux intensity, and pattern width on the folding behavior. We have developed thermo-viscoelastic finite element models to characterize and quantify the stresses, strains, and temperatures as they relate to SMP shape changes. Our predictions indicate that hinge orientation can be used to reduce the total bending angle, which is the angle traversed by the folding face of the sheet. Two parallel hinges increase the total bending angle, and heat conduction between the hinges affects the transient folding response. IR intensity and initial temperatures can also influence the transient folding behavior. These results can provide guidelines to optimize the transient folding response and the three-dimensional folded structure obtained from self-folding polymer origami sheets that can be applied for myriad applications.
Polar UVI observations of dayside auroral transient events
NASA Astrophysics Data System (ADS)
Vorobjev, V. G.; Yagodkina, O. I.; Sibeck, D. G.; Liou, K.; Meng, C.-I.
2001-12-01
We analyze Polar Ultraviolet Imager (UVI) observations of auroral transient events (ATEs) in the dayside Northern Hemisphere. During 5 winter months in 1996 and 1997, we found 31 prenoon ATEs but only 13 afternoon events. Prenoon and afternoon event characteristics differ. Prenoon ATEs generally appear as bright spots of auroral luminosity in the area from 0800 to 1000 magnetic local time (MLT) and 74.5° and 76.5° corrected geomagnetic latitude (CGL). Bright aurorae then quickly expand westward and poleward, accompanied by high-latitude magnetic impulsive events (MIE) and traveling convection vortices (TCV). Afternoon ATEs usually appear as a sudden intensification of aurorae in the area from 1400 to 1600 MLT and 75.5° to 78.5° CGL. Within 15-20 min the bright band of luminosity extends eastward to reach 2000-2100 MLT at 70°-72° CGL. Although midlatitude and low-latitude ground magnetograms in the evening sector record increases in the horizontal component of the magnetic field, no corresponding features occur at stations in the morning sector. Afternoon ATEs correspond to abrupt changes in the interplanetary magnetic field (IMF) orientation, but not to significant variations of the solar wind dynamic pressure, indicating that the auroral transient events occur as part of the magnetospheric response to abrupt changes in the foreshock geometry.
Clinical implications of increased use of MRI in TIA.
Kvistad, C E; Thomassen, L; Waje-Andreassen, U; Moen, G; Logallo, N; Naess, H
2013-07-01
Transient ischemic attack has been redefined as a tissue-based diagnosis and MRI recommended as the preferred imaging modality. We aimed to investigate whether an increased use of MRI leads to a decrease in the proportion of TIA as compared to cerebral infarction. We also sought to see whether DWI-positive patients with transient ischemic symptoms <24 h differ from DWI-negative TIA patients in terms of performed diagnostic investigations and clinical characteristics. Patients admitted with cerebral infarction or TIA in the period 2006-2011 were prospectively registered. The use of MRI in patients with transient ischemic symptoms <24 h and proportion of TIA were annually recorded. DWI-positive and DWI-negative patients with transient ischemic symptoms <24 h were compared in univariate analyses regarding baseline data, diagnostic investigations, and etiology. Multivariate analyses were performed to identify predictors of DWI lesions. The use of MRI increased from 65.0% in 2006-2008 to 89.0% in 2009-2011 (P < 0.001). The proportion of TIA as compared to cerebral infarction decreased from 12.2% in 2006-2008 to 8.3% in 2009-2011 (P = 0.002). DWI-positive patients were more often examined with 24-h Holter monitoring (P < 0.001) and echocardiography (P < 0.001). Lower age (P < 0.001) and prior myocardial infarction (P < 0.029) were independently associated with DWI lesions in patients with transient ischemic symptoms <24 h. An increased use of MRI and a tissue-based TIA definition resulted in a decrease in the proportion of TIA at discharge as compared to cerebral infarction. DWI-positive patients had a more extensive cardiac work-up and were associated with lower age and prior myocardial infarction. © 2012 John Wiley & Sons A/S.
Weitlauf, Carl; Ward, Nicholas J; Lambert, Wendi S; Sidorova, Tatiana N; Ho, Karen W; Sappington, Rebecca M; Calkins, David J
2014-11-12
Progression of neurodegeneration in disease and injury is influenced by the response of individual neurons to stressful stimuli and whether this response includes mechanisms to counter declining function. Transient receptor potential (TRP) cation channels transduce a variety of disease-relevant stimuli and can mediate diverse stress-dependent changes in physiology, both presynaptic and postsynaptic. Recently, we demonstrated that knock-out or pharmacological inhibition of the TRP vanilloid-1 (TRPV1) capsaicin-sensitive subunit accelerates degeneration of retinal ganglion cell neurons and their axons with elevated ocular pressure, the critical stressor in the most common optic neuropathy, glaucoma. Here we probed the mechanism of the influence of TRPV1 on ganglion cell survival in mouse models of glaucoma. We found that induced elevations of ocular pressure increased TRPV1 in ganglion cells and its colocalization at excitatory synapses to their dendrites, whereas chronic elevation progressively increased ganglion cell Trpv1 mRNA. Enhanced TRPV1 expression in ganglion cells was transient and supported a reversal of the effect of TRPV1 on ganglion cells from hyperpolarizing to depolarizing, which was also transient. Short-term enhancement of TRPV1-mediated activity led to a delayed increase in axonal spontaneous excitation that was absent in ganglion cells from Trpv1(-/-) retina. In isolated ganglion cells, pharmacologically activated TRPV1 mobilized to discrete nodes along ganglion cell dendrites that corresponded to sites of elevated Ca(2+). These results suggest that TRPV1 may promote retinal ganglion cell survival through transient enhancement of local excitation and axonal activity in response to ocular stress. Copyright © 2014 the authors 0270-6474/14/3415369-13$15.00/0.
Mergler, Stefan; Garreis, Fabian; Sahlmüller, Monika; Reinach, Peter S.; Paulsen, Friedrich; Pleyer, Uwe
2010-01-01
Thermosensitive transient receptor potential proteins (TRPs) such as TRPV1-TRPV4 are all heat-activated non-selective cation channels that are modestly permeable to Ca2+. TRPV1, TRPV3 and TRPV4 functional expression were previously identified in human corneal epithelial cells (HCEC). However, the membrane currents were not described underlying their activation by either selective agonists or thermal variation. This study characterized the membrane currents and [Ca 2+]i transients induced by thermal and agonist TRPV1 and 4 stimulation. TRPV1 and 4 expressions were confirmed by RT-PCR and TRPV2 transcripts were also detected. In fura2-loaded HCEC, a TRPV1-3 selective agonist, 100 µM 2-aminoethoxydiphenyl borate (2-APB), induced intracellular Ca2+ transients and an increase in non-selective cation outward currents that were suppressed by ruthenium-red (RuR) (10–20 µM), a nonselective TRPV channel blocker. These changes were also elicited by rises in ambient temperature from 25 °C to over 40 °C. RuR (5 µM) and a selective TRPV1 channel blocker capsazepine (CPZ) (10 µM) or another related blocker, lanthanum chloride (La3+) (100 µM) suppressed these temperature-induced Ca2+ increases. Planar patch-clamp technique was used to characterize the currents underlying Ca2+ transients. Increasing the temperature to over 40 °C induced reversible rises in non-selective cation currents. Moreover, a hypotonic challenge (25 %) increased non-selective cation currents confirming TRPV4 activity. We conclude that HCEC possess in addition to thermo-sensitive TRPV3 activity TRPV1, TRPV2 and TRPV4 activity. Their activation confers temperature sensitivity at the ocular surface, which may protect the cornea against such stress. PMID:21506114
Isolated transient loss of consciousness is an indicator of significant injury.
Owings, J T; Wisner, D H; Battistella, F D; Perlstein, J; Walby, W F; Tharratt, R S
1998-09-01
To determine if isolated transient loss of consciousness is an indicator of significant injury. University-based level I trauma center. Phase 1 retrospective case series of all patients with trauma admitted directly from the emergency department to the operating room or an intensive care unit who had transient loss of consciousness as their only trauma triage criterion. Phase 2 prospective case series of all trauma patients transported by emergency medical system personnel with transient loss of consciousness as their only trauma triage criterion. Emergency operation and intensive care unit admission. Phase 1: From January 1, 1992, to March 31, 1995, we admitted 10255 patients with trauma. Three hundred seven (3%) met the enrollment criteria and were admitted to the operating room (n = 168) or intensive care unit (n = 139). Of these, 58 (18.9%) were taken to the operating room emergently to manage life-threatening injuries: 11 (4%) had craniotomies and 47 (15%) had non-neurosurgical operations. Phase 2: From July 1 to December 31, 1996, 2770 trauma patients were transported to our facility; 135 (4.9%) met the enrollment criteria. Forty-one (30.4%) of these required admission, and 6 (4.4%) were taken emergently to the operating room from the emergency department (1 [1%] for a craniotomy, 3 [2.2%] for intra-abdominal bleeding, and 2 [1.5%] for other procedures). Two (1.5%) of the 135 patients died. Patients with isolated transient loss of consciousness are at significant risk of critical surgical and neurosurgical injuries. These patients should be triaged to trauma centers or hospitals with adequate imaging, surgical, and neurosurgical resources.
2014-02-25
prognosis of viral infections, particu- larly in neonates and infants at risk of developing septic shock (Griffin and Moorman, 2001; Griffin et al...2004, 2005). In their studies, it was reported that abnormal HR with reduced variabil- ity and transient decelerations preceded neonatal /infant sepsis...hospital resuscitative treatment in DHF patients. After correction for prevailing HR, LF variability was still significantly increased (both P < 0.01) on day
Hacker, David L; Bertschinger, Martin; Baldi, Lucia; Wurm, Florian M
2004-10-27
Human embryonic kidney 293 (HEK293) cells, a widely used host for large-scale transient expression of recombinant proteins, are transformed with the adenovirus E1A and E1B genes. Because the E1A proteins function as transcriptional activators or repressors, they may have a positive or negative effect on transient transgene expression in this cell line. Suspension cultures of HEK293 EBNA (HEK293E) cells were co-transfected with a reporter plasmid expressing the GFP gene and a plasmid expressing a short hairpin RNA (shRNA) targeting the E1A mRNAs for degradation by RNA interference (RNAi). The presence of the shRNA in HEK293E cells reduced the steady state level of E1A mRNA up to 75% and increased transient GFP expression from either the elongation factor-1alpha (EF-1alpha) promoter or the human cytomegalovirus (HCMV) immediate early promoter up to twofold. E1A mRNA depletion also resulted in a twofold increase in transient expression of a recombinant IgG in both small- and large-scale suspension cultures when the IgG light and heavy chain genes were controlled by the EF-1alpha promoter. Finally, transient IgG expression was enhanced 2.5-fold when the anti-E1A shRNA was expressed from the same vector as the IgG light chain gene. These results demonstrated that E1A has a negative effect on transient gene expression in HEK293E cells, and they established that RNAi can be used to enhance recombinant protein expression in mammalian cells.
Laboratory investigations of the physics of steam flow in a porous medium
Herkelrath, W.N.; Moench, A.F.
1982-01-01
Experiments were carried out in the laboratory to test a theory of transient flow of pure steam in a uniform porous medium. This theory is used extensively in modeling pressure-transient behavior in vapor-dominated geothermal systems. Transient, superheated steam-flow experiments were run by bringing a cylinder of porous material to a uniform initial pressure, and then making a step increase in pressure at one end of the sample, while monitoring the pressure-transient breakthrough at the other end. It was found in experiments run at 100?, 125?, and 146?C that the time required for steam-pressure transients to propagate through an unconsolidated material containing sand, silt, and clay was 10 to 25 times longer than predicted by theory. It is hypothesized that the delay in the steam-pressure transient was caused by adsorption of steam in the porous sample. In order to account for steam adsorption, a sink term was included in the conservation of mass equation. In addition, energy transfer in the system has to be considered because latent heat is released when steam adsorption occurs, increasing the sample temperature by as much as 10?C. Finally, it was recognized that the steam pressure was a function of both the temperature and the amount of adsorption in the sample. For simplicity, this function was assumed to be in equilibrium adsorption isotherm, which was determined by experiment. By solving the modified mass and energy equations numerically, subject to the empirical adsorption isotherm relationship, excellent theoretical simulation of the experiments was achieved. The experiments support the hypothesis that adsorption of steam can strongly influence steam pressure-transient behavior in porous media; the results suggest that the modified steam-flow theory, which includes steam adsorption terms, should be used in modeling steam flow in vapor-dominated geothermal systems.
NASA Astrophysics Data System (ADS)
Fu, Zhidong; Qin, Suyang; Liu, Hong
2014-01-01
The dynamics of dual vortex ring flows is studied experimentally and numerically in a model system that consists of a piston-cylinder apparatus. The flows are generated by double identical strokes which have the velocity profile characterized by the sinusoidal function of half the period. By calculating the total wake impulse in two strokes in the experiments, it is found that the average propulsive force increases by 50% in the second stroke for the sufficiently small stroke length, compared with the first stroke. In the numerical simulations, two types of transient force augmentation are revealed, there being the transient force augmentation for the small stroke lengths and the absolute transient force augmentation for the large stroke lengths. The relative transient force augmentation increases to 78% for L/D = 1, while the absolute transient force augmentation for L/D = 4 is twice as much as that for L/D = 1. Further investigation demonstrates that the force augmentation is attributed to the interaction between vortex rings, which induces transport of vortex impulse and more evident fluid entrainment. The critical situation of vortex ring separation is defined and indicated, with vortex spacing falling in a narrow gap when the stroke lengths vary. A new model is proposed concerning the limiting process of impulse, further suggesting that apart from vortex formation timescale, vortex spacing should be interpreted as an independent timescale to reflect the dynamics of vortex interaction.
NASA Astrophysics Data System (ADS)
Deng, Jiechun; Xu, Haiming; Shi, Ning; Zhang, Leying; Ma, Jing
2017-08-01
Roles of the Tibetan Plateau (TP) in forming and changing the seasonal Asian climate system have been widely explored. However, little is known about modulation effects of the TP on extratropical transient eddies (TEs) and subsequent synoptic responses of the East Asian rainfall. In this study, the Community Atmosphere Model version 5.1 coupled with a slab ocean model is employed to highlight the important role of the TP in regulating the upper-tropospheric transient wave train. Comparison between sensitivity experiments with and without the TP shows that the northern TP excites a strong anomalous anticyclone, which shifts the upper-level East Asian westerly jet northward and helps transfer barotropic and baroclinic energy from the mean flow to the synoptic TE flow. The transient wave train is primarily shifted northward by northern TP and is forced to propagate southeastward along the eastern flank of the TP until reaching eastern China. Before the strengthening of monsoonal southerlies, the TP-modulated transient wave train cools the troposphere, which decreases the static stability over northern China. Meanwhile, the associated anomalous warm advection induces ascending motion, leading to excessive rainfall by releasing unstable energy as the southerly strengthens. Due to the southeastward propagation of the wave train, anomalous heavy rainfall subsequently appears over eastern China from north to south, which increases day-to-day rainfall variation in this region. Additionally, occurrence of this upper-tropospheric transient wave train associated with low-level southerly peak is substantially increased by northern TP.
Etiological evaluation of primary congenital hypothyroidism cases
Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz
2017-01-01
Aim Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Material and Methods Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007–June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. Results The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Conclusions Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism. PMID:28747839
THE DIFFERENCE IMAGING PIPELINE FOR THE TRANSIENT SEARCH IN THE DARK ENERGY SURVEY
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kessler, R.; Scolnic, D.; Marriner, J.
2015-12-15
We describe the operation and performance of the difference imaging pipeline (DiffImg) used to detect transients in deep images from the Dark Energy Survey Supernova program (DES-SN) in its first observing season from 2013 August through 2014 February. DES-SN is a search for transients in which ten 3 deg{sup 2} fields are repeatedly observed in the g, r, i, z passbands with a cadence of about 1 week. The observing strategy has been optimized to measure high-quality light curves and redshifts for thousands of Type Ia supernovae (SNe Ia) with the goal of measuring dark energy parameters. The essential DiffImgmore » functions are to align each search image to a deep reference image, do a pixel-by-pixel subtraction, and then examine the subtracted image for significant positive detections of point-source objects. The vast majority of detections are subtraction artifacts, but after selection requirements and image filtering with an automated scanning program, there are ∼130 detections per deg{sup 2} per observation in each band, of which only ∼25% are artifacts. Of the ∼7500 transients discovered by DES-SN in its first observing season, each requiring a detection on at least two separate nights, Monte Carlo (MC) simulations predict that 27% are expected to be SNe Ia or core-collapse SNe. Another ∼30% of the transients are artifacts in which a small number of observations satisfy the selection criteria for a single-epoch detection. Spectroscopic analysis shows that most of the remaining transients are AGNs and variable stars. Fake SNe Ia are overlaid onto the images to rigorously evaluate detection efficiencies and to understand the DiffImg performance. The DiffImg efficiency measured with fake SNe agrees well with expectations from a MC simulation that uses analytical calculations of the fluxes and their uncertainties. In our 8 “shallow” fields with single-epoch 50% completeness depth ∼23.5, the SN Ia efficiency falls to 1/2 at redshift z ≈ 0.7; in our 2 “deep” fields with mag-depth ∼24.5, the efficiency falls to 1/2 at z ≈ 1.1. A remaining performance issue is that the measured fluxes have additional scatter (beyond Poisson fluctuations) that increases with the host galaxy surface brightness at the transient location. This bright-galaxy issue has minimal impact on the SNe Ia program, but it may lower the efficiency for finding fainter transients on bright galaxies.« less
The Difference Imaging Pipeline for the Transient Search in the Dark Energy Survey
NASA Astrophysics Data System (ADS)
Kessler, R.; Marriner, J.; Childress, M.; Covarrubias, R.; D'Andrea, C. B.; Finley, D. A.; Fischer, J.; Foley, R. J.; Goldstein, D.; Gupta, R. R.; Kuehn, K.; Marcha, M.; Nichol, R. C.; Papadopoulos, A.; Sako, M.; Scolnic, D.; Smith, M.; Sullivan, M.; Wester, W.; Yuan, F.; Abbott, T.; Abdalla, F. B.; Allam, S.; Benoit-Lévy, A.; Bernstein, G. M.; Bertin, E.; Brooks, D.; Carnero Rosell, A.; Carrasco Kind, M.; Castander, F. J.; Crocce, M.; da Costa, L. N.; Desai, S.; Diehl, H. T.; Eifler, T. F.; Fausti Neto, A.; Flaugher, B.; Frieman, J.; Gerdes, D. W.; Gruen, D.; Gruendl, R. A.; Honscheid, K.; James, D. J.; Kuropatkin, N.; Li, T. S.; Maia, M. A. G.; Marshall, J. L.; Martini, P.; Miller, C. J.; Miquel, R.; Nord, B.; Ogando, R.; Plazas, A. A.; Reil, K.; Romer, A. K.; Roodman, A.; Sanchez, E.; Sevilla-Noarbe, I.; Smith, R. C.; Soares-Santos, M.; Sobreira, F.; Tarle, G.; Thaler, J.; Thomas, R. C.; Tucker, D.; Walker, A. R.; DES Collaboration
2015-12-01
We describe the operation and performance of the difference imaging pipeline (DiffImg) used to detect transients in deep images from the Dark Energy Survey Supernova program (DES-SN) in its first observing season from 2013 August through 2014 February. DES-SN is a search for transients in which ten 3 deg2 fields are repeatedly observed in the g, r, i, z passbands with a cadence of about 1 week. The observing strategy has been optimized to measure high-quality light curves and redshifts for thousands of Type Ia supernovae (SNe Ia) with the goal of measuring dark energy parameters. The essential DiffImg functions are to align each search image to a deep reference image, do a pixel-by-pixel subtraction, and then examine the subtracted image for significant positive detections of point-source objects. The vast majority of detections are subtraction artifacts, but after selection requirements and image filtering with an automated scanning program, there are ˜130 detections per deg2 per observation in each band, of which only ˜25% are artifacts. Of the ˜7500 transients discovered by DES-SN in its first observing season, each requiring a detection on at least two separate nights, Monte Carlo (MC) simulations predict that 27% are expected to be SNe Ia or core-collapse SNe. Another ˜30% of the transients are artifacts in which a small number of observations satisfy the selection criteria for a single-epoch detection. Spectroscopic analysis shows that most of the remaining transients are AGNs and variable stars. Fake SNe Ia are overlaid onto the images to rigorously evaluate detection efficiencies and to understand the DiffImg performance. The DiffImg efficiency measured with fake SNe agrees well with expectations from a MC simulation that uses analytical calculations of the fluxes and their uncertainties. In our 8 “shallow” fields with single-epoch 50% completeness depth ˜23.5, the SN Ia efficiency falls to 1/2 at redshift z ≈ 0.7; in our 2 “deep” fields with mag-depth ˜24.5, the efficiency falls to 1/2 at z ≈ 1.1. A remaining performance issue is that the measured fluxes have additional scatter (beyond Poisson fluctuations) that increases with the host galaxy surface brightness at the transient location. This bright-galaxy issue has minimal impact on the SNe Ia program, but it may lower the efficiency for finding fainter transients on bright galaxies.
THE DIFFERENCE IMAGING PIPELINE FOR THE TRANSIENT SEARCH IN THE DARK ENERGY SURVEY
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kessler, R.; Marriner, J.; Childress, M.
2015-11-06
We describe the operation and performance of the difference imaging pipeline (DiffImg) used to detect transients in deep images from the Dark Energy Survey Supernova program (DES-SN) in its first observing season from 2013 August through 2014 February. DES-SN is a search for transients in which ten 3 deg(2) fields are repeatedly observed in the g, r, i, z passbands with a cadence of about 1 week. The observing strategy has been optimized to measure high-quality light curves and redshifts for thousands of Type Ia supernovae (SNe Ia) with the goal of measuring dark energy parameters. The essential DiffImg functionsmore » are to align each search image to a deep reference image, do a pixel-by-pixel subtraction, and then examine the subtracted image for significant positive detections of point-source objects. The vast majority of detections are subtraction artifacts, but after selection requirements and image filtering with an automated scanning program, there are similar to 130 detections per deg(2) per observation in each band, of which only similar to 25% are artifacts. Of the similar to 7500 transients discovered by DES-SN in its first observing season, each requiring a detection on at least two separate nights, Monte Carlo (MC) simulations predict that 27% are expected to be SNe Ia or core-collapse SNe. Another similar to 30% of the transients are artifacts in which a small number of observations satisfy the selection criteria for a single-epoch detection. Spectroscopic analysis shows that most of the remaining transients are AGNs and variable stars. Fake SNe Ia are overlaid onto the images to rigorously evaluate detection efficiencies and to understand the DiffImg performance. The DiffImg efficiency measured with fake SNe agrees well with expectations from a MC simulation that uses analytical calculations of the fluxes and their uncertainties. In our 8 "shallow" fields with single-epoch 50% completeness depth similar to 23.5, the SN Ia efficiency falls to 1/2 at redshift z approximate to 0.7; in our 2 "deep" fields with mag-depth similar to 24.5, the efficiency falls to 1/2 at z approximate to 1.1. A remaining performance issue is that the measured fluxes have additional scatter (beyond Poisson fluctuations) that increases with the host galaxy surface brightness at the transient location. This bright-galaxy issue has minimal impact on the SNe Ia program, but it may lower the efficiency for finding fainter transients on bright galaxies.« less
The Difference Imaging Pipeline for the Transient Search in the Dark Energy Survey
Kessler, R.
2015-09-09
We describe the operation and performance of the difference imaging pipeline (DiffImg) used to detect transients in deep images from the Dark Energy Survey Supernova program (DES-SN) in its first observing season from 2013 August through 2014 February. DES-SN is a search for transients in which ten 3 deg 2 fields are repeatedly observed in the g, r, i, zpassbands with a cadence of about 1 week. Our observing strategy has been optimized to measure high-quality light curves and redshifts for thousands of Type Ia supernovae (SNe Ia) with the goal of measuring dark energy parameters. The essential DiffImg functionsmore » are to align each search image to a deep reference image, do a pixel-by-pixel subtraction, and then examine the subtracted image for significant positive detections of point-source objects. The vast majority of detections are subtraction artifacts, but after selection requirements and image filtering with an automated scanning program, there are ~130 detections per deg 2 per observation in each band, of which only ~25% are artifacts. Of the ~7500 transients discovered by DES-SN in its first observing season, each requiring a detection on at least two separate nights, Monte Carlo (MC) simulations predict that 27% are expected to be SNe Ia or core-collapse SNe. Another ~30% of the transients are artifacts in which a small number of observations satisfy the selection criteria for a single-epoch detection. Spectroscopic analysis shows that most of the remaining transients are AGNs and variable stars. Fake SNe Ia are overlaid onto the images to rigorously evaluate detection efficiencies and to understand the DiffImg performance. Furthermore, the DiffImg efficiency measured with fake SNe agrees well with expectations from a MC simulation that uses analytical calculations of the fluxes and their uncertainties. In our 8 "shallow" fields with single-epoch 50% completeness depth ~23.5, the SN Ia efficiency falls to 1/2 at redshift z ≈ 0.7; in our 2 "deep" fields with mag-depth ~24.5, the efficiency falls to 1/2 at z ≈ 1.1. A remaining performance issue is that the measured fluxes have additional scatter (beyond Poisson fluctuations) that increases with the host galaxy surface brightness at the transient location. This bright-galaxy issue has minimal impact on the SNe Ia program, but it may lower the efficiency for finding fainter transients on bright galaxies.« less
ERIC Educational Resources Information Center
Monroe, Charles; Newman, John
2005-01-01
This simple example demonstrates the physical significance of similarity solutions and the utility of dimensional and asymptotic analysis of partial differential equations. A procedure to determine the existence of similarity solutions is proposed and subsequently applied to transient constant-flux heat transfer. Short-time expressions follow from…
Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir
2017-01-01
The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.
NASA Astrophysics Data System (ADS)
Kimura, T.; Hiraki, Y.; Tao, C.; Tsuchiya, F.; Delamere, P. A.; Yoshioka, K.; Murakami, G.; Yamazaki, A.; Kita, H.; Badman, S. V.; Fukazawa, K.; Yoshikawa, I.; Fujimoto, M.
2018-03-01
The production and transport of plasma mass are essential processes in the dynamics of planetary magnetospheres. At Jupiter, it is hypothesized that Io's volcanic plasma carried out of the plasma torus is transported radially outward in the rotating magnetosphere and is recurrently ejected as plasmoid via tail reconnection. The plasmoid ejection is likely associated with particle energization, radial plasma flow, and transient auroral emissions. However, it has not been demonstrated that plasmoid ejection is sensitive to mass loading because of the lack of simultaneous observations of both processes. We report the response of plasmoid ejection to mass loading during large volcanic eruptions at Io in 2015. Response of the transient aurora to the mass loading rate was investigated based on a combination of Hisaki satellite monitoring and a newly developed analytic model. We found that the transient aurora frequently recurred at a 2-6 day period in response to a mass loading increase from 0.3 to 0.5 t/s. In general, the recurrence of the transient aurora was not significantly correlated with the solar wind, although there was an exceptional event with a maximum emission power of 10 TW after the solar wind shock arrival. The recurrence of plasmoid ejection requires the precondition that an amount comparable to the total mass of magnetosphere, 1.5 Mt, is accumulated in the magnetosphere. A plasmoid mass of more than 0.1 Mt is necessary in case that the plasmoid ejection is the only process for mass release.
Wu, Yang; You, Huihui; Ma, Ping; Li, Li; Yuan, Ye; Li, Jinquan; Ye, Xin; Liu, Xudong; Yao, Hanchao; Chen, Ruchong; Lai, Kefang; Yang, Xu
2013-01-01
Objective Asthma is a complex pulmonary inflammatory disease characterized by the hyper-responsiveness, remodeling and inflammation of airways. Formaldehyde is a common indoor air pollutant that can cause asthma in people experiencing long-term exposure. The irritant effect and adjuvant effect are the two possible pathways of formaldehyde promoted asthma. Methodology/Principal Findings To explore the neural mechanisms and adjuvant effect of formaldehyde, 48 Balb/c mice in six experimental groups were exposed to (a) vehicle control; (b) ovalbumin; (c) formaldehyde (3.0 mg/m3); (d) ovalbumin+formaldehyde (3.0 mg/m3); (e) ovalbumin+formaldehyde (3.0 mg/m3)+HC-030031 (transient receptor potential ankyrin 1 antagonist); (f) ovalbumin+formaldehyde (3.0 mg/m3)+ capsazepine (transient receptor potential vanilloid 1 antagonist). Experiments were conducted after 4 weeks of combined exposure and 1-week challenge with aerosolized ovalbumin. Airway hyper-responsiveness, pulmonary tissue damage, eosinophil infiltration, and increased levels of interleukin-4, interleukin-6, interleukin-1β, immunoglobulin E, substance P and calcitonin gene-related peptide in lung tissues were found in the ovalbumin+formaldehyde (3.0 mg/m3) group compared with the values seen in ovalbumin -only immunized mice. Except for interleukin-1β levels, other changes in the levels of biomarker could be inhibited by HC-030031 and capsazepine. Conclusions/Significance Formaldehyde might be a key risk factor for the rise in asthma cases. Transient receptor potential ion channels and neuropeptides have important roles in formaldehyde promoted-asthma. PMID:23671638
Ramadan, Epolia; Blanchard, Helene; Cheon, Yewon; Fox, Meredith A; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I; Basselin, Mireille
2014-05-01
Fetal and perinatal exposure to selective serotonin (5-HT) reuptake inhibitors (SSRIs) has been reported to alter childhood behavior, while transient early exposure in rodents is reported to alter their behavior and decrease brain extracellular 5-HT in adulthood. Since 5-HT2A/2C receptor-mediated neurotransmission can involve G-protein coupled activation of cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (ARA) from synaptic membrane phospholipid, we hypothesized that transient postnatal exposure to fluoxetine would alter brain ARA metabolism in adult mice. Brain ARA incorporation coefficients k* and rates Jin were quantitatively imaged following intravenous [1-(14)C]ARA infusion of unanesthetized adult mice that had been injected daily with fluoxetine (10mg/kg i.p.) or saline during postnatal days P4-P21. Expression of brain ARA metabolic enzymes and other relevant markers also was measured. On neuroimaging, k* and Jin was decreased widely in early fluoxetine- compared to saline-treated adult mice. Of the enzymes measured, cPLA2 activity was unchanged, while Ca(2+)-independent iPLA2 activity was increased. There was a significant 74% reduced protein level of cytochrome P450 (CYP) 4A, which can convert ARA to 20-HETE. Reduced brain ARA metabolism in adult mice transiently exposed to postnatal fluoxetine, and a 74% reduction in CYP4A protein, suggest long-term effects independent of drug presence in brain ARA metabolism, and in CYP4A metabolites. These changes might contribute to reported altered behavior following early SSRI in rodents. Published by Elsevier Ltd.
Transient creep and semibrittle behavior of crystalline rocks
Carter, N.L.; Kirby, S.H.
1978-01-01
We review transient creep and semibrittle behavior of crystalline solids. The results are expected to be pertinent to crystalline rocks undergoing deformation in the depth range 5 to 20 km, corresponding to depths of focus of many major earthquakes. Transient creep data for crystalline rocks at elevated temperatures are analyzed but are poorly understood because of lack of information on the deformation processes which, at low to moderate pressure, are likely to be semibrittle in nature. Activation energies for transient creep at high effective confining pressure are much higher than those found for atmospheric pressure tests in which thermally-activated microfracturing probably dominates the creep rate. Empirical transient creep equations are extrapolated at 200?? to 600??C, stresses from 0.1 to 1.0 kbar, to times ranging from 3.17??102 to 3.17??108 years. At the higher temperatures, appreciable transient creep strains may take place but the physical significance of the results is in question because the flow mechanisms have not been determined. The purpose of this paper is to stimulate careful research on this important topic. ?? 1978 Birkha??user Verlag.
NASA Astrophysics Data System (ADS)
Singh, Subhash; Mohapatra, Y. N.
2017-06-01
We have investigated switch-on drain-source current transients in fully solution-processed thin film transistors based on 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-pentacene) using cross-linked poly-4-vinylphenol as a dielectric. We show that the nature of the transient (increasing or decreasing) depends on both the temperature and the amplitude of the switching pulse at the gate. The isothermal transients are analyzed spectroscopically in a time domain to extract the degree of non-exponentiality and its possible origin in trap kinetics. We propose a phenomenological model in which the exchange of electrons between interfacial ions and traps controls the nature of the drain current transients dictated by the Fermi level position. The origin of interfacial ions is attributed to the essential fabrication step of UV-ozone treatment of the dielectric prior to semiconductor deposition.
Transient Evoked and Distortion Product Otoacoustic Emissions in a Group of Neonates
Silva, Giovanna Cesar; Delecrode, Camila Ribas; Kemp, Adriana Tahara; Martins, Fabiana; Cardoso, Ana Claudia Vieira
2015-01-01
Introduction The most commonly used method in neonatal hearing screening programs is transient evoked otoacoustic emissions in the first stage of the process. There are few studies comparing transient evoked otoacoustic emissions with distortion product, but some authors have investigated the issue. Objective To correlate the results of transient evoked and distortion product otoacoustic emissions in a Brazilian maternity hospital. Methods This is a cross-sectional, comparative, and prospective study. The study included 579 newborns, ranging from 6 to 54 days of age, born in a low-risk maternity hospital and assessed for hearing loss. All neonates underwent hearing screening by transient evoked and distortion product otoacoustic emissions. The results were analyzed using the Spearman correlation test to relate the two procedures. Results The pass index on transient evoked otoacoustic emissions was 95% and on distortion product otoacoustic emissions was 91%. The comparison of the two procedures showed that 91% of neonates passed on both procedures, 4.5% passed only on transient evoked otoacoustic emissions, 0.5% passed only on distortion product otoacoustic emissions, and 4% failed on both procedures. The inferential analysis showed a significant strong positive relationship between the two procedures. Conclusion The failure rate was higher in distortion product otoacoustic emissions when compared with transient evoked; however, there was correlation between the results of the procedures. PMID:26157501
Functional Imaging of Sleep Vertex Sharp Transients
Stern, John M.; Caporro, Matteo; Haneef, Zulfi; Yeh, Hsiang J.; Buttinelli, Carla; Lenartowicz, Agatha; Mumford, Jeanette A.; Parvizi, Josef; Poldrack, Russell A.
2011-01-01
Objective The vertex sharp transient (VST) is an electroencephalographic (EEG) discharge that is an early marker of non-REM sleep. It has been recognized since the beginning of sleep physiology research, but its source and function remain mostly unexplained. We investigated VST generation using functional MRI (fMRI). Methods Simultaneous EEG and fMRI were recorded from 7 individuals in drowsiness and light sleep. VST occurrences on EEG were modeled with fMRI using an impulse function convolved with a hemodynamic response function to identify cerebral regions correlating to the VSTs. A resulting statistical image was thresholded at Z>2.3. Results Two hundred VSTs were identified. Significantly increased signal was present bilaterally in medial central, lateral precentral, posterior superior temporal, and medial occipital cortex. No regions of decreased signal were present. Conclusion The regions are consistent with electrophysiologic evidence from animal models and functional imaging of human sleep, but the results are specific to VSTs. The regions principally encompass the primary sensorimotor cortical regions for vision, hearing, and touch. Significance The results depict a network comprising the presumed VST generator and its associated regions. The associated regions functional similarity for primary sensation suggests a role for VSTs in sensory experience during sleep. PMID:21310653
Endocrinological effects of single daily ketoconazole administration in male beagle dogs.
De Coster, R; Beerens, D; Dom, J; Willemsens, G
1984-10-01
Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3-4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17 alpha-hydroxyprogesterone, progesterone and 17 alpha, 20 alpha-dihydroxyprogesterone increased within 3-10 h before returning to basal values after 24 h. Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17 alpha levels were not significantly modified by the treatment. These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17-20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17 beta plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.
Atopy as a risk factor for subclinical hypothyroidism development in children.
Pedullà, Marcella; Umano, Giuseppina Rosaria; Fierro, Vincenzo; Capuano, Francesco; Di Sessa, Anna; Marzuillo, Pierluigi; Perrone, Laura; Del Giudice, Emanuele Miraglia
2017-08-28
Increased thyroid stimulating hormone (TSH) serum concentration can be a marker of subclinical hypothyroidism (SCH) or transient hyperthyrotropinemia. The aim of our study was to evaluate whether high serum TSH concentrations in allergic children could represent true SCH or isolated and transient hyperthyrotropinemia. We enrolled 620 allergic children (1.11-12.8 years) consecutively attending to our department. They were classified as atopics and non-atopics on the basis of the atopy work-up and, at baseline, they were investigated for thyroid function and low-grade inflammation state. Further, TSH was evaluated after 6 (T1) and 12 (T2) months. Both atopics and non-atopics showed higher SCH prevalence compared to controls (p=0.0055 and p=0.02, respectively), and a significant association between atopy and SCH (OR 10.11, 95% CI 1.36-75.12) was found. Both at T1 and T2, atopics had a significant risk of developing severe SCH compared to non-atopics (RR 1.8, 95% CI 1.39-2.34 and 1.61, 95% CI 1.21-2.14; respectively). Our data may suggest that hyperthyrotropinemia in atopic children could be used as a marker of true SCH.
Jara, José L; Saeed, Nazia P; Panerai, Ronney B; Robinson, Thompson G
2018-01-01
To devise an appropriate measure of the quality of a magnetic resonance imaging (MRI) signal for the assessment of dynamic cerebral autoregulation, and propose simple strategies to improve its quality. Magnetic resonance images of 11 healthy subjects were scanned during a transient decrease in arterial blood pressure (BP). Mean signals were extracted from non-overlapping brain regions for each image. An ad-hoc contrast-to-noise ratio (CNR) was used to evaluate the quality of these regional signals. Global mean signals were obtained by averaging the set of regional signals resulting after applying a Hampel filter and discarding a proportion of the lower quality component signals. Significant improvements in CNR values of global mean signals were obtained, whilst maintaining significant correlation with the original ones. A Hampel filter with a small moving window and a low rejection threshold combined with a selection of the 50% component signals seems a recommendable option. This work has demonstrated the possibility of improving the quality of MRI signals acquired during transient drops in BP. This approach needs validation at a voxel level, which could help to consolidate MRI as a technological alternative to the standard techniques for the study of cerebral autoregulation.
Pathophysiological effect of fat embolism in a canine model of pulmonary contusion.
Elmaraghy, A W; Aksenov, S; Byrick, R J; Richards, R R; Schemitsch, E H
1999-08-01
The objective of this study was to determine the individual and combined effects of pulmonary contusion and fat embolism on the hemodynamics and pulmonary pathophysiology in a canine model of acute traumatic pulmonary injury. After a thoracotomy, twenty-one skeletally mature dogs were randomly assigned to one of three groups. Unilateral pulmonary contusion alone was produced in Group 1 (seven dogs); pulmonary contusion and fat embolism, in Group 2 (seven dogs); and fat embolism alone, in Group 3 (seven dogs). Pulmonary contusion was produced by standardized compression of the left lung with a piezoelectric force transducer. Fat embolism was produced by femoral and tibial reaming followed by pressurization of the intramedullary canals. Cardiac output, systolic blood pressure, peak airway pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, partial pressure of arterial oxygen, and partial pressure of carbon dioxide were monitored for all groups. From these data, several outcome parameters were calculated: total thoracic compliance, alveolar-arterial oxygen gradient, and ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration. All of the dogs were killed after eight hours, and tissue samples were obtained from the brain, kidneys, and lungs for histological analysis. Lung samples were assigned scores for pulmonary edema (the presence of fluid in the alveoli) and inflammation (the presence of neutrophils or hyaline membranes, or both). The percentage of the total area occupied by fat was determined. Pulmonary contusion alone caused a significant increase in the alveolar-arterial oxygen gradient but only after seven hours (p = 0.034). Fat embolism alone caused a significant transient decrease in systolic blood pressure (p = 0.001) and a significant transient increase in pulmonary arterial pressure (p = 0.01) and pulmonary capillary wedge pressure (p = 0.015). Fat embolism alone also caused a significant sustained decrease in the ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration (p = 0.0001) and a significant increase in the alveolar-arterial oxygen gradient (p = 0.0001). The combination of pulmonary contusion and fat embolism caused a significant transient increase in pulmonary capillary wedge pressure (p = 0.0013) as well as a significant sustained decrease in partial pressure of arterial oxygen (p = 0.0001) and a significant decrease in systolic blood pressure (p = 0.001) that lasted for an hour. Pulmonary contusion followed by fat embolism caused a significant increase in peak airway pressure (p = 0.015), alveolar-arterial oxygen gradient (p = 0.0001), and pulmonary arterial pressure (p = 0.01), and these effects persisted for five hours. Total thoracic compliance was decreased 6.4 percent by pulmonary contusion alone, 4.6 percent by fat embolism alone, and 23.5 percent by pulmonary contusion followed by fat embolism. The ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration was decreased 23.7 percent by pulmonary contusion alone, 52.3 percent by fat embolism alone, and 65.8 percent by pulmonary contusion followed by fat embolism. The mean pulmonary edema score was significantly higher with the combined injury than with either injury alone (p = 0.0001). None of the samples from the lungs demonstrated inflammation. Fat embolism combined with pulmonary contusion resulted in a significantly greater mean percentage of the area occupied by fat in the noncontused right lung than in the contused left lung (p = 0.001); however, no significant difference between the right and left lungs could be detected with fat embolism alone. The mean percentage of the glomerular and cerebral areas occupied by fat was greater with fat embolism combined with pulmonary contusion than with fat embolism alone (p = 0.0001 and p = 0.01, respectively). (ABSTRACT TRUNCATED)
Zhang, Jie; Deng, Yifeng; Ma, Huijie; Hou, Jiafa; Zhou, ZhenLei
2015-03-01
Ca2+ plays a major role in the regulation of signal transduction. Transient receptor potential vanilloid 6 is a Ca2+-selective channel that serves as an important rate-limiting step in the facilitation of Ca2+ entry into cells, but little is known about the regulation of transient receptor potential vanilloid 6 in chickens. In this study, we evaluated the effects of transient receptor potential vanilloid 6 gene interference on the expression of calbindin-D28K, Na+/Ca2+ exchangers, and plasma membrane Ca2+ ATPase 1b to investigate the mechanism underlying the regulation of transient receptor potential vanilloid 6. Three hairpin siRNA expression vectors targeting transient receptor potential vanilloid 6 (pSIREN- transient receptor potential vanilloid 6) and a negative control (pSIREN-control) were constructed and transfected into chicken osteoblasts. The mRNA and protein expression levels were evaluated by quantitative reverse transcription polymerase chain reaction and Western blot, respectively. The mRNA expression levels of transient receptor potential vanilloid 6 and calbindin-D28K were reduced by 45.7% (P<0.01) and 27.9% (P<0.01), respectively, 48 h after transfection with one of the three constructs (pSIREN- transient receptor potential vanilloid 6-3) compared with the level obtained in the untreated group. There was no significant difference in the mRNA expression levels of Na+/Ca2+ exchangers and plasma membrane Ca2+ ATPase 1b. The protein expression levels of transient receptor potential vanilloid 6 and calbindin-D28K were reduced by 40.2% (P<0.01) and 29.8% (P<0.01), respectively, 48 h after transfection with pSIREN-transient receptor potential vanilloid 6-3 compared with the level obtained in the untreated group. In conclusion, the vector-based transient receptor potential vanilloid 6-shRNA can efficiently suppress the mRNA and protein expression of transient receptor potential vanilloid 6 in chicken osteoblasts, and transient receptor potential vanilloid 6 regulates the expression of calbindin-D28K during Ca2+ transport. © 2015 Poultry Science Association Inc.
Aldosterone Upregulates Transient Receptor Potential Melastatin 7 (TRPM7).
Valinsky, William C; Jolly, Anna; Miquel, Perrine; Touyz, Rhian M; Shrier, Alvin
2016-09-16
Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed Mg(2+)-permeable ion channel fused to a C-terminal α-kinase domain. Recently, aldosterone was shown to increase intracellular Mg(2+) levels and alter inflammatory signaling in TRPM7-expressing HEK293 cells. This study was undertaken to assess whether these effects were related to an aldosterone-mediated increase of TRPM7 current and/or plasma membrane localization. Using HEK293 cells stably expressing WT-TRPM7, we found that 18-h application of aldosterone significantly increased TRPM7 current and TRPM7 plasma membrane protein expression by 48% and 34%, respectively. The aldosterone-mediated increase of TRPM7 current was inhibited by eplerenone, a mineralocorticoid receptor (MR) blocker, and GSK-650394, an inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1). SGK1 blockade also prevented the aldosterone-induced increase of TRPM7 plasma membrane protein. It was further determined that K1648R-TRPM7, the phosphotransferase-inactive TRPM7 mutant, was unresponsive to aldosterone. Therefore, chronic aldosterone treatment increases the plasma membrane expression of TRPM7, which is associated with an increase of TRPM7 current. This process occurs via an MR-dependent, genomic signaling cascade involving SGK1 and a functioning TRPM7 α-kinase domain. We suggest that this mechanism may be of general relevance when interpreting the effects of aldosterone because the MR receptor is found in multiple tissues, and TRPM7 and SGK1 are ubiquitously expressed. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Fluid control mechanisms in weightlessness
NASA Technical Reports Server (NTRS)
Leach, Carolyn S.
1987-01-01
Experiments performed on Space Shuttle flights have emphasized study of the earliest effects of the cephalad fluid shift resulting from microgravity. Analysis of one subject's urine collected during flight showed that a sharp increase in antidiuretic hormone occurred within 2 h of launch, followed by an increase in cortisol excretion. Although this subject had symptoms of the space adaptation syndrome (SAS), inflight data from Spacelab missions suggested that these transient changes were not caused by SAS. Unpaired t-tests and Mann-Whitney tests showed that before and after flight, plasma thyroxine and urine osmolality were significantly higher in Shuttle crewmembers who exhibited more severe symptoms of SAS than in asymptomatic crewmembers.
Ma, Xiaojian; Huang, Biao; Wang, Guoyu; Zhang, Mindi
2017-01-01
The objective of this paper is to investigate the transient conical bubble structure (CBS) and acoustic flow structure in ultrasonic field. In the experiment, the high-speed video and particle image velocimetry (PIV) techniques are used to measure the acoustic cavitation patterns, as well as the flow velocity and vorticity fields. Results are presented for a high power ultrasound with a frequency of 18kHz, and the range of the input power is from 50W to 250W. The results of the experiment show the input power significantly affects the structures of CBS, with the increase of input power, the cavity region of CBS and the velocity of bubbles increase evidently. For the transient motion of bubbles on radiating surface, two different types could be classified, namely the formation, aggregation and coalescence of cavitation bubbles, and the aggregation, shrink, expansion and collapse of bubble cluster. Furthermore, the thickness of turbulent boundary layer near the sonotrode region is found to be much thicker, and the turbulent intensities are much higher for relatively higher input power. The vorticity distribution is prominently affected by the spatial position and input power. Copyright © 2016 Elsevier B.V. All rights reserved.
Zizys, Darius; Gaidys, Rimvydas; Dauksevicius, Rolanas; Ostasevicius, Vytautas; Daniulaitis, Vytautas
2015-01-01
The piezoelectric transduction mechanism is a common vibration-to-electric energy harvesting approach. Piezoelectric energy harvesters are typically mounted on a vibrating host structure, whereby alternating voltage output is generated by a dynamic strain field. A design target in this case is to match the natural frequency of the harvester to the ambient excitation frequency for the device to operate in resonance mode, thus significantly increasing vibration amplitudes and, as a result, energy output. Other fundamental vibration modes have strain nodes, where the dynamic strain field changes sign in the direction of the cantilever length. The paper reports on a dimensionless numerical transient analysis of a cantilever of a constant cross-section and an optimally-shaped cantilever with the objective to accurately predict the position of a strain node. Total effective strain produced by both cantilevers segmented at the strain node is calculated via transient analysis and compared to the strain output produced by the cantilevers segmented at strain nodes obtained from modal analysis, demonstrating a 7% increase in energy output. Theoretical results were experimentally verified by using open-circuit voltage values measured for the cantilevers segmented at optimal and suboptimal segmentation lines. PMID:26703623
Obstructive apnea during sleep is associated with peripheral vasoconstriction
NASA Technical Reports Server (NTRS)
Imadojemu, Virginia A.; Gleeson, Kevin; Gray, Kristen S.; Sinoway, Lawrence I.; Leuenberger, Urs A.
2002-01-01
Obstructive apnea during sleep is associated with a substantial transient blood pressure elevation. The mechanism of this pressor response is unclear. In this study we measured muscle sympathetic nerve activity (MSNA), mean arterial pressure (Psa), and mean limb blood velocity as an index of blood flow (MBV, Doppler) and calculated changes in limb vascular resistance during and after apneas during both wakefulness and sleep in patients with the obstructive sleep apnea syndrome. Immediately postapnea during sleep Psa increased significantly compared with the earlier stages of apnea and this was preceded by a rise of MSNA (n = 5). In contrast to blood pressure, MBV remained unchanged. Because resistance = blood pressure/blood flow, limb vascular resistance increased by 29 +/- 8% from late apnea to postapnea (n = 7, p < 0.002). Voluntary breathhold maneuvers during room air exposure evoked similar responses (n = 10). Supplemental oxygen administered via nonrebreather face mask attenuated the MSNA and vasoconstrictor responses to obstructive (n = 2) and voluntary apneas (n = 10). Our data suggest that obstructive apneas in patients with the obstructive apnea syndrome are accompanied by transient limb vasoconstriction. This vasoconstrictor response appears to be, at least in part, mediated by the sympathetic nervous system and may be linked to hypoxia.
Zizys, Darius; Gaidys, Rimvydas; Dauksevicius, Rolanas; Ostasevicius, Vytautas; Daniulaitis, Vytautas
2015-12-23
The piezoelectric transduction mechanism is a common vibration-to-electric energy harvesting approach. Piezoelectric energy harvesters are typically mounted on a vibrating host structure, whereby alternating voltage output is generated by a dynamic strain field. A design target in this case is to match the natural frequency of the harvester to the ambient excitation frequency for the device to operate in resonance mode, thus significantly increasing vibration amplitudes and, as a result, energy output. Other fundamental vibration modes have strain nodes, where the dynamic strain field changes sign in the direction of the cantilever length. The paper reports on a dimensionless numerical transient analysis of a cantilever of a constant cross-section and an optimally-shaped cantilever with the objective to accurately predict the position of a strain node. Total effective strain produced by both cantilevers segmented at the strain node is calculated via transient analysis and compared to the strain output produced by the cantilevers segmented at strain nodes obtained from modal analysis, demonstrating a 7% increase in energy output. Theoretical results were experimentally verified by using open-circuit voltage values measured for the cantilevers segmented at optimal and suboptimal segmentation lines.
Narita, Takuma; Hatakeyama, Shingo; Koie, Takuya; Hosogoe, Shogo; Matsumoto, Teppei; Soma, Osamu; Yamamoto, Hayato; Yoneyama, Tohru; Tobisawa, Yuki; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara
2017-08-31
Urinary tract obstruction and postoperative hydronephrosis are risk factor for renal function deterioration after orthotopic ileal neobladder construction. However, reports of relationship between transient hydronephrosis and renal function are limited. We assess the influence of postoperative transient hydronephrosis on renal function in patients with orthotopic ileal neobladder construction. Between January 2006 and June 2013, we performed radical cystectomy in 164 patients, and 101 received orthotopic ileal neobladder construction. This study included data available from 64 patients with 128 renal units who were enrolled retrospectively. The hydronephrosis grade of each renal unit scored 0-4. The patients were divided into 4 groups according to the grade of hydronephrosis: control, low, intermediate, and high. The grade of postoperative hydronephrosis was compared with renal function 1 month and 1 year after surgery. There were no significant differences in renal function before surgery between groups. One month after surgery, the presence of hydronephrosis was significantly associated with decreased renal function. However, 1 year after urinary diversion hydronephrosis grades were improved significantly, and renal function was comparable between groups. Postoperative hydronephrosis at 1 month had no significant influence on renal function 1 year after ileal neobladder construction. Limitations include retrospective design, short follow-up periods, and a sample composition. The presence of transient hydronephrosis immediately after surgery may have limited influence on renal function 1 year after ileal neobladder construction.
ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS
Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.
2014-01-01
Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. PMID:24656971
[Transaxillary robot-assisted thyroidectomy: First experiences with a new operation technique].
Eckhardt, S; Maurer, E; Fendrich, V; Bartsch, D K
2015-10-01
The main advantage of transaxillary robotic-assisted thyroid surgery (TRAT) is the avoidance of a scar on the neck. As TRAT is still rarely performed in Germany, there are not yet any German reports on acceptance, operation times and complications. In a pilot study all patients with an indication for hemithyroidectomy without preoperative evidence of malignancies or previous neck surgery and a lobe size < 30 ml, a body mass index (BMI) < 30 and age > 18 years were offered transaxillary robotic-assisted hemithyroidectomy (TRAHT) after a detailed explanation of this operation. The acceptance of this new technique, the operation time, complications and patient satisfaction were prospectively recorded and analyzed. Between January 2013 and October 2014 a total of 65 patients were offered the option of a TRAHT and 21 (32%) patients opted for this surgical technique. None of these 21 operations had to be converted and there were no intraoperative complications. The median operation time was 190 min (range 106-300 min) with a significant learning curve (first 5 TRAHT 219 min and last 5 TRAHT 163 min), 10 (48%) patients had a postoperative slight transient skin dysesthesia in the area of the access route, 4 (19%) patients had a transient recurrent laryngeal nerve palsy and 2 patients (9%) had a transient upper brachial plexus palsy. After the first 21 TRAHT operations, 2 Dunhill operations for Grave's disease were also performed via a single axillary incision. The operation times were 320 min and 260 min without complications and 21 out of the 23 patients (91%) were highly satisfied with the cosmetic result and would choose TRAT again. The TRAT procedure still has low acceptance by German patients but patient satisfaction after surgery is high due to the cosmetic result. The extended operation time, new complications (e.g. transient plexus palsy) and a potentially increased rate of transient recurrent laryngeal nerve palsy must be critically considered.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Plotkowski, A.; Kirka, M. M.; Babu, S. S.
A fundamental understanding of spatial and temporal thermal distributions is crucial for predicting solidification and solid-state microstructural development in parts made by additive manufacturing. While sophisticated numerical techniques that are based on finite element or finite volume methods are useful for gaining insight into these phenomena at the length scale of the melt pool (100 - 500 µm), they are ill-suited for predicting engineering trends over full part cross-sections (> 10 x 10 cm) or many layers over long process times (> many days) due to the necessity of fully resolving the heat source characteristics. On the other hand, itmore » is extremely difficult to resolve the highly dynamic nature of the process using purely in-situ characterization techniques. This article proposes a pragmatic alternative based on a semi-analytical approach to predicting the transient heat conduction during powder bed metal additive manufacturing process. The model calculations were theoretically verified for selective laser melting of AlSi10Mg and electron beam melting of IN718 powders for simple cross-sectional geometries and the transient results are compared to steady state predictions from the Rosenthal equation. It is shown that the transient effects of the scan strategy create significant variations in the melt pool geometry and solid-liquid interface velocity, especially as the thermal diffusivity of the material decreases and the pre-heat of the process increases. With positive verification of the strategy, the model was then experimentally validated to simulate two point-melt scan strategies during electron beam melting of IN718, one intended to produce a columnar and one an equiaxed grain structure. Lastly, through comparison of the solidification conditions (i.e. transient and spatial variations of thermal gradient and liquid-solid interface velocity) predicted by the model to phenomenological CET theory, the model accurately predicted the experimental grain structures.« less
Tyrosine triple mutated AAV2-BDNF gene therapy in a rat model of transient IOP elevation
Igarashi, Tsutomu; Kobayashi, Maika; Kameya, Shuhei; Fujimoto, Chiaki; Nakamoto, Kenji; Takahashi, Hisatomo; Igarashi, Toru; Miyake, Noriko; Iijima, Osamu; Hirai, Yukihiko; Shimada, Takashi; Okada, Takashi; Takahashi, Hiroshi
2016-01-01
Purpose We examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), which provides protection to retinal ganglion cells (RGCs) in rodents, in a model of transient intraocular pressure (IOP) elevation using a mutant (triple Y-F) self-complementary adeno-associated virus type 2 vector encoding BDNF (tm-scAAV2-BDNF). Methods The tm-scAAV2-BDNF or control vector encoding green fluorescent protein (GFP; tm-scAAV2-GFP) was intravitreally administered to rats, which were then divided into four groups: control, ischemia/reperfusion (I/R) injury only, I/R injury with tm-scAAV2-GFP, and tm-scAAV2-BDNF. I/R injury was then induced by transiently increasing IOP, after which the rats were euthanized to measure the inner retinal thickness and cell counts in the RGC layer. Results Intravitreous injection of tm-scAAV2-BDNF resulted in high levels of BDNF expression in the neural retina. Histological analysis showed that the inner retinal thickness and cell numbers in the RGC layer were preserved after transient IOP elevation in eyes treated with tm-scAAV2-BDNF but not in the other I/R groups. Significantly reduced glial fibrillary acidic protein (GFAP) immunostaining after I/R injury in the rats that received tm-scAAV2-BDNF indicated reduced retinal stress, and electroretinogram (ERG) analysis confirmed preservation of retinal function in the tm-scAAV2-BDNF group. Conclusions These results demonstrate the feasibility and effectiveness of neuroprotective gene therapy using tm-scAAV2-BDNF to protect the inner retina from transiently high intraocular pressure. An in vivo gene therapeutic approach to the clinical management of retinal diseases in conditions such as glaucoma, retinal artery occlusion, hypertensive retinopathy, and diabetic retinopathy thus appears feasible. PMID:27440998
Takakusagi, Yoichi; Matsumoto, Shingo; Saito, Keita; Matsuo, Masayuki; Kishimoto, Shun; Wojtkowiak, Jonathan W; DeGraff, William; Kesarwala, Aparna H; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Munasinghe, Jeeva P; Gillies, Robert J; Mitchell, James B; Hart, Charles P; Krishna, Murali C
2014-01-01
TH-302 is a hypoxia-activated prodrug (HAP) of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR) oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2), with minimal effect under aerobic conditions (21% O2). Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3). Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3)), significantly delayed tumor growth. Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the appropriate tumor size and oxygen concentration.
Plotkowski, A.; Kirka, M. M.; Babu, S. S.
2017-10-16
A fundamental understanding of spatial and temporal thermal distributions is crucial for predicting solidification and solid-state microstructural development in parts made by additive manufacturing. While sophisticated numerical techniques that are based on finite element or finite volume methods are useful for gaining insight into these phenomena at the length scale of the melt pool (100 - 500 µm), they are ill-suited for predicting engineering trends over full part cross-sections (> 10 x 10 cm) or many layers over long process times (> many days) due to the necessity of fully resolving the heat source characteristics. On the other hand, itmore » is extremely difficult to resolve the highly dynamic nature of the process using purely in-situ characterization techniques. This article proposes a pragmatic alternative based on a semi-analytical approach to predicting the transient heat conduction during powder bed metal additive manufacturing process. The model calculations were theoretically verified for selective laser melting of AlSi10Mg and electron beam melting of IN718 powders for simple cross-sectional geometries and the transient results are compared to steady state predictions from the Rosenthal equation. It is shown that the transient effects of the scan strategy create significant variations in the melt pool geometry and solid-liquid interface velocity, especially as the thermal diffusivity of the material decreases and the pre-heat of the process increases. With positive verification of the strategy, the model was then experimentally validated to simulate two point-melt scan strategies during electron beam melting of IN718, one intended to produce a columnar and one an equiaxed grain structure. Lastly, through comparison of the solidification conditions (i.e. transient and spatial variations of thermal gradient and liquid-solid interface velocity) predicted by the model to phenomenological CET theory, the model accurately predicted the experimental grain structures.« less
[Clinical and sperm follow-up after subinguinal varicocelectomy].
Vicari, E; Arancio, A; Costanzo, C; Ingrassia, G; Cannizzaro, M A
2000-06-01
In order to evaluate the sperm output and the adverse-side-effects after subinguinal varicoceloctomy, a follow-up study of 16 months was performed on 196 selected patients (aged from 22 to 43 years) affected by left varicocele (VR). In the pre-treatment, both Doppler ultrasonography and didymo-epididymal ultrasonography allowed to distinguish two homogeneous patient groups: group A (no. = 136), including patients affected by VR alone and, group B (n. = 60), including patients with VR combined to coincidental didymo-epididymal morphological abnormalities, DEMA). These DEMA lesions (testis size < 12 ml, epididymides abnormalities: increased head- > or = 12 mm- and/or tail- > or = 6 mm-diameter, multiple microcysts, large idrocele) were omolaterally to VR in 30/60 (50%), eterolaterally in 19/60 (31.7%) or bilaterally in 11/60 (18.3%). During sperm follow-up, group A patients showed both a significant temporal change (p < 0.01 ANOVA) of all sperm parameters studied (sperm density, total sperm count, motility and morphology) from month 8 onward and sperm values significantly higher than found in group B patients. On the contrary, the sperm parameters of group B patients did not change significantly during the follow-up observations. As far as the varicocelectomy-mediated clinical symptoms, some patients complained early and transiently (on 1-2-4 weeks following varicocelectomy) the following symptoms: didymal pain (1.5%), didymo-epididymal pain (4.1%) and parasthesiaes on the anterior-medial side of the left thigh (4.1%) or scrotal (3.1%); only four patients (2%) complained permanent paresthesiaes on the anterior-medial side of the left thigh. Furthermore, the clinical follow-up also revealed a low rate of complications: persistent VR (3.6%), hydrocele (1.5%), intrascrotal venous ecstasies (6.1%), epididymitis (0.5%). Some morpho-structural abnormalities at US scans were transient (1-2 weeks): scrotal oedema (6.1%), orchitis (2%), orchi-epididymitis (1%). Subinguinal varicocelectomy performed on large population demonstrated a significant improvement of the sperm output from month 8th onward in patients with VR alone, while sperm parameters did not show any significant change in patients with VR plus coincidental DEMA. This surgical technique also demonstrated safety since both low rates of symptoms and (transient) complications were registered.
NASA Technical Reports Server (NTRS)
Tacina, R. R.
1984-01-01
Non-steady combustion problems can result from engine sources such as accelerations, decelerations, nozzle adjustments, augmentor ignition, and air perturbations into and out of the compressor. Also non-steady combustion can be generated internally from combustion instability or self-induced oscillations. A premixed-prevaporized combustor would be particularly sensitive to flow transients because of its susceptability to flashback-autoignition and blowout. An experimental program, the Transient Flow Combustion Study is in progress to study the effects of air and fuel flow transients on a premixed-prevaporized combustor. Preliminary tests performed at an inlet air temperature of 600 K, a reference velocity of 30 m/s, and a pressure of 700 kPa. The airflow was reduced to 1/3 of its original value in a 40 ms ramp before flashback occurred. Ramping the airflow up has shown that blowout is more sensitive than flashback to flow transients. Blowout occurred with a 25 percent increase in airflow (at a constant fuel-air ratio) in a 20 ms ramp. Combustion resonance was found at some conditions and may be important in determining the effects of flow transients.
On the transient dynamics of piezoelectric-based, state-switched systems
NASA Astrophysics Data System (ADS)
Lopp, Garrett K.; Kelley, Christopher R.; Kauffman, Jeffrey L.
2018-01-01
This letter reports on the induced mechanical transients for piezoelectric-based, state-switching approaches utilizing both experimental tests and a numerical model that more accurately captures the dynamics associated with a switch between stiffness states. Currently, switching models instantaneously dissipate the stored piezoelectric voltage, resulting in a discrete change in effective stiffness states and a discontinuity in the system dynamics during the switching event. The proposed model allows for a rapid but continuous voltage dissipation and the corresponding variation between stiffness states, as one sees in physical implementations. This rapid variation in system stiffness when switching at a point of non-zero strain leads to high-frequency, large-amplitude transients in the system acceleration response. Utilizing a fundamental piezoelectric bimorph, a comparison between the numerical and experimental results reveals that these mechanical transients are much stronger than originally anticipated and masked by measurement hardware limitations, thus highlighting the significance of an appropriate system model governing the switch dynamics. Such a model enables designers to analyze systems that incorporate piezoelectric-based state switching with greater accuracy to ensure that these transients do not degrade the intended performance. Finally, if the switching does create unacceptable transients, controlling the duration of voltage dissipation enables control over the frequency content and peak amplitudes associated with the switch-induced acceleration transients.
Mode and climatic factors effect on energy losses in transient heat modes of transmission lines
NASA Astrophysics Data System (ADS)
Bigun, A. Ya; Sidorov, O. A.; Osipov, D. S.; Girshin, S. S.; Goryunov, V. N.; Petrova, E. V.
2018-01-01
Electrical energy losses increase in modern grids. The losses are connected with an increase in consumption. Existing models of electric power losses estimation considering climatic factors do not allow estimating the cable temperature in real time. Considering weather and mode factors in real time allows to meet effectively and safely the consumer’s needs to minimize energy losses during transmission, to use electric power equipment effectively. These factors increase an interest in the evaluation of the dynamic thermal mode of overhead transmission lines conductors. The article discusses an approximate analytic solution of the heat balance equation in the transient operation mode of overhead lines based on the least squares method. The accuracy of the results obtained is comparable with the results of solving the heat balance equation of transient thermal mode with the Runge-Kutt method. The analysis of mode and climatic factors effect on the cable temperature in a dynamic thermal mode is presented. The calculation of the maximum permissible current for variation of weather conditions is made. The average electric energy losses during the transient process are calculated with the change of wind, air temperature and solar radiation. The parameters having the greatest effect on the transmission capacity are identified.
Strong, A J; Harland, S P; Meldrum, B S; Whittington, D J
1996-05-01
A method for the detection and tracking of propagated fluorescence transients as indicators of depolarizations in focal cerebral ischemia is described, together with initial results indicating the potential of the method. The cortex of the right cerebral hemisphere was exposed for nonrecovery experiments in five cats anesthetized with chloralose and subjected to permanent middle cerebral artery (MCA) occlusion. Fluorescence with 370-nm excitation (attributed to the degree of reduction of the NAD/H couple) was imaged with an intensified charge-coupled device camera and digitized. Sequences of images representing changes in gray level from a baseline image were examined, together with the time courses of mean gray levels in specified regions of interest. Spontaneous increases in fluorescence occurred, starting most commonly at the edge of areas of core ischemia; they propagated usually throughout the periinfarct zone and resolved to varying degrees and at varying rates, depending on proximity of the locus to the MCA input. When a fluorescence transient reached the anterior cerebral artery territory, its initial polarity reversed from an increase to a decrease in fluorescence. An initial increase in fluorescence in response to the arrival of a transient may characterize cortex that will become infarcted, if pathophysiological changes in the periinfarct zone are allowed to evolve naturally.
Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang; Detlefsen, Sönke; Antonsen, Steen; Krag, Aleksander
2018-04-01
Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P = .521 and .004 for comparison with ELF). Adding a serum marker to transient elastography analysis did not increase accuracy. For patients in primary care, ELF values below 10.5 and FibroTest values below 0.58 had negative predictive values for advanced liver fibrosis of 98% and 94%, respectively. In a prospective, direct comparison of tests, ELF and FibroTest identified advanced liver fibrosis in alcoholic patients from primary and secondary care with high diagnostic accuracy (AUROC values of 0.90 or higher using biopsy as reference). Advanced fibrosis can be ruled out in primary health care patients based on an ELF value below 10.5 or a FibroTest value below 0.58. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
Transient Thermoelectric Solution Employing Green's Functions
NASA Technical Reports Server (NTRS)
Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred
2014-01-01
The study works to formulate convenient solutions to the problem of a thermoelectric couple operating under a time varying condition. Transient operation of a thermoelectric will become increasingly common as thermoelectric technology permits applications in an increasing number of uses. A number of terrestrial applications, in contrast to steady-state space applications, can subject devices to time varying conditions. For instance thermoelectrics can be exposed to transient conditions in the automotive industry depending on engine system dynamics along with factors like driving style. In an effort to generalize the thermoelectric solution a Greens function method is used, so that arbitrary time varying boundary and initial conditions may be applied to the system without reformulation. The solution demonstrates that in thermoelectric applications of a transient nature additional factors must be taken into account and optimized. For instance, the materials specific heat and density become critical parameters in addition to the thermal mass of a heat sink or the details of the thermal profile, such as oscillating frequency. The calculations can yield the optimum operating conditions to maximize power output andor efficiency for a given type of device.
Advanced LIGO low-latency searches
NASA Astrophysics Data System (ADS)
Kanner, Jonah; LIGO Scientific Collaboration, Virgo Collaboration
2016-06-01
Advanced LIGO recently made the first detection of gravitational waves from merging binary black holes. The signal was first identified by a low-latency analysis, which identifies gravitational-wave transients within a few minutes of data collection. More generally, Advanced LIGO transients are sought with a suite of automated tools, which collectively identify events, evaluate statistical significance, estimate source position, and attempt to characterize source properties. This low-latency effort is enabling a broad multi-messenger approach to the science of compact object mergers and other transients. This talk will give an overview of the low-latency methodology and recent results.
Varner, Erika L; Leong, Chi Leng; Jaquins-Gerstl, Andrea; Nesbitt, Kathryn M; Boutelle, Martyn G; Michael, Adrian C
2017-08-16
Microdialysis is well established in chemical neuroscience as a mainstay technology for real time intracranial chemical monitoring in both animal models and human patients. Evidence shows that microdialysis can be enhanced by mitigating the penetration injury caused during the insertion of microdialysis probes into brain tissue. Herein, we show that retrodialysis of dexamethasone in the rat cortex enhances the microdialysis detection of K + and glucose transients induced by spreading depolarization. Without dexamethasone, quantification of glucose transients was unreliable by 5 days after probe insertion. With dexamethasone, robust K + and glucose transients were readily quantified at 2 h, 5 days, and 10 days after probe insertion. The amplitudes of the K + transients declined day-to-day following probe insertion, and the amplitudes of the glucose transients exhibited a decreasing trend that did not reach statistical significance. Immunohistochemistry and fluorescence microscopy confirm that dexamethasone is highly effective at preserving a healthy probe-brain interface for at least 10 days even though retrodialysis of dexamethasone ceased after 5 days.
A theory of post-stall transients in multistage axial compression systems
NASA Technical Reports Server (NTRS)
Moore, F. K.; Greitzer, E. M.
1985-01-01
A theory is presented for post stall transients in multistage axial compressors. The theory leads to a set of coupled first-order ordinary differential equations capable of describing the growth and possible decay of a rotating-stall cell during a compressor mass-flow transient. These changing flow features are shown to have a significant effect on the instantaneous compressor pumping characteristic during unsteady operation, and henace on the overall system behavior. It is also found from the theory that the ultimate mode of system response, stable rotating stall or surge, depends not only on the B parameter but also on other parameters, such as the compressor length-to-diameter ratio. Small values of this latter quantity tend to favor the occurrence of surge, as do large values of B. A limited parametric study is carried out to show the impact of the different system features on transient behavior. Based on analytical and numerical results, several specific topics are suggested for future research on post-stall transients.
Severe hydramnios and preterm delivery in association with transient maternal diabetes insipidus.
Weinberg, Lori E; Dinsmoor, Mara J; Silver, Richard K
2010-08-01
Diabetes insipidus is rare in pregnancy. It is characterized by hypoosmolar polyuria and may be central, nephrogenic, or transient in etiology; the latter is presumably related to excess placental vasopresinase production. In theory, fetal effects of this endocrine condition may include hydramnios secondary to fetal polyuria. A pregnant patient developed rapid-onset second-trimester hydramnios that prompted a thorough fetal and maternal evaluation. She ultimately was diagnosed with transient diabetes insipidus of pregnancy because of an abrupt change in her voiding pattern at 20 weeks of gestation, significant polydipsia, and laboratory studies that revealed a hypoosmolar polyuria with normal serum and urine electrolytes. Transient neonatal polyuria also was confirmed in association with this unique maternal endocrine syndrome. The most likely cause of hydramnios in this case is transient maternal diabetes insipidus of pregnancy from excessive secretion of placental vasopressinase resulting in fetal polyuria. In cases of hydramnios of unknown etiology, if a history of maternal polyuria is elicited and confirmed, diabetes insipidus of pregnancy may play a role in some cases.
Brunst, Kelly J; Ryan, Patrick H; Brokamp, Cole; Bernstein, David; Reponen, Tiina; Lockey, James; Khurana Hershey, Gurjit K; Levin, Linda; Grinshpun, Sergey A; LeMasters, Grace
2015-08-15
The timing and duration of traffic-related air pollution (TRAP) exposure may be important for childhood wheezing and asthma development. We examined the relationship between TRAP exposure and longitudinal wheezing phenotypes and asthma at age 7 years. Children completed clinical examinations annually from age 1 year through age 4 years and age 7 years. Parental-reported wheezing was assessed at each age, and longitudinal wheezing phenotypes (early-transient, late-onset, persistent) and asthma were defined at age 7 years. Participants' time-weighted exposure to TRAP, from birth through age 7 years, was estimated using a land-use regression model. The relationship between TRAP exposure and wheezing phenotypes and asthma was examined. High TRAP exposure at birth was significantly associated with both transient and persistent wheezing phenotypes (adjusted odds ratio [aOR] = 1.64; 95% confidence interval [CI], 1.04-2.57 and aOR = 2.31; 95% CI, 1.28-4.15, respectively); exposure from birth to age 1 year and age 1 to 2 years was also associated with persistent wheeze. Only children with high average TRAP exposure from birth through age 7 years were at significantly increased risk for asthma (aOR = 1.71; 95% CI, 1.01-2.88). Early-life exposure to TRAP is associated with increased risk for persistent wheezing, but only long-term exposure to high levels of TRAP throughout childhood was associated with asthma development.
Stuart, Andrew; Preast, June L
2012-01-01
In previous studies, otoacoustic emissions (OAEs) have been found to be larger in normal-hearing children with sickle cell disease (SCD). It was hypothesized that some dysfunction or reduction in the medial olivocochlear efferent suppression of outer hair cell activity was responsible for this phenomenon. To test this hypothesis, contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs) was examined in children with and without SCD. Thirteen African American school-aged normal-hearing children with homozygous SCD and 13 age- and gender-matched control children participated. TEOAEs were obtained bilaterally with 80 dB peSPL nonlinear click stimuli. To examine contralateral suppression, TEOAEs were obtained with 60 dB peSPL linear click stimuli with and without a contralateral 65 dB SPL white noise suppressor. Overall and half-octave band TEOAE levels were found to be larger in children with SCD relative to the normal control children (p < 0.05), consistent with previous reports of increased OAE levels. There was no significant difference (p > 0.05) in the absolute or proportional amount of TEOAE suppression as a function of group and ear. There were also no significant correlations or linear predictive relationships between TEOAE suppression and TEOAE level for either ear or group (p > 0.05). These findings do not support the notion that increased OAE levels in children with SCD are a consequence of abnormal medial olivocochlear system function as assessed with contralateral suppression of TEOAEs.
Lu, Xiufang; Gu, Renjun; Hu, Weimin; Sun, Zhitang; Wang, Gaiqing; Wang, Li; Xu, Yuming
2018-06-01
The aim of the present study was to identify the effect of heme oxygenase (HO)-1 gene on cerebral ischemia-reperfusion injury. Sprague-Dawley rats were divided randomly into four groups: Sham group, vehicle group, empty adenovirus vector (Ad) group and recombinant HO-1 adenovirus (Ad-HO-1) transfection group. Rats in the vehicle, Ad and Ad-HO-1 groups were respectively injected with saline, Ad or Ad-HO-1 for 3 days prior to cerebral ischemia-reperfusion injury. Subsequently, the middle cerebral artery occlusion method was used to establish the model of cerebral ischemia-reperfusion injury. Following the assessment of neurological function, rats were sacrificed, and the infarction volume and apoptotic index in rat brains were measured. Furthermore, the protein expression levels of HO-1 in brain tissues were detected using western blot analysis. Results indicated that the neurological score of the Ad-HO-1 group was significantly increased compared with the Ad or vehicle groups, respectively (P<0.001). The volume of cerebral infarction and the index score of neuronal apoptosis in the vehicle and Ad groups was significantly increased compared with the Ad-HO-1 group (P<0.01). The death of neuronal cells following cerebral ischemia-reperfusion injury reduced remarkably induced by over-expression of HO-1. These findings suggest a neuroprotective role of HO-1 against brain injury induced by transient cerebral ischemia-reperfusion injury.
Silva, Darizy Flavia; de Almeida, Monica Moura; Chaves, Cinthia Guedes; Braz, Ana Letícia; Gomes, Maria Aparecida; Pinho-da-Silva, Leidiane; Pesquero, Jorge Luiz; Andrade, Viviane Aguiar; Leite, Maria de Fátima; de Albuquerque, José George Ferreira; Araujo, Islania Giselia Albuquerque; Nunes, Xirley Pereira; Barbosa-Filho, José Maria; Cruz, Jader dos Santos; Correia, Nadja de Azevedo; de Medeiros, Isac Almeida
2015-01-01
In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the understanding of the role of these thermosensitive TRP channels in vascular tissue. Thus, message and protein levels of TRPM8 were measured by semi-quantitative PCR and western blotting in superior mesenteric arteries from 12 week-old Spague-Dawley (SD) rats. Isometric tension recordings evaluated the relaxant response in mesenteric rings were also performed. Additionally, the intracellular Ca2+ changes in mesenteric artery myocytes were measured using confocal microscopy. Using PCR and western blotting, both TRPM8 channel mRNA and protein expression was measured in SD rat mesenteric artery. Rotundifolone and menthol induced relaxation in the isolated superior mesenteric artery from SD rats and improved the relaxant response induced by cool temperatures. Also, this monoterpene induced an increase in transient intracellular Ca2+. These responses were significantly attenuated by pretreatment with capsazepine or BCTC, both TRPM8 channels blockers. The response induced by rotundifolone was not significantly attenuated by ruthenium red, a non-selective TRP channels blocker, or following capsaicin-mediated desensitization of TRPV1. Our findings suggest that rotundifolone induces relaxation by activating TRPM8 channels in rat superior mesenteric artery, more selectively than menthol, the classic TRPM8 agonist, and TRPM8 channels participates in vasodilatory pathways in isolated rat mesenteric arteries. PMID:26599698
New perspectives on the role of α- and β-amylases in transient starch synthesis.
Wu, Alex Chi; Ral, Jean-Philippe; Morell, Matthew K; Gilbert, Robert G
2014-01-01
Transient starch in leaves is synthesized by various biosynthetic enzymes in the chloroplasts during the light period. This paper presents the first mathematical model for the (bio)synthesis of the chain-length distribution (CLD) of transient starch to aid the understanding of this synthesis. The model expresses the rate of change of the CLD in terms of the actions of the enzymes involved. Using this to simulate the experimental CLD with different enzyme combinations is a new means to test for enzymes that are significant to the rate of change of the CLD during synthesis. Comparison between the simulated CLD from different enzyme combinations and the experimental CLD in the leaves of the model plant Arabidopsis thaliana indicate α-amylase, in addition to the core starch biosynthetic enzymes, is also involved in the modification of glucans for the synthesis of insoluble starch granules. The simulations suggest involvement of β-amylase, in the absence of α-amylase in mutants, slows the rate of attaining a crystalline-competent CLD for crystallization of glucans to form insoluble starch. This suggests a minor role of β-amylase in shaping normal starch synthesis. The model simulation predicts that debranching of glucans is an efficient mechanism for the attainment of crystalline-competent CLD; however, attaining this is still possible, albeit slower, through combinations of α- and β-amylase in the absence of isoamylase-type debranching enzyme. In Arabidopsis defective in one of the isoamylase-type debranching enzymes, the impact of α-amylase in starch synthesis is reduced, while β-amylase becomes significantly involved, slowing the rate of synthesis in this mutant. Modeling of transient starch CLD brings to light previously unrecognized but significant effects of α- and β-amylase on the rate of transient starch synthesis.